Conditions: Painful Diabetic Neuropathy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 112
Healthy volunteers: no

Brief summary:
This is a study investigating the effect of MEDI7352 on chronic pain in participants with painful diabetic neuropathy.

The study incudes a screening period of up to 45 days and a 12-week treatment period during which MEDI7352 or placebo will be administered intravenously (IV) on 6 occasions, with each dose separated by 14 days. There will be a 6-week follow-up period.

Participants will randomly be assigned to double-blind treatment with one of 4 dose levels of MEDI7352 or placebo.

Detailed description:

Arms:
arm 1: Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period. arm 2: Participants received 6 doses of IV MEDl7352 low dose during 12-week treatment period. arm 3: Participants received 6 doses of IV MEDl7352 medium dose during 12-week treatment period. arm 4: Participants received 6 doses of IV MEDl7352 high dose during 12-week treatment period.

Interventions: intervention 1: MEDI7352 intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive IV infusion of MEDI7352 as stated in arm description. intervention 2: Participants will receive IV infusion of placebo as stated in arm description.

Protocol document:
Prot_002.pdf: 
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PROTOCOL AMENDMENT
PRODUCT NAME/NUMBER:
MEDI7352
PROTOCOL NUMBER:
D5680C00002
EUDRACT NUMBER:
2018-002523-42
DEVELOPMENT PHASE:
2
PROTOCOL TITLE:
A Randomised, Double-Blind, Placebo-Controlled,
Dose-Response Study of the Efficacy and Safety of 
MEDI7352 in Subjects with Painful Diabetic Neuropathy
PROTOCOL DATE:
Original Protocol Version 1.0, 24-Jul-2018
AMENDMENT 1 DATE:
Amended Protocol Version 2.0, 29-May-2019
AMENDMENT 2 DATE:
Amended Protocol Version 3.0, 21-Feb-2020
AMENDMENT 3 DATE:
Amended Protocol Version 4.0, 01-Oct-2020 (Not 
submitted/not implemented at sites)
AMENDMENT 4 DATE:
Amended Protocol Version 5.0, 04-Dec-2020
AMENDMENT 5 DATE:
Amended Protocol Version 5.1, 15-Mar-2021 (Specific to 
Denmark only)
AMENDMENT 6 DATE:
Amended Protocol Version 6.0, 26-Oct-2021
AMENDMENT 7 DATE:
Amended Protocol Version 7.0, 13-Apr-2022
SPONSORED BY:
AstraZeneca AB
151 85 
Sodertalje, Sweden
CONTRACT RESEARCH 
ORGANIZATION:
Premier Research
3800 Paramount Parkway, Suite 400
Morrisville, NC 27560 USA
This study will be performed in compliance with International Conference on Harmonisation 
(ICH) Good Clinical Practices and applicable regulatory requirements, including the archiving of 
essential documents. Information contained in this protocol is confidential in nature, and may not 
be used, divulged, published, or otherwise disclosed to others except to the extent necessary to 
obtain approval of the institutional review board or independent ethics committee, or as required 
by law. Persons to whom this information is disclosed should be informed that it is confidential 
and may not be further disclosed without the express permission of AstraZeneca AB.
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1
SPONSOR SIGNATURES
PROTOCOL NUMBER:
D5680C00002
PROTOCOL TITLE:
A Randomised, Double-Blind, Placebo-Controlled,
Dose-Response Study of the Efficacy and Safety of MEDI7352 in 
Subjects with Painful Diabetic Neuropathy
This Clinical Study Protocol has been subjected to an internal AstraZeneca peer review.
I agree to the terms of this Clinical Study Protocol/Amendment.
Biopharmaceuticals R&D, Neuroscience
AstraZeneca 
Aaron Klug Building
Granta Park
Cambridge CB21 6GH
United Kingdom
Tel: 
Date
(Day Month Year)
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PROTOCOL NUMBER:
D5680C00002
PROTOCOL TITLE:
A Randomised, Double-Blind, Placebo-Controlled, 
Dose-Response Study of the Efficacy and Safety of MEDI7352 in 
Subjects with Painful Diabetic Neuropathy
This Clinical Study Protocol has been subjected to an internal AstraZeneca peer review.
I agree to the terms of this Clinical Study Protocol/Amendment.
, Clinical Development, Neuroscience
R&D Biopharmaceuticals, Neuroscience
AstraZeneca 
Aaron Klug Building
Granta Park
Cambridge CB21 6GH
United Kingdom
Tel: 
Date
(Day Month Year)
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AMENDED PROTOCOL
The following are the amended protocol and appendices, including all revisions specified in the 
Reasons for Amendment and Summary of Amended Sections.
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2
PROTOCOL SUMMARY
2.1
Synopsis
PRODUCT 
NAME/NUMBER
MEDI7352
PROTOCOL 
NUMBER
D5680C00002
EUDRACT 
NUMBER
2018-002523-42
DEVELOPMENT 
PHASE
2
PROTOCOL TITLE
A Randomised, Double-Blind, Placebo-Controlled, Dose-Response Study of the Efficacy 
and Safety of MEDI7352 in Subjects with Painful Diabetic Neuropathy
INDICATION
Painful Diabetic Neuropathy
OBJECTIVES
Primary: To assess the efficacy of MEDI7352 versus placebo on chronic pain in subjects 
with painful diabetic neuropathy (PDN) currently taking standard of care medication for 
their PDN pain.
Secondary:
To assess the safety and tolerability of MEDI7352 in subjects with PDN
To assess the pharmacokinetics (PK),
pharmacodynamics (PD), and 
immunogenicity of MEDI7352 in subjects with PDN 
To characterise the dose-response relationship of MEDI7352 on chronic pain in 
subjects with PDN
Exploratory: 
RATIONALE
The study is comprised of 4 stages. The first stage will assess safety of 
 in the 
PDN population. The second stage will compare an expected efficacious dose, 
, 
to placebo. The third stage will compare the highest expected efficacious dose, 
 
to placebo. The fourth stage will study 3 dose levels of MEDI7352 (
, and 
) versus placebo to enable a thorough characterisation of the efficacy 
dose-response relationship.
STUDY DESIGN
This is a randomised, double-blind, placebo-controlled study of MEDI7352 in subjects 
with moderate to severe chronic PDN persistent for 6 months or longer, not adequately 
controlled by standard of care treatments, caused by type 1 or type 2 diabetes mellitus. 
The study incorporates a screening period of up to 45 days and a 12-week double-blind 
treatment period during which MEDI7352 or placebo will be administered intravenously 
(IV) on 6 occasions, with each dose separated by 14 days. There will be a 6-week 
follow-up period. There will be 4 stages in the study: in the first stage, subjects will be 
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randomly assigned to placebo or the lowest dose (
) until at least 10 subjects have 
been recruited. In the second stage, up to a maximum of 30 subjects will be randomly 
assigned to placebo or 
of MEDI7352; prior to commencing the second stage, 
the safety and tolerability experience following administration of multiple doses of
in the Phase 1 study of MEDI7352 will be evaluated. In stage 3 of the study,
approximately 67 subjects will be randomly assigned to placebo or 
MEDI7352 to ensure that sufficient subjects are evaluable for the pre-planned interim 
analysis. Prior to commencing the third stage, the safety and tolerability experience 
in the Phase 1 study of 
MEDI7352 will be evaluated. Administrative analyses will also be conducted during the 
third stage of the study to confirm decision making for stage 4 with respect to the exact 
sample size and dose allocation ratio. Upon enrolment of approximately 67 subjects in 
stage 3, approximately 165 eligible subjects will be randomly assigned to treatment with 
equal allocation across 3 dose levels of MEDI7352 or placebo in stage 4, to ensure that 
approximately 236 subjects are evaluable for the efficacy analysis of stages 2-4
combined.
PLANNED NUMBER 
OF SUBJECTS
Approximately 272 eligible subjects will be randomly assigned to double-blind treatment 
with one of 4 dose levels of MEDI7352 (dependent upon stage of the study) or placebo 
to ensure that approximately 236 subjects are evaluable for the efficacy analysis of stages 
2-4 combined.
STUDY ENTRY 
CRITERIA
Inclusion criteria:
General
1.
Male, or postmenopausal or surgically sterile female, 18 to 80 years of age 
(inclusive) on the day of randomisation. Post-menopausal women must have had 
months of spontaneous amenorrhea (with follicle-stimulating hormone [FSH] 
years; women >60 years do not require a FSH test) and 
must have had a negative pregnancy test result at screening. Surgically sterile women 
are defined as those who have had a hysterectomy, bilateral ovariectomy 
(oophorectomy), bilateral salpingectomy, or bilateral tubal ligation. Women who are 
surgically sterile must provide suitable medical documentation of the adequacy of 
the procedure; eg, an operative report or confirmatory ultrasound report. Men who 
are biologically capable of having children must agree and commit to use an adequate 
form of contraception (see Appendix B) for the duration of the treatment period and 
for 3 months after the last administration of study drug. A male subject is considered 
capable of having children even if his sexual partner is sterile or using contraceptives.
2.
2.
3.
Subjects must understand the nature of the study and must provide signed and dated 
written informed consent prior to the initiation of any study procedures.
4.
The subject should be willing and able to understand and participate in all scheduled 
evaluations and to complete all required tests and procedures including the use of 
subject diaries, as judged by the investigator.
5.
The subject must be considered likely to comply with the study protocol and to have 
a high probability of completing the study, as judged by the investigator.
6.
For subjects participating in the optional genetic research, a separate signed and 
dated written informed consent must be provided. If a subject declines to participate 
in the genetic research, this will have no influence on the ability of the subject to 
participate in the study.
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Diagnostic
7.
Chronic PDN persistent for 6 months or longer, not adequately controlled by 
standard of care treatments.
8.
Pain (beginning in the feet and with relatively symmetrical onset for 6 months or 
greater) due to bilateral peripheral neuropathy caused by either type 1 or type 2 
diabetes mellitus, with bilateral decrease or absent reflexes at the ankles, or bilateral 
decrease of a sensory sign in the distal lower extremities, based on medical history 
and peripheral neurological examination. [NOTE: for sensory evaluation, the 
relevant components of the Total Neuropathy Score-Nurse (TNSn) for the lower 
limb should be undertaken, to include sensory symptom score, pin sensibility score, 
and vibration sensibility score.]
9.
4, as measured on an 11-point (0-10) NRS by 
completion of a subject diary for a minimum of 7 days prior to Day 1 (ie, Day -7 to 
Day -1). At least 5 of 7 days need to be recorded by the subject to obtain a valid 
baseline value. Pain scores from Day -7 to Day -1 will be centrally reviewed by the 
study team, and if there is significant variability in the scores during this baseline 
period of pain evaluation, it will be discussed with the investigator and the subject 
may be excluded.
Concomitant medication
10. The subject must be willing and able to discontinue all NSAID or COX-2 analgesic 
therapy from the start of the washout period until the end of follow-up. This includes 
over-the-counter (OTC) pain medications and topical analgesics that contain an 
NSAID or COX-2 inhibitor. The use of NSAIDs (eg, ibuprofen, naproxen) or COX-2
medications (eg, celecoxib) at any time during the study and through to completion 
of drug washout (5 half-lives) is prohibited and contraindicated.
11. Subjects should currently be taking medication for the treatment of PDN. Subjects 
should be taking at least one of the first-line medications (consistent with regional or 
local standard of care guidelines for PDN) belonging to either the anticonvulsant 
class (pregabalin or gabapentin) or the antidepressant class (duloxetine, venlafaxine, 
or amitriptyline), but no more than one medication from a single class. Subjects 
receiving treatment with opioids alone (as a monotherapy) should be excluded, 
unless the opioids are being prescribed as a second-line treatment for PDN because 
the first-line therapies were found to be poorly tolerated or not efficacious. For all 
drug classes, subjects should be established on a stable dosing regimen that is 
consistent with regional or local standards of accepted prescribing practice for no 
less than 3 months before the anticipated randomisation date. Subjects should be 
willing to maintain this dosing regimen for the duration of study participation until 
the last follow-up visit. Subjects must be willing to use only the protocol-specified 
rescue medications during the study.
12. If the subject is receiving permitted medications for the treatment of non-excluded 
medical conditions (eg, antihypertensive medication, cholesterol-lowering 
treatment, antidiabetic medication), the dose and dosing regimen must be stable for 
at least 28 days before randomisation and should be expected to remain stable for the 
duration of study participation until at least the last follow-up visit.
Exclusion criteria:
General
1.
Requires current treatment with another biologic therapeutic agent.
2.
Previously received any form of anti-nerve growth factor (NGF) or anti-tumor 
necrosis factor (TNF) therapy. 
A mean pain intensity score of 2: 
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3.
Participation in another clinical study with an investigational product (IP) or device 
within 60 days or 5 half-lives prior to screening, whichever is longer.
4.
Plasma donation within 28 days of screening or any blood donation or blood loss 
>500 mL within 2 months of screening.
5.
Previous allogeneic bone marrow or stem cell transplant.
6.
Received non-leukocyte-depleted whole blood transfusion within 120 days of the 
genetic research sample collection, if participating in the optional genetic research.
7.
Poor venous access such that IV drug delivery would be difficult.
8.
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca 
staff and staff at the study site) and in accordance with local regulations.
Medical history
9.
Presence of other clinically significant neuropathy (eg, hereditary neuropathy, 
inflammatory neuropathy) or other clinically significant disorder (eg, nerve 
compression injury) involving abnormal peripheral sensation, with an aetiology that 
is considered to be distinct from that of PDN, and that is likely to interfere with 
assessment of peripheral nerve function, as judged by the investigator.
10. History of osteonecrosis, rapidly progressive OA, subchondral insufficiency 
fractures, neurogenic arthropathy, or analgesia-induced arthropathy. 
11. Diagnosis of clinically significant OA currently affecting a major joint in the upper 
extremity (shoulder, elbow, or wrist) or lower extremity (hip, knee, or ankle) or axial 
spine; or other degenerative disease affecting any joint in subjects for whom, in the 
opinion of the investigator, there is an identified risk of osteonecrosis, rapidly 
progressive OA, subchondral insufficiency fractures, neurogenic arthropathy, or 
analgesia-induced arthropathy.
NOTE: The diagnosis and evaluation of OA should be guided by American College 
of Rheumatology (ACR)-endorsed criteria, where applicable, and should incorporate 
radiologic investigation for the assessment of OA severity consistent with the 
relevant ACR guidance (Altman et al. 1986, Altman et al. 1990, Altman et al. 
1991)35,36,37 at the discretion of the investigator, or otherwise guided by local 
rheumatologic, orthopaedic, or radiologic expert advice. Where Kellgren and 
Lawrence grading is used for the radiographic evaluation of major joint OA, grade 
n. In subjects for whom 
there is evidence of clinically significant sensory impairment in the distal lower 
extremity (based on medical history, clinical examination, TNSn, or evidence of 
sensory nerve conduction impairment available from nerve conduction studies), 
there is an absolute requirement for bilateral feet and ankle radiographs to be 
undertaken for the evaluation of OA severity to exclude the possibility of neuropathic 
arthropathy. All radiologic investigations should be reported locally and the reports 
should be retained in the patient files as source documentation and made available in 
the event that subsequent adjudication of rheumatologic adverse events is required.
Radiologic images should also be retained and made available in the event that 
subsequent adjudication of rheumatologic adverse events is required.
12. Chronic pain condition, other than PDN, that is likely to interfere with the evaluation 
by the investigator.
13. Presence of any major psychiatric disorder according to the criteria of the Diagnostic 
and Statistical Manual of Mental Disorders, 5th Edition, if, in the opinion of the 
investigator, the psychiatric disorder or symptom is likely to confound interpretation 
study.
~2 would be considered exclusionary for trial participatio 
of the subject's PDN pain, as judged 
of drug effect, affect pain assessment, or affect the subject's ability to complete the 
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14. Significant cardiovascular disease, including Class 3 or Class 4 (The Criteria 
Committee of the New York Heart Association (NYHA) classification standards 
1994)38 congestive heart failure (ejection fraction of <40%) or clinically significant 
stenosis or occlusion of a carotid or vertebral artery or clinically significant 
arrhythmias. 
NOTE: Validated NYHA classification standards:
Class 1: cardiac disease but no symptoms and no limitations in ordinary physical 
activity (no shortness of breath when walking, climbing stairs)
Class 2: mild symptoms (mild angina or shortness of breath) and slight limitation 
with ordinary physical activity
Class 3: marked limitation due to symptoms, even during less than ordinary 
activities such as walking 20 to 100 meters; comfortable only at rest
Class 4: severe limitations and symptoms at rest
NOTE: Subjects designated as NYHA functional Class 1 or Class 2 are not 
necessarily excluded from participation. However, such subjects should have 
left ventricular ejection fraction measured by echocardiography and 
documented at baseline.
15. Significant or chronic lung disease, including severe or unstable chronic obstructive 
pulmonary disease (COPD), or severe or unstable asthma.
16. Known or suspected systemic infection, including HIV, hepatitis B virus (HBV), 
hepatitis C virus (HCV), or tuberculosis (TB) as judged by the investigator or from 
screening testing. At screening, a QuantiFERON test will be conducted for TB
(Nyendak et al. 2009; Duarte et al. 2012; Cush et al. 2010).39,40,41
17. History or evidence of any significant autoimmune disease or disorder, including 
inflammatory bowel disease, multiple sclerosis, or systemic lupus erythematosus.
18. History of severe allergy/hypersensitivity reactions or history of hypersensitivity to 
immunisations or immunoglobulins.
19. History of cancer within 5 years of screening or between screening and 
randomisation, with the exception of non-metastatic basal cell carcinoma of the skin, 
carcinoma in situ of the cervix, or non-progressive prostate cancer.
20. Transient ischaemic attack or stroke in the last 3 years.
21. History of alcohol or recreational drug dependence according to the Diagnostic and 
Statistical Manual of Mental Disorders, 5th Edition criteria, within 2 years of 
screening, with the exception of nicotine dependence, which is permitted.
NOTE: Where there is a documented or suspected history of excessive alcohol usage 
or recreational drug usage, it is expected that the impact of this with respect to risk
be evaluated at screening using the appropriate quantitative or semi-quantitative 
methodologies according to local standards of accepted medical or psychiatric 
practice. For example, use of the Fast Alcohol Screening Test (FAST) and Alcohol 
Use Disorders Identification Test (AUDIT) alcohol screening questions for the initial 
evaluation of harm and risk associated with excessive alcohol consumption.
22. Within 1 year of screening or between screening and randomisation, any of the 
following: myocardial infarction, hospitalisation for unstable angina or arrhythmia, 
or unexplained syncope.
23. Clinically important infection, including chronic, persistent, or acute infection, 
within 3 months of screening or between screening and randomisation.
• 
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24. Current serious or unstable clinically important illness, including avascular 
necrosis, respiratory, cardiovascular, gastrointestinal, endocrinologic (excluding 
well-controlled type 1 or type 2 diabetes), immunologic, haematologic, neurologic, 
ability to complete the study, as judged by the investigator.
Procedural contraindications
25. Any significant medical or surgical procedure or trauma within 28 days of Day 1, or 
planned to be undertaken within the timeframe of the clinical trial, that will likely 
of the study data, as judged by the investigator.
Physical and neurological examination, vital signs, ECG, laboratory values, and 
imaging
26. Clinically important abnormality in the physical and neurological examination, vital 
ability to complete the study, or the integrity of the clinical trial data, as judged by 
the investigator.
27. Poorly controlled hypertension (defined as systolic blood pressure [SBP] of 
>165 mmHg and/or diastolic blood pressure [DBP] of >95 mmHg measured in the 
clinic) or orthostatic hypotension (defined as a sustained reduction of SBP of at least 
20 mmHg and/or a DBP reduction of at least 10 mmHg within 3 minutes of standing 
from a supine position). Note: If the blood pressure (BP) measured in the clinic is
out of range, the measurements can be repeated on the same day or at another 
convenient visit.
28. Prolonged QTcF of >470 msec or family history of long QT syndrome, or shortened 
QTcF of <360 msec or family history of short QT syndrome, or any clinically 
significant abnormality in ECG rhythm, conduction, or morphology, including but 
not limited to: 
PR/PQ interval prolongation (PR/PQ >220 ms)
intermittent second or third degree atrioventricular (AV) block (AV block II 
Mobitz Type I, Wenckebach, while asleep or in deep rest is not exclusionary)
bundle branch block (BBB) or intraventricular conduction delay (IVCD) with 
QRS duration >120 ms
29. Haemoglobin A1C greater than 10.0% (>10.0%).
30. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >1.5 × 
the upper limit of normal (ULN) at screening or between screening and baseline. If 
the enzyme is >1.5 × ULN, the investigator can either exclude the subject at that time 
or decide to repeat the test once. If the repeat result is still >1.5 × ULN, the subject 
must be excluded.
31. Screening creatinine clearance of <60 mL/min as determined by the Cockcroft-Gault 
formula.
32. Clinically significant abnormal findings in coagulation or haematology laboratory 
tests, as judged by the investigator.
33. A positive pregnancy test at screening. (If the screening urine pregnancy test is more 
than 7 days before the first day of treatment, it must be repeated prior to the first 
dose.)
34. Positive drug screen for drugs of abuse (including but not limited to amphetamine, 
barbiturate, 
cannabinoids, 
cocaine, 
methadone, 
methaqualone, 
opiate, 
phencyclidine, or propoxyphene), unless there is a documented medical explanation 
or other major disease that is likely to deteriorate or affect the subject's safety or 
affect the subject's safety or ability to complete the study, or the scientific integrity 
signs, or clinical laboratory test at screening that could affect the subject's safety or 
• 
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for the positive result other than drugs of abuse (eg, the subject takes opioids under 
medical supervision for pain and the prescribed opioid dosing regimen is expected 
to be stable and unchanged for the duration of the study; or where cannabinoids are 
similarly being taken for documented medical reasons). 
TEST PRODUCT
Name: MEDI7352
Dose, route, frequency: Dose levels: 
. Each 
subject will receive 6 doses, 1 dose every 2 weeks (Days 1, 14, 28, 42, 56, and 70), 
administered IV over a 60-minute period.
CONTROL
PRODUCT
Name: placebo
Dose, route, frequency: Same as MEDI7352.
PLANNED STUDY 
SITES
Approximately 40 study sites in approximately 6 countries.
CRITERIA FOR 
EVALUATION
Efficacy endpoints:
Primary efficacy endpoint: change in the weekly average of the average daily 
pain scores from the baseline week to Week 12, as measured on an 11-point 
(0-10) NRS.
Secondary efficacy endpoints:
Change in the weekly average of the average daily pain score, as measured 
on an 11-point (0-10) NRS, from baseline to Weeks 2, 4, 6, 8, and 10 of 
treatment and the week before the follow-up visit. 
Percen
the weekly average of the average daily pain score from baseline during 
Weeks 4, 8, and 12 of treatment and the week before follow-up.
Change in Galer neuropathic pain scale (NPS) from baseline to Days 28, 56, 
and 84 of treatment and the follow-up visit.  
Change in Daily Sleep Interference Scale (DSIS) from baseline to Days 28, 
56, and 84 of treatment and the follow-up visit.
,
Patient Global Impression of 
Change (PGIC) on Days 28, 56, and 84 of treatment and the follow-up visit.
Change in the 36-item Short-Form Health Survey (SF-36) from baseline to 
Day 84 of treatment.
Usage of rescue medication (yes/no) from baseline to Week 12 of treatment.
Clinical pharmacology endpoints:
Pharmacokinetic endpoints:
maximum concentration (Cmax)
time of Cmax (tmax)
area under the plasma concentration-time curve from time 0 to infinity 
(AUC0- )
area under the plasma concentration-time curve from time 0 to the time of 
the last quantifiable plasma concentration (AUC0-t)
area under the plasma concentration-time curve for the dosing interval 
(AUCtau) at steady state
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Cmax at steady state
volume of distribution at steady state
t1/2
apparent total body clearance at steady state (CLss)
Pharmacodynamic endpoints:
free and/or total NGF measurements in 
serum/plasma
Immunogenicity (ADA) assessments
Change in the weekly average of the average daily pain scores from the baseline 
week to Week 12, as measured on an 11 point (0 to 10) NRS, versus dose
Safety endpoints:
Adverse events (AEs) and serious AEs (SAEs)
Physical and neurological examinations
Neuropathy assessments (TNSn), strength (dorsiflexion), and deep tendon reflex 
(knee and ankle) assessments
Vital signs
12-lead electrocardiograms (ECGs)
Clinical laboratory testing
(haematology, chemistry, coagulation, and 
urinalysis)
Motor and sensory nerve conduction studies
Concomitant medications and therapies
Injection site reactions and infusion reactions
STATISTICAL 
METHODS
Analysis Populations:
Screening: all subjects who provide informed consent and/or assent and provide 
randomisation and treatment status in the study. 
Safety: The safety population will include all subjects who receive at least 
1 dose of double-blind study medication.
Modified intent-to-treat (mITT): The modified intent-to-treat population will be 
used for all efficacy analyses and will include all randomised subjects who 
receive at least 1 dose of double-blind study medication and have at least 
1 post-baseline NRS assessment.
PK: The PK population will include all subjects for whom a PK sample was 
obtained and analysed.
Subject Characteristics and Disposition: Baseline subject characteristics will be listed and 
included in summaries as appropriate. Investigational product administration will be 
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using 
descriptive statistics.
Efficacy Analyses: All efficacy variables will be summarized descriptively including 
number of observations, mean, standard deviation (SD), minimum, median, and 
maximum for continuous variables, and frequency of observations in each category and 
percentage for categorical variables. Primary and secondary endpoint efficacy data will 
data at a key analysis time-point (Weeks 4, 8, and 12) then results will also be tabulated 
-Observation-Carried-Forwar
-Observation-
Carried-
The main statistical analysis of the primary efficacy endpoint 
at Week 12 will use the multiple comparison procedure modelling (MCP-Mod) approach 
on LOCF data, which is a well-established statistical methodology for establishing both 
the existence of a dose response and modelling the underlying dose-response relationship.
In addition, changes from baseline in continuous endpoints will be compared between 
treatment groups using mixed models repeated measures including terms for pooled site, 
treatment (as a factor), time point (as a factor), the interaction between treatment and time 
point, and the baseline value of the variable undergoing analysis. Binary outcomes will 
be analysed using generalized estimating equations, with the models including the same 
terms as the mixed models repeated measures. Other non-binary categorical endpoints 
will be analysed using Cochran-Mantel-Haenszel statistics. These analyses will be 
conducted on observed cases. Further details of the longitudinal modelling will be 
included in the statistical analysis plan (SAP).
Clinical Pharmacology Analyses:
PK: Noncompartmental analysis methods will be used. The PK parameters will be 
summarized by MEDI7352 dose using descriptive statistics.
.
Safety Analyses: Safety and tolerability data will be summarised descriptively, including 
tables, listings, and graphs, as appropriate.
SAMPLE SIZE 
DETERMINATION
There is no formal sample size calculation for stage 1; 10 subjects in stage 1 is considered 
sufficient for the initial assessment of safety. The sample size for stages 2-4 combined 
was determined by a formal power calculation (see below) and the size of stage 3 was 
defined to confirm decision making for the stage 4 sample size and dose allocation ratio.
This study is powered at greater than 80% to detect a statistically significant (1-sided 
alpha = 0.025) dose-response relationship when the true Week 12 placebo-corrected
change from baseline difference at the
1.25 on the 11-point NRS scale 
(MEDI7352-placebo treatment) and the true dose-response follows a hyperbolic Emax
relationship, with the effective dose for 50% of the population (ED50) within the range 
The true SD is 2.4, which is based on other studies undertaken with pregabalin 
in PDN 
The data from stages 2, 3 and 4 are combined so that the number of subjects 
evaluable for the dose response analysis is 236. The total number of subjects 
evaluable for efficacy for the placebo, 
 and 
is equal to
81, 37, 51 and 67, respectively.
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The dose-response hypothesis test is multiplicity adjusted in order to control the 
type 1-error.
The above calculations were performed using the following parameters:
Population SD (of change from baseline to week 12) = 2.4
Placebo effect = 1-point reduction in NRS and 450
from baseline, ie, delta = 1.25
which are all Emax models with decreasing potency/increasing ED50: 7.5, 15, 30, 
linear in dose. 
Power was assessed across 16 alternative true dose response curves, 12 Emax
having a Week 12 placebo-corrected change from baseline difference at the 
of 1.25. 
The overall withdrawal rate is anticipated to be approximately 10%. However, since the 
primary analysis will use LOCF for withdrawn subjects, and the SD estimate is taken 
from studies which also used the LOCF approach, the only additional subjects recruited 
will be to account for withdrawals in stages 2, 3 and 4 if withdrawal occurs at, or prior 
to, the Week 2 visit.
The number of subjects who will agree to participate in the genetic research is unknown. 
It is therefore not possible to establish whether sufficient data will be collected to allow 
a formal statistical evaluation or whether only descriptive statistics will be generated.
STUDY AND 
TREATMENT
DURATION
The planned sequence and maximum duration of the study periods will be as follows:
1.
Screening: 45 days
2.
Treatment: 12 weeks
3.
Follow-up: 42 days
The maximum treatment duration for each subject is approximately 12 weeks. 
The maximum study duration for each subject is approximately 25 weeks.
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2.2
Schedule of Events
Table 2-1:
Schedule of Events
Screening
/Baseline 
(7 to 45 
Days)a
Double-blind Treatment Period (12 Weeks)
Follow-up
(or Early 
Termination)
(6 Weeks)
Study Day / Week 
Day -45 
to 
Day -1a
Day 
1
Day 14
Week 2
±3 days
Day 28
Week 4
±3 days
Day 42
Week 6
±3 days
Day 56
Week 8
±3 days
Day 70
Week 10
±3 days
Day 71
V7+24 hr
Day 77
V7+7 days
±3 days
Day 84
Week 12
±3 days
Week 18
±7 days
Clinic Visit (V) 
V1a
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
Informed Consent
X
Inclusion/Exclusion Criteria
X
X
Height and Weight (BMI)
X
Demographics and Medical History
X
Physical and Neurological Examination
(C=complete; T=targeted)
C
T
T
T
T
T
T
C
C
12-lead Electrocardiogram (ECG)
X
Xb
X
X
X
X
Motor and Sensory Nerve Conduction Studies
X
X
Urine Drug Screen and Urine Pregnancy Test
X a
X
X
Total Neuropathy Score-Nurse (TNSn)
X
X
X
X
X
X
X
X
X
Strength and Deep Tendon Reflexesi
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
Vital Signs c
X
X
X
X
X
X
X
X
X
X
X
Randomisation
Xe
Training and Reminders on Rating Pain and 
Entering Ratings on ePRO Systemd
X
X
X
X
X
X
X
X
Study Drug Infusion (Dosing)
X
X
X
X
X
X
Injection Site Assessment 
X
X
X
X
X
X
X
X
Daily Pain Diary (NRS) via ePRO
Xd
X
X
X
X
X
X
X
X
X
X
Daily Sleep Interference Scale (DSIS) via 
ePRO
Xd
X
X
X
X
X
X
X
X
X
X
Galer Neuropathic Pain Scale
X
X
X
X
X
Patient Global Impression of Change (PGIC)
X
X
X
X
36-item Short-Form Health Survey (SF-36)
X
X
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Screening
/Baseline 
(7 to 45 
Days)a
Double-blind Treatment Period (12 Weeks)
Follow-up
(or Early 
Termination)
(6 Weeks)
Study Day / Week 
Day -45 
to 
Day -1a
Day 
1
Day 14
Week 2
±3 days
Day 28
Week 4
±3 days
Day 42
Week 6
±3 days
Day 56
Week 8
±3 days
Day 70
Week 10
±3 days
Day 71
V7+24 hr
Day 77
V7+7 days
±3 days
Day 84
Week 12
±3 days
Week 18
±7 days
Clinic Visit (V) 
V1a
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
Blood Collection for:
Haematology, Chemistry, and Coagulation
X
X
X
X
X
X
X
X
X
Serology (HIV, hepatitis B and C, and 
tuberculosis)
X
Pharmacogenetic Sampling (Optional)
X
Haemoglobin A1c
X
Immunogenicity (ADA) Sampling
X
Xf
Xf
Xf
Xf
X
X
Pharmacokinetic Samplingh
Xf
Xf
Xf
Xf
Xf
Xh
Xh
Xh
Xh
Xg
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Rescue Medication Used
Xd
X
X
X
X
X
X
X
X
X
Concomitant Medications and Therapies
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: ADA = anti-drug antibody; BMI = body mass index; C = complete; 
 
; DSIS = Daily Sleep Interference Scale; ECG = electrocardiogram; ePRO = electronic patient-reported outcome system;
IP = investigational product; IWRS = interactive web response system;
NRS = numeric rating scale;
PD = pharmacodynamics; PGIC = Patient Global Impression of Change; PK = pharmacokinetics; SF-36 = 36-item Short-Form Health Survey;
T = targeted; TNSn = Total Neuropathy Score-Nurse
a
The subject must be screened within 45 days before enrolment in the study and at least 7 days before the first day of treatment to allow for 
7 days of baseline pain ratings and sleep monitoring. Screening procedures may be performed at 1 or more visits. If the screening urine 
pregnancy test is more than 7 days before the first day of treatment, it must be repeated prior to the first dose. Urine drug screen tests will be 
performed at Screening only.
b
On Day 1, 12-lead ECGs (3 replicates) will be performed pre-dose; 60 (±10) minutes after start of IP administration; and 2 and 4 hours 
(±10 minutes) after start of IP administration.
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c
Vital signs (heart rate [HR], blood pressure [BP], respiratory rate, and body temperature):
Screening and Day 1: Supine and orthostatic.
From Day 14 onwards: Sitting and orthostatic.
e
If necessary, the randomisation transaction in IWRS can be performed on Day -1.
 
i
Strength (dorsiflexion) and deep tendon reflexes (knee and ankle) are to be scored at every visit alongside the TNSn assessments.
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Table 2-2:
Timing of Safety Assessments and Safety Blood Sampling on Day 1
Time after Start of IP Administration
Assessment
Pre-dose
0 min
15 mins
30 mins
45 mins
60 mins
2 hours
4 hours
Administration of IP
Injection site assessments and infusion reaction assessments
X
X
X
X
X
X
12-lead ECGs (3 replicates)
X
X
X
X
Supine blood pressure, heart rate
X
X
X
X
X
X
X
Standing (orthostatic) blood pressure, heart rate
X
X
X
X
Body temperature
X
X
X
X
Respiration rate
X
X
X
X
X
Total Neuropathy Score, nurse (TNSn)
X
Targeted physical and neurological exam
X
Adverse events
Safety laboratory tests
X
Concomitant medication use
Abbreviations: BP = blood pressure; ECG = electrocardiogram; HR = heart rate; IP = investigational product, mins = minutes; RR = respiratory
rate; TNSn = Total Neuropathy Score-Nurse
Note:
60-minute orthostatic and supine vital sign assessments (blood pressure, heart rate, respiratory rate, body temperature) should be 
undertaken within 10 minutes window of completing the infusion. For all other vital signs an acceptable window for measurement is 
±5 mins of the specified time-point.
Standing blood pressure and heart rate (orthostatic vital signs) should be measured after 1 minute (>1 minute, <3 minutes) of adopting 
the standing position.
Where multiple assessments are being undertaken at the same time-point, the order of assessments should be (1) 12-lead ECG, (2) Vital 
signs (supine BP, HR, RR and temperature should be performed before standing vital signs), and (3) Blood sampling.
Safety laboratory tests taken pre-dose will include haematology, clinical chemistry, coagulation, and urinalysis.
Strength (dorsiflexion) and deep tendon reflexes (knee and ankle) are to be scored at every visit alongside the Total Neuropathy Score-
nurse (TNSn) assessments.
12-lead ECGs: 60 (±10) minutes after start of IP administration, 2 hours (±10 minutes) after start of IP administration, and 4 hours 
(±10 minutes) after start of IP administration.
• 
• 
• 
• 
• 
• 
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3
TABLE OF CONTENTS
1 
SPONSOR SIGNATURES ......................................................................................................2 
AMENDED PROTOCOL ...............................................................................................................4 
2 
PROTOCOL SUMMARY........................................................................................................5 
2.1 
Synopsis ..........................................................................................................................5 
2.2 
Schedule of Events........................................................................................................15 
3 
TABLE OF CONTENTS .......................................................................................................19 
3.1 
LIST OF TABLES........................................................................................................23 
3.2 
LIST OF FIGURES ......................................................................................................23 
4 
LIST OF ABBREVIATIONS AND DEFINITIONS.............................................................24 
5 
INTRODUCTION..................................................................................................................27 
5.1 
Background and Rationale............................................................................................27 
5.2 
Clinical Experience.......................................................................................................28 
5.2.1 Phase I Painful Osteoarthritis of the Knee Study..............................................29 
5.2.2 Current Phase 2 Painful Diabetic Neuropathy Study ........................................30 
5.2.3 Phase 2b Painful Osteoarthritis of the Knee Study ...........................................30 
5.2.4 Phase I Study in Healthy Volunteers.................................................................31 
5.3 
Summary of Potential Risks and Benefits.....................................................................31 
6 
OBJECTIVES.........................................................................................................................34 
6.1 
Primary Objective .........................................................................................................34 
6.2 
Secondary Objectives....................................................................................................34 
6.3 
Exploratory Objectives..................................................................................................34 
7 
STUDY DESIGN ...................................................................................................................36 
7.1 
Overall Study Design and Plan .....................................................................................36 
7.2 
Rationale and Discussion of Study Design ...................................................................39 
7.3 
Selection of Doses in the Study ....................................................................................39 
7.4 
Study Sites.....................................................................................................................39 
7.5 
Point of Contact ............................................................................................................39 
7.6 
End of Study Definition ................................................................................................39 
8 
SUBJECT POPULATION .....................................................................................................40 
8.1 
Selection of Study Population and Diagnosis ...............................................................40 
8.2 
Study Entry Criteria ......................................................................................................40 
8.2.1 Inclusion Criteria...............................................................................................40 
8.2.2 Exclusion Criteria..............................................................................................41 
8.3 
Premature Subject Withdrawal .....................................................................................45 
8.4 
Subject Replacement Criteria........................................................................................46 
9 
TREATMENTS......................................................................................................................47 
9.1 
Identification of Investigational Products .....................................................................47 
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9.1.1 Dose, Route of Administration, and Dosing Schedule......................................48 
9.1.2 Current Treatment of Painful Diabetic Neuropathy..........................................48 
9.1.3 Rescue Medication ............................................................................................48 
9.2 
Selection of Timing of Dose for Each Subject..............................................................49 
9.3 
Dose Adjustment Criteria..............................................................................................49 
9.3.1 Safety Stopping Rules .......................................................................................49 
9.4 
Treatment Compliance..................................................................................................50 
9.5 
Method of Assigning Subjects to Treatment Groups....................................................50 
9.6 
Blinding and Unblinding Treatment Assignment .........................................................50 
9.7 
Permitted and Prohibited Therapies..............................................................................51 
9.7.1 Permitted Therapies...........................................................................................51 
9.7.2 Prohibited Therapies..........................................................................................52 
9.7.3 Restrictions........................................................................................................53 
9.8 
Treatment after End of Study........................................................................................53 
9.9 
Dispensing and Storage.................................................................................................53 
9.10 Drug Accountability......................................................................................................53 
9.11 Labelling and Packaging...............................................................................................54 
9.11.1 Labelling............................................................................................................54 
9.11.2 Packaging ..........................................................................................................54 
10 STUDY PROCEDURES........................................................................................................55 
10.1 Study Duration ..............................................................................................................55 
10.2 Study Periods and Visits ...............................................................................................55 
10.2.1 Screening and Washout.....................................................................................55 
10.2.1.1 Screening...............................................................................................55 
10.2.2 Double-blind Treatment Period (Days 1-84 [Weeks 1-12])..............................56 
10.2.2.1 Day 1 (Treatment 1)..............................................................................56 
10.2.2.2 Days 14, 28, 42, 56, and 70 (Treatments 2 to 6)...................................57 
10.2.2.3 Day 71...................................................................................................59 
10.2.2.4 Day 77...................................................................................................59 
10.2.2.5 Day 84 (End-of-treatment; Week 12) ...................................................59 
10.2.3 Follow-up (or Early Termination) Evaluation (Week 18).................................60 
10.3 Assessments ..................................................................................................................61 
10.3.1 Efficacy Variables .............................................................................................61 
10.3.1.1 Numerical Rating Scale.........................................................................61 
10.3.1.2 Galer Neuropathic Pain Scale ...............................................................61 
10.3.1.3 Daily Sleep Interference Scale..............................................................61 
10.3.1.4 Patient Global Impression of Change ...................................................62 
10.3.1.5 Short-Form Health Survey....................................................................62 
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10.3.1.6 Rescue Medication Use.........................................................................62 
10.3.1.7 
 
10.3.2 Clinical Pharmacology ......................................................................................62 
10.3.2.1 Pharmacokinetic Analysis Methods......................................................62 
10.3.2.2 Pharmacodynamic Variables.................................................................63 
10.3.2.3 Pharmacogenetic Variables...................................................................63 
10.3.2.4 
 
10.3.2.5 Immunogenicity ....................................................................................64 
10.3.3 Safety Variables ................................................................................................64 
10.3.3.1 Clinical Laboratory Assessments..........................................................64 
10.3.3.2 Adverse Events......................................................................................67 
11 ADVERSE EVENTS..............................................................................................................68 
11.1 Definitions.....................................................................................................................68 
11.1.1 Adverse Events..................................................................................................68 
11.1.2 Adverse Drug Reaction .....................................................................................68 
11.1.3 Unexpected Adverse Event/Adverse Drug Reaction ........................................68 
11.1.4 Serious Adverse Events.....................................................................................69 
11.1.5 Significant Adverse Events ...............................................................................69 
11.1.6 Treatment-Emergent Adverse Events ...............................................................69 
11.2 Event Assessment and Follow-up of Adverse Events ..................................................70 
11.2.1 Assessment ........................................................................................................70 
11.2.2 Evaluation..........................................................................................................71 
11.2.2.1 Severity of Adverse Events...................................................................71 
11.2.2.2 Seriousness............................................................................................71 
11.2.2.3 Action(s) Taken.....................................................................................71 
11.2.2.4 Outcome at the Time of Last Observation ............................................71 
11.2.2.5 Adverse Event Relationship to Investigational Product........................72 
11.2.3 Documentation ..................................................................................................72 
11.2.4 Treatment of Adverse Events............................................................................72 
11.2.5 Follow-up ..........................................................................................................73 
11.2.6 Reporting...........................................................................................................73 
11.2.6.1 Serious Adverse Events.........................................................................73 
11.2.6.2 Adverse Drug Reactions .......................................................................74 
11.2.6.3 Nonserious Adverse Events ..................................................................74 
11.3 Special Considerations..................................................................................................74 
11.3.1 Adverse Events of Special Interest....................................................................74 
11.3.2 Pregnancy..........................................................................................................75 
11.3.3 Overdose............................................................................................................75 
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12 DATA SAFETY MONITORING BOARD ...........................................................................77 
13 STATISTICS ..........................................................................................................................78 
13.1 Statistical Analysis........................................................................................................78 
13.1.1 Analysis Populations .........................................................................................78 
13.1.2 Study Subjects and Demographics....................................................................78 
13.1.2.1 Disposition and Withdrawals ................................................................78 
13.1.2.2 Protocol Deviations...............................................................................78 
13.1.2.3 Demographics and Other Baseline Characteristics...............................79 
13.1.3 Exposure and Compliance.................................................................................79 
13.1.4 Efficacy Analysis ..............................................................................................79 
13.1.4.1 Efficacy Endpoints................................................................................80 
13.1.4.2 
 
13.1.5 Clinical Pharmacology Analyses.......................................................................81 
13.1.5.1 Pharmacokinetics ..................................................................................81 
13.1.5.2 Pharmacodynamics ...............................................................................81 
13.1.5.3 
 
13.1.5.4 
 
13.1.5.5 Immunogenicity ....................................................................................81 
13.1.6 Safety and Tolerability Analyses ......................................................................81 
13.1.6.1 Adverse Events......................................................................................82 
13.1.6.2 Clinical Laboratory Evaluations ...........................................................82 
13.1.6.3 Vital Signs.............................................................................................82 
13.1.6.4 Twelve-lead Electrocardiograms ..........................................................82 
13.1.6.5 Physical and Neurological Examination Findings ................................83 
13.1.6.6 Other Safety Assessments.....................................................................83 
13.1.7 Interim Analysis ................................................................................................83 
13.2 Sample Size Determination...........................................................................................83 
14 STUDY CONDUCT...............................................................................................................85 
14.1 Sponsor and Investigator Responsibilities ....................................................................85 
14.1.1 Sponsor Responsibilities ...................................................................................85 
14.1.2 Investigator Responsibilities .............................................................................85 
14.1.3 Confidentiality and Privacy...............................................................................85 
14.2 Site Initiation.................................................................................................................86 
14.3 Screen Failures..............................................................................................................86 
14.4 Study Documents ..........................................................................................................87 
14.4.1 Informed Consent..............................................................................................87 
14.4.2 Good Clinical Practice Documents ...................................................................87 
14.4.3 Case Report Forms ............................................................................................88 
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14.4.4 Source Documents.............................................................................................88 
14.5 Data Quality Control.....................................................................................................88 
14.5.1 Monitoring Procedures......................................................................................88 
14.5.2 Data Management..............................................................................................89 
14.5.3 Quality Assurance/Audit ...................................................................................89 
14.6 Study Termination.........................................................................................................90 
14.6.1 Regular Study Termination ...............................................................................90 
14.6.2 Premature Study Termination ...........................................................................90 
14.7 Study Site Closure.........................................................................................................90 
14.7.1 Record Retention...............................................................................................91 
14.7.2 Sample Retention ..............................................................................................91 
14.8 Changes to the Protocol ................................................................................................91 
14.9 Use of Information and Publication..............................................................................92 
15 FINAL CLINICAL STUDY REPORT ..................................................................................93 
16 ETHICAL AND LEGAL CONSIDERATIONS....................................................................94 
16.1 Declaration of Helsinki and Good Clinical Practice.....................................................94 
16.2 Subject Information and Informed Consent..................................................................94 
16.3 Approval by Institutional Review Board or Independent Ethics Committee ...............95 
16.4 Finance and Insurance...................................................................................................95 
17 REFERENCES .......................................................................................................................96 
18 ATTACHMENTS.................................................................................................................100 
18.1 
............................................................................................100 
APPENDICES .............................................................................................................................101 
A. 
........................................................................................................101 
B.
Contraception Guidance..............................................................................................104 
C.
Other Study-Specific Requirements............................................................................104 
D.
Regulations and Good Clinical Practice Guidelines ...................................................105 
REASONS FOR AMENDMENT ...............................................................................................106 
SUMMARY OF AMENDED SECTIONS..................................................................................107 
3.1
LIST OF TABLES
Table 2-1:
Schedule of Events ............................................................................................15 
Table 2-2:
Timing of Safety Assessments and Safety Blood Sampling on Day 1 .............18 
Table 9-1:
Identification of Investigational Product...........................................................47 
Table 10-1:
Local Reactions to Injectable Product...............................................................67 
Table B-1:
Highly Effective Methods of Contraception ...................................................104 
3.2
LIST OF FIGURES
Figure 7-1: 
Study Design .....................................................................................................38 
Investigator's Agreement 
Hy's Law Criteria 
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4
LIST OF ABBREVIATIONS AND DEFINITIONS
ACR
American College of Rheumatology
ADA
anti-drug antibody
ADR
adverse drug reaction
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase 
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
AUC0-
area under the plasma concentration-time curve from time 0 to infinity 
AUC0-t
area under the plasma concentration-time curve from time 0 to the time of 
the last quantifiable plasma concentration
AUDIT
Alcohol Use Disorders Identification Test
BOCF
Baseline-Observation-Carried-Forward
BP
blood pressure
CLss
apparent total body clearance at steady state
Cmax
maximum plasma concentration
CMP
clinical monitoring plan
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CRA
clinical research associate
CRF
case report form
CRP
C-reactive protein
CSR
clinical study report
DBP
diastolic blood pressure
DSIS
Daily Sleep Interference Scale
ECG
electrocardiogram
eCRF
electronic case report form
ED50/ED90
the effective dose for 50%/90% of the population
Emax
the maximum effect of the drug
ePRO
electronic patient-reported outcome (system)
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FAST
Fast Alcohol Screening Test 
FDA
Food and Drug Administration
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
HR
heart rate
IB
investigator brochure
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
IEC
independent ethics committee
IP
investigational product
IRB
institutional review board
IV
intravenous
IWRS
interactive web response system
LOCF
Last-Observation-Carried-Forward
MAD
multiple ascending dose
MCP-Mod
multiple comparison procedure modelling
mITT
modified intent-to-treat
NCA
noncompartmental analysis
NCS
nerve conduction studies
NGF
nerve growth factor
NPS
neuropathic pain scale
NRS
numeric rating scale
NSAID
nonsteroidal anti-inflammatory drug
NYHA
New York Heart Association
OA
osteoarthritis
OTC
over-the-counter
PD
pharmacodynamic
PDN
painful diabetic neuropathy
PGIC
Patient Global Impression of Change
PK
pharmacokinetic
PRN
pro re nata (where necessary)
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PR (PQ)
ECG interval measured from the onset of the P wave to the onset of the QRS 
complex
PT
preferred term
QRS
ECG interval measured from the onset of the QRS complex to the J point
QT
ECG interval measured from the onset of the QRS complex to the end of the 
T wave
QTc
QT interval corrected for heart rate
QTcF
RBC
red blood cell
RPOA
rapidly progressive osteoarthritis
RR
the time elapsed between 2 consecutive R waves as measured by 
electrocardiogram
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SBP
systolic blood pressure
SD
standard deviation
SF-36
36-item Short-Form Health Survey
SUSAR
suspected unexpected serious adverse reaction
sWFI
sterile water for injection
tmax
time of Cmax
TNF
tumor necrosis factor
TNFR2
tumor necrosis factor receptor 2
TNSn
Total Neuropathy Score-Nurse 
UADR
unexpected adverse drug reaction
ULN
upper limit of normal
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5
INTRODUCTION
5.1
Background and Rationale
The latest estimates show that the number of people with diabetes worldwide has risen from 108 
million in 1980 to 422 million in 2014,1 making it one of the most common chronic diseases. The 
global prevalence of diabetes among adults over 18 years of age has risen from 4.7% in 1980 to 
8.5% in 2014 (WHO).1 This increase in incidence parallels an increasing trend in ageing and in 
obesity. 
There is considerable morbidity and mortality associated with diabetes, not only because of the 
primary disease but also because of secondary complications. Diabetic neuropathy is the most 
common long-term complication of diabetes and is a leading cause of peripheral neuropathy (Dyck 
et al. 1993).2 The most common form is a chronic distal symmetric sensorimotor polyneuropathy
that predominantly affects the feet and legs. The prevalence of diabetic neuropathy increases with 
duration of diabetes, from 10% at diagnosis to >50% after 25 years. In a large diabetes patient 
cohort drawn from 28 community clinics in the US, 75% of the subjects had at least one 
abnormality on nerve conduction studies (NCS) (Vinik et al. 2006).3 Approximately 10% to 20% 
of patients with diabetes have peripheral neuropathic pain (painful diabetic neuropathy; PDN). 
Around 40% to 50% of those with chronic diabetic neuropathy will have PDN and the majority 
have features of chronic sensorimotor neuropathy (Veves et al. 2008; Young et al. 1993; Galer et 
al. 2000; Gordois et al. 2003).4,5,6,7 One epidemiological study reported tingling, shooting, or 
burning pain in 34% of over 15,000 diabetic patients surveyed in the community (Abbott et al. 
2011).8 Prevalence of pain was greater in patients with type 2 diabetes than for those with type 1 
diabetes (35% vs. 22%), greater in females with diabetes than in males (38% vs. 31%), and showed 
variability between ethnic groups within the study cohort. PDN is often experienced in terms of a 
burning, stabbing, pricking or aching sensation that is chronic and difficult to manage; it carries a 
substantial physical, social, and economic burden. Patients frequently experience anxiety, 
depression, and sleep disturbance. It is estimated that almost half of these patients do not receive 
any treatment for pain.
First-line treatments for PDN include tricyclic antidepressants, pregabalin, gabapentin, and 
duloxetine; other treatments include opioids, topical treatments (lidocaine and capsaicin), and 
non-pharmacological treatments including transcutaneous electrical nerve stimulation and 
acupuncture. All of these treatments have limitations, with variable efficacy and responder rates; 
many carry serious safety concerns and the potential for abuse and dependence. The number 
needed to treat for at least 50% pain relief for duloxetine (60 to 120 mg/day) is 6 (Sultan et al. 
2008)9; for gabapentin (>1200 mg/day) it is 5.8, and for pregabalin (300 to 600 mg/day) it is 5.0 
(Javed et al. 2015).10 Thus, despite the poly-pharmacy approach to PDN management, fewer than 
20% of patients can be expected to achieve meaningful pain relief with the current treatment
paradigms. There is a great medical need for new drugs for the treatment of PDN that have 
improved and more sustained symptomatic effects and better tolerability.
MEDI7352 is a bispecific fusion protein composed of a single chain variable domain fragment
(scFv) that binds nerve growth factor (NGF), linked by CH2 and CH3 domains of a human 
immunoglobulin 1 to tumor necrosis factor (TNF) receptor 2 (TNFR2). The scFv end of 
MEDI7352 effectively neutralises NGF, preventing its interaction with both its high- and 
low-affinity receptors, the tropomyosin-related kinase A receptor and the p75 neurotrophin 
receptor, respectively. The TNFR2 end of MEDI7352 binds TNF in solution, thereby preventing 
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its interaction with cell surface TNFR2 and the consequent intracellular signalling and biologic 
effects. MEDI7352 is thus designed to engage two biological mediators, NGF and TNF, both of 
which are considered to play an important role in sensitisation of the nervous system and in pain 
pathophysiology (Pezet and McMahon 2006; Hefti et al. 2006; Petty et al. 1994; Dimitroulas et al. 
2017; Leung and Cahill 2010).11,12,13,14,15 In humans, anti-NGF antibodies demonstrate efficacy in 
clinical studies of osteoarthritis (OA) and chronic lower back pain (Lane et al. 2010; Katz et al. 
2011; Brown et al. 2012, 2013; Kivitz et al. 2013; Schnitzer et al. 2015; Spierings et al. 
2013).16,17,18,19,20,21,22 This clinical efficacy appears to require doses of anti-NGF antibodies that 
are projected to sequester almost all circulating NGF (Neubert et al. 2013).23 Such high levels of 
NGF sequestration have, however, raised concerns with regard to the safety of this therapeutic 
approach (Holmes 2012; Hochberg et al. 2012; Bannwarth and Kostine 2017).24,25,26 TNF receptor 
blockers have a well-established role for disease modification in the management of rheumatoid 
arthritis and other inflammatory joint diseases in which pain is often an important component of
the phenotype (Croft et al. 2013).27 While anti-TNF therapeutics do not carry a primary indication 
for the provision of analgesia, there is some evidence to suggest that a selected sub-group of OA 
patients with a marked inflammatory profile may benefit from this therapy (Dimitroulas et al. 
2017),14 and it is thought that TNF blockers can be at least partially efficacious in the setting of 
clinical neuropathic pain (Leung and Cahill 2010; Cohen et al. 2012).15,28
In preclinical studies, administration of MEDI7352 has been shown to produce a significant 
antihyperalgesic effect at doses that are believed to sequester <10% of circulating NGF. As such, 
it is hypothesised that the observed efficacy, which occurs at very low levels of NGF suppression, 
may result as a function of synergy with respect to the co-sequestration of NGF and TNF. Evidence 
to support such synergy is based on observations of MEDI7352-mediated analgesia being observed 
with doses at which the individual components of the protein (anti-NGF or anti-TNF), when dosed 
separately, are inactive. The observation has been made in animal models of both inflammatory 
pain and neuropathic pain. While the molecular mechanisms underpinning such efficacy remain 
to be elucidated, MEDI7352 represents a potentially novel approach to the management of chronic 
pain that may further help to avoid unwanted effects associated with high levels of NGF 
suppression.
5.2
Clinical Experience
As of 01 June 2021, it is estimated that approximately 116 subjects have been exposed to 
MEDI7352 in clinical studies. A first-in-human study of MEDI7352 evaluating safety, 
pharmacokinetics (PK), pharmacodynamics (PD), and efficacy in subjects with painful OA of the 
knee has been completed, and 3 clinical studies with MEDI7352 are ongoing:
Study D5680C00001, the completed first-in-human study 
Study D5680C00002, the present study described within this protocol
Study D5680C00003, a Phase IIb, randomised, double-blind, placebo-controlled, 
dose-response study to evaluate the efficacy, safety, tolerability, PK, immunogenicity, and 
PD of MEDI7352 in subjects with painful OA of the knee
Study D5680C00004, a Phase I, randomised, double-blind, placebo-controlled study to 
evaluate the safety, tolerability, PK, and immunogenicity of MEDI7352 in healthy 
volunteers
• 
• 
• 
• 
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5.2.1
Phase I Painful Osteoarthritis of the Knee Study
Completed study D5680C00001
was a clinical evaluation of MEDI7352 for safety, 
pharmacokinetics (PK), pharmacodynamics (PD), and efficacy in a first-in-human study in 
subjects with painful OA of the knee (ClinicalTrials.gov Identifier: NCT02508155). 
Single (SAD) and multiple (MAD) ascending doses were evaluated against placebo, with review 
of blinded safety data from each completed dosage cohort undertaken by a Safety Review 
Committee before further dose escalation. Study Part 1 (SAD) included a total of 53 male and 
nonfertile female subjects, aged 36 through 75 years, who received single doses of MEDI7352 or 
placebo. Overall, 39 subjects received MEDI7352 (33 intravenous [IV] and 6 subcutaneous [SC]), 
and 14 subjects received placebo (12 IV and 2 SC). The MEDI7352 IV doses studied were
 
Study Part 2 (MAD) included a total of 
75 male and nonfertile female subjects, aged 31 through 75 years, who received up to 4 planned 
IV doses of MEDI7352 or placebo administered 2 weeks apart. Overall, 53 subjects received 
was enrolled and randomised but not dosed due to poor venous access.
In the SAD phase, 17 of 39 subjects (43.6%) treated with MEDI7352 (across all dose levels) and 
9 of 14 subjects (64.3%) treated with placebo had at least one treatment-emergent adverse event 
(TEAE). Most TEAEs were considered by the investigator to be mild or moderate intensity and 
not related to investigational product (IP). There were no deaths, serious TEAEs, or 
discontinuations due to TEAEs.
The most common TEAEs among subjects treated with MEDI7352 in the SAD phase (across all 
dose levels) were headache (12.8%), back pain (7.7%), and epistaxis (5.1%), with no clear dose-
response relationship. Among subjects treated with placebo, the most common TEAEs were 
headache (28.6%) and oropharyngeal pain (14.3%).
In Study Part 2 (MAD), 44 of 53 subjects (83.0%) treated with MEDI7352 (across all dose levels), 
and 16 of 22 subjects (72.7%) treated with placebo had at least one TEAE. Most TEAEs were 
considered by the investigator to be of mild or moderate intensity and not related to IP. There were 
no deaths. There was 1 reported serious TEAE (pneumonia in a subject treated with MEDI7352), 
which led to the subject
severe in intensity and not related to the IP or study procedures, as it was considered a complication 
of influenza (reported simultaneously by several other family members). Four subjects were 
withdrawn from the MAD phase of the study due to non-serious TEAEs: viral upper respiratory 
tract infection; erysipelas; nasopharyngitis and pyrexia; and infusion-related reaction. A higher 
proportion of subjects treated with MEDI7352 had TEAEs of oral herpes and urinary tract 
infection (5.7% each) compared with subjects treated with placebo (0%). However, the overall 
incidence of TEAEs in the SOC of infections and infestations was similar among subjects treated 
with MEDI7352 and those treated with placebo (39.6% and 36.4%, respectively). The most 
common TEAEs among subjects treated with MEDI7352 in the MAD phase (across all dose 
levels) were nasopharyngitis (26.4%), headache (28.3%), back pain (11.3%), and arthralgia and 
oropharyngeal pain (9.4% each). Among subjects treated with placebo, the most common TEAEs 
were nasopharyngitis and headache (27.3% each). No infusion-related reactions were reported in 
the SAD phase of the study. One subject treated with MEDI7352 in the MAD phase had a 
nonserious infusion-related reaction (dyspnoea, flushing, dizziness), which led to discontinuation 
as noted above. The TEAE began within 3 minutes of the start of the second IV infusion of 
MEDI7352 (Day 15); treatment was discontinued, and the event resolved in less than 1 hour.
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No cases of rapidly progressive OA (RPOA) or osteonecrosis were reported during the study. 
There were no discernible differences in the TEAE profiles of subjects with and without ADA in 
either study phase, suggesting that there were no apparent effects of immunogenicity on safety.No
clinically significant changes or dose-related trends for mean changes from baseline or differences 
between MEDI7352- and placebo-treated subjects in either study phase were observed for other 
safety parameters, including laboratory safety tests (haematology, coagulation, clinical chemistry 
and urinalysis), vital signs (blood pressures, temperature, and pulse rate), electrocardiogram (ECG) 
assessments, physical examinations, or neuropathy assessments (Total Neuropathy Score, nurse).
Please refer to the investigator brochure (IB) for further details.
5.2.2
Current Phase 2 Painful Diabetic Neuropathy Study
Here we present the study protocol to evaluate the analgesic efficacy of MEDI7352 further in a 
human neuropathic pain condition, by conducting a placebo-controlled trial in subjects with PDN. 
MEDI7352 or placebo will be administered to subjects as an adjunct to existing therapeutics 
prescribed for PDN. To enable efficient modelling of the dose-response relationship for 
MEDI7352 in neuropathic pain, it is planned to evaluate 4 dose levels of MEDI7352 and placebo.
As of 01 June 2021, a total of 41 subjects with PDN have received blinded study treatment (up to 
6 planned IV doses, administered every 2 weeks). It is estimated that 21 subjects have received 
MEDI7352 
) and 20 subjects have received placebo.
A review of blinded safety data showed that 26 of 41 treated subjects (63.4%) have had at least 
one reported TEAE as of 01 June 2021. There have been no deaths or serious TEAEs. 
Three subjects have discontinued IP due to nonserious adverse events (AEs) as listed below; none 
of which was considered by the investigator to be related to IP:
A TEAE of cellulitis of moderate intensity (Stage 1,
 MEDI7352 or placebo)
A TEAE of infection (symptoms of sore throat, fever, nasopharyngitis, tongue burning, 
and sweating) of mild intensity (Stage 2, 
MEDI7352 or placebo)
An AE of alanine aminotransferase (ALT) increased of mild intensity that was reported in 
Stage 2 before the treatment period began and thought to be due to excessive alcohol 
consumption, and which led to the subject
IP (
MEDI7352 or placebo). 
Headache was the most commonly reported TEAE overall: 7 of 41 subjects (17.1%), including 
3 of 10 subjects (30.0%) in the completed Stage 1 (
MEDI7352 or placebo), 3 of 26 subjects
(11.5%) in the completed Stage 2 (
MEDI7352 or placebo) and 1 of 5 subjects (20%) in 
the ongoing Stage 3 (MEDI7352 
or placebo). All TEAEs reported in each study stage 
were considered by the investigator to be of mild or moderate intensity. 
No clinically significant changes or trends for changes from baseline have been observed for other 
safety parameters, including ECG assessments; vital signs; laboratory safety tests; and Total 
Neuropathy Score-Nurse (TNSn) or for parameters measured during motor and sensory NCS.
5.2.3
Phase 2b Painful Osteoarthritis of the Knee Study
In the ongoing Phase IIb study D5680C00003, one subject had received blinded SC study 
treatment (MEDI7352 
 and 
or placebo) as of 01 June 2021. This subject had 
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nonserious TEAEs of diarrhoea and irritability, both considered by the investigator to be of 
moderate intensity. The subject withdrew from the study (ie, consent withdrawal) after receiving 
5 of 6 planned SC injections of study treatment.
5.2.4
Phase I Study in Healthy Volunteers
In the Phase I study D5680C00004, 5 subjects had received blinded SC study treatment 
(MEDI7352 
or placebo) as of 01 June 2021. Two of the of 5 treated subjects (40.0%) have 
had a total of 4 TEAEs as follows (1 subject each): dyspepsia, catheter site erythema, injection site 
pain, and paraesthesia. All reported TEAEs were considered by the investigator to be of mild 
intensity. There have been no deaths, treatment-emergent SAEs, or withdrawals due to AEs.
5.3
Summary of Potential Risks and Benefits
The potential benefits of study participation are that subjects with PDN may experience a reduction 
in symptoms as a result of treatment with MEDI7352. No other benefits of participation are 
anticipated.
The potential risks of study participation include those associated with exposure to MEDI7352, as 
well as those related to medical procedures, including venepuncture undertaken for blood sampling 
and administration of investigational product (IP). Although no important risks have been 
identified for MEDI7352 to date in the completed Phase 1 clinical study or the 3 ongoing studies,
MEDI7352 may have risks similar to those reported with both anti-NGF and anti-TNF therapies, 
as well as those reported with therapeutic proteins in general.
Potential risks associated with MEDI7352 include:
Potential risks based on class effects and mechanisms of action
o
Risks associated with the anti-NGF mechanism
Rapidly progressive OA and other joint safety events. This risk is not 
limited to osteoarthritic joints 
Sensory abnormalities and peripheral neuropathy 
Autonomic neuropathy and sympathetic dysfunction 
o
Risks associated with the anti-TNF mechanism 
Increased risk of infection, including tuberculosis, bacterial sepsis, and 
invasive fungal infections 
Warnings and precautions for etanercept (anti-
hypersensitivity reactions; exacerbation or new onset of demyelinating 
disease; malignancies, including lymphoma, leukaemia, melanoma and 
non-melanoma skin cancer; serious haematological reactions including 
pancytopenia, or aplastic anaemia; new onset or worsening congestive heart 
failure; reactivation of hepatitis B; autoimmune conditions including 
autoimmune hepatitis, autoimmune renal disease and a lupus-like syndrome 
(ENBREL Prescribing Information, ENBREL Summary of Product 
Characteristics). 
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General risks associated with protein therapeutics include immunological reactions: 
hypersensitivity reactions, injection site reactions, and the consequences of 
immunogenicity (eg, immune-complex disease). 
The most significant adverse effect of anti-NGF monoclonal antibodies has been infrequent 
clinical cases of RPOA (type 1 and 2) observed in large-scale clinical studies, which led the Food 
and Drug Administration (FDA) to impose a clinical hold on this mechanism in 2010. At a 2012 
Arthritis Advisory Committee meeting that reviewed results of the tanezumab, fulranumab, and 
fasinumab programs, sponsors presented data showing that these events increased with increased 
doses of anti-NGFs and particularly when the drugs were dosed concurrently with nonsteroidal 
anti-inflammatory drugs (NSAIDs).29
At the FDA Advisory Committee Meeting in 2021, safety data from 3 studies of tanezumab were 
presented using a composite joint safety event endpoint to capture events including RPOA type 1, 
RPOA type 2, osteonecrosis, subchondral insufficiency fracture, and pathological fracture.30 There 
was a significantly higher incidence of events in subjects treated with tanezumab (3.2% and 6.2% 
of subjects treated with tanezumab 2.5 mg and 5 mg, respectively) compared to NSAIDs (1.5% of 
subjects) or placebo (0% of subjects).31 In addition, a greater proportion of subjects treated with 
tanezumab (5.5% and 7.8% of subjects treated with tanezumab 2.5 mg and 5 mg, respectively) 
required total joint replacements when compared to those treated with NSAIDs (2.6% of subjects)
or placebo (4.5% of subjects). 30, 31 Overall, approximately 85% of the total joint replacements 
31 however, some joint safety events including total 
joint replacement occurred in joints KL grade 0 or 1 at baseline. 30, 31
It was also notable in the tanezumab programme that composite joint safety events are not limited 
to arthritis joints. For subjects with joints KL grade 0 or 1 enrolled in the tanezumab study 1058, 
there was a higher incidence of CJSE in the tanezumab 5 mg treatment arm (19 events, 1.9%) than 
in the NSAID arm (2 events, 0.2%).32
There have been no reports of RPOA or destructive arthropathy in the MEDI7352 clinical program
to date.
Peripheral neuropathy
both autonomic and sensory
has also been identified as a risk with 
anti-NGF antibodies (Bélanger et al. 2018; Dewanjee et al. 2018).33,34 In the MEDI7352 13-week 
good laboratory practice toxicology study undertaken in rats, axonal degeneration has been 
observed in peripheral nerves. No clear dose-response relationship has been observed for this 
unclear whether sensory nerves or motor nerves or both are affected. No functional consequences 
have been observed in neurobehavioural assessments in the animals and the effect has been 
described as non-adverse in the rodents. The underlying mechanism and potential relevance of the 
finding to humans is unknown. It is not known whether MEDI7352 might worsen a pre-existing 
neuropathy as a function of NGF inhibition. For the present clinical study, the risk will be managed 
through appropriate peripheral nervous system monitoring and will include nerve conduction 
studies (NCS).
TNF-alpha inhibitors carry labelled safety warnings and precautions regarding the risk of serious 
infections (including tuberculosis [TB], bacterial sepsis, invasive fungal infections, and other 
opportunistic infections) and malignancies (including lymphoma and other malignancies). 
Additional warnings and precautions for etanercept include exacerbation or new onset of 
• 
occurred in joints KL grade 2: 3 at baseline; 
effect, although a trend for increased 'average' severity with increasing dose was noted. It is 
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demyelinating disease, lymphoma, pancytopenia or aplastic anaemia, new onset or worsening 
congestive heart failure, and reactivation of hepatitis B virus (HBV).
General risks of biologic therapies include infusion-related reactions (defined as a collection of 
signs and symptoms ranging from local skin reactions at the injection site, pyrexia, and an 
influenza-like syndrome, to an acute anaphylaxis, usually occurring within 2 hours of the infusion; 
hypersensitivity reactions; and development of anti-drug antibodies to MEDI7352. Antidrug 
antibodies to MEDI7352 could result in immune-complex disease (with manifestations including 
arthralgia, serum-sickness, and vasculitis), auto-immunity, or altered MEDI7352 levels or activity.
A summary of the pharmacological properties and known potential risks of MEDI7352 is provided 
in the current version of the IB. The investigator must become familiar with all sections of the 
MEDI7352 IB before the start of the study.
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6
OBJECTIVES
6.1
Primary Objective
The primary objective is to assess the efficacy of MEDI7352 versus placebo on chronic pain in 
subjects with PDN currently taking standard of care medication for their PDN pain.
6.2
Secondary Objectives
To assess the safety and tolerability of MEDI7352 in subjects with PDN
To assess the PK, PD, and immunogenicity of MEDI7352 in subjects with PDN
To characterise the dose-response relationship of MEDI7352 on chronic pain in subjects 
with PDN
6.3
Exploratory Objectives
Objectives
Endpoints
Primary
To assess the efficacy of MEDI7352 
versus placebo on chronic pain in 
subjects with PDN currently taking 
standard of care medication for their 
PDN pain
Primary:
Change in the weekly average of the average daily pain scores 
from the baseline week to Week 12 of MEDI7352 compared to 
placebo, as measured on an 11-point (0-10) NRS.
Secondary:
Change in the weekly average of the average daily pain score, 
as measured on an 11-point (0-10) NRS, from baseline to 
Weeks 2, 4, 6, 8, and 10 of treatment and the week before the 
follow-up visit. 
Percen
reductions in the weekly average of the average daily pain score 
from baseline during Weeks 4, 8, and 12 of treatment and the 
week before follow-up.
Change in Galer Neuropathic Pain Scale (NPS) from baseline
to Days 28, 56, and 84 of treatment and the follow-up visit.  
Change in Daily Sleep Interference Scale (DSIS) from baseline 
to Days 28, 56, and 84 of treatment and the follow-up visit.
,
Patient 
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Global Impression of Change (PGIC) on Days 28, 56, and 84 of 
treatment and the follow-up visit.
Change in the 36-item Short-Form Health Survey (SF-36) from 
baseline to Day 84 of treatment.
Change in the amount of rescue medication used (in terms of 
dosage/day) from baseline to Week 12 of treatment.
Secondary
To assess the safety and tolerability of 
MEDI7352 in subjects with PDN 
Safety and tolerability assessments: AEs and SAEs, physical 
and neurological examinations, neuropathy assessments
(TNSn), strength (dorsiflexion) and deep tendon reflex (knee 
and ankle) assessments, vital signs, 12-lead ECGs, clinical 
laboratory testing (haematology, clinical chemistry, 
coagulation, and urinalysis), motor and sensory nerve 
conduction, concomitant medication assessment, injection site 
reaction assessment, and infusion reaction assessments.
To assess the PK, PD, and 
immunogenicity of MEDI7352 in 
subjects with PDN
Primary PK parameters of MEDI7352 will include maximum 
concentration (Cmax), time of Cmax (tmax), area under the plasma 
concentration-time curve from time 0 to infinity (AUC0- ), area 
under the plasma concentration-time curve from time 0 to the 
time of the last quantifiable plasma concentration (AUC0-t), area 
under the plasma concentration-time curve for the dosing 
interval (AUCtau) at steady state, Cmax at steady state, volume of 
distribution at steady state, t1/2, and apparent total body 
clearance at steady state (CLss).
Pharmacodynamics: free and/or total NGF measurements in 
serum/plasma.
Immunogenicity (ADA) assessments.
To characterise the dose-response 
relationship of MEDI7352 on chronic 
pain in subjects with PDN
Change in the weekly average of the average daily pain scores 
from the baseline week to Week 12, as measured on an 
11-point (0-10) NRS, versus dose.
Exploratory
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7
STUDY DESIGN
7.1
Overall Study Design and Plan
This is a randomised, double-blind, placebo-controlled study of MEDI7352 in subjects with 
moderate to severe PDN. The study incorporates a screening period of up to 45 days and a 12-week 
double-blind treatment period during which MEDI7352 or placebo will be administered IV on 
6 occasions, with each dose separated by 14 days. There will be a 6-week follow-up period.
Subjects must have chronic PDN persistent for 6 months or longer, not adequately controlled by 
standard of care treatments, caused by type 1 or type 2 diabetes mellitus. Subjects must have 
bilateral decrease or absent reflexes at the ankles, or bilateral decrease of a sensory sign in the 
distal lower extremities, based on medical history and physical or neurological examination.
NSAIDs and COX-2 inhibitors are strictly contraindicated throughout the study. If eligible subjects 
are using NSAIDs or COX-2 inhibitors at the time of screening, they must be willing to withdraw 
from them. 
Subjects will be required to report pain scores on an 11-point (0-10) numeric rating scale (NRS) 
by completion of a subject diary for a minimum of 7 days prior to Day 1 (ie, Day -7 to Day -1). If 
the diary is started prior to Day -7, then data from Day -7 to Day -1 will be used to determine 
eligibility. At least 5 of 7 days need to be recorded by the subject to obtain a valid baseline value. 
To be el
4 is required. There will be 4
stages in the study: in the first stage, subjects will be randomly assigned to placebo or the lowest 
dose (
) until at least 10 subjects have been recruited. In the second stage, up to a maximum 
of 30 subjects will be randomly assigned to
; prior to 
commencing the second stage, the safety and tolerability experience following administration of 
e 1 study of MEDI7352 will be evaluated. In stage 3 of the 
study, approximately 67 subjects will be randomly assigned to placebo or
.
The third stage will include an interim analysis to assess key assumptions of the sample size 
calculation. Upon enrolment of approximately 67 subjects in stage 3, approximately 165 eligible 
subjects will be randomly assigned to treatment with equal allocation across 3 dose levels of 
MEDI7352 or placebo to ensure approximately 236 subjects are evaluable for the efficacy analysis 
of stages 2 to 4 combined. In summary, the numbers of subjects randomised to receive treatment 
in the various stages is as follows: at least 10 subjects in stage 1, up to a maximum of 30 subjects 
in stage 2, an estimated 67 subjects in stage 3, and an estimated 165 subjects in stage 4 (ie, 272 in 
total across all study stages 1 to 4).
All treatments and assessments will be undertaken in a double-blind fashion. Treatments will be 
administered IV over a 60-minute period. Subjects will be dosed as outpatients and will participate 
in 6 independent dosing sessions, once every 2 weeks. Safety and efficacy assessments will be 
undertaken at each of the dosing sessions and during follow-up visits.
 
Efficacy will be evaluated by subject assessments of daily average pain, as measured on an 
11-point (0-10) NRS; the Galer Neuropathic Pain Scale (NPS); the Daily Sleep Interference Scale 
(DSIS); the Patient Global Impression of Change (PGIC); and the 36-item Short-Form Health 
Survey (SF-36).
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The PK, PD (free and/or total plasma/serum NGF) and immunogenicity of MEDI7352 will be 
characterized.
 
.
 
.
Safety will be assessed by evaluating adverse events (AEs), clinical laboratory test results, vital 
sign measurements, and 12-lead ECGs. Physical and neurological examinations will be 
undertaken. Additional monitoring of the peripheral nervous system will be undertaken through 
evaluation of TNSn, strength (dorsiflexion), deep tendon reflexes (knee and ankle), and NCS of 
motor and sensory nerves. Monitoring will be undertaken for injection site reactions and infusion-
related reactions. Concomitant medication use will be monitored.
All AEs observed by the study personnel or reported by the subject during the study (from the time 
of the signing of the informed consent and/or assent through the posttreatment visits) will be 
documented.
Medical monitors will review safety data on an ongoing basis. An interim review of blinded
aggregate safety data will be undertaken following completion of follow-up for approximately 
every 30 subjects enrolled in the study (see Section 9.3.1). The interim review will be performed 
by AstraZeneca Neuroscience in conjunction with the pharmacovigilance and safety agent, MMS 
Holdings.
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Figure 7-1:
Study Design
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7.2
Rationale and Discussion of Study Design
A randomised, double-blind, placebo-controlled study design with multiple dose levels of 
MEDI7352 is appropriate to assess the efficacy, safety, tolerability, PK, PD, and immunogenicity 
of MEDI7352 as compared to placebo. Subjects must have chronic PDN that is not adequately 
controlled by standard of care treatments, and will receive MEDI7352 as adjunctive therapy for 
12 weeks. Placebo is included in the study to permit comparative assessment of the safety, 
tolerability, PK, PD, and immunogenicity of MEDI7352, and to further evaluate the balance of 
benefit and risk of MEDI7352. The study is comprised of 4 stages. The first stage will assess safety 
of
in the PDN population. The second stage will compare an expected efficacious dose,
, to placebo. The third stage will compare the highest expected efficacious dose, 
 to placebo and includes an interim analysis that will confirm decision making for stage 
4 with respect to exact sample size and dose allocation ratio. If there are no changes following the 
interim analysis, the fourth stage will study 3 doses of MEDI7352 (
) versus 
placebo to enable a robust characterisation of the efficacy dose-response relationship.
7.3
Selection of Doses in the Study
MEDI7352 has undergone clinical evaluation for safety, PK, PD, and efficacy in a first-in-human 
study in subjects with painful OA of the knee (ClinicalTrials.gov Identifier: NCT02508155). In 
that study, testing of single IV doses of up to
and repeat ascending IV doses of 
 and
every 2 weeks have been completed. Single SC doses of 
have 
also been evaluated. No safety or tolerability concerns were reported. A full description of the 
current clinical experience with MEDI7352 is in Section 5.2.
Based on the results of the first-in-human study, the planned dosages in this protocol are
 and
 administered every 2 weeks with a total of 6 doses per
subject. Thus, the dose range to be explored in this study encompasses an equivalent dose range 
that has been studied in the preceding Phase 1 study and the highest dose planned for the current 
study is the same as the highest dose assessed in the Phase 1 study.
7.4
Study Sites
The study will take place at approximately 40 sites in approximately 6 countries. Each site is 
anticipated to screen a sufficient number of subjects to randomise approximately 8 subjects. A
study site with a high recruitment rate may be allowed to recruit more subjects if other sites have 
slow enrolment.
7.5
Point of Contact
A point of contact will be identified to provide information to subjects about where to obtain 
information on the study, the rights of subjects, and whom to contact in case of a study-related 
injury. This information will be provided in the subject information and informed consent form
(ICF).
7.6
End of Study Definition
The clinical trial is considered completed when the last 
last study visit has occurred.
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8
SUBJECT POPULATION
8.1
Selection of Study Population and Diagnosis
Approximately 272 eligible subjects will be randomly assigned to double-blind treatment with 1
of 4 dose levels of MEDI7352 (
and 
 dependent upon the stage of the study)
or placebo to ensure that approximately 236 subjects are eligible for the efficacy analysis of 
stages 2, 3 and 4 combined.
Subjects who do not meet all of the eligibility criteria will not be enrolled.
8.2
Study Entry Criteria
8.2.1
Inclusion Criteria
A subject will be eligible for study participation if he or she meets all of the following criteria:
General
1. Male, or postmenopausal or surgically sterile female, 18 to 80 years of age (inclusive) on the 
day of randomisation. Post-menopausal women
amenorrhea (with follicle-stimulating hormone [FSH]
years; 
women >60 years do not require a FSH test) and must have had a negative pregnancy test result 
at screening. Surgically sterile women are defined as those who have had a hysterectomy, 
bilateral ovariectomy (oophorectomy), bilateral salpingectomy, or bilateral tubal ligation. 
Women who are surgically sterile must provide suitable medical documentation of the 
adequacy of the procedure; eg, an operative report or confirmatory ultrasound report. Men who 
are biologically capable of having children must agree and commit to use an adequate form of 
contraception (see Appendix B) for the duration of the treatment period and for 3 months after 
the last administration of study drug. A male subject is considered capable of having children 
even if his sexual partner is sterile or using contraceptives.
2.
2.
3. Subjects must understand the nature of the study and must provide signed and dated written 
informed consent prior to the initiation of any study procedures.
4. The subject should be willing and able to understand and participate in all scheduled 
evaluations and to complete all required tests and procedures including the use of subject 
diaries, as judged by the investigator.
5. The subject must be considered likely to comply with the study protocol and to have a high 
probability of completing the study, as judged by the investigator.
6. For subjects participating in the optional genetic research, a separate signed and dated written 
informed consent must be provided. If a subject declines to participate in the genetic research, 
this will have no influence on the ability of the subject to participate in the study.
Diagnostic
7. Chronic PDN persistent for 6 months or longer, not adequately controlled by standard of care 
treatments.
8. Pain (beginning in the feet and with relatively symmetrical onset for 6 months or greater) due 
to bilateral peripheral neuropathy caused by either type 1 or type 2 diabetes mellitus, with
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bilateral decrease or absent reflexes at the ankles, or bilateral decrease of a sensory sign in the 
distal lower extremities, based on medical history and peripheral neurological examination.
[NOTE: for sensory evaluation, the relevant components of the TNSn for the lower limb should 
be undertaken, to include sensory symptom score, pin sensibility score, and vibration 
sensibility score.]
9.
4, as measured on an 11-point (0 to 10) NRS by completion 
of a subject diary for a minimum of 7 days prior to Day 1 (ie, Day -7 to Day -1). At least 5 of 
7 days need to be recorded by the subject to obtain a valid baseline value. Pain scores from 
Day -7 to Day -1 will be centrally reviewed by the study team, and if there is significant 
variability in the scores during this baseline period of pain evaluation, it will be discussed with 
the investigator and the subject may be excluded.
Concomitant medication
10. The subject must be willing and able to discontinue all NSAID or COX-2 analgesic therapy 
from the start of the washout period until the end of follow-up. This includes over-the-counter 
(OTC) pain medications and topical analgesics that contain an NSAID or COX-2 inhibitor. 
The use of NSAIDs (eg, ibuprofen, naproxen) or COX-2 medications (eg, celecoxib) at any 
time during the study and through to completion of drug washout (5 half-lives) is prohibited 
and contraindicated.
11. Subjects should currently be taking medication for the treatment of PDN. Subjects should be 
taking at least one of the first-line medications (consistent with regional or local standard of 
care guidelines for PDN) belonging to either the anticonvulsant class (pregabalin or 
gabapentin) or the antidepressant class (duloxetine, venlafaxine, or amitriptyline), but no more 
than one medication from a single class. Subjects receiving treatment with opioids alone (as a 
monotherapy) should be excluded, unless the opioids are being prescribed as a second-line 
treatment for PDN because the first-line therapies were found to be poorly tolerated or not 
efficacious. For all drug classes, subjects should be established on a stable dosing regimen that 
is consistent with regional or local standards of accepted prescribing practice for no less than 
3 months before the anticipated randomisation date. Subjects should be willing to maintain this 
dosing regimen for the duration of study participation until the last follow-up visit. Subjects 
must be willing to use only the protocol-specified rescue medications during the study.
12. If the subject is receiving permitted medications for the treatment of non-excluded medical 
conditions (eg, antihypertensive medication, cholesterol-lowering treatment, antidiabetic 
medication), the dose and dosing regimen must be stable for at least 28 days before 
randomisation and should be expected to remain stable for the duration of study participation 
until at least the last follow-up visit.
8.2.2
Exclusion Criteria
A subject will be excluded from the study if he or she meets any of the following criteria:
General
1. Requires current treatment with another biologic therapeutic agent.
2. Previously received any form of anti-NGF or anti-TNF therapy. 
A mean pain intensity score of~ 
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3. Participation in another clinical study with an IP or device within 60 days or 5 half-lives prior 
to screening, whichever is longer.
4. Plasma donation within 28 days of screening or any blood donation or blood loss >500 mL 
within 2 months of screening.
5. Previous allogeneic bone marrow or stem cell transplant.
6. Received non-leukocyte-depleted whole blood transfusion within 120 days of the genetic 
research sample collection, if participating in the optional genetic research.
7. Poor venous access such that IV drug delivery would be difficult.
8. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and 
staff at the study site) and in accordance with local regulations.
Medical history
9. Presence of other clinically significant neuropathy (eg, hereditary neuropathy, inflammatory 
neuropathy) or other clinically significant disorder (eg, nerve compression injury) involving 
abnormal peripheral sensation, with an aetiology that is considered to be distinct from that of 
PDN, and that is likely to interfere with assessment of peripheral nerve function, as judged by 
the investigator.
10. History of osteonecrosis, rapidly progressive OA, subchondral insufficiency fractures, 
neurogenic arthropathy, or analgesia-induced arthropathy. 
11. Diagnosis of clinically significant OA currently affecting a major joint in the upper extremity 
(shoulder, elbow, or wrist) or lower extremity (hip, knee, or ankle) or axial spine; or other 
degenerative disease affecting any joint in subjects for whom, in the opinion of the investigator,
there is an identified risk of osteonecrosis, rapidly progressive OA, subchondral insufficiency 
fractures, neurogenic arthropathy, or analgesia-induced arthropathy.
NOTE: The diagnosis and evaluation of OA should be guided by American College of 
Rheumatology (ACR)-endorsed criteria, where applicable, and should incorporate radiologic 
investigation for the assessment of OA severity consistent with the relevant ACR guidance 
(Altman et al. 1986, Altman et al. 1990, Altman et al. 1991)35,36,37 at the discretion of the 
investigator, or otherwise guided by local rheumatologic, orthopaedic, or radiologic expert 
advice. Where Kellgren and Lawrence grading is used for the radiographic evaluation of major 
joint OA, gra
whom there is evidence of clinically significant sensory impairment in the distal lower 
extremity (based on medical history, clinical examination, TNSn, or evidence of sensory nerve 
conduction impairment available from NCS), there is an absolute requirement for bilateral feet 
and ankle radiographs to be undertaken for the evaluation of OA severity to exclude the 
possibility of neuropathic arthropathy. All radiologic investigations should be reported locally 
and the reports should be retained in the patient files as source documentation and made 
available in the event that subsequent adjudication of rheumatologic adverse events is required.
Radiologic images should also be retained and made available in the event that subsequent 
adjudication of rheumatologic adverse events is required.
12. Chronic pain condition, other than PDN, that is likely to interfere with the evaluation of the 
the investigator.
de 2:2 would be considered exclusionary for trial participation. In subjects for 
subject's PDN pain, as judged by 
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13. Presence of any major psychiatric disorder according to the criteria of the Diagnostic and 
Statistical Manual of Mental Disorders, 5th Edition, if, in the opinion of the investigator, the 
psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect pain 
14. Significant cardiovascular disease, including Class 3 or Class 4 (The Criteria Committee of the 
New York Heart Association (NYHA) classification standards 1994)38 congestive heart failure 
(ejection fraction of <40%) or clinically significant stenosis or occlusion of a carotid or 
vertebral artery or clinically significant arrhythmias. 
NOTE: Validated NYHA classification standards:
Class 1: cardiac disease but no symptoms and no limitations in ordinary physical activity 
(no shortness of breath when walking, climbing stairs)
Class 2: mild symptoms (mild angina or shortness of breath) and slight limitation with 
ordinary physical activity
Class 3: marked limitation due to symptoms, even during less than ordinary activities such 
as walking 20 to 100 meters; comfortable only at rest
Class 4: severe limitations and symptoms at rest
NOTE: Subjects designated as NYHA functional Class 1 or Class 2 are not necessarily 
excluded from participation. However, such subjects should have left ventricular ejection 
fraction measured by echocardiography and documented at baseline
15. Significant or chronic lung disease, including severe or unstable chronic obstructive pulmonary 
disease (COPD), or severe or unstable asthma.
16. Known or suspected systemic infection, including HIV, HBV, hepatitis C virus (HCV), or TB 
as judged by the investigator or from screening testing. At screening, a QuantiFERON test will
be conducted for TB (Nyendak et al. 2009; Duarte et al. 2012; Cush et al. 2010).39,40,41
17. History or evidence of any significant autoimmune disease or disorder, including inflammatory 
bowel disease, multiple sclerosis, or systemic lupus erythematosus.
18. History of severe allergy/hypersensitivity reactions or history of hypersensitivity to 
immunisations or immunoglobulins.
19. History of cancer within 5 years of screening or between screening and randomisation, with 
the exception of non-metastatic basal cell carcinoma of the skin, carcinoma in situ of the cervix, 
or non-progressive prostate cancer.
20. Transient ischaemic attack or stroke in the last 3 years.
21. History of alcohol or recreational drug dependence according to the Diagnostic and Statistical 
Manual of Mental Disorders, 5th Edition criteria, within 2 years of screening, with the 
exception of nicotine dependence, which is permitted.
NOTE: Where there is a documented or suspected history of excessive alcohol usage or 
recreational drug usage, it is expected that the impact of this with respect to risk be evaluated 
at screening using the appropriate quantitative or semi-quantitative methodologies according 
to local standards of accepted medical or psychiatric practice. For example, use of the Fast 
Alcohol Screening Test (FAST) and Alcohol Use Disorders Identification Test (AUDIT)
assessment, or affect the subject's ability to complete the study . 
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alcohol screening questions for the initial evaluation of harm and risk associated with excessive 
alcohol consumption.  
22. Within 1 year of screening or between screening and randomisation, any of the following: 
myocardial infarction, hospitalisation for unstable angina or arrhythmia, or unexplained 
syncope.
23. Clinically important infection, including chronic, persistent, or acute infection, within 
3 months of screening or between screening and randomisation.
24. Current serious or unstable clinically important illness, including avascular necrosis, 
respiratory, cardiovascular, gastrointestinal, endocrinologic (excluding well-controlled type 1 
or type 2 diabetes), immunologic, haematologic, neurologic, or other major disease that is 
the investigator.
Procedural contraindications
25. Any significant medical or surgical procedure or trauma within 28 days of Day 1, or planned 
safety or ability to complete the study, or the scientific integrity of the study data, as judged by 
the investigator.
Physical and neurological examination, vital signs, ECG, laboratory values, and imaging
26. Clinically important abnormality in the physical and neurological examination, vital signs, or 
o complete 
the study, or the integrity of the clinical trial data, as judged by the investigator.
27. Poorly controlled hypertension (defined as systolic blood pressure [SBP] of >165 mmHg 
and/or diastolic blood pressure [DBP] of >95 mmHg measured in the clinic) or orthostatic 
hypotension (defined as a sustained reduction of SBP of at least 20 mmHg and/or a DBP 
reduction of at least 10 mmHg within 3 minutes of standing from a supine position). Note: If 
the blood pressure (BP) measured in the clinic is out of range, the measurements can be 
repeated on the same day or at another convenient visit.
28. Prolonged QTcF of >470 msec or family history of long QT syndrome, or shortened QTcF of 
<360 msec or family history of short QT syndrome, or any clinically significant abnormality 
in ECG rhythm, conduction, or morphology, including but not limited to: 
PR/PQ interval prolongation (PR/PQ >220 ms)
intermittent second or third degree atrioventricular (AV) block (AV block II Mobitz 
Type I, Wenckebach, while asleep or in deep rest is not exclusionary)
bundle branch block (BBB) or intraventricular conduction delay (IVCD) with QRS 
duration >120 ms
29. Haemoglobin A1C greater than 10.0% (>10.0%).
30. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >1.5 × the upper 
limit of normal (ULN) at screening or between screening and baseline. If the enzyme is 
>1.5 × ULN, the investigator can either exclude the subject at that time or decide to repeat the 
test once. If the repeat result is still >1.5 × ULN, the subject must be excluded.
likely to deteriorate or affect the subject's safety or ability to complete the study, as judged by 
to be undertaken within the timeframe of the clinical trial, that will likely affect the subject's 
clinical laboratory test at screening that could affect the subject's safety or ability t 
• 
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31. Screening creatinine clearance of <60 mL/min as determined by the Cockcroft-Gault formula.
32. Clinically significant abnormal findings in coagulation or haematology laboratory tests, as 
judged by the investigator.
33. A positive pregnancy test at screening. (If the screening urine pregnancy test is more than 
7 days before the first day of treatment, it must be repeated prior to the first dose.)
34. Positive drug screen for drugs of abuse (including but not limited to amphetamine, barbiturate, 
cannabinoids, cocaine, methadone, methaqualone, opiate, phencyclidine, or propoxyphene), 
unless there is a documented medical explanation for the positive result other than drugs of 
abuse (eg, the subject takes opioids under medical supervision for pain and the prescribed 
opioid dosing regimen is expected to be stable and unchanged for the duration of the study; or 
where cannabinoids are similarly being taken for documented medical reasons).
8.3
Premature Subject Withdrawal
All subjects will be advised that they are free to withdraw from participation in this study at any 
time, for any reason, and without prejudice. Subjects must be withdrawn from the study if they 
withdraw consent to participate. Investigators must attempt to contact subjects who fail to attend 
scheduled visits by telephone or other means to exclude the possibility of an AE being the cause 
of withdrawal. Should this be the cause, the AE must be documented, reported, and followed as 
described in Section 11.2.
The sponsor reserves the right to request the withdrawal of a subject due to protocol deviations or
other reasons.
The investigator also has the right to withdraw subjects from the study at any time for lack of 
therapeutic effect that is intolerable or otherwise unacceptable to the subject, for intolerable or 
unacceptable AEs, intercurrent illness, noncompliance with study procedures, administrative 
reasons, or in the investigator
If a subject is withdrawn before completing the study, the reason for withdrawal and the date of 
discontinuation will be recorded on the appropriate page of the case report form (CRF) or 
electronic case report form (eCRF). Whenever possible and reasonable, the evaluations that were 
to be conducted at the completion of the study should be performed at the time of premature 
discontinuation.
A participant will be considered lost to follow-up if he or she fails to return for scheduled visits 
and is unable to be contacted by the study site staff. 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit:
The site will attempt to contact the participant and reschedule the missed visit and counsel 
the participant on the importance of maintaining the assigned visit schedule and ascertain 
if the participant wishes to and/or should continue in the study.
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
ddress or local 
medical record or study file. 
's opinion, to protect the subject's best interest . 
• 
• 
necessary, a certified letter to the participant's last known mailing a 
equivalent methods). These contact attempts should be documented in the participant's 
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Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.
8.4
Subject Replacement Criteria
Withdrawn subjects may be replaced if withdrawal occurs at, or prior to, the Week 2 visit.
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9
TREATMENTS
9.1
Identification of Investigational Products
The products that will be used in this study are outlined in Table 9-1.
Table 9-1:
Identification of Investigational Product
Product 
Strength and dosage form 
Manufacturer/Supplier 
MEDI7352 
Solvent for reconstitution of 
MEDI7352 
Diluent for reconstituted 
MEDI7352 and placebo 
IV bag protectant 
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9.1.1
Dose, Route of Administration, and Dosing Schedule
Once randomized, subjects will be dosed with either MEDI7352 or placebo on Day 1, Day 14, 
Day 28, Day 42, Day 56, and Day 70. MEDI7352 or placebo will be administered IV over a
60-minute period.
MEDI7352 or placebo should be administered by the investigator or site personnel prepared to 
manage infusion reactions and anaphylaxis. The infusion rate may be slowed or interrupted if the 
subject develops an infusion reaction. [NOTE: If the infusion is slowed or interrupted, the total 
infusion time should not exceed 4 hours at room temperature.] Investigators/site personnel should 
be aware of the risk of hypersensitivity reactions, which may present as infusion reactions, and 
monitor subjects closely. In the event of a serious reaction, MEDI7352 or placebo administration 
must be discontinued immediately and the appropriate medical therapy administered.
Subjects will be dosed as outpatients but should remain under clinical supervision and should be 
monitored for no less than 4 hours after completion of each infusion. Should clinical features of 
acute hypersensitivity occur, an extended period of monitoring in an appropriate environment may 
be relevant, based on clinical judgement. This may include, but is not necessarily limited to, 
monitoring vital signs and observing for any untoward reactions. Consultation with the appropriate 
local clinical services may be warranted (eg, high dependency or intensive therapy unit).
Subjects should be made aware of the potential risks of acute hypersensitivity and infusion-related 
reactions, the signs and symptoms of such reactions, and the importance of immediately seeking 
medical attention should they occur.
9.1.2
Current Treatment of Painful Diabetic Neuropathy
Subjects should currently be taking medication for the treatment of PDN. Subjects should be taking 
at least one of the first-line medications (consistent with regional or local standard of care 
guidelines for PDN) belonging to either the anticonvulsant class (pregabalin or gabapentin) or the 
antidepressant class (duloxetine, venlafaxine, or amitriptyline), but no more than one medication 
from a single class. Subjects receiving treatment with opioids alone (as a monotherapy) should be 
excluded, unless the opioids are being prescribed as a second-line treatment for PDN because the 
first-line therapies were found to be poorly tolerated or not efficacious. For all drug classes, 
subjects should be established on a stable dosing regimen that is consistent with regional or local 
standards of accepted prescribing practice for no less than 3 months before the anticipated 
randomisation date. Subjects should be willing to maintain this stable dosing regimen for the 
duration of study participation until the last follow-up visit.  
9.1.3
Rescue Medication
Subjects who develop unacceptable pain during any stage of the study (including during the 
washout period prior to randomisation) will be permitted to initiate rescue analgesic therapy with 
paracetamol up to a maximum dose of two 500 mg tablets (ie, 1 g per dose) up to 4 times daily 
(ie, 4 g per 24-hour period).
investigator
consultation with the medical monitor.
Subjects may use sedative/hypnotics (eg, benzodiazepines) on a pro re nata (PRN; where 
necessary) basis, but these should not be taken more than 3 times a week or within 24 hours of a 
If paracetamol does not relieve the subject's pain, they may receive stronger analgesics as rescue 
medication (including tramadol and other 'weak' opiates) at the 
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clinic visit and such use will be considered a protocol deviation. Prohibited therapies are listed in 
Section 9.7.2. Other restrictions are listed in Section 9.7.3.
As a guideline, rescue medication should not generally be given for more than 3 consecutive days. 
All rescue medication use must be captured in the CRF and subjects will be required to record 
reasons for use. 
The study site will not supply rescue medication. 
The date and time of rescue medication administration as well as the name and dosage regimen of 
the rescue medication must be recorded.
9.2
Selection of Timing of Dose for Each Subject
The 2-weekly dose interval has been chosen based on PK, PD (NGF suppression) and efficacy 
considerations. In the first-in-human study in subjects with OA, the dosing schedule was 2-weekly,
and preliminary (blinded) data indicated that the effect of MEDI7352 on OA pain was detectable 
for 2 weeks.
9.3
Dose Adjustment Criteria
Dose adjustment is not allowed in this study. Subjects will be allocated to a single dosing regimen 
at randomisation.
9.3.1
Safety Stopping Rules
Safety will be monitored by the study-appointed medical monitors from Premier Research and 
AstraZeneca throughout the study in accordance with the Medical Monitoring Plan. In addition, 
an Interim Safety Review of blinded aggregate safety data will be undertaken following 
completion of follow-up visits for approximately every 30 subjects enrolled in the study and no 
less frequently than every 3 months. The interim review will be performed by AstraZeneca 
Neuroscience in conjunction with the pharmacovigilance and safety agent, MMS Holdings in
accordance with the Safety Management Plan.
Based on the interim safety reviews of aggregate safety data, the study may be stopped if the risks 
are found to outweigh the potential benefits.
For any individual subject, further administration of IP will be stopped if any of the following 
scenarios occur with a reasonable possibility of a causal relationship to administration of 
MEDI7352:
Reports of drug-related serious AE (SAE[s]) or drug-related severe AE(s) including (but
not necessarily limited to):
o
Infusion reactions and injection site reactions
o
Worsening of existing cutaneous sensory abnormalities or development of new 
cutaneous sensation AEs (eg, paraesthesia, dysesthesia, burning, pins and needles) 
that are considered serious or severe and drug-related
o
Positively adjudicated destructive arthropathy
o
Serious systemic infection
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o
Anaphylactic reaction, defined as an immediately life-threatening allergic reaction 
with bronchoconstriction, angioedema, and/or hypotension (refer to FDA Guidance 
for Industry, Immunogenicity assessment for therapeutic protein products, 2014).42
o
3 ×
2 × ULN, 
in the absence of a significant increase in alkaline phosphatase (ALP) and in the 
absence of an alternative diagnosis that could explain the increase in bilirubin
o
Severe autonomic AEs, including but not limited to symptomatic orthostatic 
hypotension and orthostatic intolerance, that are considered drug-related
o
Renal toxicity,
1.5 × ULN
o
Haematologic toxicity, defined as one or more of the following:
Leukocyte count <2.0 × 109/L
Neutrophil count <1.0 × 109/L
Platelet count <75 × 109/L
9.4
Treatment Compliance
All subjects will receive the IP infusion at the study site under the surveillance of appropriate study 
9.5
Method of Assigning Subjects to Treatment Groups
The randomisation schedule will be computer generated using a permuted block algorithm
appropriate to the treatment groups included in each stage and will randomly allocate IP to 
randomisation numbers. The randomisation numbers will be assigned sequentially through a 
central interactive web response system (IWRS) as subjects are entered into the study. The 
randomisation schedule will not be stratified and study center will not be a blocking factor in the 
randomisation schedule.
The randomisation schedule will be prepared by Premier Research before the start of the study.
No one involved in the study performance will have access to the randomisation schedule before 
official unblinding of treatment assignment. No subject will be randomised into this study more 
than once.
9.6
Blinding and Unblinding Treatment Assignment
All subjects, investigators, and study personnel involved in the conduct of the study, including 
data management, will be blinded to treatment assignment with the exception of a specified 
unblinded statistician and programmer from Premier Research who will have access to the 
randomization code, unblinded site monitors and clinical manager from Premier Research, and the 
unblinded pharmacist at each study site. The unblinded study personnel will not participate in 
study procedures or data analysis prior to unblinding of the study data to all study-related 
personnel. Unblinded personnel who are not otherwise involved in the study will prepare data for 
review and interim analysis.
Study personnel will make every effort to safeguard the integrity of the study blind to minimize 
bias in the conduct of the study. Treatment unblinding is discouraged if knowledge of the treatment 
assignment will not materially change the planned management of a medical emergency. 
Unblinding will be permitted in a medical emergency that requires immediate knowledge of the 
Fulfilling Hy's Law, defined as AST or ALT:::: 
defined as serum creatinine :::=: 
personnel. Infusion details will be recorded in the subject's eCRF. 
subject's treatment assignment. 
ULN and bilirubin :::: 
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Unblinding should be discussed in advance with the medical monitor if possible. For emergency 
unblinding, study personnel will use the IWRS. Only authorized users will have access to the 
unblinding function in the IWRS, and the IWRS will reveal the treatment information for the 
selected subject only. If the investigator is not able to discuss treatment unblinding in advance, 
then he/she must notify the medical monitor as soon as possible about the unblinding incident 
The IWRS will also send a blinded 
notification to the clinical team alerting them that a break blind occurred.
The investigator or designee must record the date and reason for treatment unblinding on the 
appropriate CRF for that subject. In all cases that are not emergencies, the investigator must discuss 
If treatment assignment is unblinded for an individual subject, study personnel will be notified of 
remaining subjects in the study. Thus, the overall study blind will not be compromised. If a 
tment assignment is unblinded, he/she will be asked to withdraw from the study. The 
investigator will make this decision after consultation with the medical monitor.
Overall unblinding will take place at the end of the study only after database lock has been 
achieved.
9.7
Permitted and Prohibited Therapies
All concomitant medications used (including OTC medications and herbal supplements) will be 
recorded in the source document and on the appropriate eCRF.
9.7.1
Permitted Therapies
As detailed in Section 9.1.2, subjects should continue to take their prescribed medication for the 
treatment of PDN.
The following medications are permitted during the study, with restrictions:
Subjects who develop unacceptable pain due to PDN or other conditions (eg, headache, 
muscular pain, etc.) during any stage of the study (including during the washout period 
prior to randomisation) will be permitted to initiate rescue/analgesic therapy with 
paracetamol up to a maximum dose of two 500 mg tablets (ie, 1 g per dose) up to 4 times 
daily (ie, 4 g per 24-hour period).
As a guideline, rescue medication should not generally be given for more than 
3 consecutive days. All rescue medication use must be captured in the CRF and subjects 
will be required to record reasons for use. Subjects will be requested not to take any rescue 
therapy within 24 hours of a clinic visit.
PDN pain, they may receive stronger 
analgesics as rescue medicat
investigator
medical monitor.
Subjects may use sedative/hypnotics (eg, benzodiazepines) on a PRN basis, but these 
should not be taken more than 3 times a week or within 24 hours of a clinic visit.
Low dose aspirin for cardiovascular prophylaxis.
without revealing the subject's treatment assignment. 
the event with the medical monitor prior to unblinding the subject's treatment assignment. 
that subject's treatment assignment without unblinding the treatment assignments for the 
subject's trea 
• 
• 
• 
If paracetamol does not relieve the subject's 
• 
• 
ion (including tramadol and other 'weak' opiates) at the 
's discretion and in consultation with the 
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If the subject is receiving permitted medications for the treatment of non-excluded medical 
conditions (eg, antihypertensive medication, cholesterol-lowering treatment, antidiabetic 
medication), the dose and dosing regimen must be stable for at least 28 days before 
randomisation and should be expected to remain stable for the duration of study 
participation until at least the last follow-up visit.
Other medicat
-being may be 
given at the discretion of the investigator (eg, a regular prescribed treatment regimen for 
glycaemic control in the management of diabetes; antihypertensive medication). 
9.7.2
Prohibited Therapies
The following therapies are prohibited during the study:
NSAIDs or analgesic doses of aspirin (325 mg/day or higher). The subject must be willing 
and able to discontinue all NSAID or COX-2 analgesic therapy from the start of the 
washout period until the end of follow-up. This includes OTC pain medications and topical 
analgesics that contain an NSAID or COX-2 inhibitor. The use of NSAIDs (eg, ibuprofen, 
naproxen) or COX-2 medications (eg, celecoxib) at any time during the study and through 
to completion of drug washout (5 half-lives) is prohibited and contraindicated.
Any other investigational drug or device, including other immunotherapeutics and live 
viral or attenuated bacterial vaccines.
Any drug of abuse including but not limited to: amphetamine, barbiturate, cannabinoids,
cocaine, methadone, methaqualone, opiate, phencyclidine, or propoxyphene, unless there 
is a documented medical explanation other than drugs of abuse (eg, the subject takes 
opioids under medical supervision for pain and the prescribed opioid dosing regimen is 
expected to be stable and unchanged for the duration of the study; or where cannabinoids 
are similarly being taken for documented medical reasons); or sedative/hypnotics used as 
described above.
Muscle relaxants, anticonvulsants, anti-Parkinsonian medications, or neuroleptic 
medications, unless used for non-excluded conditions such as Restless Leg Syndrome or 
as an adjuvant for pain on a regular schedule.
Oral, IV, intramuscular, or any other parenteral
steroids
(inhaled steroids for 
well-controlled COPD or asthma, or topical steroids for eczema, are permitted).
Treatment with another biologic therapeutic agent.
The following therapies are prohibited both before and during the study:
Previously received any form of anti-NGF or anti-TNF therapy. 
Participation in another clinical study with an IP or device within 60 days or 5 half-lives 
prior to screening, whichever is longer.
Any significant medical or surgical procedure or trauma within 28 days of Day 1, or 
planned to be undertaken within the timeframe of the clinical trial, that will likely affect 
the subject s safety or ability to complete the study, or the scientific integrity of the study 
data, as judged by the investigator.
• 
• 
ion considered necessary for the subject's safety and well 
• 
• 
• 
• 
• 
• 
• 
• 
• 
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Subjects receiving excluded therapies will be ineligible for study enrolment or for continuation in 
the study, at the discretion of the investigator.
9.7.3
Restrictions
Subjects will be asked to avoid foods containing poppy seeds for 5 days prior to the 
screening visit.
Subjects will be asked to avoid any changes in OTC products and herbals, vitamins, and 
minerals from at least 14 days before first dosing on Day 1 through to the end of follow-up. 
If needed, a nasal spray for nasal congestion may be used occasionally. If a change in 
concomitant medication is needed, the investigator must decide if the subject should remain 
in the study or be dismissed from the study.
Subjects who use nicotine patches or other nicotine formulations may continue to use them 
at the same dose regimen.
Subjects must refrain from blood and plasma donation during the study and up to 2 months 
after the final follow-up visit.
Male subjects must use appropriate contraception (see Appendix B) and must refrain from 
sperm donation from first dosing on Day 1 until at least 3 months after the last dose.
Discharge from the clinical unit after administration of study drug may be delayed for 
safety reasons at the discretion of the investigator.
9.8
Treatment after End of Study
After the end of the study, each subject will be treated according to standard clinical practice.
9.9
Dispensing and Storage
AstraZeneca will provide the investigators with adequate quantities of MEDI7352 using 
designated distribution centers. Pharmacy personnel will prepare all the IPs for each subject 
according to handling instructions provided by AstraZeneca and the randomisation scheme.
The IP supplied by AstraZeneca is to be used exclusively in the clinical study according to the 
instructions of this protocol. The investigator is responsible for dispensing the IP according to the 
dosage scheme and for ensuring proper storage of the IP.
The investigator (or designee) must confirm the receipt of the IP with his or her signature. A copy 
of this receipt must be kept by the investigator and another copy will be stored at AstraZeneca
and/or Premier Research. 
 
9.10 Drug Accountability
The investigator (or designee) must maintain adequate records showing the receipt, dispensing, 
return, or other disposition of the IPs, including the date, quantity, batch or code number, and 
identification of subjects (subject number) who received the IPs. The investigator will not supply 
the IP to any person except those named as sub-investigators, designated study personnel, and 
subjects in this study. The investigator will not dispense the IPs from any study sites other than 
those authorized. Investigational product(s) may not be relabelled or reassigned for use by other 
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subjects. If any of the IPs are not dispensed, are lost, stolen, spilled, unusable, or are received in a 
damaged container, this information must be documented and reported to the sponsor and 
appropriate regulatory agencies, as required.
Upon completion of the study, the IPs (partly used, unused, and empty packaging) must be left in 
the original packaging until the study site has been instructed in writing to either destroy the IP 
according to approved procedures or to return the IP to the sponsor or designee for destruction.
9.11 Labelling and Packaging
9.11.1 Labelling
Each vial of IP will have a label affixed that meets the applicable regulatory requirements and may 
include the following: IP name/study drug, dosage form, directions for use including route of 
administration, protocol number, regulatory statements if required, storage conditions, expiry date,
and sponsor identification. Each IP kit will have a unique number that is printed on all labels within 
the kit (ie, the outer carton label and the label of each container within the carton). Each carton 
and vial will be labelled with the same unique sequence number range.
Final labelling will comply with the regulatory requirements of each country where the study will 
be conducted.
9.11.2 Packaging
 
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10
STUDY PROCEDURES
Subjects must provide written informed consent before any study-related procedures are initiated, 
including the cessation of prohibited concomitant therapy.
For the timing of assessments and procedures throughout the study, refer to the Schedule of Events 
(Table 2-1). Throughout the study, every reasonable effort should be made by study personnel to 
follow the timing of assessments and procedures in the Schedule of Events for each subject. If a
subject misses a study visit for any reason, the visit should be rescheduled as soon as possible.
10.1 Study Duration
The planned sequence and maximum duration of the study periods will be as follows:
1. Screening: 45 days
2. Treatment: 12 weeks
3. Follow-up: 42 days
The maximum treatment duration for each subject is approximately 12 weeks. 
The maximum study duration for each subject is approximately 25 weeks.
10.2 Study Periods and Visits
The study consists of a total of 11 visits: 1 (or more) screening visit(s), 6 treatment visits, 2 visits 
solely for blood draws, an end-of-treatment visit, and a follow-up visit.
10.2.1 Screening and Washout
10.2.1.1 Screening
The subject must be screened within 45 days before enrolment in the study and at least 7 days 
before the first day of treatment to allow for 7 days of baseline pain ratings. Screening procedures 
may be performed at 1 or more visits. The following procedures will be performed at screening:
1. Obtain written informed consent.
2. Assess inclusion/exclusion criteria.
3. Collect demographic information.
4. Record medical history, including current therapies (eg, prescription and non-prescription
medications).
5. Perform a complete physical and neurological examination (excluding the genitourinary 
examination, unless warranted), including weight and height.
6. Measure vital signs in supine position (HR, BP [in supine position after a 5-minute rest], 
respiratory rate, and temperature). To assess orthostasis, repeat the measurement of BP and 
pulse 1 minute (>1 minute, <3 minutes) after the subject stands.
7. Perform 3 replicates of 12-lead ECGs (with printouts) after the subject has been resting in the 
supine position for at least 10 minutes.
8. Perform motor and sensory NCS.
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9. Perform TNSn, strength (dorsiflexion), and deep tendon reflex (knee and ankle) assessments.
10. Collect blood sample for the following:
serology (HIV, hepatitis B and C, and TB [QuantiFERON] testing)
chemistry, haematology, and coagulation
hemoglobin A1c
immunogenicity (ADA) testing
pharmacogenetic testing (optional)
11. Collect urine sample for the following:
urinalysis
urine drug screen
urine pregnancy test (for women who are not surgically sterile) (If the screening urine 
pregnancy test is more than 7 days before the first day of treatment, it must be repeated 
prior to the first dose)
12. Perform Galer NPS.
13. Perform SF-36.
14. Train the subject on rating their daily pain and DSIS, and entering these data into the electronic 
patient-reported outcome (ePRO) system. To determine eligibility, pain scores from Days -7
to -1 are required.
15.
Procedures for rescreening subjects who initially fail to meet study entry criteria are described in 
Section 14.3.
10.2.2 Double-blind Treatment Period (Days 1-84 [Weeks 1-12])
The treatment period consists of 6 treatment visits every 2 weeks (from Day 1 to Day 70), 2 blood 
draw visits on Days 71 and 77, and an end-of-treatment visit on Day 84 (2 weeks after the last 
dose).
10.2.2.1 Day 1 (Treatment 1)
The timing of safety assessments and safety blood sampling on Day 1 is presented in Table 2-2.
The following procedures will be performed on Day 1 before treatment with the IP:
1. Record AEs and concomitant medications and therapies.
2. Perform a targeted physical and neurological examination. 
3. Perform TNSn, strength (dorsiflexion), and deep tendon reflex (knee and ankle) assessments.
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4. Perform 3 replicates of 12-lead ECGs (with printouts) after the subject has been resting in the 
supine position for at least 10 minutes.
5. Measure supine vital signs (HR, BP [supine after a 5-minute rest], respiratory rate, and 
temperature). To assess orthostasis, repeat the measurement of BP and pulse 1 minute 
(>1 minute, <3 minutes) after the subject stands.
6. Confirm that all inclusion/exclusion criteria are satisfied.
7. Assign a randomisation number via IWRS. If necessary, the randomisation transaction in 
IWRS can be performed on Day -1. [Note: Subjects who have been randomised in the IWRS,
but who do not receive a subsequent dose and do not continue study participation, will be 
classified as Early Terminated Subjects].
The following procedures will be performed on Day 1 after randomisation:
8. Collect pre-dose blood samples for the following:
chemistry, haematology, and coagulation
PK 
9. Collect urine sample for urinalysis.
10. Administer the IP infusion.
11. Repeat 3 replicates of ECGs (with printouts) at 60 (±10) minutes after the start of IP 
administration, and 2 and 4 hours (±10 minutes) after the start of IP administration. Subjects 
must rest in the supine position for 10 minutes prior to each ECG recording session.
12. Vital signs measurements. Assess supine blood pressure and heart rate at 15 mins, 30 mins, 
45 mins, 60 mins (within 10 minutes of infusion end), 2 hours, and 4 hours after start of 
infusion. Orthostatic vital signs (standing heart rate and BP) should be measured at 60 mins 
(within 10 minutes of infusion end), 2h and 4h after start of infusion. These orthostatic 
measurements should be taken after the supine measurements and after the subject has 
adopted the standing position for 1 minute (>1 minute, <3 minutes). Assess body temperature
at 60 mins, 2h and 4h after start of infusion. Assess respiratory rate at 15 mins, 60 mins, 
2 hours, and 4 hours after start of infusion. [Note: unless where stated, an acceptable window 
for measurement of vital signs is ± 5 minutes in relation to the specified time-point].
13. Assess the IV injection site for local reactions at 15 mins, 30 mins, 45 mins, 60 mins, 2 hours, 
and 4 hours after start of infusion.
14. Assess and record any AEs occurring during the visit.
15. Remind the subject to continue entering their daily pain and DSIS into the ePRO system and 
rescue medication into the paper diary.
10.2.2.2 Days 14, 28, 42, 56, and 70 (Treatments 2 to 6)
The following procedures will be performed on Days 14, 28, 42, 56, and 70:
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1. Perform Galer Neuropathic Pain Scale (NPS) (Days 28 and 56 only).
2. Perform PGIC (Days 28 and 56 only).
3. Perform a targeted physical and neurological examination. 
4. Perform TNSn, strength (dorsiflexion), and deep tendon reflex (knee and ankle) assessments.
5. Perform 3 replicates of 12-lead ECGs (with printouts) after the subject has been resting in the 
supine position for at least 10 minutes (Days 28 and 56 only).
6. Measure pre-dose sitting vital signs (HR, BP [sitting after a 5-minute rest], respiratory rate, 
and temperature). To assess orthostasis, repeat the measurement of BP and pulse 1 minute 
(>1 minute, <3 minutes) after the subject stands.
7. Collect pre-dose blood samples for the following:
chemistry, haematology, and coagulation
immunogenicity (ADA) testing (Days 14, 28, 56, and 70 only)
PK 
8. Collect urine sample for the following:
urinalysis
9. Administer the IP infusion.
11. Five (5) minutes (± 5 minutes) after completion of the infusion, repeat sitting vital signs (HR, 
BP [sitting after a 5-minute rest], respiratory rate, and temperature). Orthostatic vital signs
(standing heart rate and BP) should be measured at 5 minutes (± 5 mins) after completion of 
the infusion. These orthostatic measurements should be taken after the sitting measurements 
and after the subject has adopted the standing position for 1 minute (>1 minute, <3 minutes).
12. Assess the IV injection site for local reactions.
13. Approximately 8 hours (± 15 mins) after the start of the infusion, collect a blood sample for
the following (Day 70 only):
PK
14. Record AEs and concomitant/rescue medications and therapies.
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15. Remind the subject to continue entering their daily pain and DSIS into the ePRO system and 
rescue medication into the paper diary.
16. Schedule the subject to return to the clinic for the next visit (on Day 70, schedule the subject 
to return to the clinic for the 24-hour blood sample).
10.2.2.3 Day 71
1. Measure sitting vital signs (HR, BP [sitting after a 5-minute rest], respiratory rate, and 
temperature). To assess orthostasis, repeat the measurement of blood pressure and pulse 
1 minute (>1 minute, <3 minutes) after the subject stands.
2. Approximately 24 hours (± 4 hours) after the start of the Day 70 infusion, collect a blood
sample for the following:
PK
3. Record AEs and concomitant/rescue medications and therapies.
4. Schedule the subject to return to the clinic for the Day 77 blood sample at approximately the 
same time of day as the Day 70 infusion.
10.2.2.4 Day 77
1. Measure sitting vital signs (HR, BP [sitting after a 5-minute rest], respiratory rate, and 
temperature). To assess orthostasis, repeat the measurement of blood pressure and pulse 
1 minute (>1 minute, <3 minutes) after the subject stands.
2. At approximately the same time of day (± 4 hours) as the Day 70 infusion, collect a blood 
sample for the following:
PK
3. Record AEs and concomitant/rescue medications and therapies.
4. Schedule the subject to return to the clinic for the Day 84 visit.
10.2.2.5 Day 84 (End-of-treatment; Week 12)
The following procedures will be performed at the end-of-treatment visit on Day 84 (2 weeks after 
the last dose):
1. Perform Galer NPS.
2. Perform PGIC.
3. Perform SF-36.
4. Perform a complete physical and neurological examination (excluding the genitourinary 
examination, unless warranted).
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5. Perform TNSn, strength (dorsiflexion), and deep tendon reflex (knee and ankle) assessments.
6. Perform 3 replicates of 12-lead ECGs (with printouts) after the subject has been resting in the 
supine position for at least 10 minutes.
7. Measure sitting vital signs (HR, BP [sitting after a 5-minute rest], respiratory rate, and 
temperature). To assess orthostasis, repeat the measurement of blood pressure and pulse 
1 minute (>1 minute, <3 minutes) after the subject stands.
8. Collect blood samples for the following:
chemistry, haematology, and coagulation
immunogenicity (ADA) testing
PK
9. Collect urine sample for the following:
urinalysis
urine pregnancy test (for women who are not surgically sterile)
10. Assess the IV injection site for local reactions.
11. Record AEs and concomitant/rescue medications and therapies.
12. Remind the subject to continue entering their daily pain and DSIS into the ePRO system and 
rescue medication into the paper diary.
13. Schedule the subject to return to the clinic for the Week 18 visit.
10.2.3 Follow-up (or Early Termination) Evaluation (Week 18)
At 6 weeks after the last visit (8 weeks after the last administration of the IP) or upon early 
termination of the study, the following procedures will be performed:
1. Perform Galer NPS.
2. Perform PGIC.
3. Perform a complete physical and neurological examination (excluding the genitourinary 
examination, unless warranted).
4. Perform TNSn, strength (dorsiflexion), and deep tendon reflex (knee and ankle) assessments.
5. Perform 3 replicates of 12-lead ECGs (with printouts) after the subject has been resting in the 
supine position for at least 10 minutes.
6. Perform motor and sensory NCS.
7. Collect blood samples for the following:
chemistry, haematology, and coagulation
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immunogenicity (ADA) testing
PK and 
(only if this is an Early Termination Visit)
8. Collect urine sample for the following:
urinalysis
urine pregnancy test (for women who are not surgically sterile)
9. Measure sitting vital signs (HR, BP [sitting after a 5-minute rest], respiratory rate, and 
temperature). To assess orthostasis, repeat the measurement of BP and pulse 1 (>1 minute, 
<3 minutes) minute after the subject stands.
10. Assess the IV injection site for local reactions.
11. Record AEs and concomitant medications and therapies.
10.3 Assessments
10.3.1 Efficacy Variables
Efficacy will be assessed by daily average pain, as measured on an 11-point (0-10) NRS; the Galer 
NPS the DSIS; the PGIC; and the SF-36.
 
The time points for each assessment are listed in Schedule of Events 
(Table 2-1).
10.3.1.1 Numerical Rating Scale
Subjects will assess their perceived average neuropathic pain over the previous 24 hours using an 
11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Subjects 
will be instructed to assess their average daily pain at approximately the same time every morning,
and to record their response in a subject diary (ePRO).
10.3.1.2 Galer Neuropathic Pain Scale
Subjects will assess their neuropathic pain using the Galer NPS. The NPS includes 2 descriptors 
of pain, including intensity and unpleasantness, and 8 descriptors that assess specific qualities of 
neuropathic pain: sharp, hot, dull, cold, sensitive, itchy, deep, and surface pain. Each of these 
10 dimensions has a 0 to 10 NRS in which 0 is equal to no pain and 10 equals the most intense 
pain.
10.3.1.3 Daily Sleep Interference Scale
Subjects will assess how their neuropathic pain interferes with their sleep using the DSIS. The 
DSIS is an 11-point Likert scale, with 0 indicating that pain did not interfere with sleep and 10 
indicating that pain completely interfered with sleep. The DSIS is completed by subjects once a 
day (upon awakening) to accurately capture variability in sleep interference due to pain on a daily 
basis, thus minimizing recall bias.
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10.3.1.4 Patient Global Impression of Change
Subjects will rate their overall improvement in health status using the PGIC. The PGIC consists 
of a 7-point scale where 1 =
=
. Subjects will be 
Very Much Improved
1
Much Improved
2
Minimally Improved
3
No Change
4
Minimally Worse
5
Much Worse
6
Very Much Worse
7
10.3.1.5 Short-Form Health Survey
-36.
The SF-36 assesses 8 health concepts: 1) limitations in physical activities because of health 
problems; 2) limitations in social activities because of physical or emotional problems; 
3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general 
mental health (psychological distress and well-being); 6) limitations in usual role activities because 
of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The 
items use Likert-type scales with either 5 or 6 points, or 2 or 3 points.
10.3.1.6 Rescue Medication Use
Subjects will record all rescue medications they take for neuropathic pain in a paper diary.
10.3.1.7
10.3.2 Clinical Pharmacology
Samples will be collected at the time points specified in the Schedule of Events (Table 2-1).
10.3.2.1 Pharmacokinetic Analysis Methods 
The PK characterization of drug concentrations for each dose to be profiled will use 
noncompartmental analysis (NCA). Standard PK parameters assessed will include measures of the 
extent of absorption using estimates of the area-under-the-curve (AUC) and rate-of-absorption 
using the Cmax and Tmax. The following PK parameters will be determined:
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Maximum plasma concentration (Cmax)
Time to maximum plasma concentration (Tmax)
Apparent first order terminal elimination half-life (t½) 
Area under the plasma concentration-time curve from time 0 to the time of the last 
quantifiable plasma concentration (AUC0-t)
Area under the plasma concentration-time curve from time 0 to infinity (AUC 0- )
AUCtau at steady state
Cmax at steady state
Volume of distribution at steady state
Apparent total body clearance at steady state (CLss)
Actual sampling times will be used for all PK parameter estimation.
Additional details of the parameters and their calculation and evaluation will be included in the 
SAP.
10.3.2.2 Pharmacodynamic Variables
Plasma or serum samples will be collected for exploration of free and/or total NGF.
10.3.2.3 Pharmacogenetic Variables
Pharmacogenetic analysis is optional. If a subject declines to participate in the genetic research, 
this will have no influence on the ability of the subject to participate in the study. 
 
 
10.3.2.4
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standard operating procedures and analytical requirements. 
10.3.2.5 Immunogenicity
Blood samples will be collected for assessment of ADA levels.
10.3.3 Safety Variables
Safety assessments will include the evaluation of AEs, clinical laboratory tests, vital signs, 12-lead 
ECGs, physical and neurological examination findings, neuropathy assessments (TNSn), strength 
(dorsiflexion), and deep tendon reflex (knee and ankle) assessments, motor and sensory nerve
conduction, concomitant medications, injection site reactions, and infusion reactions.
10.3.3.1 Clinical Laboratory Assessments
10.3.3.1.1 Clinical Laboratory Tests to be Performed 
Samples for laboratory tests will be collected at the time points specified in the Schedule of Events 
(Table 2-1) and will include the following:
Haematology:
hemoglobin, haematocrit, red blood cell (RBC) count, RBC indices, mean 
corpuscular hemoglobin, mean corpuscular hemoglobin concentration, 
platelet count (or estimate), white blood cell count including differential
Serum Chemistry:
albumin, total bilirubin, total protein, calcium, ALP, ALT, AST, blood 
urea nitrogen, creatinine*, glucose, sodium, potassium, chloride, 
bicarbonate, lactate dehydrogenase, uric acid, C-reactive protein (CRP)
*serum chemistry reports should include calculation of creatinine 
clearance using the Cockcroft-Gault equation for estimation of GFR 
(eGFR)
Coagulation Panel:
prothrombin time, partial thromboplastin time, fibrinogen
Urinalysis:
pH, specific gravity, blood urine, glucose, protein, ketones
Pregnancy Test 
[urine]:
for women who are not surgically sterile
Urine Drug Screen:
including but not limited to amphetamine, barbiturate, cannabinoids, 
cocaine, 
methadone, 
methaqualone, 
opiate, 
phencyclidine,
and 
propoxyphene
Serology:
HIV, hepatitis B and C, and tuberculosis (QuantiFERON)
Blood and urine samples for haematology, serum chemistry, urinalysis, and serology will be sent 
to a central laboratory for analysis. Urine drug screens and pregnancy tests will be conducted at 
the study sites.
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10.3.3.1.2 Specimen Handling Requirements 
The transmission of infectious agents may occur through contact with contaminated needles and 
blood or blood products. Consequently, appropriate blood and body fluid precautions should be 
employed by all study personnel involved in the collection of blood and handling of specimens in 
both the clinic and laboratory settings. Refer to current recommendations of the appropriate 
authorities.
In addition to appropriate handling of subject samples, specific regulations exist regarding the 
shipment of biologic/etiologic samples. Procedures and regulations for the packaging and shipping 
of infectious samples are outlined in the study manual. The investigator is responsible for ensuring 
that all study samples that are to be transported to another location are packed and shipped 
appropriately according to the applicable regulations.
10.3.3.1.3 Evaluation of Clinical Laboratory Values 
The normal ranges of values for the clinical laboratory assessments in this study will be provided 
by the responsible laboratory and submitted to AstraZeneca prior to the beginning of the study.
They will be regarded as the reference ranges on which decisions will be made.
If a laboratory value is out of the reference range, it is not necessarily clinically relevant. The 
investigator must evaluate the out-of-range values and record his or her assessment of the clinical 
relevance in the appropriate CRF/eCRF.
All clinical laboratory values that
pathological changes during or after termination of treatment must be reported as AEs and 
followed, as described in Section 11.2.5.
All measurements described in this section are recognized standard methods.
10.3.3.1.4 Clinical Examinations 
10.3.3.1.5 Vital Signs 
Vital signs (HR, BP, respiratory rate, and temperature) will be measured after the subject has been 
in a supine position for 5 minutes at screening and Day 1 and in a sitting position for 5 minutes at 
all other visits. To assess orthostasis, BP and pulse will be measured again 1 minute (>1 minute, 
<3 minutes) after the subject stands.
Vital signs will be assessed as follows:
Screening: Measure respiratory rate, temperature, and HR and BP after a 5-minute rest in 
supine position. To assess orthostasis, repeat BP and HR 1 minute after the subject stands. 
Day 1 pre-dose: Measure respiratory rate, temperature, and HR and BP after a 5-minute 
rest in supine position. To assess orthostasis, repeat BP and HR 1 minute after the subject 
stands.
Day 1 post-dose: Supine and orthostatic BP and HR at 15 mins, 30 mins, 45 mins, 
60 mins, 2 hours, and 4 hours after start of infusion. Temperature and supine and 
orthostatic BP and HR at 60 mins, 2 hours, and 4 hours after start of infusion. Respiratory 
rate at 15 mins, 60 mins, 2 hours, and 4 hours after start of infusion. The 60-minute 
assessments should be performed within 10 minutes of the end of the infusion. [Note: An
acceptable window for these vital sign assessments is ± 5 mins in relation to the specified 
time.]
m the investigator's opm10n show clinically relevant or 
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Days 14, 28, 42, 56, and 70 pre-dose: Measure respiratory rate, temperature, and HR and 
BP after a 5-minute rest in sitting position. To assess orthostasis, repeat BP and HR 
1 minute after the subject stands.
Days 14, 28, 42, 56, and 70 post-dose: 5 minutes after completion of infusion, measure
respiratory rate, temperature, and HR and BP after a 5-minute rest in sitting position. After 
measuring sitting vital signs, assess orthostatic BP and HR 1 minute after the subject 
stands.
Days 71, 77, and Week 18 or early termination: Measure respiratory rate, temperature, and 
HR and BP after a 5-minute rest in sitting position. To assess orthostasis, repeat BP and 
HR 1 minute after the subject stands. 
10.3.3.1.6 Twelve-lead Electrocardiogram 
All subjects will undergo ECGs as indicated in the schedule of assessments. Where applicable, 
digital ECGs will be collected using the ECG equipment delivered by the central ECG laboratory 
(ECG lab) and will be transferred to and analys
operating procedures. Further details are provided in the ECG Manual.
Paper printouts of the 12-lead ECGs will be reviewed in real time by the principal investigator, or 
delegate, for safety monitoring. The results of the evaluation will be reported in the eCRF as 
normal or abnormal (if abnormal, the ECG is also to be reported as not clinically significant or 
clinically significant). The details of any ECG abnormalities should be described and captured in 
the eCRF (irrespective of whether they are considered not clinically significant or clinically 
significant).
10.3.3.1.7 Physical and Neurological Examination 
A complete physical and neurological examination (excluding the genitourinary examination,
unless warranted) will be performed at Screening, Week 12, and Week 18/Early Termination, as 
indicated in the schedule of assessments.
A targeted physical and neurological examination based on symptoms and previous findings will 
be performed at all other visits.
Height and weight will be measured at Screening.
10.3.3.1.8 Total Neuropathy Scores--Nurse  
The TNSn, a semi-quantitative clinical assessment of peripheral nervous system function, will be 
administered at Screening, Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12 and 
Week 18/Early Termination. The TNSn provides for an assessment of motor symptoms, autonomic 
symptoms, pin sensibility, vibration sensibility, and deep tendon reflexes. Strength (dorsiflexion) 
and deep tendon reflexes (knee and ankle) are to be scored at every visit alongside the TNSn 
assessments.
10.3.3.1.9 Motor and Sensory Nerve Conduction Studies 
Motor and sensory NCS will be undertaken in relevant lower and upper limb nerves (sural,
peroneal, and median/ulnar nerves). Relevant endpoints including peak latency, amplitude, 
conduction velocity and duration of nerve action potentials will be captured using standard 
antidromic or orthodromic determination according to protocol and will be recorded at baseline 
and at the follow-up visit.
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• 
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10.3.3.1.10 Injection Site or Infusion Reactions 
Investigators should evaluate infusion reactions that occur during or immediately following 
infusion per the FDA Guidance for Industry, Immunogenicity Assessment for Therapeutic Protein 
Products (2014) and FDA Guidance for Industry, Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (2007).42,43 See Section 5.3
for discussion of potential infusion reactions.
Investigators should evaluate injection site reactions using the toxicity grading scale summarized 
in Table 10-1.
Table 10-1:
Local Reactions to Injectable Product
Local Reaction 
Mild 
Moderate 
Severe 
Pain 
Does not interfere 
with activity 
Repeated use of non-narcotic 
pain reliever >24 hours or 
interferes with activity 
Any use of narcotic pain 
reliever or prevents daily 
activity 
Tenderness 
Mild discomfort to touch 
Discomfort with movement 
Significant 
discomfort at rest 
Erythema/rednessa
2.5 to 5 cm 
5.1 to 10 cm 
>10 cm 
Induration/swellingb
2.5 to 5 cm and does not 
interfere with activity 
5.1 to 10 cm or interferes 
with activity 
>10 cm or prevents daily 
activity 
Source: FDA 200743
a In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
recorded as a continuous variable.
b Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement.
10.3.3.2 Adverse Events
The definitions and management of AEs, and any special considerations for AEs, are provided in 
Section 11.
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11
ADVERSE EVENTS
11.1 Definitions
11.1.1 Adverse Events
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavourable and unintended sign (including an
abnormal laboratory finding, for example), symptom, or disease temporally associated with the 
use of a medicinal product, whether or not related to the medicinal product.
Pre-existing diseases or conditions will not be considered AEs unless there is an increase in the 
frequency or severity, or a change in the quality, of the disease or condition. (Worsening of a 
pre-existing condition is considered an AE.)
Events that occur in subjects treated with placebo, or during treatment-free periods of the study,
are also considered AEs.
11.1.2 Adverse Drug Reaction
All noxious and unintended responses to an IP related to any dose should be considered adverse 
drug reactions (ADRs).
n investigational 
n
IP and an AE is at least a reasonable possibility, ie, the relationship cannot be ruled out. All AEs 
judged by either the reporting investigator or the sponsor as having a reasonable causal relationship 
to an IP qualify as ADRs.
All AEs
ADRs. If a relationship to IP is not provided, then the AE must be treated as if it were
.
11.1.3 Unexpected Adverse Event/Adverse Drug Reaction
An expected AE or ADR is one for which the nature or severity is consistent with the known AE 
profile of the product. For a pre-approval test product, the known information is contained in the 
IB. For a marketed product, the known information is contained in the current package insert for 
the product.
An unexpected AE or unexpected adverse drug reaction (UADR) is one for which the nature or 
Brochure for an unapproved IP or package insert/summary of product characteristics for an 
approved product). For example, hepatic necrosis would be unexpected (greater severity) if the IB 
only listed elevated hepatic enzymes or hepatitis. Likewise, cerebral thromboembolism and 
cerebral vasculitis would be unexpected (greater specificity) if the IB only listed cerebral vascular 
accidents.
Furthermore, reports that add significant information on specificity or severity of a known, already 
documented adverse reaction constitute unexpected events. Examples would be (a) acute renal 
failure as an expected adverse reaction with a subsequent new occurrence of interstitial nephritis 
(interstitial nephritis would be unexpected) and (b) hepatitis with a first occurrence of fulminant
hepatitis (fulminant hepatitis would be unexpected.)
The phrase "responses to a 
product" means that a causal relationship between a 
for which the judgment of relationship to IP is "possible" or higher will be considered 
"possible" 
severity of which is not consistent with the applicable product information (eg, Investigator's 
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11.1.4 Serious Adverse Events
An SAE is any untoward medical occurrence that at any dose:
results in death
is life-threatening
-
the patient was at risk of death at the time of the event; it does not refer to an event that
hypothetically might have caused death if it were more severe.
requires inpatient hospitalization or prolongation of existing hospitalization
NOTE: Outpatient treatment in an emergency room is not in itself a serious AE, although the 
reasons for it may be (eg, bronchospasm, laryngeal oedema). Hospital admissions and/or 
surgical operations planned before or during a study are not considered AEs if the illness or 
disease existed before the subject was enrolled in the study, provided that it did not deteriorate 
in an unexpected way during the study.
results in persistent or significant disability/incapacity
is a congenital anomaly
NOTE: A congenital anomaly in an infant born to a mother who was exposed to the IP during 
pregnancy is an SAE. However, a newly diagnosed pregnancy in a subject that has received an
IP is not considered an SAE unless it is suspected that the IP(s) interacted with a contraceptive 
method and led to the pregnancy. 
is an important medical event
NOTE: Medical and scientific judgment should be exercised in deciding whether it is 
appropriate to consider other situations serious, such as important medical events that may not 
be immediately life-threatening or result in death or hospitalization but may jeopardize the 
patient or may require intervention to prevent one of the other outcomes listed in the definition 
above. Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, 
development of drug dependency, or drug abuse. The occurrence of malignant tumors is also 
to be considered serious.
11.1.5 Significant Adverse Events
Other significant AEs are defined as marked haematological and other laboratory abnormalities 
(other than those meeting the definition of serious) and any events that led to an intervention, 
including withdrawal of test drug, dose reduction, or significant additional concomitant therapy.
11.1.6 Treatment-Emergent Adverse Events
An AE is defined as treatment-emergent if the first onset or worsening is after the first 
administration of IP and not more than 30 days after the last administration of IP.
• 
• 
NOTE: The term "life threatening" in the definition of "serious" refers to an event in which 
• 
• 
• 
• 
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11.2 Event Assessment and Follow-up of Adverse Events
The occurrence of an AE or SAE may come to the attention of study personnel during study visits 
and interviews of a study participant presenting for medical care, or upon review by a study 
monitor.
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured 
on the appropriate eCRF. Information to be collected includes event description, time of onset, 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All 
AEs occurring while on study must be documented appropriately regardless of relationship. All 
AEs will be followed to adequate resolution.
Any medical condition that is present at the time that the participant is screened will be considered 
at any time during the study, it will be recorded as an AE. 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode.
The site staff will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for nonserious AEs) or 30 days (for SAEs) after the last day of study 
participation. At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit. Events will be followed for outcome information until resolution or 
stabilization.
11.2.1 Assessment
The investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE described previously. At each visit, the subject will be allowed 
time to spontaneously report any issues since the last visit or evaluation. The investigator will then 
monitor and/or ask about or evaluate AEs using nonleading questions, such as
nce your last visit?
Any clinically relevant observations made during the visit will also be considered AEs.
clinician's assessment of severity, relationship to study product (assessed only by those with the 
as baseline and not reported as an AE. However, if the study participant's condition deteriorates 
• 
"How are you feeling?" 
• 
"Have you experienced any issues si 
" 
• 
"Have you taken any new medications since your last visit?" 
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11.2.2 Evaluation
11.2.2.1 Severity of Adverse Events
The clinical severity of an AE will be classified as:
Mild
Usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of 
daily living.
Moderate
Usually alleviated with additional specific therapeutic intervention. The event 
interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the subject.
Severe
Interrupts usual activities of daily living, or significantly affects clinical status,
or may require intensive therapeutic intervention.
It is important to distinguish between severe AEs and SAEs. Severity is a classification of intensity 
whereas an SAE is an AE that meets serious criteria, as described in Section 11.1.4.
11.2.2.2 Seriousness
The investigator is to evaluate whether the AE meets serious criteria, as described in 
Section 11.1.4.
11.2.2.3 Action(s) Taken
Action(s) taken may consist of:
Dose increased
An indication that a medication schedule was modified by addition; either 
by changing the frequency, strength, or amount.
Dose not changed
An indication that a medication schedule was maintained.
Dose reduced
An indication that a medication schedule was modified by subtraction, 
either by changing the frequency, strength, or amount.
Drug interrupted
An indication that a medication schedule was modified by temporarily 
terminating a prescribed regimen of medication.
Drug withdrawn
An indication that a medication schedule was modified through 
termination of a prescribed regimen of medication.
Not applicable
Determination of a value is not relevant in the current context.
Unknown
Not known, not observed, not recorded, or refused.
11.2.2.4 Outcome at the Time of Last Observation
The outcome at the time of last observation will be classified as:
Recovered/resolved
Recovered/resolved with sequelae
Recovering/resolving
Not recovered/not resolved
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Fatal*
Unknown
*Only select fatal as an outcome when the AE results in death. If more than one AE is judged to 
be 
d for each such 
death should be reported as SAEs.]
11.2.2.5 Adverse Event Relationship to Investigational Product
relationship to the IP. The categories for 
he relationship are as follows:
Related
A reasonable possibility exists of a relationship between the AE and IP.
Not related
No reasonable possibility exists of a relationship between the AE and IP.
11.2.3 Documentation
All AEs that occur within the period of observation for the study must be documented in the CRF 
with the following information, where appropriate. (The period of observation for the study is 
described in Section 11.2.)
AE name or term
When the AE first occurred (start date and time)
Severity of the AE
Seriousness (hospitalization, death, etc.)
Actions taken
Outcome
Investigator opinion regarding the AE relationship to the IP(s)
11.2.4 Treatment of Adverse Events
Adverse events that occur during the study will be treated, if necessary, by established standards 
of care. If such treatment constitutes a deviation from the protocol, the decision about whether the 
subject may continue in the study will be made by the sponsor after consultation with the 
investigator and/or medical monitor.
If AEs occur in a subject that are not tolerable, the investigator must decide whether to stop the
study and/or treat the subject. Special procedures may be 
recommended for the specific IP, such as the collection of a serum sample for determining blood 
concentrations of IP, specific tapering procedures, or treatment regimens, as appropriate.
For double-blinded studies, it is not necessary to unblind a 
circumstances, even if an SAE has occurred. If unblinding is necessary, see Section 9.6 for a
description of the unblinding procedures.
• 
• 
possibly related to the subject's death, the outcome of death should be indicate 
AE. [ Although "fatal" is usually an event outcome, events such as sudden death or unexplained 
The investigator must make an assessment of each AE's 
classifying the investigator's opinion oft 
• 
• 
• 
When the AE stopped (stop date and time or an indication of "ongoing") 
• 
• 
• 
• 
• 
subject's involvement m the 
subject's treatment assignment in most 
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11.2.5 Follow-up
Any AE will be followed to a satisfactory resolution, until it becomes stable, or until it can be 
explained by another known cause(s) (ie, concurrent condition or medication) and clinical 
judgment indicates that further evaluation is not warranted. All findings relevant to the final 
and recorded on the eCRF.
11.2.6 Reporting
11.2.6.1 Serious Adverse Events
The investigator or designee must report all SAEs promptly to MMS Holdings Inc. (MMS) within 
24 hours of first becoming aware of the event by completing, signing and dating the Serious 
Adverse Event Report Form, verifying the accuracy of the information recorded in the form with 
the source documents and eCRF, and sending the SAE form to MMS by one of the following 
methods:
Email: drugsafety@mmsholdings.com
Fax number: +1 734 468 0850
This written report should be submitted on the SAE form provided for this purpose. At the time of 
first notification, the investigator or designee should provide the following information, if
available:
Protocol number
Reporter (study site and investigator)
Suspect IP
year of birth
Date of first dose of IP
Date of last dose of IP, if applicable
Adverse event term
Date of occurrence of the event
A brief description of the event, outcome to date, and any actions taken
The seriousness criteria that were met
Concomitant medication at onset of the event
outcome of an AE must be reported in the subject's medical record 
• 
• 
• 
• 
Subject's study number 
• 
Subject's 
• 
Subject's gender 
• 
• 
• 
• 
• 
• 
• 
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Relevant medical history information
Relevant laboratory test findings
IP
ility that the IP
Whether and when the investigator was unblinded as to the subject
Any missing or additional relevant follow-up information concerning the SAE should be sent to 
the sponsor/sponsor representative via the same contact details above as soon as possible on a
follow-up SAE Report Form, together with the following minimal information (initial report, AE,
date of occurrence, subject identification (ID), study ID, IP, and site number); this will allow the 
follow-up information to be linked to the initial SAE report.
Specific information may be requested by the MMS Pharmacovigilance Department using a 
follow-up request form or via email communication.
The investigator is required to comply with applicable regulations (including local laws and 
guidances) regarding the notification of his or her health authorities, institutional review board 
(IRB)/independent ethics committee (IEC), principal and coordinating investigators, study 
investigators, and institutions. Each investigator is obligated to learn about the reporting 
requirements for investigators in his/her country. 
11.2.6.2 Adverse Drug Reactions
All ADRs should be reported by the investigator in the eCRF.
Suspected serious ADRs must be reported to the sponsor immediately, regardless of the time 
elapsed since the end of the observation period.
11.2.6.3 Nonserious Adverse Events
Nonserious AEs will be recorded in the eCRF and reported by Premier Research to the sponsor
according to the Safety Management Plan.
11.3 Special Considerations
11.3.1 Adverse Events of Special Interest
An AESI is a treatment-emergent AE of scientific and medical interest specific to understanding 
of the effects of the IP and may require close monitoring and collection of additional information
by the investigator. An AESI may be serious or nonserious. The rapid reporting of AESIs allows 
ongoing surveillance of these events in order to characterise and understand them in association 
with the use of MEDI7352.
Refer to Section 5.3 for a summary of potential risks and the IB for a detailed discussion of 
potential risks.
The following AESIs have been identified specifically for this MEDI7352 protocol and are to be 
reported as described in Section 11.2.6.1.
• 
• 
• 
Investigator's opinion of the relationship to 
caused the SAE? Yes or No?") 
• 
("Is there a reasonable possib 
's treatment assignment 
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Positively-adjudicated possible or probable RPOA, subchondral insufficiency fractures,
primary osteonecrosis, or pathological fracture 
Infections that meet SAE or severe AE criteria*
Anaphylactic reactions or infusion-related reactions that lead to permanent discontinuation 
of administration of IP
Adverse events of special interest irrespective of their severity and seriousness should be reported 
immediately using the same procedure as for SAE reporting (Section 11.2.6.1).
*Note: A serious infection is any infection that meets the SAE criteria in Section 11.1.4. Serious
infection AEs should be reported as SAEs. A severe infection is any infection that does not meet 
SAE criteria but is incapacitating, with inability to perform normal activities. Non-serious severe 
infections are reported as AEs. It is expected that microorganism culture results and all diagnostic 
or therapeutic procedure results performed on a study participant experiencing a serious or severe 
infection will be provided as an SAE/AESI update.
11.3.2 Pregnancy
All women who participate in the study must be postmenopausal or surgically sterile. Women 
should be instructed to contact the investigator or study staff immediately if pregnancy occurs or 
is suspected.
Pregnancy testing will be conducted prior to administration of the IP on every woman who is not 
surgically sterile. A woman who is found to be pregnant at the screening visit will be excluded 
from the study and considered to be a screening failure.
Men who are biologically capable of having children must agree and commit to use an adequate
form of contraception (see Appendix B) for the duration of the treatment period and for 3 months 
after the last administration of study drug. A male subject is considered capable of having children 
even if his sexual partner is sterile or using contraceptives.
A woman who becomes pregnant during IP treatment or within 30 days of discontinuing the IP 
will be immediately discontinued from study participation. The investigator must report the 
pregnancy as if it were an SAE within 24 hours of learning of the pregnancy, to MMS 
Pharmacovigilance using the Pregnancy Notification and Outcome Form via the same fax number 
and/or email address as for SAE reporting.
Early Termination Visit assessments are required as soon as possible after learning of the 
pregnancy. The investigator is also responsible for following the pregnancy until delivery or 
termination. The follow-up information must be reported to MMS Pharmacovigilance using a new 
Pregnancy Notification and Outcome Form. The event meets the SAE criterion only if it results in 
a spontaneous abortion or a congenital anomaly.
11.3.3 Overdose
The maximal dose of IP should not be exceeded during the study. The investigator must report any 
overdose to MMS PV within 24 hours of learning of the overdose using the Overdose Report Form 
provided by MMS PV. In case of known or suspected overdose, symptomatic treatment as well as 
monitoring of vital functions should be performed based on the judgment of the investigator. If the 
overdose does not result in an AE, it should be reported in written form to the designated 
individuals who receive SAE notification. The information contained therein should include study 
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• 
• 
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site identification, reporter identification, subject identification, IP, dose, action taken (eg, 
supportive measures or therapy), and any comments.
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DATA SAFETY MONITORING BOARD
A data safety monitoring board will not be used in this study. 
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13
STATISTICS
13.1 Statistical Analysis
This section presents a summary of the planned statistical analyses. A statistical analysis plan 
(SAP) that describes the details of the analyses to be conducted will be finalized prior to database 
lock for the interim analysis.
Unless otherwise indicated, all formal testing of statistical significance will be one-sided, and a 
difference resulting in a 1-sided
25 will be considered statistically significant. For 
estimation purposes, 2-sided 90% and 95% confidence intervals will be presented.
Summary statistics will be provided for the variables described below. For continuous variables, 
these statistics will typically include the number of subjects, mean, standard deviation (SD), 
median, minimum, and maximum. For categorical variables, these statistics will typically include 
the number and percentage of subjects in each category.
13.1.1 Analysis Populations
The following 4 analysis populations are planned for this study: 
Screening: all subjects who provide informed consent and/or assent and provide 
randomisation and treatment status in the study. 
Safety: The safety population will include all subjects who receive at least 1 dose of 
double-blind study medication.
Modified intent-to-treat (mITT): The modified intent-to-treat population will be used for 
all efficacy analyses and will include all randomised subjects who receive at least 1 dose 
of double-blind study medication and have at least 1 post-baseline NRS assessment.
PK: The PK population will include all subjects for whom a PK sample was obtained and 
analysed.
Inclusion in the analysis populations will be determined prior to database lock.
If a subject is randomised incorrectly or is administered the incorrect IP, analyses of the mITT 
population will be based on the IWRS-assigned treatment whereas all other analyses will be based 
on the actual treatment.
13.1.2 Study Subjects and Demographics
13.1.2.1 Disposition and Withdrawals
The numbers of subjects randomised, completing, and withdrawing, along with reasons for 
withdrawal, will be tabulated overall and by treatment group. The number of subjects in each 
analysis population will be reported.
13.1.2.2 Protocol Deviations
Subjects who violate any inclusion and/or exclusion criteria or who have major protocol deviations 
during the study (such as incorrect treatment assignment or use of prohibited medications) will be 
summarised and listed.
P value of S0.0 
• 
demographic and/or baseline screenmg assessments, regardless of the subject's 
• 
• 
• 
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13.1.2.3 Demographics and Other Baseline Characteristics
These analyses will be conducted for all analysis populations. 
Demographic variables will be collected for any eventual analysis of differences in response to the 
IP, in accordance with local regulatory requirements. Baseline subject characteristics including
medical history, physical and neurological examination findings, and other baseline disease history
will be listed and included in summaries as appropriate.
Prior and concomitant medications will be summarized by treatment group, by the number and 
percentage of subjects taking each medication, classified using World Health Organization Drug 
Dictionary Anatomical Therapeutic Chemical classes and preferred terms (PTs).
13.1.3 Exposure and Compliance
Investigational product administr
and number of infusions received. Descriptive statistics for these quantities, including the mean, 
median, SD, minimum, maximum, and quartiles, will be provided by treatment group. In addition,
any incomplete infusions will be listed. 
13.1.4 Efficacy Analysis
All efficacy variables will be summarized descriptively including number of observations, mean, 
SD, minimum, median, and maximum for continuous variables, and frequency of observations in 
each category and percentage for categorical variables. 
Primary and secondary endpoint e
approach. In addition, if there is missing data at a key analysis time-point (Weeks 4, 8, and 12) 
then resul
-Observation-Carried-
-Observation-Carried-
For example, if an endpoint is missing from a 
post-randomisation visit then the last non-missing post-baseline endpoint recorded prior to the visit 
will replace the missing value. For endpoints with separate scales, if an individual scale item is 
missing then the item will be carried forward from the previous visits rather than the total score. 
For post-baseline diary data, if a subject has at least 4 out of 7 days diary data prior to the visit,
then this will be taken as a valid observed weekly average score. However, if a subject has 3 or 
fewer days of diary data, this will be counted as a missing weekly score, and the LOCF approach 
will carry forward the last 7 non-missing entries of the diary data prior to the visit in order to 
calculate the weekly mean score at endpoint score.
The main statistical analysis of the primary efficacy endpoint at Week 12 will use the multiple 
comparison procedure modelling (MCP-Mod) approach on LOCF data, which is a well-established 
statistical methodology for establishing both the existence of a dose response and modelling the 
underlying dose-response relationship. Both EMA (2014)44 and FDA (2015)45 have recognized 
MCP-Mod as an efficient statistical methodology for model-based design and analysis of Phase 2
dose finding studies under model uncertainty. 
There are two steps to MCP-Mod:
1.
protecting the type I error and, if the dose-response relationship is statistically significant, 
then
2.
el parameters, 
such as ED50 (the effective dose for 50% of the population) in the case of Emax relationship.
ation will be summarized in terms of each subject's total dose 
fficacy data will be tabulated according to the 'Observed Cases' 
ts will also be tabulated according to 'Last 
Forward' (LOCF) and 
'Baseline 
Forward' (BOCF). 
The 'MCP' step is a rigorous method to establish presence of a dose response while 
The 'MOD' step estimates the dose response function and associated mod 
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The MCP test will use linear contrasts corresponding to the five candidate models described in 
Section 13.2. The underlying model will be an analysis of covariance (ANCOVA) with dependent 
Week
o-medication type. The random error is assumed to be normally and independently 
distributed with constant variance.
If the MCP test is statistically significant, then the MOD step will select the most appropriate 
model from hyperbolic Emax, sigmoidal Emax, or l
maxlin
Kirby et al. (2011).46 From this model (including the same covariates as the ANCOVA model), 
various estimates will be derived (together with confidence intervals) of parameters of interest 
such as ED50, ED90, dose to achieve selected target effects, and model estimates of the treatment 
effect at doses studied.
In addition to the analysis of all stages combined, a supplementary analysis using an adaptive 
MCP-MOD method will be conducted where stages 2+3 and stage 4 will be analysed separately 
and the results combined using an inverse-normal p-value combination function, with weights 
related to the original planned sample sizes. Further details of the analysis will be included in the 
SAP.
To complement the MCP-MOD outputs, estimates and confidence intervals of each pairwise 
comparison versus placebo from the ANCOVA model described in the MCP step will be produced.
In addition, changes from baseline in continuous endpoints will be compared between treatment 
groups using mixed models repeated measures including terms for pooled site, treatment (as a 
factor), time point (as a factor), the interaction between treatment and time point, and the baseline 
value of the variable undergoing analysis. Binary outcomes will be analysed using generalized 
estimating equations, with the models including the same terms as the mixed models repeated 
measures. 
Other 
non-binary 
categorical 
endpoints 
will 
be 
analysed 
using 
Cochran-Mantel-Haenszel statistics. These analyses will be conducted on observed cases. Further 
details of the longitudinal modelling will be included in the SAP.
13.1.4.1 Efficacy Endpoints
The primary efficacy endpoint is the change in the weekly average of the average daily pain scores 
from the baseline week to Week 12, as measured on an 11-point (0-10) NRS.
The secondary endpoints are the following:
Change in the weekly average of the average daily pain score, as measured on an 11-point 
(0-10) NRS, from baseline to Weeks 2, 4, 6, 8, and 10 of treatment and the week before 
the follow-up visit. 
average of the average daily pain score from baseline during Weeks 4, 8, and 12 of 
treatment and the week before follow-up.
Change in Galer NPS from baseline to Days 28, 56, and 84 of treatment and the follow-up
visit.  
Change in DSIS from baseline to Days 28, 56, and 84 of treatment and the follow-up visit.
variable 'change from baseline to 
score' and c 
• 
12', and independent variables will include dose, 'baseline 
inear using the 'E 
'approach as described by 
• 
Percentage of subjects who have achieved 2:30% and 2:50% reductions in the weekly 
• 
• 
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Proportion of subjects who have improved , much improved , or very much improved
relative to baseline on the PGIC on Days 28, 56, and 84 of treatment and the follow-up
visit.
Change in the SF-36 from baseline to Day 84 of treatment.
Usage of rescue medication (yes/no) from baseline to Week 12 of treatment.
13.1.4.2
13.1.5 Clinical Pharmacology Analyses
13.1.5.1 Pharmacokinetics
For noncompartmental analysis, plasma concentrations will be listed and summarized at each time 
point using descriptive statistics; graphical representations will also be provided. The PK 
parameters will be summarized by dose using descriptive statistics including geometric mean, 
geometric SD, arithmetic coefficients of variation, and geometric coefficients of variation. The 
potential relationships between PK and efficacy and safety parameters may be explored 
graphically. Statistical analyses of PK parameters will be outlined in the SAP. Subjects receiving 
placebo will not be included in the summary and analysis of PK parameters.
13.1.5.2 Pharmacodynamics
The PD variables (free and/or total NGF) will be summarized using descriptive statistics. The 
association between PD variables and efficacy endpoints will be explored. Further details will be 
included in the SAP.
13.1.5.3
13.1.5.4
13.1.5.5 Immunogenicity
Immunogenicity results will be listed and the effects of ADAs on PK and PD will be explored.
13.1.6 Safety and Tolerability Analyses
Safety and tolerability data will be summarised descriptively, including tables, listings, and graphs, 
as appropriate. Unless otherwise stated, descriptive summary statistics for continuous variables 
will include number of observations, mean (ie, arithmetic mean), SD, minimum, median, and 
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maximum. Descriptive summary statistics for categorical data will include frequencies and 
percentages. 
13.1.6.1 Adverse Events
All AEs will be coded using the latest version of the Medical Dictionary for Regulatory Activities 
(MedDRA).
Treatment-emergent AEs are defined as:
AEs with onset at the time of or following the start of treatment with IP through the
Follow-up Visit or Early Termination Visit, whichever occurs first, or
AEs starting prior to the start of treatment but increasing in severity or relationship at the 
time of, or following, the start of treatment with IP through the Follow-up Visit or Early 
Termination Visit, whichever occurs first.
The number and percentage of subjects with AEs will be displayed for each treatment group by 
system organ class and preferred term (PT). Summaries of AEs by severity and relationship to IP 
will also be provided. Serious adverse events and AEs resulting in discontinuation of IP will be 
summarized separately in a similar manner. Subject listings of AEs, SAEs, and AEs causing 
discontinuation of IP will be produced.
13.1.6.2 Clinical Laboratory Evaluations
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual (absolute) values 
and changes from baseline values will be presented for clinical laboratory values for each treatment 
group at each time point.
The number of subjects with clinical laboratory values categorized as below, within, or above 
normal ranges, or other specific ranges of interest, will be tabulated showing change from baseline 
(shift tables) for each clinical laboratory analyte by treatment group and by study visit. 
Laboratory values that are outside the normal range will also be flagged in the data listings and 
presented with the corresponding normal ranges. Any out-of-range values that are identified by 
the investigator as being clinically significant will also be shown in a data listing.
13.1.6.3 Vital Signs
Descriptive summaries (mean, SD, median, minimum, and maximum) of actual values and 
changes from baseline will be calculated for SBP, DBP, HR, respiratory rate, and temperature.
13.1.6.4 Twelve-lead Electrocardiograms
The number and percentage of subjects with normal and abnormal ECG findings will be 
summarized for each treatment group at each time point. Abnormal results will be grouped as
clinically significant and not clinically significant. A description of ECGs evaluated as abnormal
will be provided.
If applicable (digital ECGs), descriptive summaries will be provided for measures provided by the 
ECG core laboratory from the digital ECGs for PR, QRS, QT, RR intervals and for the calculated 
variables QTcF and HR for each treatment group and time point.
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13.1.6.5 Physical and Neurological Examination Findings
Physical and neurological examination findings will be listed.
13.1.6.6 Other Safety Assessments
Findings from other safety assessments (TNSn, strength (dorsiflexion), deep tendon reflexes (knee 
and ankle), motor and sensory NCS, and injection site reactions) will be listed and may be 
summarized if warranted.
13.1.7 Interim Analysis
Interim analyses are planned after approximately 60 subjects have completed at least 2 weeks of 
randomised treatment across placebo and
in stage 3. Unblinded personnel who are not 
otherwise involved in the study will prepare the data for review by an Interim Analysis Review 
Committee.
The members of the Interim Analysis Review Committee are independent of the day-to-day study 
activities. The study team will remain blinded to the results of the interim analysis for the duration 
of the study. Firewalls will be put in place to ensure that information is not inadvertently 
disseminated to the blinded members of the study team.
The primary aim of the analysis is to validate the key assumptions of the original sample size 
calculation, which could result in a recommendation to adjust the sample size (overall and/or to 
individual dose groups) or the treatment allocation ratio in stage 4. Further details of the sample 
size adjustment methodology will be included in an Interim Analysis SAP.
In addition, administrative analyses of efficacy data are planned to enable the sponsor to plan 
future project-related activities, but without making any changes to the design of the current study.
13.2 Sample Size Determination
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14
STUDY CONDUCT
Steps to ensure the accuracy and reliability of data include the selection of qualified investigators 
and appropriate study sites, review of protocol procedures with the investigator and associated 
personnel before the study, periodic monitoring visits, and meticulous data management.
14.1 Sponsor and Investigator Responsibilities
14.1.1 Sponsor Responsibilities
The sponsor is obligated to conduct the study in accordance with strict ethical principles 
(Section 16). The sponsor reserves the right to withdraw a subject from the study (Section 8.3), to 
terminate participation of a study site at any time (Section 14.7), and/or to discontinue the study 
(Section 14.6.2).
AstraZeneca agrees to provide the investigator with sufficient material and support to permit the 
investigator to conduct the study according to the study protocol.
14.1.2 Investigator Responsibilities
18.1), the investigator indicates that he or she 
has read the protocol carefully, fully understands the requirements, and agrees to conduct the study 
in accordance with the procedures and requirements described in this protocol.
The investigator also agrees to conduct this study in accordance with all laws, regulations, and 
guidelines of the pertinent regulatory authorities, including the April 1996 International 
Conference on Harmonisation (ICH) Guidance for Industry E6 Good Clinical Practice (GCP), the
Integrated Addendum to ICH E6 (R2) of November 2016, and in agreement with the 2013 version 
of the Declaration of Helsinki. While delegation of certain aspects of the study to sub-investigators
and study coordinators is appropriate, the investigator will remain personally accountable for 
overseeing the study closely and for ensuring compliance with the protocol and all applicable 
regulations and guidelines. The investigator is responsible for maintaining a list of all persons that 
are/have been delegated study-related responsibilities (eg, sub-investigators
and study 
coordinators) and their specific study-related duties.
Investigators should ensure that all persons who are delegated study-related responsibilities are 
adequately qualified and informed about the protocol, the IP(s), and their specific duties within the 
context of the study. Investigators are responsible for providing AstraZeneca with documentation 
of the qualifications, GCP training, and research experience for themselves and their staff as 
required by the sponsor and the relevant governing authorities.
To ensure compliance with the guidelines, the study may be audited by an independent person. 
The investigator agrees, by written consent to this protocol, to cooperate fully with compliance 
checks by allowing access to all study documentation by authorized individuals.
14.1.3 Confidentiality and Privacy
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor and their interventions. This confidentiality is extended to cover testing 
of biological samples and genetic tests in addition to the clinical information relating to 
participants. Therefore, the study protocol, documentation, data, and all other information 
By signing the Investigator's Agreement (Section 
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generated will be held in strict confidence. No information concerning the study or the data will 
be released to any unauthorized third party without prior written approval of the sponsor. 
All research activities will be conducted in as private a setting as possible.
The study monitor, other authorized representatives of the sponsor, representatives of the IRB, 
regulatory agencies, or pharmaceutical company supplying study product may inspect all 
documents and records required to be maintained by the investigator, including but not limited to, 
medical records (office, clinic, or hospital) and pharmacy records for the participants in this study. 
The clinical study site will permit access to such records.
use during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by the reviewing IRB, institutional policies, or sponsor 
requirements.
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored by Premier Research
contact or identifying information. Rather, individual participants and their research data will be 
identified by a unique study identification number. The study data entry and study management 
systems used by clinical sites and by Premier Research staff will be secured and password 
protected. At the end of the study, all study databases will be de-identified and archived.
14.2 Site Initiation
Study personnel may not screen or enrol subjects into the study until after receiving notification 
from the sponsor or its designee that the study can be initiated at the study site. The study site will 
not be authorized for study initiation until:
1. The study site has received the appropriate regulatory authority and IRB/IEC approval for 
the protocol and the appropriate ICF.
2. All GCP documents have been submitted to and approved by the sponsor or its designee.
3. The study site has a Clinical Trial Agreement in place.
4. Study site personnel, including the investigator, have participated in a study initiation 
meeting.
14.3 Screen Failures
Subjects who do not meet the criteria for participation in this trial (screen failure) because of a 
laboratory result, disallowed medication, or other reversible condition may be rescreened at the 
discretion of the investigator.
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently randomly assigned to the study intervention or entered in the study. A minimal 
set of screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials publishing requirements and 
to respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE.
The study participant's contact information will be securely stored at each clinical site for internal 
. This will not include the participant's 
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14.4 Study Documents
All documentation and material provided by AstraZeneca for this study are to be retained in a 
secure location and treated as confidential material.
14.4.1 Informed Consent
Consent forms describing in detail the study intervention, study procedures, and risks are given to 
the participant and written documentation of informed consent is required prior to starting 
intervention/administering study intervention.
IRB-approved and the participant will be asked to read and review the document. The investigator 
will explain the research study to the participant and answer any questions that may arise. A verbal 
poses, 
procedures, and potential risks of the study and of their rights as research participants. Participants 
will have the opportunity to carefully review the written consent form and ask questions prior to 
signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must 
be informed that participation is voluntary and that they may withdraw from the study at any time, 
without prejudice. A copy of the informed consent document will be given to the participants for 
their records. The informed consent process will be conducted and documented in the source 
document (including the date), and the form signed, before the participant undergoes any study-
specific procedures. The rights and welfare of the participants will be protected by emphasizing to 
them that the quality of their medical care will not be adversely affected if they decline to 
participate in this study.
14.4.2 Good Clinical Practice Documents
The GCP documents are listed below.
Curricula vitae of all investigators and sub-investigators
Name and address of the laboratories
List of laboratory reference ranges, and if available, a quality certificate
Form Signature Log/Delegation of Study-related Duties
Any other relevant GCP documents
The GCP documents must be received from the investigator and reviewed and approved by 
AstraZeneca or its designee before the study site can initiate the study and before AstraZeneca will 
GCP documents must be 
retained at the study site in a secure location. Additional documents, including a copy of the 
protocol and applicable amendment(s), the IB, eCRF completion guidelines, copies of regulatory 
references, copies of IRB/IEC correspondence, and IP accountability records should also be 
GCP
Informed consent is a process that is initiated prior to the individual's agreeing to participate in the 
study and continues throughout the individual's study participation. Consent forms will be 
explanation will be provided in terms suited to the participant's comprehension of the pur 
• 
Signed original protocol (ie, Investigator's Agreement) 
• 
• 
• 
• 
• 
authorize shipment of IP to the study site. Copies of the investigator's 
retained as part of the investigator's 
documents. It is the investigator's responsibility to 
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ensure that copies of all required GCP documents are organized, current, and available for 
inspection.
14.4.3 Case Report Forms
s Agreement (Section 18.1), the investigator agrees to maintain 
accurate eCRFs and source documentation as part of the case histories for all subjects who sign an 
ICF.
Case report forms are considered confidential documents and should be handled and stored 
accordingly. The sponsor or its designee will provide the necessary training on the use of the 
specific eCRF system used during the study to ensure that the study information is captured 
accurately and appropriately.
To ensure data accuracy, eCRF data for individual subject visits should be completed as soon as 
possible after the visit. All requested information must be entered in the electronic data capture 
(EDC) system according to the completion guidelines provided by the sponsor or its designee.
The eCRFs must be signed by the investigator or a sub-investigator. These signatures serve to 
attest that the information contained in the eCRF is accurate and true.
14.4.4 Source Documents
Information recorded in the EDC system should be supported by corresponding source 
documentation. Examples of acceptable source documentation include, but are not limited to,
hospital records, clinic and office charts, laboratory notes, and recorded data from automated 
instruments, memoranda, and pharmacy dispensing records.
Clinical laboratory data required by the protocol will be electronically transferred from the 
central/local laboratory to the sponsor or its designee. A paper copy of the laboratory results will 
be provided to the study site
14.5 Data Quality Control
AstraZeneca and its designees will perform quality control checks on this clinical study.
14.5.1 Monitoring Procedures
AstraZeneca and/or its designee will conduct site visits to monitor the study and ensure compliance 
with the protocol, GCP, and applicable regulations and guidelines. The assigned clinical research 
associates (CRAs) will visit the investigator and study site at periodic intervals and maintain 
periodic communication. The investigator agrees to allow the CRAs and other authorized 
personnel access. The CRAs will maintain current personal knowledge of the study through 
observation, review of study records and source documentation, and discussion of the conduct of 
the study with the investigator and staff. While on site, the CRAs will review
regulatory documents, directly comparing entries in the EDC system with the source 
documents
consenting procedures
AE procedures
storage and accountability of IP and study materials
By signing the Investigator' 
and should be retained with each subject's source data . 
• 
• 
• 
• 
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The CRA will ask for clarification and/or correction of any noted inconsistencies. Procedures for 
correcting eCRF are described in the study manual. As representatives of the sponsor, CRAs are 
responsible for notifying project management of any noted protocol deviations.
By signing the 
18.1), the investigator agrees to meet with the 
CRA(s) during study site visits; to ensure that study staff is available to the CRA(s) as needed; to
provide the CRA(s) access to all study documentation, to the clinical supplies dispensing and 
storage area; and to assist the monitors in their activities, if requested. Further, the investigator 
agrees to allow AstraZeneca or its designee
auditors or inspectors from regulatory agencies to 
review records, and to assist the inspectors in their duties, if requested.
A protocol deviation is any noncompliance with the clinical trial protocol or ICH GCP 
requirements. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations. All deviations must be addressed in study source documents, reported to the sponsor. 
Protocol deviations must be sent to the reviewing IRB per their policies. The site investigator is 
responsible for knowing and adhering to the reviewing IRB requirements. 
14.5.2 Data Management
AstraZeneca or its designee will be responsible for activities associated with the data management 
of this study. The standard procedures for handling and processing records will be followed per 
standard operating procedures. A comprehensive data management 
plan will be developed, including a data management overview, description of database contents,
annotated CRF, pre-entry review list, self-evident correction conventions, query contacts, and 
consistency checks.
Study site personnel will be responsible for providing resolutions to all data queries. The 
investigator will be required to document electronic data review to ensure the accuracy of the 
corrected and/or clarified data. Procedures for soliciting and documenting resolution to data 
queries are described in the study manual.
14.5.3 Quality Assurance/Audit
This study will be subject to audit by AstraZeneca or its designee. Audits may be performed to
check compliance with GCP guidelines, and can include:
site audits
Trial Master File audits
database audits
document audits (eg, protocol and/or clinical study report [CSR])
AstraZeneca or its designee may conduct additional audits on a selection of study sites, requiring 
access to subject notes, study documentation, and facilities or laboratories used for the study.
The study site, facilities, all data (including source data), and documentation will be made available 
for audit by quality assurance auditors and for IRB/IEC or regulatory authorities according to GCP 
guidelines. The investigator agrees to cooperate with the auditor during the visit and will be 
Investigator's Agreement (Section 
GCP and Premier Research's 
• 
• 
• 
• 
's 
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available to supply the auditor with CRFs or other files necessary to conduct that audit. Any 
findings will be strictly confidential.
If a regulatory authority informs the investigator that it intends to conduct an inspection, the
investigator shall notify AstraZeneca immediately.
14.6 Study Termination
The study may be terminated at AstraZeneca
discretion at any time and for any reason.
14.6.1 Regular Study Termination
The end of this study is defined as the date of the last visit of the last subject (last subject out or
last subject last visit) participating in the study. Within 90 days of the end of the clinical study,
AstraZeneca or designee will notify the IECs and regulatory authorities of the regular termination 
of the study as required according to national laws and regulations.
14.6.2 Premature Study Termination
The study may be temporarily suspended or terminated prematurely if there is sufficient reasonable 
cause at any time by AstraZeneca, IECs, regulatory authorities, respective steering committees, or 
the coordinating investigator. A decision to prematurely terminate the study is binding to all 
investigators of all study sites.
Within 15 days of premature termination of a clinical study, AstraZeneca or its designee will notify 
the IECs and regulatory authorities about the premature termination as required according to 
national laws and regulations. AstraZeneca or its designee must clearly explain the reasons for 
premature termination.
Circumstances that may warrant termination or suspension include, but are not limited to:
Determination of unexpected, significant, or unacceptable risk to participants
Demonstration of efficacy that would warrant stopping   
Insufficient compliance to protocol requirements
Data that are not sufficiently complete and/or evaluable
Determination that the primary endpoint has been met
If the study is terminated prematurely, all investigators have to inform their subjects and take care 
of appropriate follow-up and further treatment of the subjects to ensure protection of the 
interests. Study sites may be asked to have all subjects currently participating in the study complete 
all of the assessments for the Early Termination Visit.
14.7 Study Site Closure
At the end of the study, all study sites will be closed. AstraZeneca may terminate participation of 
a study site at any time. Examples of conditions that may require premature termination of a study 
site include, but are not limited to, the following:
Noncompliance with the protocol and/or applicable regulations and guidelines
's 
• 
• 
• 
• 
• 
subjects' 
• 
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Inadequate subject enrolment
14.7.1 Record Retention
After completing the study, AstraZeneca will receive the original CRFs or at least a legible copy 
and retain the documents for at least 5 years after the completion of the study.
One copy will remain with the investigator. The investigator shall arrange for the retention of the 
subject identification codes, subject files and other source data until at least 5 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or until at least 2 years have elapsed since 
the formal discontinuation of the clinical development of the product. These documents need to be 
retained for a longer period of time if required by applicable regulatory authorities or by agreement 
with the sponsor.
At the end of such period, the investigator shall notify the sponsor in writing of his or her intent to 
destroy all such material. The sponsor shall have 30 days to respond to the 
Copies of these study records (and all study-related documents, including source data) shall be 
kept by the investigator for the maximum period of time permitted by the hospital, institution, or 
private practice.
14.7.2 Sample Retention
Samples may be used for purposes related to this research. The samples will be stored until the 
sponsor has determined that specimens are no longer needed and the decision has been made that 
none of the samples needs to be reanalysed. In addition, identifiable samples can be destroyed at 
any time at the request of the subject.
-identified biological samples 
may be stored with the same goal as the sharing of data. These samples could be used to research 
the causes of PDN, its complications and other conditions for which individuals with PDN are at 
increased risk, and to improve treatment. A code-link will allow linking the biological specimens 
with the phenotypic data from each participant, maintaining the blinding of the identity of the 
participant.
During the conduct of the study, an individual participant can choose to withdraw consent to have 
biological specimens stored for future research. However, withdrawal of consent with regard to 
biosample storage may not be possible after the study is completed. 
14.8 Changes to the Protocol
This protocol cannot be altered or changed except through a formal protocol amendment, which 
requires the written approval of AstraZeneca. The protocol amendment must be signed by the 
investigator and approved by the regulatory authorities and IRB or IEC, if applicable, before it 
may be implemented. Protocol amendments will be filed with the appropriate regulatory agency(s) 
having jurisdiction over the conduct of the study as applicable in accordance with local 
requirements.
• 
investigator's notice, 
and the sponsor shall have a further opportunity to retain such materials at the sponsor's expense. 
With the participant's approval and as approved by local IRBs, de 
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14.9 Use of Information and Publication
All information concerning MEDI7352, AstraZeneca operations, patent applications, formula, 
manufacturing processes, basic scientific data, and formulation information supplied by 
AstraZeneca or its designee to the investigator and not previously published, is considered 
confidential and remains the sole property of AstraZeneca. Case report forms also remain the 
property of AstraZeneca. The investigator agrees to use this information for purposes of study 
execution through finalization and will not use it for other purposes without the written consent of 
the sponsor.
The information developed in this study will be used by AstraZeneca in connection with the 
continued development of MEDI7352 and thus may be disclosed as required to other clinical 
investigators or government regulatory agencies.
The information generated by this study is the property of AstraZeneca. Publication or other public 
presentation of MEDI7352 data resulting from this study requires prior review and written 
approval of AstraZeneca. Publication policies will be specified in a separate document.
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15
FINAL CLINICAL STUDY REPORT
AstraZeneca will retain ownership of the data.
The final CSR will be written within 1 year of completion of the clinical part of the study. This 
report will include a summary of the study results based on a statistical evaluation and clinical
assessment of the protocol-defined endpoints.
The final CSR may be submitted to the regulatory authorities.
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16
ETHICAL AND LEGAL CONSIDERATIONS
16.1 Declaration of Helsinki and Good Clinical Practice
This study will be conducted in compliance with the April 1996 ICH Guidance for Industry E6 
GCP (including archiving of essential study documents), the Integrated Addendum to ICH E6 (R2) 
of November 2016, the 2013 version of the Declaration of Helsinki, the applicable regulations of 
the countries in which the study is conducted, and with the Commission Directives 2001/20/EC 
and 2005/28/EC.
See Appendix D for regulation and guidelines.
16.2 Subject Information and Informed Consent
A properly constituted, valid IRB or IEC must review and approve the protocol, the i
ICF, and related subject information and recruitment materials before the start of the study.
It is the responsibility of the investigator to ensure that written informed consent and/or assent is 
obtained from the subject before any activity or procedure is undertaken that is not part of routine 
care.
According to the Declaration of Helsinki and ICH GCP, subjects must provide their written 
informed consent prior to enrolment in a clinical study and before any protocol-specified 
procedures are performed. Subjects must declare their consent by personally signing and dating 
the ICF. The written ICF will embody the elements of informed consent and/or assent as described 
in the Declaration of Helsinki and will also comply with local regulations. 
Each subject should be made aware by the investigator of the nature of the study (objectives,
methods, and potential hazards and benefits) and the procedures involved, using the information 
on the ICF. Information should be given in both oral and written form whenever possible and 
deemed appropriate by the IRB/IEC. Subjects, their relatives, or, if necessary, legal representatives 
must be given ample opportunity to inquire about details of the study. 
Subject information and the ICF must be in a language fully comprehensible to the prospective 
subject. The written information must be provided to the subject to give him or her sufficient time 
to understand the information and to prepare questions before being asked for his or her consent. 
The investigator must confirm that the text was understood by the subject. The subject will then 
sign and date the IRB/IEC-approved consent form indicating that he or she has given his or her 
consent to participate in the study. The signature confirms that the consent is based on information 
that has been understood. The form will also be signed by the investigator obtaining the consent 
ICF must be kept on file by 
the investigator for possible inspection by regulatory authorities, AstraZeneca and/or 
designee. Collection of informed consent and/or assent has to be documented on the eCRF.
Furthermore, the subject will be informed that if he or she wishes to drop-out or withdraw at any 
time during the study, this will not have any negative consequences. Subjects may be withdrawn 
by the investigator if any change related to safety or ethics precludes further participation in the 
study. Subjects will be asked to agree to a final assessment in the event of an early termination of 
the study.
Subjects will be informed that data from their case may be stored in a computer without inclusion 
of their name and that such data will not be revealed to any unauthorized third party. Data will be 
nvestigator' s 
and annotated with the study subject number. Each subject's signed 
the sponsor's 
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reviewed by the monitor, an independent auditor, and possibly by representatives of regulatory 
authorities and/or IRBs/IECs. The terms of the local data protection legislation will be applied as 
appropriate.
16.3 Approval by Institutional Review Board or Independent Ethics Committee
A valid IRB/IEC must review and approve this protocol before study initiation. Written 
notification of approval is to be provided by the investigator to the sponsor
representative before 
shipment of investigational drug supplies, and will include the date of t
Until written approval by the IRB/IEC has been received by the investigator, no subject may 
undergo any procedure not part of routine care for the subject s condition.
Protocol amendments must also be reviewed and approved by the IRB/IEC. Written approval from 
the IRB/IEC, or a designee, must be received by
representative before 
implementation. 
16.4 Finance and Insurance
Details on finance and insurance will be provided in a separate agreement between the investigator 
and the sponsor.
's 
he committee's approval 
and the chairperson's signature. 
the sponsor's 
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17
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51. Pinheiro J, Bornkamp B, Bretz F. Design and analysis of dose-finding studies combining 
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18
ATTACHMENTS
18.1
PROTOCOL NUMBER:
D5680C00002
PROTOCOL TITLE:
A Randomised, Double-Blind, Placebo-Controlled,
Dose-Response Study of the Efficacy and Safety of MEDI7352 
in Subjects with Painful Diabetic Neuropathy
AMENDED PROTOCOL:
13-Apr-2022
IP
and has discussed these data with the study monitor. Having considered fully all the available 
information, the undersigned considers that it is ethically justifiable to give the IP to selected 
subjects in his/her care, according to the amended study protocol.
He or she agrees to use the study material, including IP, only as specified in the protocol. He or 
she understands that changes cannot be made to the protocol without prior written approval of 
AstraZeneca.
He or she understands that any deviation from the protocol may lead to early termination of the 
study.
He or she agrees to report to AstraZeneca within time any clinical AE or abnormal laboratory 
value that is serious, whether or not considered related to the administration of IP.
He or she agrees to comply with AstraZeneca and regulatory requirements for the monitoring and 
auditing of this study.
In addition, he or she agrees that the study will be carried out in accordance with the revised 
Declaration of Helsinki (2013) and the local laws and regulations relevant to the use of new 
therapeutic agents.
I, the undersigned, have carefully read this amended protocol and agree that it contains all the 
necessary information required to conduct the study.
Principal Investigator:
Printed Name:
Signature:
Date:
Investigator's Agreement 
The undersigned acknowledges possession of and has read the Investigator's Brochure on the 
Investigator's name and address (stamp) 
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APPENDICES
A.
B.
Contraception Guidance
C.
Other Study-Specific Requirements
D.
Regulations and Good Clinical Practice Guidelines
A.
During the course of the study, the investigator will remain vigilant for increases in liver 
biochemistry. The investigator is responsible for determining whether a subject meets potential 
The investigator participates, together with AstraZeneca Neuroscience Innovative Medicines 
(NS iMed) clinical project representatives, in review and assessment of cases meeting PHL criteria 
is no alternative 
explanation for the elevations in liver biochemistry other than drug-induced liver injury (DILI) 
caused by the investigational medicinal product (IMP). 
The investigator is responsible for recording data pertaining to PHL/HL cases and for reporting 
adverse events (AEs) and serious adverse events (SAEs) according to the outcome of the review 
and assessment in line with standard safety reporting processes.
DEFINITIONS 
× ULN at any point during the study irrespective of an increase 
in alkaline phosphatase (ALP). The elevations do not have to occur at the same time or within a 
specified time frame. 
×
× ULN, where no other reason, other than the IMP, can be 
found to explain the combination of increases
eg, elevated ALP indicating cholestasis, viral 
hepatitis, or another drug. The elevations do not have to occur at the same time or within a specified 
time frame.
In order to identify cases of PHL, it is important to perform a comprehensive review of laboratory 
data for any subject who meets any of the following identification criteria in isolation or in 
combination:
× ULN 
× ULN 
× ULN
Hy's Law Criteria 
Hy's Law Criteria 
Hy's Law (PHL) criteria at any point during the study. 
to agree whether Hy's Law (HL) criteria are met. HL criteria are met if there 
Potential Hy's Law (PHL) 
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 2 3 x upper limit of normal 
(ULN) and total bilirubin (TBL) 2 2 
Hy's Law (HL) 
AST or ALT 2 3 
ULN and TBL 2 2 
IDENTIFICATION OF POTENTIAL HY'S LAW CASES 
• 
ALT2 3 
• 
AST2 3 
• 
TBL22 
Hy’s Law Criteria
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When a subject meets any of the identification criteria, in isolation or in combination, the central 
laboratory will immediately send an alert to the investigator (also sent to NS iMED medical 
monitoring and drug safety representatives). 
The investigator will also remain vigilant for any local laboratory reports in which the 
identification criteria are met. Where this is the case, the investigator will: 
Request a repeat of the test (new blood draw) by the central laboratory 
Complete the appropriate unscheduled laboratory CRF module(s) with the original local 
laboratory test result 
When the identification criteria are met from central or local laboratory results, the investigator 
will, without delay: 
Determine whether the subject meets PHL criteria by reviewing laboratory reports from all 
previous visits (including both central and local laboratory results)
FOLLOW-UP 
If the subject does not meet PHL criteria, the investigator will: 
Inform the NS IMED representatives (medical monitoring and patient safety physicians) that 
the subject has not met PHL criteria. 
Perform follow-up on subsequent laboratory results according to the guidance provided in the 
Clinical Study Protocol.
If the subject does meet PHL criteria, the investigator will: 
Notify the NS IMED representatives (medical monitoring and patient safety physicians), who 
will then inform the central study team 
The medical monitor will contact the investigator, to provide guidance, discuss, and agree on an 
-up and the continuous review of data. Subsequent to this 
contact, the investigator will:
Monitor the subject until liver biochemistry parameters and appropriate clinical symptoms and 
signs return to normal or baseline levels, or as long as medically indicated
Investigate the etiology of the event and perform diagnostic investigations, as discussed with 
the study physician 
Complete the three liver CRF modules as information becomes available 
If at any time (in consultation with the study physician) the PHL case meets serious criteria, 
report it as an SAE using standard reporting procedures
• 
• 
• 
Potential Hy's Law Criteria Not Met 
• 
• 
Potential Hy's Law Criteria Met 
• 
approach for the study subjects' follow 
• 
• 
• 
• 
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The instructions in this section should be followed for all cases where PHL criteria are met. 
No later than 3 weeks after the biochemistry abnormality was initially detected, the medical 
monitor will contact the investigator in order to review available data and agree on whether there 
is an alternative explanation for meeting PHL criteria other than DILI caused by the IMP. The
NS IMED physician and the NS IMED representative safety physician will also be involved in this 
review together with other subject matter experts as appropriate. 
According to the outcome of the review and assessment, the investigator will follow the 
instructions below. 
If there is an agreed alternative explanation for the ALT or AST and TBL elevations, a 
determination of whether the alternative explanation is an AE will be made and, subsequently, a 
determination of whether the AE meets the criteria for a SAE: 
If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate CRF. 
If the alternative explanation is an AE/SAE, record the AE/SAE in the CRF accordingly 
and follow the NS IMED standard reporting processes. 
If it is agreed that there is no explanation that would explain the ALT or AST and TBL elevations 
other than the IMP: 
er criteria for 
seriousness apply. 
should be assigned.
If there is an unavoidable delay of over 3 weeks in obtaining the information necessary to assess 
whether or not the case meets the criteria for HL, then it is assumed that there is no alternative 
explanation until such time as an informed decision can be made:
causality assessment as described above. 
Continue follow-up and review according to the agreed-on plan. Once the necessary 
supplementary information is obtained, repeat the review and assessment to determine 
whether HL criteria are met. Update the SAE report according to the outcome of the 
review.
REFERENCES
FDA Guidance for Industry (issued July 2009), Drug-Induced Liver Injury: Premarketing 
Clinical Evaluation:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidance
s/UCM174090.pdf
REVIEW AND ASSESSMENT OF POTENTIAL HY'S LAW CASES 
• 
• 
• 
Report an SAE (report term, "Hy's Law") according to NS IMED standard processes. 
• 
The "medically important" criterion for seriousness should be used if no oth 
• 
As there is no alternative explanation for the HL case, a causality assessment of "related" 
• 
Report an SAE (report term "Potential Hy's Law") applying criteria for seriousness and 
• 
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B. Contraception Guidance
For females:
Females without childbearing potential will be included in this study. Females without 
childbearing potential are defined as those who are surgically sterile (ie, women who have had a 
hysterectomy, bilateral ovariectomy (oophorectomy), bilateral salpingectomy, or bilateral tubal 
ligation) or those who are postmenopausal (defined as 12 months or more with no menses without 
an alternative medical cause).
For males:
Non-sterilized males who are sexually active with a female partner of childbearing potential must 
use condom and spermicide for the duration of the treatment period and for 3 months after the last 
administration of study drug. As male condom and spermicide are not considered to constitute a 
highly effective contraception method it is strongly recommended that female partners of a male 
study subjects also use a highly effective method of contraception throughout the study, including 
the protocol-specified follow-up period. A highly effective method of contraception is defined as 
one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly. 
The acceptable methods of contraception are described in Table B-1.
Table B-1:
Highly Effective Methods of Contraception
Barrier Methods
Hormonal Methods
Intrauterine device
Intrauterine hormone-releasing system (UIS) a
Bilateral tubal occlusion
Vasectomized partner b
Sexual abstinence c
Combined (estrogen and progestogen containing 
hormonal contraception)
Oral (combined pill)
Injectable
Transdermal (patch)
Progestogen-only hormonal contraception associated 
with inhibition of ovulation d
Injectable
Implantable
Intravaginal
a
This is also considered a hormonal method.
b
With appropriate post-vasectomy documentation of surgical success (absence of sperm inejaculate).
c
Sexual abstinence is considered a highly effective method only if defined asrefraining from heterosexual
intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the subject.
d
Progestogen-only hormonal contraception, where inhibition of ovulation is not the primarymode of
action (eg, minipill), is not accepted as a highly effective method).
C. Other Study-Specific Requirements
All scales and details of blood volumes for assessments will be provided in a study-specific 
manual.
0 
0 
0 
0 
0 
0 
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D. Regulations and Good Clinical Practice Guidelines
1. Regulations
European Directive 2001/20/EC and related guidance documents
European Directive 2005/28/EC and related guidance documents>
2. Good Clinical Practice Guidelines
ICH GCP guidelines can be found at the following URL:
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R1_G
uideline.pdf
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__
Step_4.pdf
• 
• 
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REASONS FOR AMENDMENT
1. Broadened ECG language to allow paper ECGs as an alternative to digital ECGs.
2. Clarifi
eCRF as normal, abnormal and clinically significant, or abnormal and not clinically 
significant.
4. Clarified the details relating to the interim analysis after completion of stage 3.
5. Provided additional details of vital signs capture, particularly with regard to the use of a 
supine or sitting position.
6. Corrected typographical errors, capitalizations, and abbreviation definitions.
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SUMMARY OF AMENDED SECTIONS
The changes being made in this version of the protocol are considered to be substantial.
Section 2.1 
Synopsis
The synopsis was revised to incorporate the changes to the protocol that are described in this 
amendment.
Section 2.2
Schedule of Events
The Schedule of Events was revised to incorporate the changes to the protocol that are described 
in this amendment.
Section 4
LIST OF ABBREVIATIONS AND DEFINITIONS
The List of Abbreviations was revised to incorporate definitions for terms in the protocol that were 
not previously defined. 
Section 5.2.4
Phase I Painful Osteoarthritis of the Knee Study
Text formerly read:
In the ongoing Phase I study D5680C00004, 5 subjects had received 
blinded SC study treatment (MEDI7352 150 mg or placebo) as of 
01 June 2021. Two of the of 5 treated subjects (40.0%) have had a 
total of 4 TEAEs as follows (1 subject each): dyspepsia, catheter site 
erythema, injection site pain, and paraesthesia. 
Now reads:
In the Phase I study D5680C00004, 5 subjects had received blinded 
SC study treatment (MEDI7352 150 mg or placebo) as of 01 June 
2021. Two of the of 5 treated subjects (40.0%) have had a total of 4 
TEAEs as follows (1 subject each): dyspepsia, catheter site 
erythema, injection site pain, and paraesthesia. 
Section 6.3
Exploratory Objectives
Text formerly read:
Objectives
Endpoints
Secondary
To assess the safety and tolerability of 
MEDI7352 in subjects with PDN
Safety and tolerability assessments: AEs and SAEs, physical 
and neurological examinations, neuropathy assessments
(TNSn), strength (dorsiflexion) and deep tendon reflex (knee 
and ankle) assessments, vital signs, 12-lead digital ECGs (with 
printouts), clinical laboratory testing (haematology, clinical 
chemistry, coagulation, and urinalysis), motor and sensory 
nerve conduction, concomitant medication assessment, 
injection site reaction assessment, and infusion reaction 
assessments.
• 
• 
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Now reads:
Objectives
Endpoints
Secondary
To assess the safety and tolerability of 
MEDI7352 in subjects with PDN
Safety and tolerability assessments: AEs and SAEs, physical 
and neurological examinations, neuropathy assessments
(TNSn), strength (dorsiflexion) and deep tendon reflex (knee 
and ankle) assessments, vital signs, 12-lead ECGs, clinical 
laboratory testing (haematology, clinical chemistry, 
coagulation, and urinalysis), motor and sensory nerve 
conduction, concomitant medication assessment, injection site 
reaction assessment, and infusion reaction assessments.
Section 7.1
Overall Study Design and Plan
Text formerly read:
In stage 3 of the study, approximately 67 subjects will be randomly 
2. The third stage will 
include an interim analysis to assess key assumptions of the sample 
size calculation. In stage 4 of the study, if there are no changes 
made following the interim analysis, eligible subjects will be 
randomly assigned to treatment with equal allocation across 3 dose 
levels of MEDI7352 or placebo to ensure approximately 236 
subjects are evaluable for the efficacy analysis of stages 2 to 4 
combined.
Now reads:
In stage 3 of the study, approximately 67 subjects will be randomly 
assigned to plac
include an interim analysis to assess key assumptions of the sample 
size calculation. Upon enrolment of approximately 67 subjects in 
stage 3, approximately 165 eligible subjects will be randomly 
assigned to treatment with equal allocation across 3 dose levels of 
MEDI7352 or placebo to ensure approximately 236 subjects are 
evaluable for the efficacy analysis of stages 2 to 4 combined.
Section 7.2
Rationale and Discussion of Study Design
Text formerly read:
The third stage will compare the highest expected efficacious dose,
, to placebo and an interim analysis that will enable
decision making for stage 4 with respect to sample size re-
estimation and dose allocation ratio.
Now reads:
The third stage will compare the highest expected efficacious dose, 
, to placebo and includes an interim analysis that will 
confirm decision making for stage 4 with respect to exact sample 
size and dose allocation ratio.
Section 7.3
Selection of Doses in the Study
Text formerly read:
MEDI7352 is currently undergoing clinical evaluation for safety, 
PK, PD, and efficacy in a first-in-human study in subjects with 
painful 
OA 
of 
the 
knee 
(ClinicalTrials.gov 
Identifier: 
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NCT02508155). In that study, testing of single IV doses of up to 
 and repeat ascending IV doses of 
, and
every 2 weeks have been completed. The final cohort 
comprising repeat IV doses of 
 is ongoing. Single SC 
doses of 
 have also been evaluated. To date, no safety or 
tolerability concerns have been reported. A full description of the 
current clinical experience with MEDI7352 is in Section 5.2.
Now reads:
MEDI7352 has undergone clinical evaluation for safety, PK, PD, 
and efficacy in a first-in-human study in subjects with painful OA 
of the knee (ClinicalTrials.gov Identifier: NCT02508155). In that 
study, testing of single IV doses of up to 
and repeat 
ascending IV doses of 
and 
every 2 weeks 
have been completed. Single SC doses of 
have also been 
evaluated. No safety or tolerability concerns were reported. A full 
description of the current clinical experience with MEDI7352 is in 
Section 5.2.
Section 10.1
Study Duration
Deleted:
The overall study duration is expected to be 40 months (35 
months of active screening and enrolment and 5 months of 
follow-up), but this may be extended depending on the 
requirements and recommendations of international and 
national public health authorities in relation to the coronavirus 
disease 2019 (COVID-19) pandemic.
Section 10.2.1.1
Screening
Added:
11. Collect urine sample for the following:
urinalysis
urine drug screen
urine pregnancy test (for women who are not surgically 
sterile) (If the screening urine pregnancy test is more than 7 
days before the first day of treatment, it must be repeated 
prior to the first dose.)
Section 10.2.2.1
Day 1 (Treatment 1)
Text formerly read:
4. Perform 3 replicates of 12-lead dECGs (with printouts) after the
subject has been resting in the supine position for at least
10 minutes.
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Now reads:
4. Perform 3 replicates of 12-lead ECGs (with printouts) after the 
subject has been resting in the supine position for at least 
10 minutes.
Text formerly read:
11. Repeat 3 replicates of dECGs (with printouts) at 60 (±10) 
minutes after the start of IP administration, and 2 and 4 hours (±10 
minutes) after the start of IP administration. Subjects must rest in 
the supine position for 10 minutes prior to each ECG recording 
session.
Now reads:
11. Repeat 3 replicates of ECGs (with printouts) at 60 (±10) minutes 
after the start of IP administration, and 2 and 4 hours (±10 minutes) 
after the start of IP administration. Subjects must rest in the supine 
position for 10 minutes prior to each ECG recording session.
Section 10.2.2.2
Days 14, 28, 42, 56, and 70 (Treatments 2 to 6)
Text formerly read:
5. Perform 3 replicates of 12-lead dECGs (with printouts) after the 
subject has been resting in the supine position for at least 10 minutes
(Days 28 and 56 only).
Now reads:
5. Perform 3 replicates of 12-lead ECGs (with printouts) after the 
subject has been resting in the supine position for at least 10 minutes
(Days 28 and 56 only).
Added:
8. Collect urine sample for the following:
urinalysis
Section 10.2.2.5
Day 84 (End-of-Treatment; Week 12)
Text formerly read:
6. Perform 3 replicates of 12-lead dECGs (with printouts) after the 
subject has been resting in the supine position for at least 
10 minutes.
Now reads:
6. Perform 3 replicates of 12-lead ECGs (with printouts) after the 
subject has been resting in the supine position for at least 
10 minutes.
Added:
9. Collect urine sample for the following:
urinalysis
urine pregnancy test (for women who are not surgically 
sterile)
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from all subjects who had a baseline sample collected at 
the screening visit.
Section 10.2.3
Follow-up (or Early Termination) Evaluation (Week 18)
Added:
8. Collect urine sample for the following:
urinalysis
urine pregnancy test (for women who are not surgically 
sterile)
Section 10.3.2.4
Text formerly read:
Now reads:
Section 10.3.3.1.5
Vital Signs
Added:
Vital signs will be assessed as follows:
Screening: Measure respiratory rate, temperature, and HR 
and BP after a 5-minute rest in supine position. To assess 
orthostasis, repeat BP and HR 1 minute after the subject 
stands. 
Day 1 pre-dose: Measure respiratory rate, temperature, and 
HR and BP after a 5-minute rest in supine position. To assess 
orthostasis, repeat BP and HR 1 minute after the subject 
stands.
Day 1 post-dose: Supine and orthostatic BP and HR at 15 
mins, 30 mins, 45 mins, 60 mins, 2 hours, and 4 hours after 
start of infusion. Temperature and supine and orthostatic BP 
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and HR at 60 mins, 2 hours, and 4 hours after start of infusion. 
Respiratory rate at 15 mins, 60 mins, 2 hours, and 4 hours 
after start of infusion. The 60-minute assessments should be 
performed within 10 minutes of the end of the infusion. [Note: 
An acceptable window for these vital sign assessments is ± 5 
mins in relation to the specified time].
Days 14, 28, 42, 56, and 70 pre-dose: Measure respiratory rate, 
temperature, and HR and BP after a 5-minute rest in sitting
position. To assess orthostasis, repeat BP and HR 1 minute 
after the subject stands.
Days 14, 28, 42, 56, and 70 post-dose: 5 minutes after 
completion of infusion, measure respiratory rate, temperature, 
and HR and BP after a 5-minute rest in sitting position. After 
measuring sitting vital signs, assess orthostatic BP and HR 1 
minute after the subject stands.
Days 71, 77, and Week 18 or early termination: Measure
respiratory rate, temperature, and HR and BP after a 
5-minute rest in sitting position. To assess orthostasis, repeat 
BP and HR 1 minute after the subject stands. 
Section 10.3.3.1.6
Twelve-lead Electrocardiogram
Text formerly read:
The digital ECGs will be collected using the ECG equipment 
delivered by the central ECG laboratory (ECG lab) and will be 
standard operating procedures. Further details are provided in the 
ECG Manual.
Paper printouts of the digital ECGs will be reviewed in real time by 
the principal investigator, or delegate, for safety monitoring. The 
following variables will be reported by the ECG Core 
laboratory: RR, PR/PQ, QRS, and QT intervals. Derived 
parameters (QTcF, HR, and others, as applicable) will be 
calculated by the statistician or designee.
Now reads:
All subjects will undergo ECGs as indicated in the schedule of 
assessments. Where applicable, digital ECGs will be collected 
using the ECG equipment delivered by the central ECG laboratory 
(ECG lab) and will be transferred to and analysed by the ECG lab 
are provided in the ECG Manual.
Paper printouts of the 12-lead ECGs will be reviewed in real time 
by the principal investigator, or delegate, for safety monitoring. The 
results of the evaluation will be reported in the eCRF as normal
or abnormal (if abnormal, the ECG is also to be reported as not 
clinically significant or clinically significant). The details of any 
ECG abnormalities should be described and captured in the 
eCRF (irrespective of whether they are considered not clinically 
significant or clinically significant).
• 
• 
• 
transferred to and analysed by the ECG lab according to the lab's 
according to the lab's standard operating procedures. Further details 
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Section 13.1.6.4
Twelve-lead Electrocardiogram
Text formerly read:
The number and percentage of subjects with normal and abnormal 
ECG findings will be summarized for each treatment group at each 
time point. Abnormal results will be grouped as clinically significant 
and not clinically significant.
If warranted, a comparison of QT results will be presented and 
descriptive summaries (mean, SD, median, minimum, and 
maximum) will be presented for ECG measures of PR interval, 
QRS interval, QT interval, QTc interval (both correction 
methods), and HR for each treatment group at each time point.
Now reads:
The number and percentage of subjects with normal and abnormal 
ECG findings will be summarized for each treatment group at each 
time point. Abnormal results will be grouped as clinically significant 
and not clinically significant. A description of ECGs evaluated as 
abnormal will be provided.
If applicable (digital ECGs), descriptive summaries will be 
provided for measures provided by the ECG core laboratory 
from the digital ECGs for PR, QRS, QT, RR intervals and for 
the calculated variables QTcF and HR for each treatment group 
and time point.
Section 13.2
Sample Size Determination
Text formerly read:
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Now reads:
General
Minor typographical, abbreviation, and capitalization corrections were made throughout the 
protocol as necessary.
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SAP_003.pdf: 
Clinical Study Report Appendix 16.1.9 
AstraZeneca 
MEDI7352 - D5680C00002 
CONFIDENTIAL AND PROPRIETARY 
Clinical Study Report Appendix 16.1.9 
Drug Substance MEDI7352 
Study Code 
D5680C00002 
Appendix 16.1.9 
Documentation of Statistical Methods and Supporting Statistical 
Analysis 
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Clinical Study Report Appendix 16.1.9 
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CONFIDENTIAL AND PROPRIETARY 
Document Name 
Edition/Version No. 
Edition/Version Date 
NRS Pain/PK/ADA/Total NGF Analysis Plan 
(Interim Analyses) 
1.0 
10 February 2023 
Statistical Analysis Plan 
1.0 
12 July 2023 
Statistical Analysis Plan 
1.1 
31 August 2023 
Table, Listing, and Figure Shells 
1.0 
12 July 2023 
Table, Listing, and Figure Shells 
1.1 
31 August 2023 
Table, Listing, and Figure Shells 
1.2 
04 October 2023 
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NRS pain/PK/ADA/Total NGF Analysis Plan 
 
Drug Substance 
MEDI7352 
 
Study Code 
D5680C00002 
 
Edition Number 
1.0 
 
Date 
10/February/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
NRS pain/PK/ADA/Total NGF Analysis Plan (Interim Analyses) 
Study D5680C00002 
A Randomised, Double-Blind, Placebo-Controlled, 
Dose-Response Study of the Efficacy and Safety of 
MEDI7352 in Subjects with Painful Diabetic Neuropathy 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
TITLE PAGE ............................................................................................................................. 1 
TABLE OF CONTENTS .......................................................................................................... 2 
INTERIM ANALYSIS SAP SIGNATURE PAGE .................................................................. 4 
1 
INTRODUCTION .................................................................................................. 5 
2 
EFFICACY OBJECTIVES .................................................................................... 6 
3 
PK
AND IMMUNOGENICITY OBJECTIVES ........................ 6 
4 
PK
AND IMMUNOGENICITY ASSESSMENTS ................... 6 
5 
PROCESS & DATA FLOW .................................................................................. 7 
5.1 
PREMIER-SUPPLIED ANALYSES ..................................................................... 7 
5.2 
INTIQUAN-SUPPLIED ANALYSES ................................................................... 7 
6 
STATISTICAL METHODS ................................................................................... 8 
6.1 
NRS Pain ................................................................................................................ 9 
6.1.1 
Data Conventions for Statistical Analysis of ePRO Pain Diary Data .................... 9 
6.1.2 
Handling of Missing Diary Data........................................................................... 10 
6.1.3 
Derivation of Endpoints ........................................................................................ 11 
6.1.4 
Descriptive Statistics ............................................................................................ 11 
6.1.5 
Statistical Analysis................................................................................................ 12 
6.1.6 
Updated Statistical Power Calculation ................................................................. 13 
6.2 
PK ......................................................................................................................... 13 
6.3 
Total NGF ............................................................................................................. 14 
6.4 
Anti-drug Antibody .............................................................................................. 14 
6.5 
Individual Subject Profiles ................................................................................... 14 
6.6 
Other Data ............................................................................................................. 15 
6.6.1 
Subject Disposition and eligibility for statistical analysis .................................... 15 
6.6.2 
Demographic data ................................................................................................. 15 
7 
SOFTWARE DETAILS ....................................................................................... 16 
8 
STATISTICAL APPENDIX ................................................................................ 16 
9 
REPORTING ........................................................................................................ 18 
10 
OUTPUT SHELLS EXAMPLES ......................................................................... 21 
 
LIST OF TABLES 
Table 1 
Planned Tables ............................................................................................ 18 
Table 2 
Planned Figures ........................................................................................... 19 
 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation or special term 
Description 
ADA 
Anti-drug antibody 
ADaM 
Analysis Data Model 
AZ 
AstraZeneca 
BLQ 
Below the limit of quantification 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence interval 
CPQP 
Clinical Pharmacology and Quantitative Pharmacology 
CTX-II 
C-terminal cross-linked telopeptide of type II collagen 
CXCL13 
Chemokine C-X-C motif ligand 13 
IA 
Interim analysis 
IARC 
Interim Analysis Review Committee 
ID 
Identification 
IP 
Investigational product 
NONMEM 
Non-linear mixed effect modelling 
NGF 
Nerve growth factor 
MAD 
Multiple-ascending dose 
PDN 
Painful Diabetic Neuropathy 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
SAD 
Single-ascending dose 
SDTM 
Study Data Tabulation Model 
TNFα 
Tumour necrosis factor alpha 
VPC 
Visual predictive check 
 
 
 
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INTERIM ANALYSIS SAP SIGNATURE PAGE 
This document has been reviewed and approved by the signatories listed below: 
 
 
Author and Statistical Consultant to AstraZeneca 
Neuroscience  
 
Date 
  
  
AstraZeneca Neuroscience  
Date 
 
 
 Clinical Pharmacology and 
Quantitative Pharmacology 
AstraZeneca  
 
Date 
 
  
Biostatistician (Blinded) 
Premier Research, Spain  
 
Date 
 
  
Biostatistician (Unblinded)  
Premier Research, UK 
 
Date 
 
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1 
INTRODUCTION 
MEDI7352 is a new modality bispecific fusion protein targeting both nerve growth factor 
(NGF) and tumour necrosis factor alpha (TNFα) that is being developed to treat chronic pain. 
Both the anti-NGF and anti-TNFα pathways are precedented. This data analysis plan 
document provides a high-level description of the dataflow that will be followed and the 
outputs to be generated for the NRS pain scores, PK, ADA and total NGF variables in support 
of the interim analysis(es) for the Phase 2 dose response study D5680C00002 conducted with 
MEDI7352 in subjects with painful diabetic neuropathy. Full details of the study design can 
be found in the Clinical Study Protocol version 7.0 (13th April 2022). 
Interim analyses are planned after approximately 60 subjects have completed at least 2 weeks 
of randomised treatment across placebo and MEDI7352 
 IV dose in stage 3 of the 
study. Unblinded personnel who are not otherwise involved in the study conduct will prepare 
the data for review by an Interim Analysis Review Committee. The members of the Interim 
Analysis Review Committee are independent of the day-to-day study activities. The study 
team will remain blinded to the results of the interim analysis for the duration of the study. 
Firewalls will be put in place to ensure that information is not inadvertently disseminated to 
the blinded members of the study team. The primary aim of the interim analysis is to validate 
the key assumptions of the original sample size calculation, which could result in a 
recommendation to adjust the sample size (overall and/or to individual dose groups) or the 
treatment allocation ratio in stage 4 of the study. In support of the interpretation of the efficacy 
(NRS) data analysis, PK, ADA and total NGF data will also be analysed. 
Study Description Overview 
 
Phase of development: Phase 2. 
 
Patient population: Participants with painful diabetic neuropathy. 
 
Study size: Approximately 272 eligible subjects will be randomly assigned to double-
blind treatment with one of 4 dose levels of MEDI7352 (dependent upon stage of the 
study) or placebo to ensure that approximately 236 subjects are evaluable for the efficacy 
analysis of stages 2-4 combined. 
 
General design: This is a multicentre, multinational, randomised, double-blind, placebo-
controlled, parallel-group study. 
 
Route of administration: intravenous. 
 
Doses investigated: 
. Each subject will receive 6 doses, 1 dose 
every 2 weeks (Days 1, 14, 28, 42, 56, and 70), administered IV over a 60-minute period. 
Note: only 
 and 
 doses are included in the Interim Analysis (from stages 2 
and 3). 
 
Development objectives: proof of efficacy. 
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2 
EFFICACY OBJECTIVES 
The primary objective is to assess the efficacy of MEDI7352 versus placebo on chronic pain 
in subjects with PDN currently taking standard of care medication for their PDN pain. A 
secondary objective is to characterise the dose-response relationship of MEDI7352 on chronic 
pain in subjects with PDN. However, this interim analysis plan will not cover the latter 
objective. 
3 
PK
AND IMMUNOGENICITY OBJECTIVES 
The Pharmacokinetics, pharmacodynamic (total NGF) and immunogenicity of MEDI7352 are 
secondary objectives/endpoints in the study. 
 
. A description of these objectives/endpoints is provided 
below. 
Secondary objectives: 
 
To assess the PK, PD, and immunogenicity of MEDI7352 in subjects with PDN 
 
Exploratory objectives:  
4 
PK
 AND IMMUNOGENICITY 
ASSESSMENTS 
Blood samples for determination of serum MEDI7352 concentrations and serum total NGF 
concentrations are collected at the following time-points: 
Day 1 (pre-treatment), Day 14, Day 28, Day 42, Day 56, Day 70 (pre-dose, end of infusion, 
and 8 h), Day 71, Day 77, Day 84 and Early termination (if relevant).  
Blood samples for determination of presence of anti MEDI7352 antibodies (ADA) are 
collected at the following time-points: 
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Baseline, Day 14, Day 28, Day 56, Day 70, Day 84 and Week 18.  
Note: on dosing days, blood samples are taken prior to IP administration. 
5 
PROCESS & DATA FLOW  
Prior to the interim database lock, it is expected that data within scope of the Interim Analysis 
will be cleaned and have no outstanding edit checks. 
5.1 
PREMIER-SUPPLIED ANALYSES 
Prior to the interim analysis, a dummy run will be performed on a blinded data transfer using 
dummy randomization codes. This blinded analysis step will also be used by the sponsor 
blinded statistician to perform the sponsor QC of the primary analysis.  Premier will perform 
their own QC as per standard operating procedures. The unblinded interim analysis will be 
performed by the unblinded Premier statistician.  Both the blinded Premier statistician and 
blinded Sponsor statistician will be prohibited from access to the unblinded interim analysis. 
5.2 
INTIQUAN-SUPPLIED ANALYSES 
Data Management and Biostatistics at PREMIER will generate datasets containing the PK, 
ADA (immunogenicity) and total NGF data with additional study variables (i.e. baseline 
weight; dosing time; treatment allocation; PK, ADA and total NGF sampling time), and a 
dataset containing the efficacy data (i.e. NRS scores) for the purpose of generating individual 
profile plots (generated by IntiQuan) in support of the main efficacy data analysis conducted 
by PREMIER Biostatistics. The data structure and transfer process from Premier to AZ will be 
detailed in a separate Data Transfer Guideline document, and control of blinding will be 
described in MEDI7352 Study D5680C00002 Interim Analysis Review Committee Charter. 
 
 
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6 
STATISTICAL METHODS 
Handling of missing or unquantifiable data:  
Except for specific NRS pain analyses (described in section 6.1) missing data will not be 
imputed. PK and Total NGF data below the limit of quantification will be handled using a left 
censoring approach (i.e. values BLQ are defined as >=0 and <BLQ).  ADA titre reported as 
<30 (below the minimum required dilution) is a negative result for the presence of ADA and 
will be treated as missing in the calculation of ADA titre summary statistics. 
Populations for analysis:  
Details of the populations for analysis as described in the CSP are presented below: 
 Modified intent-to-treat (mITT): all randomised subjects who receive at least 1 dose of 
double-blind study medication and have at least 1 post-baseline NRS assessment. If a 
subject is randomised incorrectly or is administered the incorrect IP, analyses of the 
mITT population will be based on the IWRS-assigned treatment. In addition, for the 
purposes of the efficacy interim analysis of weekly average NRS pain score, it is also 
required that subjects have an evaluable ‘Average Week 12 Pain NRS (LOCF)’score, 
which is defined as having completed two doses of IP and recorded sufficient pain 
NRS data for at least 2 weeks to enable the week 2 average calculation as described in 
section 6.1. 
 Safety set: The safety population will include all subjects who receive at least 1 dose 
of double-blind study medication. 
  PK set: all subjects for whom a PK sample was obtained and analysed. 
In addition, a “Completers” set will be analysed for efficacy, defined as the subset of the 
mITT population who have a week 12 average NRS score. 
A further subset of the mITT population “Week 6 LOCF” may be used to for efficacy 
analyses if the number of subjects with week 6 to week 11 NRS weekly averages (but no week 
12 weekly average) is at least 20% the size of those with complete week 12 NRS averages. 
For the purposes of the IA ‘all PK and PD data available by the data cut-off date for the 
IA’ will be included in the population PK and population PKPD analyses. 
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For the Safety set data presentations, The following clarifies how to handle the situation 
where a participant receives a treatment other than that to which the participant was 
randomised: 
 
If a participant randomised to placebo receives at least one dose of MEDI7352 XX 
µg/kg during the entire double-blind treatment period then the actual treatment arm = 
MEDI7352 XX, where XX corresponds to the lowest dose of MEDI7352 that the 
participant received during the double-blind treatment period. 
 If a participant took only MEDI7352 XX µg/kg treatment during the entire double-
blind treatment period, then the actual treatment arm = MEDI7352 XX, where XX 
corresponds to the dose of MEDI7352 that the participant took during the entire 
double-blind treatment period, regardless of what treatment the participant was 
randomized to.  
 If a participant took a mix of MEDI7352 XX µg/kg treatments during the entire 
double-blind treatment period, then the actual treatment arm = MEDI7352 XX, where 
XX corresponds to the lowest dose of MEDI7352 that the participant received during 
the double-blind treatment period, regardless of what treatment the participant was 
randomized to. 
 
6.1 
NRS Pain 
For all outputs the placebo group will include subjects pooled across stages 2 and 3. 
6.1.1 
Data Conventions for Statistical Analysis of ePRO Pain Diary Data  
▪ 
‘Baseline’ period: is defined as the seven day period prior to randomization i.e. 
Day -7 to Day -1, inclusive. A subject is considered to have a valid Baseline Pain 
score at study entry if there are at least 5 days of recorded diary pain scores in the 
7 day period. This is consistent with the protocol inclusion criterion 9. However, 
for the purposes of inclusion in the statistical analysis of ePRO Pain Diary data, a 
subject is considered to have an evaluable baseline if they have at least 4 days out 
of 7 have recorded diary pain scores. 
▪ 
‘Week 12’ period: is defined for each subject as the seven day period ending within 
the protocol stipulated window (day 84 + 3), where at least 4 days out of 7 have 
recorded diary pain scores. Where several such windows exist the one ending 
closest to day 84 will be selected. If there are two such windows that are equidistant 
from day 84 then the one with the largest number of diary entries will take 
precedence.  If they have the same number of entries then the later of the two end 
dates will be chosen. If no such window exists then week 12 will be considered 
missing for the purposes of weekly average scoring. For example: 
-
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Day 
77 78 79 80 81 82 83 84 85 Number non missing 
7-day Window 85 Y N Y Y N N Y N Y 4 
7-day Window 84 Y N Y Y N N Y N Y 3 (So technically Missing) 
7-day Window 83 Y N Y Y N N Y N Y 4 
In the example above, the 7 day window ending at day 84 has only 3 days of entries, so cannot be used 
as week 12 average. However Day 83 and day 85 have exactly 4 entries in their 7 day 
windows.  These are equidistant from the ideal day 84, so the algorithm chooses day 85 to take the 
average i.e. the later of the two. 
The same approach as for week 12 will be taken for weeks 2,4,6,8 and 10, but using the 
corresponding nominal study days and the + 3 days visit windows as described in the protocol, 
as follows: 
▪ 
‘Week 2’ period:  is defined for each subject as the seven day period ending within 
the protocol stipulated window (day 14 + 3), where at least 4 days out of 7 have 
recorded diary pain scores. 
▪ 
‘Week 4’ period:  is defined for each subject as the seven day period ending within 
the protocol stipulated window (day 28 + 3), where at least 4 days out of 7 have 
recorded diary pain scores. 
▪ 
‘Week 6’ period:  is defined for each subject as the seven day period ending within 
the protocol stipulated window (day 42 + 3), where at least 4 days out of 7 have 
recorded diary pain scores. 
▪ 
‘Week 8’ period:  is defined for each subject as the seven day period ending within 
the protocol stipulated window (day 56 + 3), where at least 4 days out of 7 have 
recorded diary pain scores. 
▪ 
‘Week 10’ period:  is defined for each subject as the seven day period ending within 
the protocol stipulated window (day 70 + 3), where at least 4 days out of 7 have 
recorded diary pain scores. 
 
6.1.2 
Handling of Missing Diary Data 
 
▪ 
‘Missing Baseline’: Subjects with missing baseline data (i.e. zero or 1-3 days of 
diary pain scores will not be included in the Interim Analysis because the primary 
analysis is change-from-baseline.   
▪ 
‘Missing Week 12’: If a subject has zero or < 3 days of diary pain data in each of 
the possible seven day periods ending within the protocol definition of week 12 
(day 84 + 3),  then an imputed ‘week 12 LOCF’ will be calculated from the latest 
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7 ‘non-missing’ entries of the subject’s diary closest to their nominal week 12 
visit (i.e. the latest 7 day period containing at least 4 NRS values), provided that 
this would qualify as at least ‘week 2’ according to the windowing definition 
above.  Otherwise, the week 12 LOCF weekly average NRS pain score will be set 
to missing.   
6.1.3 
Derivation of Endpoints 
▪ 
‘Average Baseline Pain NRS’: is defined as the arithmetic average of the ‘non-
missing’ daily pain scores within the baseline period defined above. For example, 
if a subject has 4 days of non-missing pain scores their average will be calculated 
over 4 days, not the full 7 day baseline period. 
▪ 
‘Average Week 12 Pain NRS’: is defined as the arithmetic average of the ‘non-
missing’ daily pain scores within each subject’s specific week 12 period defined 
above. 
▪ 
‘Average Week 12 Pain NRS (LOCF)’: is defined as the arithmetic average of the 
‘non-missing’ daily pain scores within each subject’s specific week 12 period or 
according to the imputed ‘week 12 LOCF’ approach described above. 
▪ 
‘Change from Baseline to Week 12 Pain NRS’: is defined for each subject as 
‘Average Week 12 Pain NRS’ minus ‘Average Baseline Pain NRS’. 
▪ 
‘Change from Baseline to Week 12 Pain NRS (LOCF)’: is defined for each 
subject as ‘Average Week 12 Pain NRS (LOCF)’ minus ‘Average Baseline Pain 
NRS’. 
 
6.1.4 
Descriptive Statistics 
Tables of arithmetic mean, standard deviation, minimum, maximum, median, 1st 
and 3rd quartiles and N, will be provided by treatment group and total, for the 
following NRS endpoints: 
 Baseline weekly average pain NRS 
 Weekly average pain NRS for weeks 2, 4, 6, 8, 10 and 12  
 Change from Baseline Pain NRS to weeks 2, 4, 6, 8, 10 and 12 
 Week 12 LOCF: Weekly average pain NRS and Change from Baseline 
In addition, the following plots will be produced:  
 Mountain plots (also known as folded empirical distribution plots) and 
boxplots, by treatment group, of Weekly Average and ‘Change from Baseline 
to Week 12 Pain NRS (LOCF)’ will be presented.  
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 Line plots of the observed Weekly Average and Change from baseline in 
mean Daily NRS scores for each treatment group from baseline through to 
the day 87 (the upper limit of the week 12 visit window), with Week 12 
LOCF as an additional plotting point. 
 Spaghetti/Connected line time plot of individual subjects for observed 
Weekly Average (these will be presented as individual profiles as in section 
6.5) and Change from Baseline to week 12.  
6.1.5 
Statistical Analysis 
ANCOVA of ‘Change from Baseline to Week 12 Pain NRS (LOCF)’: 
The linear model will be an analysis of covariance (ANCOVA) with dependent 
variable ‘Change from Baseline to Week 12 Pain NRS (LOCF)’, and independent 
variables will be dose group (as a factor, with placebo group as the reference 
level), and ‘Baseline weekly average pain NRS’ as the continuous covariate. The 
random error is assumed to be normally and independently distributed with 
constant variance. The following outputs from the fitted model will be tabulated: 
▪ 
Parameter estimates of the difference between each dose group and placebo, t-
value, degrees of freedom, standard error, conventional 95% 2-sided and also 
‘Lalonde-type’ asymmetric confidence intervals (i.e. lower limit of 1-sided 
90% CI and upper limit of 1-sided 80% CI), and model residual standard 
deviation (RMSE). 
▪ 
Least squares means estimates of change from baseline to week 12 for 
 
 
 and Placebo groups, with 95% 2-sided confidence intervals. 
The least squares mean is a model estimate using fitted group parameter and 
the baseline weekly average pain NRS parameter evaluated at the grand mean 
over both groups. 
▪ 
As a sensitivity analysis, an estimate of the treatment effect at week 12, 
together with 95 % 2-sided confidence intervals and also ‘Lalonde-type’ 
asymmetric confidence intervals (i.e. lower limit of 1-sided 90% CI and upper 
limit of 1-sided 80% CI), will also be obtained from a “Mixed Effects 
Repeated Measures model”, which assumes a Multivariate Normal distribution 
across visits within patient, with a fully parameterized unstructured covariance 
matrix and contains treatment, baseline NRS, visit and treatment-by-visit 
interaction as fixed effects, using all available data (but not LOCF). If there are 
convergence issues then a simpler covariance structure, such as AR1 will be 
implemented. 
▪ 
Bayesian posterior probabilities that the ‘Reduction’ in Week 12 Pain NRS 
(LOCF) of 
 versus Placebo is (a) Greater than zero i.e. the probability 
of a non-zero treatment effect.  (b) Greater than the target 1.25-point reduction 
treatment effect. Superimpose the above values on a plot of Bayesian posterior 
probability versus reduction on a grid ranging from zero to 2. The Bayesian 
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linear model will be fitted using the bfitmod function within the R Dosefinding 
package. Further details are included in the appendix. 
6.1.6 
Updated Statistical Power Calculation 
The original power calculation will be re-visited using knowledge about the 
observed residual standard deviation (RMSE) from the 
 and 
 
versus placebo ANCOVA analysis, and the observed effects of 
 and 
 
 versus placebo. The eMax dose response curve used for any power 
simulations of stage 4 data will be based upon the ED50 required to fit the 
observed effect of 
 at the IA and two scenarios of the 
 
assumed effect size: 1) the Protocol assumed effect size of 1.25 versus placebo, 
and 2) the observed effect of 
 versus placebo at the IA. If the estimated 
ED50 is negative, then linear interpolation will be used instead of an Emax 
approach. 
 Revised power calculation will be performed as follows:  
Conditional Power of Test of Dose Response Curve under original stage 4 
sample size and dose allocation 
The conditional power of the pre-planned final test of the dose response curve 
will be simulated under the above two assumptions regarding the true 
maximum treatment effect for 
 for data accruing after the interim 
analysis with sample sizes per group as per protocol and using the observed 
data in stage 2 and 3 combined. Further details are given in the programming 
appendix. 
 
The above analyses will be performed by Premier. 
6.2 
PK 
Pharmacokinetic data from this phase 2 study conducted in subjects with PDN will be 
appended to the existing PK data from other MEDI7352 studies conducted in subjects with 
painful osteoarthritis of the knee. Data will subsequently be analysed by population methods 
using nonlinear mixed-effects modelling. The existing 1-compartment population PK model 
with time-dependent clearance reflecting ADA-mediated elimination of the drug developed 
based on the SAD/MAD and phase 2B OA study data will be used as a starting point and 
updated as required based on the emerging new data. The analysis will be carried out using 
appropriate software (e.g., NONMEM, MONOLIX). The impact of prospectively selected 
covariates (i.e. weight), if available, on MEDI7352 exposure (e.g. clearance, volumes) will be 
evaluated. Population PK parameter estimates (e.g., clearance, volume, rate of absorption and 
bioavailability) with 95% CI from the final model will be tabulated. The uncertainty in the 
parameter estimates in the final model will be assessed (e.g. from the standard error estimates 
provided by NONMEM or from the 95% CI estimates provided by other appropriate analysis 
conducted using other software). Finally, the final model performance will be investigated 
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using a set of goodness of fit plots as well as Visual Predictive Check (VPC) method. Other 
evaluation methods may be used (e.g., bootstrapping) if deemed appropriate. 
The above analyses will be performed by IntiQuan. Premier will supply the Serum MEDI7352 
concentration dataset and ancillary variables as described in the Data Transfer Guidelines 
document. 
6.3 
Total NGF  
Total NGF data collected in this phase 2 study conducted in subjects with PDN will be 
appended to the existing total NGF data from other MEDI7352 studies and will subsequently 
be analysed by population methods using nonlinear mixed-effects modelling. 
 
 
The existing semi-
mechanistic drug-target binding population PKPD model developed based on the SAD/MAD 
and phase 2B OA study data will be used as a starting point and updated as required based on 
the emerging new data. The analysis will be carried out using appropriate software (e.g., 
NONMEM, MONOLIX). The impact of potential covariates (if available) on the PD 
parameters (e.g. maximum effect) will be evaluated, if deemed appropriate. The population 
PD parameter estimates with 95% CI from the final model will be tabulated. The uncertainty 
in the parameter estimates in the final model will be assessed (e.g. from the standard error 
estimates provided by NONMEM or from the 95% CI estimates provided by other appropriate 
analysis conducted using other software). Finally, the final model performance will be 
investigated using a set of goodness of fit plots as well as Visual Predictive Check (VPC) 
method. Other evaluation methods may be used (e.g., bootstrapping) if deemed appropriate. 
The above analyses will be performed by IntiQuan. 
6.4 
Anti-drug Antibody 
Anti-Drug Antibody response during the entire study period and at each study assessment will 
be summarised according to prevalence, incidence and titre value for the Safety Set. 
The above analyses will be performed by Premier. 
6.5 
Individual Subject Profiles 
Individual subject trellis-type plots presenting observed PK (concentration), ADA titre, total 
NGF concentration and predicted free NGF concentration profiles over time as well as 
individual observed daily and weekly averaged NRS score (six plots on 1 page per subject) 
will be generated by IntiQuan in support of the interpretation of the main efficacy data 
analysis conducted by PREMIER.  
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The time axis of each sub-plot will be in weeks. The Y-axis of each of the 6 sub-plots will be 
as follows: 
a) Serum MEDI7352 Concentration (ng/mL) on log10 scale, with a separate plot symbol 
for BLOQ values. 
b) ADA Titre on log scale, with a red symbol for ADA positive values and green symbol 
for ADA negative values 
c) Serum free NGF % change from baseline (predicted) on linear scale 
d) Serum total NGF concentration on log10 scale 
e) NRS Daily score, values connected by lines. Reference lines for baseline average daily 
score and minimum daily score post-baseline. 
f) Average weekly NRS score, values connected by lines. Weekly value taken from 
efficacy analysis approach. Reference lines for baseline average Weekly score and 
minimum Weekly score post-baseline. 
6.6 
Other Data 
6.6.1 
Subject Disposition and eligibility for statistical analysis 
A table will be produced to show for stage 2 and 3 of the study the number of 
subjects: 
◦ 
Screened 
◦ 
Enrolled 
For Total and by dose group the number of subjects: 
◦ 
Randomized  
◦ 
Included in the mITT population 
▪ 
Evaluable Week 12 efficacy 
▪ 
Evaluable LOCF efficacy 
◦ 
Not efficacy evaluable 
◦ 
Completed study 
◦ 
Reasons for withdrawal 
 
6.6.2 
Demographic data 
A table of arithmetic mean, standard deviation, minimum, maximum, median, 1st 
and 3rd quartiles and N (observed and missing), will be provided by treatment 
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group and total, for age. And frequency tables by treatment group and total for 
gender and race. 
The above analyses will be performed by Premier. 
 
7 
SOFTWARE DETAILS 
Efficacy: SAS version 9.4 and R version 4.2.1 will be used to create the D5680C00002 
interim analysis outputs, as appropriate. 
Monolix version 2019R1 (Lixoft) will be used for conducting the cross-study population 
analyses and R version 3.6.3 (R-project, www.r-project.org) will be used for generation of the 
associated outputs. 
8 
STATISTICAL APPENDIX 
 
A1.    Bayesian linear model to calculate posterior probabilities of the maximum treatment 
effect (
 versus Placebo data) using bFitMod function within DoseFinding 
package 
◦ 
Calculate the Least Squares Means for each dose group and their variance-
covariance matrix (using package ‘emmeans’) 
◦ 
Create indicator variable for dose: 0=Placebo and 1=
 
◦ 
Execute bFitMod with:  
a.  model as “linear” 
b. Independent Gaussian Priors for intercept and slope parameters: N(0,100). 
With starting values of 0. 
c. Lsmean Estimates and Variance-Covariance for placebo and 
 as 
inputs from the ANCOVA described in section 6.1.5,  and  
d. simulate 100,000 draws from the posterior distribution, with seed = 301020 (to 
allow for independent replication). 
e. Process the saved bFitMod object as follows: 
 Select the ‘samples’ element from the saved bFitMod object 
 The ‘delta’ variable within the ‘samples’ element is the posterior value of 
the treatment difference between 
 and placebo 
◦ 
Estimate the posterior probabilities that the treatment effect is 
a. Greater than zero 
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b. Greater than a 1.25-point reduction from the posterior sample of the slope 
parameter.  
by computing the proportion of posterior ‘delta’ values less than zero and -1.25, 
respectively. 
 
A2. Simulation of Conditional Power of the Dose Response Curve test under original stage 
4 sample size and dose allocation  
◦ 
There is no formula available to compute conditional power of the dose response 
test, therefore a simulation approach will be taken as follows: 
◦ 
Calculate the residual standard deviation (RMSE) from the ANCOVA model fitted 
to the interim data. 
◦ 
Simulate the stage 4 data for each of the four dose groups from an emax model 
with an appropriate ED50 and random error = residual standard deviation.  
 
The parameters for the emax model, from which to simulate from, will be 
calculated (fixed) as follows: 
      ED50 = 450*(YIA-Y450)/(Y450 – 450*YIA/150)   and 
       emax = Y450*(ED50 + 450)/450 
            where YIA= observed effect of 
 versus placebo, Y450 = one of the 
two scenarios of the 
 effect versus placebo. 
If the estimated ED50 is negative then the data are not consistent with an Emax 
model therefore linear interpolation between zero and 
 will be used 
instead of an Emax approach for estimating the effect of the 
 dose in stage 
4 as follows: Lsmean for 
 versus placebo = (
)*Lsmean 
 
versus placebo . 
 
The ‘intercept’ (E0) of the Emax model is set to the ‘intercept plus the regression 
term for baseline value evaluated at the average of the baseline values’ from the 
ANCOVA model of the interim analysis.  The maximum effect over placebo at the 
highest dose studied in stage 4 (currently planned to be 
 is set at values 
as specified in section 6.1.6.  
The algorithm for simulating Change-from-baseline and baseline values for each 
subject is as follows: 
▪ 
Simulate 10,000 stage 4 datasets.  Each simulation consists of: 
 For each dose group, select a sample of baseline values of size as per 
protocol with replacement from the combined distribution of baseline 
values in the interim dataset. 
 For each dose group, simulate a change-from-baseline value for each 
subject from the simulation model conditional upon the subject’s baseline 
value 
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 Combine stage 2 and 3 observed data and stage 4 simulated data and 
analyze using the MCTtest function of the R Dosefinding package, with 
the candidate models as specified in the protocol and options 
type=”normal”, alternative="one.sided", alpha=0.025 and addCovars = 
baseline. 
 Output the minimum adjusted p-value of the multiplicity adjusted test 
▪ 
Calculate conditional Power of the dose response test as  
100*(number of minimum p-values < 0.025 / number of simulations) 
▪ 
Repeat for each 
 effect scenario. If the estimated ED50 is negative 
then linear interpolation will be used instead of an Emax approach scenario. 
 
9 
REPORTING 
In support of the interim analysis which have for primary focus efficacy, Tables and Figures 
will be created. In addition, results from the PK, ADA and total NGF data analysis may also 
be summarised in a PowerPoint presentation created by AZ CPQP/IntiQuan.  
Tables and figures listed in Table 1 and Table 2, respectively, will be generated, as data 
permits. 
Table 1 
Planned Tables 
 
Number 
Description 
Producer 
Table 1.1.1 
Demography 
 
PREMIER 
Table 1.1.2 
Subject Disposition 
PREMIER 
Table 1.2.1 
Descriptive Statistics of Weekly Average Pain NRS from Baseline and all 
visits to Week 12: Observed Values and Week 12 LOCF: mITT Population 
PREMIER 
Table 1.2.2 
Descriptive Statistics of Weekly Average Pain NRS from Baseline and all 
visits to Week 12: Observed Values: mITT Population with week 12 NRS Weekly 
Averages 
PREMIER 
Table 1.2.3 
Statistical Analysis of Change from Baseline to Week 12 Pain NRS (LOCF): 
ANCOVA: mITT Population 
PREMIER 
Table 1.2.4 
Statistical Analysis of Change from Baseline to Week 12 Pain NRS: 
ANCOVA: mITT Population with week 12 NRS Weekly Averages 
PREMIER 
Table 1.2.5 
Statistical Analysis of Change from Baseline to Week 12 Pain NRS: MMRM: 
mITT Population 
PREMIER 
Table A1.1 
Population PK parameter estimates with 95% CI from the final PK model 
IntiQuan 
Table A1.2 
Population PD parameter estimates with 95% CI from the final PKPD model 
IntiQuan 
Table A1.3 
Summary of Anti-Drug Antibody responses during the study  
PREMIER 
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Table 1 
Planned Tables 
 
Number 
Description 
Producer 
Table A1.4 
Anti-Drug Antibody results and titre summary by timepoint  
PREMIER 
Table A1.5 
Predicted average % change from baseline in serum free NGF concentration 
following intravenous administration of MEDI7352 and tanezumab 2.5 and 5 
mg SC 
IntiQuan 
 
Table 2 
Planned Figures 
 
Number 
Description 
 
Figure 1.1 
Mountain plot of Weekly Average to Week 12 Pain NRS (LOCF) by treatment 
group 
PREMIER 
Figure 1.2 
Mountain plot of Change from Baseline to Week 12 Pain NRS (LOCF) by 
treatment group 
PREMIER 
Figure 1.3 
Boxplot of Weekly Average to Week 12 Pain NRS (LOCF) by treatment group 
PREMIER 
Figure 1.4 
Boxplot of ‘Change from Baseline to Week 12 Pain NRS (LOCF)  
PREMIER 
Figure 1.5 
Mean Weekly Average Pain NRS from Baseline to Week 12 (including Week 12 
LOCF) 
PREMIER 
Figure 1.6 
Mean Change from Baseline Pain NRS from Week 1 to Week 12 (including 
Week 12 LOCF) 
PREMIER 
Figure 1.7 
Individual Spaghetti plot of Mean Weekly Average Pain NRS from Baseline to 
Week 12 
PREMIER 
Figure 1.8 
Individual Spaghetti plot Change from Baseline Pain NRS from Week 1 to Week 
12 
PREMIER 
Figure 1.9 
Bayesian Predicted Probabilities of Effect Size versus Placebo  
PREMIER 
Figure 1.10 
Conditional Power of MCP-MOD test 
PREMIER 
Figure A1.1 
Model goodness of fit plots (population PK analysis) 
IntiQuan 
Figure A1.2 
Visual predictive check (population PK analysis) 
IntiQuan 
Figure A1.3 
Observed/predicted serum MEDI7352 concentration-time profiles (by participant) 
(population PK analysis) 
IntiQuan 
Figure A1.4 
Observed serum MEDI7352 concentration-time profiles by ADA status (by 
treatment) 
IntiQuan 
Figure A1.5 
Population mean (95% CI) serum MEDI7352 concentration-time profiles by 
treatment 
IntiQuan 
Figure A1.6 
Population mean (95% CI) serum MEDI7352 concentration-time profiles by 
ADA status and by treatment 
IntiQuan 
Figure A1.7 
Model goodness of fit plots (population PKPD analysis) 
IntiQuan 
Figure A1.8 
Visual predictive check (population PKPD analysis) 
IntiQuan 
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Table 2 
Planned Figures 
 
Number 
Description 
 
Figure A1.9 
Observed/predicted serum total NGF concentration-time profiles (by participant) 
(population PKPD analysis) 
IntiQuan 
Figure 
A1.10 
Predicted serum free NGF concentration-time profiles (by participant) 
(population PKPD analysis) 
IntiQuan 
Figure 
A1.11 
Observed serum total NGF concentration-time profiles by ADA status (by 
treatment) 
IntiQuan 
Figure 
A1.12 
Predicted serum free NGF concentration-time profiles by ADA status (by 
treatment) 
IntiQuan 
Figure 
A1.13 
Predicted median % change from baseline serum free NGF concentration-time 
profiles by treatment 
IntiQuan 
Figure 
A1.14 
Predicted median % change from baseline serum free NGF concentration-time 
profiles by ADA status and by treatment 
IntiQuan 
Figure 
A1.15 
Predicted median % change from baseline serum free NGF concentration-time 
profiles following intravenous administration of MEDI7352 and tanezumab 2.5 
and 5 mg SC 
IntiQuan 
Figure 
A1.16 
Individual observed serum MEDI7352 concentration, ADA titre and serum total 
NGF concentration profiles over time, observed daily as well as weekly averaged 
NRS pain scores as well as predicted serum free NGF concentration -time profiles 
(6 plots per participant) 
IntiQuan 
 
 
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10 
OUTPUT SHELLS EXAMPLES 
 
The format of selected tables and figures created by Premier is described in separate 
documents 
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   Statistical Analysis Plan 
Sponsor 
AstraZeneca 
Protocol Title: 
A Randomised, Double-Blind, Placebo-Controlled, Dose-
Response Study of the Efficacy and Safety of MEDI7352 in 
Subjects with Painful Diabetic Neuropathy 
Development Phase 
2 
Protocol Number: 
D5680C00002 
Premier Research PCN: 
MEDU177093 
Document Version: 
Final Version 1.0 
Document Date:  
12-Jul-2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Approvals 
Role 
Signatures 
Biostatistician 
Print Name: 
 
Biostatistician, Premier Research 
 
 
 
Sign Name: 
 
 
 
 
 
Peer Reviewer 
Print Name: 
 
 Biostatistics, Premier Research 
 
 
 
Sign Name: 
 
 
 
 
 
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Role 
Signatures 
AstraZeneca 
Biostatistician 
Print Name:
 
Statistical Consultant to AstraZeneca 
Sign Name: 
 
 
 
 
 
AstraZeneca 
Representative 
Print Name: 
 
 
AstraZeneca Neuroscience 
Sign Name: 
 
 
 
 
 
 
 
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Document History 
Version 
Date 
Author 
Description 
0.1 
27-Mar-2019 
 
Draft Version 
0.2 
16-Apr-2021 
 
Draft Version 
0.3 
25-Jun-2021 
 
Draft Version 
0.4 
24-Mar-2023 
 
Draft Version 
0.5 
21-Apr-2023 
 
Draft Version 
0.6 
24-May-2023 
 
Draft Version 
0.7 
20-Jun-2023 
 
Draft Version 
 
 
 
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Table of Contents 
Approvals................................................................................................................................ 2 
Document History ................................................................................................................... 4 
Table of Contents .................................................................................................................... 5 
List of Tables .......................................................................................................................... 7 
List of Figures ......................................................................................................................... 7 
List of Abbreviations ............................................................................................................... 8 
1. 
Overview ................................................................................................................... 12 
2. 
Study Objectives and Endpoints.................................................................................. 12 
2.1. 
Study Objectives .................................................................................................. 12 
2.1.1. Primary Objective................................................................................................. 12 
2.1.2. Secondary Objectives ........................................................................................... 12 
2.1.3. Exploratory Objectives ......................................................................................... 13 
2.2. 
Study Endpoints ................................................................................................... 13 
2.2.1. Efficacy Endpoints ............................................................................................... 13 
2.2.2. Safety Endpoints .................................................................................................. 14 
2.2.3. Pharmacokinetic/Pharmacodynamic Variable(s) .................................................... 14 
2.2.4. Other Endpoints ................................................................................................... 15 
3. 
Overall Study Design and Plan ................................................................................... 15 
3.1. 
Overall Design ..................................................................................................... 15 
3.2. 
Sample Size and Power......................................................................................... 15 
3.3. 
Study Population .................................................................................................. 16 
3.4. 
Treatments Administered ...................................................................................... 17 
3.5. 
Method of Assigning Subjects to Treatment Groups .............................................. 17 
3.6. 
Blinding and Unblinding....................................................................................... 17 
3.7. 
Schedule of Events ............................................................................................... 18 
4. 
Statistical Analysis and Reporting............................................................................... 18 
4.1. 
Introduction.......................................................................................................... 18 
4.2. 
Interim Analysis and Data Monitoring................................................................... 19 
5. 
Analysis Populations .................................................................................................. 19 
6. 
General Issues for Statistical Analysis ......................................................................... 20 
6.1. 
Statistical Definitions and Algorithms ................................................................... 20 
6.1.1. Baseline ............................................................................................................... 20 
6.1.2. Adjustments for Covariates ................................................................................... 20 
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6.1.3. Multiple Comparisons .......................................................................................... 20 
6.1.4. Handling of Dropouts or Missing Data .................................................................. 21 
6.1.5. Analysis Visit Windows ....................................................................................... 21 
6.1.6. Pooling of Sites .................................................................................................... 22 
6.1.7. Efficacy Variables ................................................................................................ 22 
6.1.8. Derived Variables................................................................................................. 23 
6.1.9. Data Adjustments/Handling/Conventions .............................................................. 25 
7. 
Study Patients/Subjects and Demographics ................................................................. 26 
7.1. 
Disposition of Patients/Subjects and Withdrawals .................................................. 26 
7.2. 
Protocol Deviations .............................................................................................. 27 
7.3. 
Demographics and Other Baseline Characteristics ................................................. 27 
7.4. 
Exposure .............................................................................................................. 28 
8. 
Efficacy Analysis ....................................................................................................... 28 
8.1. 
Primary Efficacy Analysis .................................................................................... 28 
8.1.1. Sensitivity Analyses of the Primary Efficacy Endpoint .......................................... 30 
8.2. 
Secondary Efficacy Analysis................................................................................. 30 
8.3. 
Exploratory Efficacy Analysis............................................................................... 31 
9. 
Safety and Tolerability Analysis ................................................................................. 31 
9.1. 
Adverse Events .................................................................................................... 33 
9.1.1. Adverse Events Leading to Discontinuation of IP .................................................. 33 
9.1.2. Deaths and Serious Adverse Events....................................................................... 34 
9.1.3. Drug-Induced Liver Injury .................................................................................... 34 
9.1.4. Infection Risk ....................................................................................................... 34 
9.2. 
COVID-19 Vaccination and Screening .................................................................. 34 
9.3. 
Clinical Laboratory Evaluations ............................................................................ 34 
9.4. 
Vital Signs ........................................................................................................... 35 
9.5. 
Electrocardiograms ............................................................................................... 35 
9.6. 
Physical and Neurological Examination ................................................................ 36 
9.7. 
Total Neuropathy Score-Nurse .............................................................................. 36 
9.8. 
Motor and Sensory Nerve Conduction Studies ....................................................... 36 
9.9. 
Strength and Deep Tendon Reflexes ...................................................................... 36 
9.10. Hypersensitivity/Anaphylactic Reactions, Injection Site or Infusion Reactions ....... 36 
9.11. Prior and Concomitant Medication and Procedures ................................................ 37 
10. 
Changes from Planned Analysis.................................................................................. 38 
11. 
Other Planned Analysis .............................................................................................. 38 
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11.1. Biomarkers........................................................................................................... 38 
11.2. Immunogenicity ................................................................................................... 39 
11.3. Pharmacokinetic Analysis ..................................................................................... 39 
12. 
References ................................................................................................................. 40 
13. 
Tables, Listings, and Figures ...................................................................................... 41 
13.1. Demographic Data................................................................................................ 41 
13.2. Efficacy Data ....................................................................................................... 42 
13.3. Safety Data........................................................................................................... 43 
13.4. Pharmacokinetic/Pharmacodynamic Data .............................................................. 46 
13.5. Planned Listing Descriptions................................................................................. 46 
13.6. Planned Figure Descriptions ................................................................................. 48 
14. 
Tables, Listing and Figure Shells ................................................................................ 50 
14.1. Standard Layout for all Tables, Listings, and Figures ............................................. 50 
15. 
Appendix: Calculation of Dose to achieve target effects .............................................. 52 
 
List of Tables 
Table 1: Demographic Data Summary Tables and Figures ...................................................... 41 
Table 2: Efficacy Data ........................................................................................................... 42 
Table 3: Safety Data .............................................................................................................. 43 
Table 4: Pharmacokinetic/Pharmacodynamic Data.................................................................. 46 
Table 5: Planned Listings....................................................................................................... 46 
Table 6: Planned Figures........................................................................................................ 49 
 
List of Figures 
Figure 1: Standardized Layout ............................................................................................... 51 
 
 
 
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List of Abbreviations 
Abbreviation 
Definition 
ADA 
Anti-Drug Antibody 
AE 
Adverse Event 
AIC 
Akaike Information Criterion 
ALT 
Alanine Aminotransferase 
ANCOVA 
Analysis of Covariance 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
BOCF 
Baseline Observation Carried Forward 
CI 
Confidence Interval 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
Coronavirus Disease 2019 
CSR 
Clinical Study Report 
DSIS 
Daily Sleep Interference Scale 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
ED50, ED90 
The Dose to achieve 50%, 90% of the Maximum Effect. 
EMA 
European Medicines Agency 
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Abbreviation 
Definition 
Emax 
The Model-Based Maximum Treatment Effect Versus Placebo 
ePRO 
Electronic Patient-Reported Outcome System 
FDA 
Food and Drug Administration 
gCV% 
Geometric Coefficient of Variation 
GEE 
Generalized Estimating Equation 
gmean 
Geometric Mean 
gSD 
Geometric Standard Deviation 
HL 
Hy’s Law 
HR 
Heart Rate 
ICH 
International Council for Harmonization  
IP 
Investigational Product 
IV 
Intravenous 
IWRS 
Interactive Web Response System 
LLOQ 
Lower Limit of Quantification 
LOCF 
Last Observation Carried Forward 
LS 
Least Squares 
MCP-mod 
Multiple Comparison Procedure Modelling 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
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Abbreviation 
Definition 
MMRM 
Mixed Effects Models Repeated Measures 
NC 
Not Calculable 
NCA 
Noncompartmental Analysis 
NPS 
Neuropathic Pain Scale 
NQ 
Not Quantifiable 
NRS 
Numeric Rating Scale 
PD 
Pharmacodynamics 
PDN 
Painful Diabetic Neuropathy 
PGIC 
Patient Global Impression of Change 
PHT 
Potential Hy’s Law 
PK 
Pharmacokinetic 
PT 
Preferred Term 
QTcF 
QT Fridericia’s Correction 
RPOA 
Rapidly Progressive Osteoarthritis 
SAE 
Serious Adverse Event 
SAF 
Safety 
SAP 
Statistical Analysis Plan 
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Abbreviation 
Definition 
SAS®  
a Software System Used for Data Analysis 
SDTM 
Study Data Tabulation Model 
SF-36 
36-Item Short Form Health Survey 
SiAP 
Statistical Interim Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TBL 
Total Bilirubin 
TEAE 
Treatment-Emergent Adverse Event 
tNGF 
Total Nerve Growth Factor 
TNSn 
Total Neuropathy Score-Nurse 
ULN 
Upper Limit of Normal 
ULOQ 
Upper Limit of Quantification 
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1. 
Overview 
This statistical analysis plan (SAP) describes the planned analysis and reporting for AstraZeneca 
protocol number D5680C00002 (A Randomised, Double-Blind, Placebo-Controlled, Dose-
Response Study of the Efficacy and Safety of MEDI7352 in Subjects with Painful Diabetic 
Neuropathy), dated 13-Apr-2022 version 7.0. Reference materials for this statistical plan include 
the protocol and the accompanying sample data collection documents. Operational aspects 
related to collection and timing of planned clinical assessments are not repeated in this SAP 
unless relevant to the planned analysis. 
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA), 
and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical 
Trials (ICH, 1998). All work planned and reported for this SAP will follow internationally 
accepted guidelines, published by the American Statistical Association (ASA, 2018) and the 
Royal Statistical Society (RSS, 2014), for ethical statistical practice. 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. 
 
 
 
The statistical plan described hereafter has been developed by blinded study team members prior 
to the Interim Analysis but after the Administrative Analysis has been conducted. It will be 
approved before final unblind, performing inferential or descriptive analysis of hard-locked data 
from AstraZeneca’s study D5680C00002. 
2. 
Study Objectives and Endpoints 
2.1. 
Study Objectives 
2.1.1. Primary Objective 
The primary objective is to assess the efficacy of MEDI7352 versus placebo on chronic pain in 
subjects with painful diabetic neuropathy (PDN) currently taking standard of care medication for 
their PDN pain. 
2.1.2. Secondary Objectives 
The secondary objectives are: 
• To assess the safety and tolerability of MEDI7352 in subjects with PDN 
• To assess the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of 
MEDI7352 in subjects with PDN  
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• To characterise the dose-response relationship of MEDI7352 on chronic pain in subjects 
with PDN 
2.1.3. Exploratory Objectives 
2.2. 
Study Endpoints 
2.2.1. Efficacy Endpoints 
2.2.1.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint of this study is the change in the weekly average of the average 
daily pain scores from the baseline week to Week 12 of MEDI7352 compared to placebo, as 
measured on an 11-point (0-10) numeric rating scale (NRS). 
The target population is the entire patient population, i.e., the collection of all patients eligible to 
be included in the randomized clinical trial based on prespecified (and duly justified) 
inclusion/exclusion criteria.  
The study was not designed using the Estimand framework. However, the following general 
aspects of an Estimand can be inferred: the Estimand can be generically defined as the true 
between‐treatment difference in the target population endpoint means for the change from 
baseline for the Pain NRS at Week 12, while-on-treatment and regardless of prohibited or rescue 
medication use. 
 
2.2.1.2. 
Secondary Efficacy Endpoint(s) 
The secondary efficacy endpoints of this study include the following:  
• Change in the weekly average of the average daily pain score, as measured on an 11-
point (0-10) NRS, from baseline to Weeks 2, 4, 6, 8, and 10 of treatment and the week 
before the follow-up visit.  
• Percentage of subjects who have achieved ≥30% and ≥50% reductions in the weekly 
average of the average daily pain score from baseline during Weeks 4, 8, and 12 of 
treatment and the week before follow-up. 
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• Change in Galer Neuropathic Pain Scale (NPS) from baseline to Days 28, 56, and 84 of 
treatment and the follow-up visit. 
• Change in Daily Sleep Interference Scale (DSIS) from baseline to Days 28, 56, and 84 of 
treatment and the follow-up visit. 
• Proportion of subjects who have ‘improved’, ‘much improved,’ or ‘very much improved’ 
relative to baseline on the Patient Global Impression of Change (PGIC) on Days 28, 56, 
and 84 of treatment and the follow-up visit. 
• Change in the 36-item Short-Form Health Survey (SF-36) from baseline to Day 84 of 
treatment. 
• Usage of rescue medication (yes/no) from baseline to Week 12 of treatment. 
2.2.1.3. 
Exploratory Efficacy Endpoint(s) 
2.2.2. Safety Endpoints 
The safety endpoints of this study include the following: 
• Adverse events (AEs) and serious adverse events (SAEs) 
• Physical and neurological examinations 
• Neuropathy assessments Total Neuropathy Score-Nurse (TNSn) S 
• Strength (dorsiflexion), and deep tendon reflex (knee and ankle) assessments 
• Vital signs 
• 12 lead digital electrocardiogram (ECGs) 
• Clinical laboratory testing (hematology, chemistry, coagulation, and immunology) 
• Motor and sensory nerve conduction studies 
• Concomitant medications and therapies 
• Injection site reactions and infusion reactions 
2.2.3. Pharmacokinetic/Pharmacodynamic Variable(s) 
The pharmacokinetic (PK) endpoints of the study include the MEDI7352 concentrations 
measurements in serum/plasma.  
The pharmacodynamic (PD) endpoints of the study include total nerve growth factor (tNGF) 
measurements in serum/plasma. 
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2.2.4. Other Endpoints 
The following endpoints will be assessed:  
• Change in the weekly average of the average daily pain scores from the baseline week to 
Week 12, as measured on an 11-point (0-10) NRS, versus dose. 
• 
Immunogenicity (ADA) assessments. 
3. 
Overall Study Design and Plan 
This is a randomised, double-blind, placebo-controlled study of MEDI7352 in subjects with 
moderate to severe chronic PDN persistent for 6 months or longer, not adequately controlled by 
standard of care treatments, caused by type 1 or type 2 diabetes mellitus. The study incorporates 
a screening period of up to 45 days and a 12-week double-blind treatment period during which 
MEDI7352 or placebo will be administered intravenously (IV) on 6 occasions, with each dose 
separated by 14 days. There will be a 6-week follow-up period.  
3.1. 
Overall Design 
3.2. 
Sample Size and Power 
There will be 4 stages in the study: in the first stage, subjects will be randomly assigned to 
placebo or the lowest dose (
) until at least 10 subjects have been recruited. In the second 
stage, up to 30 subjects will be randomly assigned to a placebo or
 of MEDI7352; prior 
to commencing the third stage, the safety and tolerability experience following administration of 
multiple doses of 
 in the Phase 1 study of MEDI7352 will be evaluated. In stage 3 of 
the study, approximately 67 subjects will be randomly assigned to placebo or
 of 
MEDI7352. The third stage will include an interim analysis to enable decision making for stage 
4 with respect to the sample size and dose allocation ratio. If no changes are made following the 
interim analysis, in stage 4 of the study, approximately 165 eligible subjects will be randomly 
assigned to treatment across 3 dose levels of MEDI7352 (
) or placebo, to 
ensure that approximately 236 subjects are evaluable for the efficacy analysis of stages 2 to 4 
combined. The number of subjects in the fourth stage is currently planned to follow an equal 
treatment allocation to each of the 4 treatment groups. However, the exact number of subjects 
and the allocation to each dose in stage 4 will be determined after the interim analysis. 
There is no formal sample size calculation for stage 1; 10 subjects in stage 1 are considered 
sufficient for the initial assessment of safety. The sample size for stages 2-4 combined was 
determined by a formal power calculation (see below) and the size of stage 3 was defined to 
enable decision making for the stage 4 sample size and dose allocation ratio. 
This study is powered at greater than 80% to detect a statistically significant (1-sided alpha = 
0.025) dose-response relationship when the true Week 12 placebo-corrected change from 
baseline difference at the 
 dose is 1.25 on the 11-point NRS scale (MEDI7352-placebo 
treatment) and the true dose-response follows a hyperbolic Emax relationship, with ED50 within 
the range 
. This calculation also assumes: 
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• The true standard deviation (SD) is 2.4, which is based on other studies undertaken with 
pregabalin in PDN (Satoh et al. 2011, Lesser et al. 2004, Rosenstock et al. 2004, Tӧlle et 
al. 2008). 
• The data from stages 2, 3, and 4 are combined so that the number of subjects for the dose-
response analysis is 236 with the total number evaluable for placebo, 
 
 doses equal to 81, 37, 51, and 67, respectively. This is comprised of, assuming an 
overall 10% non-evaluability rate: 
o 28 out of 30 randomised in stage 2; 14 per arm  
o 60 out of 67 randomised in stage 3; 30 per arm, and  
o 148 out of 165 randomised in stage 4; 37 per arm 
• The dose-response hypothesis test is multiplicity adjusted as described by Pinheiro et al. 
2006 in order to control the type 1-error. 
The above calculations were performed using the software R and the R-package ‘DoseFinding’ 
[https://cran.r-project.org/web/packages/DoseFinding/DoseFinding.pdf] with the following 
parameters: 
• Population SD (of change from baseline to week 12) = 2.4  
• Placebo effect = 1 point reduction in NRS and 
 effect = 2.25 reduction from 
baseline, ie, delta= 1.25 
• Linear contrasts were determined from 5 ‘candidate dose’ response models which are all 
Emax models with decreasing potency/increasing ED50: 7.5, 15, 30, 60, 750 μg/kg. The 
5th case is essentially linear in dose. Emax models were chosen following the 
recommendations in a recent meta-analysis of dose response studies by Thomas et al., 
2014. 
• Power was assessed across 16 alternative true dose response curves, 12 Emax with ED50 
ranging from 0.375 to 750 μg/kg, 3 logistic and 1 quadratic, all having a Week 12 
placebo-corrected change from baseline difference at the 
 dose of 1.25. 
The overall withdrawal rate is anticipated to be approximately 10%. However, since the primary 
analysis will use Last Observation Carried Forward (LOCF) for withdrawn subjects, and the SD 
estimate is taken from studies which also used the LOCF approach, the only additional subjects 
recruited will be to account for withdrawals in stages 2, 3, and 4 if withdrawal occurs at, or prior 
to, the Week 2 visit. 
The number of subjects who will agree to participate in the genetic research is unknown. It is 
therefore not possible to establish whether sufficient data will be collected to allow a formal 
statistical evaluation or whether only descriptive statistics will be generated. 
3.3. 
Study Population 
Male or female (postmenopausal or surgically sterile) subjects aged ≥18 to ≤80 years with 
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chronic PDN persistent for 6 months or longer, not adequately controlled by standard of care 
treatments . 
3.4. 
Treatments Administered 
Once randomized, subjects will be dosed with either MEDI7352 or placebo on Day 1, Day 14, 
Day 28, Day 42, Day 56, and Day 70. MEDI7352 or placebo will be administered IV over a 
60-minute period. To maintain the blind, a placebo volume equivalent to the MEDI7352 volume 
will be administered for each dosing. 
3.5. 
Method of Assigning Subjects to Treatment Groups 
The randomisation schedule will be computer generated using a permuted block algorithm 
appropriate to the treatment groups included in each stage and will randomly allocate 
investigational product (IP) to randomisation numbers. The randomisation numbers will be 
assigned sequentially through a central interactive web response system (IWRS) as subjects are 
entered into the study. The randomisation schedule will not be stratified, and study centre will 
not be a blocking factor in the randomisation schedule. 
The randomisation schedule has been prepared by Premier Research before the start of the study. 
No one involved in the study performance will have access to the randomisation schedule before 
official unblinding of treatment assignment. No subject will be randomised into this study more 
than once. 
3.6. 
Blinding and Unblinding 
All subjects, investigators, and study personnel involved in the conduct of the study, including 
data management, will be blinded to treatment assignment with the exception of a specified 
unblinded statistician and programmer from Premier Research who will have access to the 
randomization code, unblinded site monitors and clinical manager from Premier Research, and 
the unblinded pharmacist at each study site. The unblinded study personnel will not participate in 
study procedures or data analysis prior to unblinding of the study data to all study related 
personnel. Unblinded personnel who are not otherwise involved in the study will prepare data for 
review and interim analysis. 
Study personnel will make every effort to safeguard the integrity of the study blind to minimize 
bias in the conduct of the study. Treatment unblinding is discouraged if knowledge of the 
treatment assignment will not materially change the planned management of a medical 
emergency. Unblinding will be permitted in a medical emergency that requires immediate 
knowledge of the subject’s treatment assignment. 
Unblinding should be discussed in advance with the medical monitor if possible. For emergency 
unblinding, study personnel will use the IWRS. Only authorized users will have access to the 
unblinding function in the IWRS, and the IWRS will reveal the treatment information for the 
selected subject only. If the investigator is not able to discuss treatment unblinding in advance, 
then he/she must notify the medical monitor as soon as possible about the unblinding incident 
without revealing the subject’s treatment assignment. The IWRS will also send a blinded 
notification to the clinical team alerting them that a break blind occurred. 
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The investigator or designee must record the date and reason for treatment unblinding on the 
appropriate electronic case report form (eCRF) for that subject. In all cases that are not 
emergencies, the investigator must discuss the event with the medical monitor prior to 
unblinding the subject’s treatment assignment. 
If treatment assignment is unblinded for an individual subject, study personnel will be notified of 
that subject’s treatment assignment without unblinding the treatment assignments for the 
remaining subjects in the study. Thus, the overall study blind will not be compromised. If a 
subject’s treatment assignment is unblinded, he/she will be asked to withdraw from the study. 
The investigator will make this decision after consultation with the medical monitor. 
Overall unblinding will take place at the end of the study only after database lock has been 
achieved. 
3.7. 
Schedule of Events 
Please see the protocol Tables 2-1, 2-2 for a detailed schedule of events. 
4. 
Statistical Analysis and Reporting 
All efficacy and safety statistical analysis will be based on data from stages 1, 2, 3 and 4 
combined, unless specified otherwise. 
4.1. 
Introduction 
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations will primarily use SAS (release 9.4 or higher). The multiple 
comparison and modelling (MCP-Mod) analysis will be performed using R (release 4.2.1 or 
higher) and the DoseFinding package (version 1.0-3 or higher). If a use of other software is 
warranted, the final statistical methodology report will detail what software was used for what 
purposes. 
Continuous (quantitative) variable summaries will include the number of subjects (n) with 
non-missing values, the number of missing values, arithmetic mean, SD, median, 1st, and 3rd 
quartiles (where applicable), minimum, and maximum.  
Categorical (qualitative) variable summaries will include the frequency and percentage of 
subjects who are in the particular category or each possible value. In general, the denominator 
for the percentage calculation will be based upon the total number of subjects in the study 
population for the treatment group, unless otherwise specified. The denominator for by-visit 
displays will be the number of subjects in the relevant study population with non-missing data at 
each visit, unless otherwise specified.  
The minimum and maximum will be reported with the same degree of precision (i.e., the same 
number of decimal places) as the observed data. Measures of location (mean and median) will be 
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reported to 1 degree of precision more than the observed data and measures of spread will be 
reported to 2 degrees of precision more than the observed data. 
Percentages will be presented to 1 decimal place, unless otherwise specified. 
Unless otherwise indicated, all statistical tests will be conducted at the 0.025 significance level 
using 1-tailed tests, and P values will be reported. For estimation purposes, 2-sided 95% 
confidence intervals (CI) will be presented. 
Total NGF and PK concentration data will be summarized by dose as per the quantitative 
variables and presenting the number (n) of non-missing observations, and the n < lower limit of 
quantification (LLOQ). PD and PK parameters will be summarized by dose and will include the 
arithmetic mean, SD, geometric mean (gmean), gmean ± geometric SD, geometric coefficient of 
variation (gCV%), median, minimum and maximum. 
4.2. 
Interim Analysis and Data Monitoring 
Details of the interim analysis have been included in the Statistical Interim Analysis Plan (SiAP) 
version 1.0 dated 10-Feb-2023. 
5. 
Analysis Populations 
The following analysis populations are planned for this study:  
• Screening Population (Screened): All subjects who provide informed consent and/or 
assent and provide demographic and/or baseline screening assessments, regardless of the 
subject’s randomisation and treatment status in the study. The Screening Set will be 
analysed as randomised, according to planned treatment. 
• Safety Population (SAF): The Safety Population includes all subjects who receive at 
least 1 dose of double-blind study medication. The Safety Set will be analysed according 
to actual treatment. 
• Modified Intent-To-Treat Population (mITT): The modified intent-to-treat population 
will be used for all efficacy analyses and will include all randomised subjects who 
receive at least 1 dose of double-blind study medication and have at least 1 daily NRS 
assessment while receiving double-blind treatment. The mITT Set will be analysed as 
randomised, according to planned treatment. 
• Pharmacokinetic Population (PK): The PK Population will include all subjects for who 
a PK sample was obtained and analysed. The PK Set will be analysed according to actual 
treatment. 
Assignment of subjects to populations will be confirmed at a blinded data review meeting to be 
held before the study database is locked. 
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If a subject is randomised incorrectly or is administered the incorrect IP, analyses of the mITT 
population will be based on the IWRS-assigned treatment whereas all other analyses will be 
based on the actual treatment. 
6. 
General Issues for Statistical Analysis 
6.1. 
Statistical Definitions and Algorithms 
6.1.1. Baseline 
For all safety endpoints, the last observation recorded prior to the first dose of treatment will be 
used as the baseline observation for calculations of change from baseline.  
For pain diary data the baseline period is defined as the seven-day period prior to randomization, 
i.e., Day -7 to Day -1, inclusive. A subject is considered to have an evaluable baseline pain score 
if there are at least 4 days of recorded diary pain scores in the 7-day period.  
6.1.2. Adjustments for Covariates 
In addition to treatment group, the baseline value of the variable undergoing analysis and the 
co-medication type (Anticonvulsant versus Antidepressant) will be included in the analysis of 
covariance (ANCOVA) model as additive covariates. Co-medication type will be determined by 
blinded clinical review of each subject’s medication record at baseline. 
Covariates in the mixed effects models repeated measures (MMRM) and generalized estimating 
equations (GEE) analyses include those specified for the ANCOVA analyses, together with time 
and its interaction with dose group.  
The crossing of co-medication type and median baseline pain score will be used as strata in the 
Cochran-Mantel-Haenszel (CMH) model tests. Assuming two co-medication types, the strata 
will be: 
1) Anticonvulsant (Baseline NRS < Median), 
2) Anticonvulsant (Baseline NRS > Median), 
3) Antidepressant (Baseline NRS < Median), 
 
4) Antidepressant (Baseline NRS > Median).  
Where the median baseline NRS is calculated over all subjects. 
6.1.3. Multiple Comparisons 
A multiple comparison procedure modelling approach (MCP-Mod) on LOCF data will be used 
for primary efficacy endpoints.  
No adjustments will be made for multiple comparisons outside the MCP-Mod approach.  
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6.1.4. Handling of Dropouts or Missing Data 
For the analyses of the primary efficacy endpoints based on the mITT Population, a variety of 
methods will be used to deal with missing data, including:  
• Primary Method: LOCF. 
• Observed cases analysis. 
• Baseline observation carried forward (BOCF) 
Subjects with missing weekly average NRS baseline data (i.e., zero or 1-3 days of diary pain 
scores) will not be included in the efficacy analysis because the primary analysis is change-from-
baseline. If a subject has zero or <3 days of diary pain data in each of the possible post-baseline 
seven day periods ending within the protocol definition of week 12 (day 84 + 3),  then an 
imputed ‘week 12 LOCF’ weekly average NRS pain score will be calculated from the latest 7 
‘non-missing’ entries of the subject’s diary closest to their nominal week 12 visit (i.e., the latest 
7 day period containing at least 4 NRS values), provided that this would qualify as at least ‘week 
2’ according to the windowing outlined in Section 6.1.5.  Otherwise, the week 12 LOCF weekly 
average NRS pain score will be set to missing.   
6.1.5. Analysis Visit Windows 
Statistical analyses will be based on scheduled visits and windows as per Protocol Table 2-1: 
Schedule of Events. If an assessment falls between 2 windows, then the closest visit will be used 
only if an assessment result is not provided within that window. All other visits will be listed only 
as unscheduled visits. For presentation purposes these will be mapped to the visit prior and labeled, 
e.g., Unscheduled Visit 3.1, if Visit 3 was the closest date prior. 
For pain diary data the following analysis periods will be defined:  
• Week Xi: the 7-day period ending within the protocol window Day Yi ± 3 where at least 4 
days out of 7 have recorded diary pain scores. Where several such windows exist the one 
ending closest to day Yi will be selected. If there are two such windows that are equidistant 
from day Yi, then the one with the largest number of diary entries will take precedence. If 
they have the same number of entries, then the later of the two end dates will be chosen. If 
no such window exists, then week Xi will be considered missing for the purposes of weekly 
average scoring.  
Where: 
• X1=2, Y1=14 
• X2=4, Y2=28 
• X3=6, Y3=42 
• X4=8, Y4=56 
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• X5=10, Y5=70 
• X6=12, Y6=84 
• The week before follow-up is defined as the 7-day period prior to the last day of pain diary 
data for subjects completing the study (i.e., entering in the Week 18) where at least 4 days 
out of 7 have recorded diary pain scores.  
6.1.6. Pooling of Sites 
Analysis by investigative site will not be conducted. 
6.1.7. Efficacy Variables 
6.1.7.1. 
Pain Numerical Rating Scale 
Subjects will assess their perceived average neuropathic pain over the previous 24 hours using an 
11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. 
Subjects will be instructed to assess their average daily pain at approximately the same time 
every morning, and to record their response in a subject diary (ePRO). 
6.1.7.2. 
  Neuropathic Pain Scale 
Subjects will assess their neuropathic pain using the Galer NPS. The NPS includes 2 descriptors 
of pain, including intensity and unpleasantness, and 8 descriptors that assess specific qualities of 
neuropathic pain: sharp, hot, dull, cold, sensitive, itchy, deep, and surface pain. Each of these 10 
dimensions has a 0 to 10 NRS in which 0 is equal to no pain and 10 equals the most intense pain. 
There is an additional descriptor about duration and frequency of pain, which has a 1 to 3 NRS. 
In which 1 = I feel a background pain all the time and occasional flare-ups (breakthrough pain) 
some of the time, 2 = I feel a single type of pain all the time, and 3 = I feel a single type of pain 
only sometimes. Other times, I am pain free. 
6.1.7.3. 
Daily Sleep Interference Scale 
Subjects will assess how their neuropathic pain interferes with their sleep using the DSIS. The 
DSIS is an 11-point Likert scale, with 0 indicating that pain did not interfere with sleep and 10 
indicating that pain completely interfered with sleep. The DSIS is completed by subjects once a 
day (upon awakening) to accurately capture variability in sleep interference due to pain on a 
daily basis, thus minimizing recall bias. 
6.1.7.4. 
Patient Global Impression of Change 
Subjects will rate their overall improvement in health status using the PGIC. The PGIC consists 
of a 7-point scale where 1 = “very much improved” and 7 = “very much worse.” Subjects will be 
asked the following question: “How would you rate your overall improvement with treatment 
during the clinical study?” The response options include the following:  
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• Very Much Improved - 1 
• Much Improved - 2 
• Minimally Improved - 3 
• No Change - 4 
• Minimally Worse - 5 
• Much Worse - 6 
• Very Much Worse - 7 
6.1.7.5. 
Short-Form Health Survey 
The subject’s health status and quality of life will be assessed using the SF-36. The SF-36 
assesses 8 health concepts: 1) limitations in physical activities because of health problems; 2) 
limitations in social activities because of physical or emotional problems; 3) limitations in usual 
role activities because of physical health problems; 4) bodily pain; 5) general mental health 
(psychological distress and well-being); 6) limitations in usual role activities because of 
emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The 
items use Likert-type scales with either 5 or 6 points, or 2 or 3 points. Scores will be derived by 
the validated built-in scoring tool. Higher SF-36 scores indicate a better state of health. 
6.1.7.6. 
Rescue Medication Use 
Subjects will record all rescue medications they take for neuropathic pain in a paper diary. This 
will be transcribed in to the eCRF collecting usage, date and time of rescue medication, 
medication administered, dose, frequency and route.  
Subjects will be grouped by the following for rescue medication use: 
• 
Compliant with protocol guidance on permitted therapies 
• 
Non-compliant with protocol guidance on permitted therapies 
A review of medications will be conducted at a blinded data review meeting to be held before the 
study database is locked. 
6.1.7.7. 
 
6.1.8. Derived Variables 
• Change from baseline = value at current time point – value at baseline.  
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• Reference End Date = Date of completion/discontinuation. 
• Study duration = Reference end date – date of first dose of treatment + 1 
• Duration of exposure (days) = min(date of last dose of treatment + 14 days or date of death) 
– date of first dose of treatment + 1. 
• Treatment-emergent AEs (TEAEs) are defined as: 
o AEs with onset at the time of or following the start of treatment with IP and not 
more than 30 days after the last administration of IP, or 
o AEs starting prior to the start of treatment but increasing in severity or relationship 
at the time of, or following, the start of treatment with IP and not more than 30 days 
after the last administration of IP. 
• Average Baseline Pain NRS = the arithmetic average of the ‘non-missing’ daily pain scores 
within the baseline period defined in Section 6.1.1. For example, if a subject has 5 days of 
non-missing pain scores their average will be calculated over 5 days, not the full 7-day 
baseline period. 
• Average Week X Pain NRS = the arithmetic average of the ‘non-missing’ daily pain scores 
within each subject’s specific week X period defined in Section 6.1.5. 
• Average Week 12 Pain NRS (LOCF) = the arithmetic average of the ‘non-missing’ daily 
pain scores within each subject’s specific week 12 period or according to the imputed 
LOCF/BOCF approach defined in Section 6.1.4. 
• Change from Baseline to Week X Pain NRS = for each subject ‘Average Week X Pain 
NRS’ minus ‘Average Baseline Pain NRS’. 
• Change from Baseline to Week 12 Pain NRS (LOCF/BOCF) = for each subject ‘Average 
Week 12 Pain NRS (LOCF)’ minus ‘Average Baseline Pain NRS’. 
• Galer NPS Total Score (ranges from 0 to 100): sum of Pain Intensity, Pain Unpleasantness, 
Pain Sharpness, Pain Hotness, Pain Dullness, Pain Coldness, Pain Sensitivity, Pain Itching, 
Deep Pain Intensity, and Surface Pain Intensity (All in an 11-point NRS). 
• Change from Baseline to Week X Galer NPS Total Score = for each subject ‘Galer NPS 
Total Score’ minus ‘Baseline Galer NPS Total Score’. 
• Total number of days rescue medication was used = End Date of Medication - Start Date 
of medication + 1. Each day on which rescue medication was used at least once is 
counted. 
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• Cumulative consumption (mg) of paracetamol rescue medication use = Total dose of 
rescue medication (mg) consumed during the days in which paracetamol was used. 
• Average daily dose (mg) of paracetamol rescue medication use = Cumulative 
consumption of paracetamol rescue medication (mg) /total number of days paracetamol 
rescue medication was used. 
6.1.9. Data Adjustments/Handling/Conventions 
All collected data will be presented in listings. Data not subject to analysis according to this plan 
will not appear in any tables or graphs but will be included only in the data listings. 
All P values will be displayed in four decimals and rounded using standard scientific notation (e.g., 
0.XXXX). If a P value less than 0.0001 occurs it will be shown in tables as <0.0001. 
AEs and medical histories will be coded using the latest version of the Medical Dictionary for 
Regulatory Activities (MedDRA) thesaurus available at time of programming. 
If partial dates of AEs occur, the convention for replacing missing dates for the purpose of TEAE 
is as follows: if just day is missing then the day assigned is the first day of the month or the date 
of first dose (if in the same month), whichever is later; if just month is missing then the month 
assigned is the month of the first dose, unless that results in a date prior to the first dose in which 
case the month after the first dose is used; and if both month and day are missing then the month 
assigned is the month of the first dose and the day assigned is either the first day of the month or 
the first dose date, whichever is later. 
If partial times occur, the convention is as follows: if the missing time occurs on the day of the 
first dose and both the hour and minute are missing then the time assigned is the time of the first 
dose, otherwise if both the hour and minute are missing and the date is not the date of first dose 
the time assigned is 12:00; if the date is the same as the date of the first dose and only hour is 
missing the hour assigned is 12 or the hour of first dose, whichever is later, and if the date is the 
same as the date of first dose and only the minute is missing the minute assigned is 30 or the 
minute of first dose, whichever is later. Otherwise the hour assigned is 12 if the hour is missing 
and the date is not the same as the date of first dose and the minute assigned is 30 is the the date 
is not the same as the date of first dose. 
These conventions will be applied only to AE onset dates and times with the following 
precaution:  if the missing date and time reflect the date and time of onset of an AE, the modified 
date and time will be constructed to match the first documented date/time post drug 
administration while preserving the order in which the AE was reported in the eCRF. 
In general, for quantitative laboratory values reported as ‘<X’ or ‘≤X’, the LLOQ will be used 
for analysis (i.e., the value of X will be used in the analysis for lab values reported as ‘<X’ or 
‘≤X’). Similarly, for quantitative laboratory values reported as ‘>X’ or ‘≥X’, the upper limit of 
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quantification (ULOQ) will be used for analysis (i.e., the value of X will be used in the analysis 
for lab values reported as ‘>X’ or ‘≥X’). 
For analysis purposes, repeat laboratory test results will not be used unless the original 
laboratory value is missing or indicated as invalid, in which case the first non-missing repeated 
laboratory value will be used for data analysis. 
ADA titre reported as <30 (below the minimum required dilution) is a negative result for the 
presence of ADA. 
For descriptive statistics of serum concentration summaries: 
• 
At a time-point where less than or equal to 50% of the values are not quantifiable (NQ, 
below LLOQ), all NQ values will be set to the LLOQ, and all descriptive statistics will be 
calculated accordingly. 
• 
If more than 50%, but not all, of the concentrations are NQ, the geometric mean, 
geometric mean ± geometric SD and gCV% will be reported as not calculable (NC). The 
maximum value is reported from the individual data, and the minimum and median are 
set as NQ. 
• 
If all concentrations are NQ at a time-point, the geometric mean, minimum, median and 
maximum are reported as NQ and the gCV% and geometric mean ± geometric SD as NC. 
7. 
Study Patients/Subjects and Demographics 
7.1. 
Disposition of Patients/Subjects and Withdrawals 
The total number of subjects for each of the following analysis populations will be presented for 
the Screening Population by randomized treatment group and overall: 
• Screening Population 
• Safety Population 
• mITT Population 
• Included in the mITT population 
▪ Evaluable Week 12 efficacy 
▪ Evaluable LOCF efficacy 
• Not efficacy evaluable 
• PK Population 
For the Screening Population, disposition will include tabulation of: 
• the number of screened subjects 
• the number of re-screened subjects 
• the number of enrolled subjects 
The output will be further presented by treatment group and overall summarising: 
• the number of randomized subjects 
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• the number of subjects who completed study treatment 
• the number of completed subjects 
• the number of subjects withdrawing (discontinued)  
• the reasons for discontinuation from study treatment and withdrawal from the 
study. 
For all categories of subjects by treatment group, percentages will be calculated using the 
number of subjects randomized as the denominator. 
7.2. 
Protocol Deviations 
Major protocol deviations, as determined by a Sponsor blinded review of the data prior to 
database lock and unblinding of the study will be reported in listings.  
The Sponsor or designee will be responsible for producing the final deviation file. This file will 
be finalized prior to database lock, and all information will be included in the SDTM.DV domain 
(deviations domain). 
All protocol deviations will be presented in a data listing, with a flag to indicate if a deviation 
was considered major.  
A summary table by treatment group and overall will be generated based on protocol deviation 
severity (minor/major) and the classification of protocol using the following categories:  
o Inclusion  
o Exclusion  
o Study drug  
o Assessment – safety  
o Assessment– efficacy  
o Lab/endpoint data  
o Visit window  
o Informed consent  
o Prohibited co-medication  
o Overdose/misuse 
o Other 
7.3. 
Demographics and Other Baseline Characteristics 
Descriptive summaries of the demographic and other baseline characteristics will be presented 
for all analysis populations. All demographic and baseline characteristics will be presented both 
overall and by treatment group. 
The following demographic and baseline data will be presented in tables: 
• Demographics: age, gender, ethnicity, race, height, weight, and body mass index (BMI)  
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• For female the number and percentage of women surgically sterile and postmenopausal 
will be described.  
• Diagnosis of osteoarthritis: number of subjects with osteoarthritis diagnosis and area 
affected, clinical significance, radiological investigations, radiological significance, 
Kellgren-Lawrence score. 
The number and percent of subjects reporting various medical histories, grouped by MedDRA 
system organ class (SOC) and preferred term (PT), will be tabulated by treatment group.  
This analysis will be conducted for the Safety Population. 
7.4. 
Exposure 
The following parameters of study drug exposure and compliance will be summarized by 
treatment group for the Safety Population: 
 
• Maximum number of doses administered 
• Total duration of exposure 
• Total (cumulative) dose infused 
In addition, any incomplete infusions will be listed. 
8. 
Efficacy Analysis 
All efficacy variables will be summarized descriptively including number of observations, 
number of missing values, mean, SD, minimum, median, and maximum for continuous variables, 
and frequency of observations in each category and percentage for categorical variables.  
Primary and secondary endpoint efficacy data will be tabulated according to the observed cases, 
LOCF, and BOCF approaches. 
8.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint of this study is the change in the weekly average of the average 
daily pain scores from the baseline week to Week 12 measured on an 11-point (0-10) NRS. 
MCP-Mod approach. The main statistical analysis of the primary efficacy endpoint will use the 
MCP-Mod approach on LOCF data, which is a well-established statistical methodology for 
establishing both the existence of a dose response and modelling the underlying dose-response 
relationship. The modelling step (‘MOD’ step) from the MCP-MOD approach will only be 
conducted if stage 4 is initiated, otherwise there would be insufficient dosing data to fit the non-
linear models. 
There are two steps to MCP-Mod: 
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1. The ‘MCP’ step is a rigorous method to establish presence of a dose response while 
protecting the type I error and, if the dose-response relationship is statistically significant, 
then  
2. The ‘MOD’ step estimates the dose response function and associated model parameters. 
The MCP test will use linear contrasts corresponding to the five candidate models described in 
Section 3.2. The test will use pre-specified model parameters and optimal contrasts for each will 
be generated. The hypotheses are as follows: 
 
Null hypothesis (H0): Optimal contrasts µ ≥0 for all models 
 
Alternative hypothesis (HA): Optimal contrasts µ <0 for at least one model 
where µ is the true event rate. 
The underlying model will be an ANCOVA with dependent variable ‘change from baseline to 
Week 12 (LOCF)’, and independent variables will include: 
• dose group as a factor variable with the placebo group as the reference level 
• baseline score, i.e., baseline weekly average pain (NRS), as a continuous variable 
• co-medication type. 
The random error is assumed to be normally and independently distributed with constant 
variance. The parameter estimates of the difference between each dose group and placebo, least 
square (LS) Means estimates of change from baseline to Week 12 for each dose, standard errors, 
95% unadjusted, ‘Lalonde-type’ asymmetric CI (i.e., lower limit of 1-sided 90% CI and upper 
limit of 1-sided 80% CI), and P values will be presented. 
If the MCP test is statistically significant, then the MOD step will select the most appropriate 
model from hyperbolic Emax, sigmoidal Emax or linear using the ‘Emaxlin’ approach as described by 
Kirby et al (2011). From this model (including the same covariates as the ANCOVA model), 
various estimates will be derived (together with CI) of parameters of interest such as ED50, 
effective dose to achieve 90% of maximum effect (ED90), dose to achieve selected target effects, 
and model estimates of the treatment effect at doses studied (see Appendix in Section 15). 
MMRM: In addition, changes from baseline in continuous endpoints will be compared between 
treatment groups using mixed models repeated measures including terms for: 
• co-medication type (as a factor) 
• treatment (as a factor) 
• time (as a factor) 
• the interaction between treatment and time point 
• and the baseline value of the variable undergoing analysis  
The mixed model for repeated measure will use average of average daily pain score of observed 
data at week 2, 4, 6, 8, 10, and 12. An unstructured covariance matrix will be used to model the 
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within-subject errors. The Kenwards-Roger method will be used to estimate degrees of freedom. 
If this analysis fails to converge, a simpler structure (e.g., first-order ante-dependent or 
heterogeneous compound symmetry structures) will be found using Akaike information criterion 
(AIC). 
The results will be presented using LS Means estimates, corresponding 95% CI for each 
treatment group and timepoint, along with the LS Means of differences with Placebo, standard 
error, 95% CI and p-values. 
The primary efficacy analysis will be based on the mITT population.  
8.1.1. Sensitivity Analyses of the Primary Efficacy Endpoint  
To complement the MCP-MOD outputs, estimates and CI of each pairwise comparison versus 
placebo from the ANCOVA model described in the MCP step will be produced. 
8.2. 
Secondary Efficacy Analysis 
The MMRM model outlined in Section 8.1 will be applied for secondary endpoints using 
observed cases: 
• Change in Galer NPS total score from baseline to Days 28, 56, and 84 of treatment and the 
follow-up visit.   
• Change in DSIS from baseline to Days 28, 56, and 84 of treatment and the follow-up visit. 
• Change in the eight SF-36 parameters from baseline to Day 84 of treatment. 
A GEE approach for binary data will be used for the following dichotomous endpoints: 
• Percentage of subjects who have achieved ≥30% reductions in the weekly average of the 
average daily pain score from baseline during Weeks 4, 8, and 12 of treatment and the week 
before follow-up. 
• Percentage of subjects who have achieved ≥50% reductions in the weekly average of the 
average daily pain score from baseline during Weeks 4, 8, and 12 of treatment and the week 
before follow-up. 
The GEE model specification will include a binomial distribution, a logit link function, and an 
unstructured covariance matrix. If this analysis fails to converge, a simpler structure (e.g. first-
order autoregressive or compound symmetry structures) will be found using AIC. The model will 
include terms for:  
• co-medication type (as a factor) 
• treatment (as a factor) 
• time (as a factor) 
• the interaction between treatment and time  
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A CMH test stratified by the crossing of co-medication subgroup and median baseline pain score 
will also be carried out for the above dichotomous endpoints. The CMH risk difference at Week 
12 will be estimated between the treatment group and placebo. The number and percentage of 
subjects meeting the reduction response will be displayed, along with the risk difference, 95% CI 
and P value.  
The proportion of subjects who have ‘improved’, ‘much improved,’ or ‘very much improved’ 
relative to baseline on the PGIC on Days 28, 56, and 84 of treatment and the follow-up visit will 
be tested using a CMH statistics. 
The efficacy analysis of secondary endpoints will be based on the observed cases and on the 
mITT population.  
Usage of rescue medication (yes/no) will be summarized by dose group for each visit from 
baseline to Week 12 of treatment and over the whole treatment period. The following additional 
variables will be derived and summarised: 
• 
Total number of days rescue medication was used. 
− Each day on which rescue medication was used at least once is counted. 
• 
Cumulative consumption (mg) of paracetamol rescue medication use. 
− Calculated as the total dose of rescue medication (mg). 
• 
Average daily dose (mg) of paracetamol rescue medication use. 
− Calculated as: cumulative consumption of rescue medication (mg)/total number of 
days rescue medication was used. 
8.3. 
Exploratory Efficacy Analysis 
9. 
Safety and Tolerability Analysis 
All safety analyses will be performed on the Safety Population using descriptive statistics. 
Descriptive summaries by treatment group and overall will be produced. No inferential statistical 
tests will be performed.  
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The analysis of safety assessments in this study will include summaries of the following 
categories of safety and tolerability data collected for each patient: 
• Adverse events 
o TEAEs 
o SAEs 
o Significant AEs 
▪ TEAEs leading to discontinuation of IP 
o AEs of Special Interest 
▪ Positively-adjudicated possible or probable rapidly progressive 
osteoarthritis (RPOA), subchondral insufficiency fractures, primary 
osteonecrosis, or pathological fracture 
▪ Infections that meet SAE and/or severe AE criteria   
▪ Anaphylactic reactions or infusion-related reactions that lead to permanent 
discontinuation of administration of IP 
o TEAEs associated with abnormal liver  
o Any deaths 
Drug induced liver injuryClinical laboratory investigations  
• Vital signs 
• Electrocardiograms (ECG) 
• COVID-19 screening 
• Physical and neurological examination 
• Total neuropathy score-nurse 
• Motor and sensory nerve conduction studies 
• Strength and deep tendon reflexes 
• Hypersensitivity /Anaphylactic reactions 
• Injection site or infusion reactions 
• Liver diagnostic investigations, risk factors, signs and symptoms. 
• Infection diagnostic investigations, risk factors, signs and symptoms. 
• Prior and concomitant medications and therapies 
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9.1. 
Adverse Events 
A summary table by treatment group will present the number and percent of subjects reporting: 
• Any AEs 
• Non-serious AEs occurring in more than 5% of subjects 
• Any TEAEs 
• Any SAEs 
• Any TEAEs possibley related to study drug 
• Any TEAEs leading to discontinuation of IP 
• Any SAEs possibley related to study drug 
• Life-threatenings SAEs 
• SAEs resulting in death 
Summaries of the incidence of TEAEs will be displayed by treatment group, by ADA status, by 
severity and by: 
• SOC and PT 
• SOC, PT, and maximum severity (mild, moderate, severe) 
• SOC, PT, and maximum causality (not related, possibly related) to the study drug 
In the summaries showing severity and relationship to study drug the event with the maximum 
severity or strongest relationship will be reported. If a particular event is missing the severity 
and/or relationship, then the strongest possible severity or relationship will be assumed for 
analysis (severity = severe, relationship = related). 
In the case of multiple occurrences of the same AE within the same subject, each subject will 
only be counted once for each level of summarization.  
All AEs will be presented in a by-treatment and by-subject listing, detailing the verbatim term 
given by the Investigator, the PT, SOC, onset date and time, end date and time, severity, 
outcome, relationship to study drug, action taken with study drug, other action taken, 
seriousness, and criteria for seriousness.  
9.1.1. Adverse Events Leading to Discontinuation of IP 
A summary of incidence rates (frequencies and percentages) of TEAEs leading to 
discontinuation of IP, by treatment group, SOC, and PT will be prepared. The table will also be 
produced separately by maximum severity and maximum causality. 
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A data listing of TEAEs leading to discontinuation of IP will also be provided, displaying details 
of the event(s) captured on the rCRF. 
9.1.2. Deaths and Serious Adverse Events 
Any deaths that occur during the study and serious adverse events will be listed. 
A summary of incidence rates (frequencies and percentages) of SAEs by treatment group, SOC, 
and PT will be prepared. The table will also be produced separately for life-threatening SAEs, 
for SAEs with outcome death and for SAEs by relationship to study medication. 
9.1.3. Drug-Induced Liver Injury 
A summary of incidence rates of TEAEs associated with abnormal liver by treatment group, 
SOC, and PT will be prepared.  
The type and the results of the liver diagnostic investigation performed will be tabulated by 
treatment group.  
The number and percentage of subjects within each type of liver risk factors and style events will 
be tabulated by treatment group. Liver signs and symptoms will be presented in the same way. 
9.1.4. Infection Risk 
A summary of incidence rates of infections that meet SAE or severe AE criteria by treatment 
group, SOC, and PT will be prepared.  
The type and the results of infection diagnostic investigation performed will be tabulated by 
treatment group.  
The number and percentage of subjects within each type of infection risk factors and style events 
will be tabulated by treatment group. Infection signs and symptoms will be presented in the same 
way. 
9.2. 
COVID-19 Vaccination and Screening 
The number and percentage of fully vaccinated subjects at baseline will be summarized by 
treatment group. 
The symptoms, tests, and results from coronavirus disease 2019 (COVID-19) screening will be 
tabulated for each visit by treatment group. 
COVID-19 vaccination, signs, symptoms and impact will be presented in listings. 
9.3. 
Clinical Laboratory Evaluations 
Absolute values and changes from baseline will be summarized using descriptive statistics by 
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treatment group and visit for chemistry, hematology, coagulation, and urinalysis tests. 
The number of subjects with clinical laboratory values (chemistry, hematology, coagulation, and 
urinalysis) categorized as below, within, or above normal ranges (or as either normal or 
abnormal for urinalysis variables that do not have quantitative ranges) and whether they are 
clinically significant or not will be tabulated for each clinical laboratory analyte by treatment 
group and visit. A shift table showing change from baseline in range categories for each clinical 
laboratory analyte will be produced by treatment group and by visit.  
The number of subjects with values for Aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN), and with values for total bilirubin 
(TBL) ≥ 2 × ULN will be summarized in AST, ALT vs. TBL shift tables to identify Potential 
Hy’s Law (PHL) and Hy’s Law (HL) cases by treatment group. 
Diagnostic immunology, urine pregnancy, and urine drug tests will be presented in by-subject 
listings only. 
All laboratory values will be displayed in the data listings and those that are outside the normal 
range will be flagged, along with corresponding normal ranges. 
9.4. 
Vital Signs 
Descriptive summaries of actual values and changes from baseline by treatment group, visit and 
time point will be presented for: 
• Supine heart rate 
• Supine systolic blood pressure 
• Supine diastolic blood pressure 
• Respiratory rate 
• Body temperature 
• Standing heart rate 
• Standing systolic blood pressure 
• Standing diastolic blood pressure 
Height, weight, and BMI will be presented at baseline only.  
9.5. 
Electrocardiograms 
The number and percentage of subjects with normal, abnormal not clinically significant, and 
abnormal clinically significant ECG results will be summarized by treatment group and by visit. 
If applicable (digital ECGs), descriptive summaries will be presented by treatment group, visit 
and time point (for Day 1 only) for ECG measures of PR, QRS, QT, RR intervals and for the 
calculated variables QTcF and HR for each treatment group and time point.  
Heart rate (HR) and Fridericia’s correction (QTcF) will be derived as follows: 
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Heart Rate (HR) 
𝐻𝑅= 103 60
𝑅𝑅𝑚𝑠𝑒𝑐
 
Fridericia’s Correction 
(QTcF) 
3
sec
RR
QT
QTc
m
f =
sec 
9.6. 
Physical and Neurological Examination 
The physical and neurological examination findings will be presented in listings.  
9.7. 
Total Neuropathy Score-Nurse 
Descriptive summaries of the TNSn will be presented by treatment groups and by visit. 
Additionally, the number and percentage of subjects within each category (0, 1, 2, 3, and 4) for 
each sub-score (sensory symptom, motor symptom, autonomic symptom, pin sensibility, 
vibration sensibility) will be summarized by treatment group and by visit. 
9.8. 
Motor and Sensory Nerve Conduction Studies 
Amplitude, peak latency, conduction velocity, and duration of nerve action potentials will be 
summarized by treatment group and visit for each location and evaluation type. The number of 
subjects with normal and abnormal evaluation will be tabulated by treatment group and by visit.  
9.9. 
Strength and Deep Tendon Reflexes 
The number and percentage of subjects within each category of the ankle dorsiflexion strength 
and the deep tendon reflexes will be tabulated by treatment group and by visit . 
9.10. Hypersensitivity/Anaphylactic Reactions, Injection Site or Infusion Reactions 
The type and symptoms of hypersensitivity/ anaphylactic reactions will be tabulated by treatment 
group.  
Injection site reactions will be tabulated describing the severity of pain, tenderness, 
erythema/redness, and induration/swelling by treatment group and by visit. 
Anaphylactic reactions and infusion related reactions will be summarized in line with AEs, 
displayed by treatment group and by: 
• SOC and PT 
• SOC, PT, and maximum severity (mild, moderate, severe) 
Hypersensitivity/anaphylactic and infusion related reactions will also be presented in a by-
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Statistical Analysis Plan,  
 
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Protocol Number D5680C00002  
 
PCN Number MEDU177093 
 
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treatment and by-subject listings, detailing type of reaction, severity grade for symptom with 
highest severity and onset time for hypersensitivity/anaphylactic reactions, and assessment result 
for injection site or infusion related reactions.  
9.11. Prior and Concomitant Medication and Procedures 
Prior medications will be presented separately from concomitant medications.  
Medications will be coded using the latest version of the WHO Drug Dictionary. 
Medications that started before first dose of study medication will be considered prior, whether 
they were stopped before first dose of study medication or not.  
A concomitant medication is defined as any medication continuing or starting after first dose of 
study medication. This includes medications which start before first dose of study medication 
and continue while on-treatment, and medications that started after first dose of study 
medication. 
The frequency and percentage of concomitant medications will be summarized by Anatomical 
Therapeutic Chemical (ATC) class 2 and preferred name by treatment groups, unless otherwise 
specified.  
In listings, all medications will be displayed. 
If the start/stop dates of a medication are partially or completely missing, then the medication 
will be assumed to be concomitant if it cannot be definitely shown from the start/stop dates that 
it was not administered while on-treatment. Missing dates will not be replaced.  
Thus, the following approach will be taken for exclusion from concomitant medications because 
of discontinuation before start of treatment:  
• If the stop day is missing but the month is complete, then the medication will be excluded 
from concomitant medications only if the stop month is before the month of the first dose 
of study medication.  
• If the stop day and month are missing but the year is complete, then the medication will 
be excluded from concomitant medications only if the stop year is before the year of the 
first dose of study medication.  
• If the stop date is completely missing, then the medication will not be excluded.  
For concomitant medication exclusion (because of the late start after the end of the treatment 
period):  
• If the start day is missing but the month is complete, then the medication will be excluded 
from concomitant medications only if the start month is after the last month of the 
treatment period.  
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• If the start day and month are missing but the year is complete, then the medication will 
be excluded from concomitant medications only if the start year is after the year of the 
treatment period.  
• If the start date is completely missing, then the medication will not be excluded. 
A similar approach will be used for summarizing concomitant procedures. 
10. 
Changes from Planned Analysis 
 
The PK endpoints involving derivation of PK parameters for each dose and for each subject will 
be conducted by a population PK analysis of the data as part of a pooled data analysis instead of 
by a noncompartmental analysis (NCA). This will be documented in the CSR as a change in 
planned analysis. The pooled data analysis will be described in a separate modelling analysis 
plan. As a result, description of TLFs related to PK parameters are removed from this SAP. 
 
Additional analyses with pooled site as a covariate are not going to be conducted and as such, 
they are removed from this SAP. 
 
It was planned to have a supplementary analysis to the primary using an adaptive MCP-MOD 
method. In this analysis, stages 2+3 and stage 4 were going to be analysed separately and the 
results combined using an inverse-normal P value combination function (with weights related to 
the original planned sample sizes). This supplementary analysis is removed from this SAP. 
 
The Cochran-Mantel-Haenszel test for the non-binary categorical endpoints has been extended to 
include the secondary endpoint of pain response. 
11. 
Other Planned Analysis 
11.1. 
 
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11.2. Immunogenicity 
Blood samples will be collected for assessment of ADA levels. Anti-Drug Antibody response 
during the entire study period and at each study assessment will be summarised according to 
ADA category and titre value for the Safety population with evaluable ADA results. A listing of 
the ADA test results will be produced.  
For immunogenicity analysis, the presence of detectable (i.e., positive) ADAs against 
MEDI7352 will be reported. ADA results from each sample are reported as either positive or 
negative. In addition, the ADA titer result will be reported for samples confirmed positive for the 
presence of ADAs. A participant is defined as being ADA-positive if a positive ADA result is 
available at any time, including baseline and all post-baseline measurements, otherwise ADA 
negative. 
The following ADA categories will be determined: 
• ADA positive if a collected sample is tested positive at any time during the study, 
including baseline and/or post-baseline. (The percentage of these participants in a 
population is known as ADA prevalence). 
• Treatment-emergent ADA positive (TE-ADA+): A positive post-baseline result and 
either of the following statements holds: 
o Baseline is ADA negative and at least one post-baseline assessment is ADA 
positive. This is called treatment-induced ADA positive. 
o Baseline is ADA positive, and the baseline titre is boosted by greater than the 
variability of the assay (i.e., ≥X-fold increase, commonly 4-fold) at ≥1 post-
baseline timepoint. This is called treatment-boosted ADA positive. 
(The percentage of these participants in a population is known as ADA incidence) 
• Only baseline positive if a collected sample is tested positive at baseline. 
• Non-Treatment-emergent ADA positive (non-TE-ADA+): Participants who are ADA 
positive but not fulfilling the conditions for TE-ADA+. 
• Treatment-emergent Persistently ADA positive: ADA negative at baseline and having at 
least 2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between 
first and last positive, or an ADA positive result at the last available post-baseline 
assessment. 
• Treatment-emergent Transiently ADA positive: ADA negative at baseline and at least 
one post-baseline ADA positive measurement and not fulfilling the conditions for 
persistently positive 
• ADA positive post-baseline and positive at baseline. 
11.3.  Pharmacokinetic Analysis 
Pharmacokinetic concentration data will be summarized using descriptive statistics by dose and 
treatment visit overall and by ADA status (positive/negative) presenting the number (n) of non-
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missing observations, and the n < LLOQ. A figure of geometric mean (with and without gSD) 
serum MEDI7352 concentration over time by treatment group will be generated (overall and by 
ADA status (positive/negative)). Additionally, pharmacokinetic concentration data will be listed 
and presented graphically as spaghetti plots of individual participant profiles by treatment group 
and ADA status (positive/negative). 
12.
References
1. ICH (1998) ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials E9; 
1998. https://database.ich.org/sites/default/files/E9_Guideline.pdf
2. ASA. (2018) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April 2018. http://www.amstat.org/about/ethicalguidelines.cfm
3. RSS. (2014) The Royal Statistical Society: Code of Conduct, 2014.
http://www.rss.org.uk/Images/PDF/join-us/RSS-Code-of-Conduct-2014.pdf.
4. Satoh J, Yagihashi S, Baba M, Suzuki M, Arakawa A, Yoshiyama T. Efficacy and safety 
evaluation of pregabalin treatment over 52 weeks in patients with diabetic neuropathic pain 
extended after a double-blind placebo-controlled trial. J Diabetes Investig. 2011;2(6):457-463. 
Doi: 10.1111/j.2040-1124.2011.00122.x.
5. Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful 
diabetic neuropathy: a randomized controlled trial. Neurology. 2004;63(11):2104-2110.
6. Rosenstock J, Tuchman M, LaMoreaux L, Sharma U. Pregabalin for the treatment of painful 
diabetic 
peripheral neuropathy: a 
double-blind, placebo-controlled trial. 
Pain. 
2004;110(3):628-638.
7. Tӧlle T, Freynhagen R, Versavel M, Trostmann U, Young JP Jr. Pregabalin for relief of 
neuropathic pain associated with diabetic neuropathy: a randomized, double-blind study. Eur 
J Pain. 2008;12(2):203-213.
8. Pinheiro J, Bornkamp B, Bretz F. Design and analysis of dose-finding studies combining 
multiple comparisons and modelling procedures. J Biopharm Stat. 2006;16(5):639-656. Doi: 
10.1080/10543400600860428.
9. Thomas N, Sweeney K, Somayaji V. Meta-analysis of clinical dose–response in a large drug 
development 
portfolio. 
Stat 
Biopharm 
Res. 
2014;6(4):302-317. 
Doi: 
10.1080/19466315.2014.924876.
10. Kirby S, Brain P, Jones B. Fitting E(max) models to clinical trial dose-response data. Pharma Stat. 
2011;10(2):143-149. Doi: 10.1002/pst.432.
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13. 
Tables, Listings, and Figures 
All listings, tables, and graphs will have a header showing the sponsor company name and 
protocol and a footer showing the version of SAS, the file name and path, and the source of  the 
data (eCRF page or listing number). 
The following are planned summary tables for protocol number D5680C00002. The table 
numbers and page numbers are place holders only and will be determined when the tables are 
produced. 
 
13.1. Demographic Data 
Table 1: Demographic Data Summary Tables and Figures 
Table Number 
Population 
Table Title/Summary 
Table 14.1.2 
Screening 
Subject Disposition 
Table 14.1.3 
Screen Failure 
Summary of Reasons for Screening Failure 
Table 14.1.4.1 
Screening 
Demographics and Baseline Characteristics 
Table 14.1.4.2 
Safety 
Demographics and Baseline Characteristics 
Table 14.1.4.3 
mITT 
Demographics and Baseline Characteristics 
Table 14.1.4.4 
PK 
Demographics and Baseline Characteristics 
Table 14.1.5.1 
Screening 
Osteoarthritis Characteristics 
Table 14.1.5.2 
Safety 
Osteoarthritis Characteristics 
Table 14.1.5.3 
mITT 
Osteoarthritis Characteristics 
Table 14.1.5.4 
PK 
Osteoarthritis Characteristics 
Table 14.1.6 
Safety 
Medical History by System Organ Class and Preferred Term 
Table 14.1.7 
Safety 
Prior Medications by ATC Class and Preferred Name 
Table 14.1.8 
Safety 
Protocol Deviations 
Table 14.1.9 
Safety 
Overall Study Drug Exposure 
 
 
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13.2. Efficacy Data 
Table 2: Efficacy Data 
Table Number 
Population 
Table Title / Summary 
Table 14.2.1.1.1 mITT 
Daily Pain NRS: Summary Statistics (Observed Cases) 
Table 14.2.1.1.2 mITT 
Daily Pain NRS: Summary Statistics (LOCF) 
Table 14.2.1.1.3 mITT 
Daily Pain NRS: Summary Statistics (BOCF) 
Table 14.2.1.2.1 mITT 
Daily Pain NRS: Primary MCP-Mod Analysis (LOCF) 
Table 14.2.1.2.2 mITT 
Statistical Analysis of CFB to Week 12 Daily Pain NRS: Primary ANCOVA 
Analysis (LOCF) 
Table 14.2.1.3.1 mITT 
Statistical Analysis of CFB Daily Pain NRS: MMRM Analysis. (Observed 
Cases) 
Table 14.2.1.3.2 mITT 
Daily Pain NRS: Sensitivity of Primary MCP-Mod Analysis (BOCF) 
Table 14.2.2.1 
mITT 
Galer NPS: Summary Statistics (Observed Cases) 
Table 14.2.2.2 
mITT 
Galer NPS: MMRM Analysis (Observed Cases) 
Table 14.2.3.1 
mITT 
DSIS: Summary Statistics (Observed Cases) 
Table 14.2.3.2 
mITT 
DSIS: MMRM Analysis (Observed Cases) 
Table 14.2.4.1 
mITT 
SF-36: Summary Statistics (Observed Cases) 
Table 14.2.4.2 
mITT 
SF-36: MMRM Analysis (Observed Cases) 
Table 14.2.5.1 
mITT 
Rescue Medication Use: Summary Statistics 
Table 14.2.6.1 
mITT 
Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel-Haenszel 
(Observed Cases) 
Table 14.2.6.2 
mITT 
Daily Pain NRS Responder Analysis (≥30%): GEE Analysis (Observed 
Cases) 
Table 14.2.7.1 
mITT 
Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel-Haenszel 
(Observed Cases) 
Table 14.2.7.2 
mITT 
Daily Pain NRS Responder Analysis (≥50%): GEE Analysis (Observed 
Cases) 
Table 14.2.8.1 
mITT 
Patient Global Impression of Change: Summary Statistics 
Table 14.2.8.2 
mITT 
Patient Global Impression of Change: Cochran-Mantel-Haenszel 
 
 
 
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13.3. Safety Data 
Table 3: Safety Data 
Table Number 
Population 
Table Title / Summary 
14.3.1 Displays of Adverse Events 
Table 14.3.1.1 
Safety 
Summary of Overall Adverse Events 
Table 14.3.1.2 
Safety 
Treatment Emergent Adverse Events by System Organ Class and 
Preferred Term 
Table 14.3.1.3 
Safety 
Treatment Emergent Adverse Events by Severity, System Organ Class 
and Preferred Term 
Table 14.3.1.4 
Safety 
Treatment Emergent Adverse Events by Relationship to Study 
Medication, System Organ Class and Preferred Term 
Table 14.3.1.5 
Safety 
Treatment Emergent Adverse Events by ADA Status Category, System 
Organ Class and Preferred Term 
Table 14.3.1.6 
Safety 
Treatment Emergent Adverse Events Leading to Discontinuation of 
Study drug by System Organ Class and Preferred Term 
Table 14.3.1.7 
Safety 
Non-Serious Adverse Events Occurring in More than 5% of Subjects by 
System Organ Class and Preferred Term 
Table 14.3.1.8 
Safety 
Treatment Emergent Adverse Events Occurring in More than 5% of 
Subjects by Preferred Term 
Table 14.3.1.9 
Safety 
Treatment Emergent Adverse Events by Preferred Term 
14.3.2 Summary of Deaths, Other Serious and Significant Adverse Events 
Table 14.3.2.1.1 Safety 
Serious Adverse Events by System Organ Class and Preferred Term 
Table 14.3.2.1.2 Safety 
Life-Threatening Serious Adverse Events by System Organ Class and 
Preferred Term 
Table 14.3.2.1.3 Safety 
Serious Adverse Events with Outcome Death by System Organ Class and 
Preferred Term 
Table 14.3.2.1.4 Safety 
Serious Adverse Events by Relationship to Study Medication, System 
Organ Class and Preferred Term 
14.3.2.2 Displays of Significant Adverse Events and Adverse Events of Special Interest 
Table 14.3.2.2.1 Safety 
Treatment Emergent Adverse Events Associated with Abnormal Liver by 
System Organ Class and Preferred Term 
Table 14.3.2.2.2 Safety  
Potential Joint Related Adverse Events of Special Interest by System 
Organ Class and Preferred Term  
Table 14.3.2.2.3 Safety 
Serious and/or severe Infections by System Organ Class and Preferred 
Term 
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Table Number 
Population 
Table Title / Summary 
Table 14.3.2.2.4 Safety 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions 
Leading to Discontinuation of IP by System Organ Class and Preferred 
Term 
14.3.3 Narratives of Deaths and Other Serious Adverse Events 
Table 14.3.3.1 
Safety 
Listing of Serious Adverse Events 
Table 14.3.3.2 
Safety 
Listing of Deaths 
14.3.4 Laboratory Data Summary Tables 
Table 14.3.4.1 
Safety 
Descriptive Summary of Clinical Chemistry 
Table 14.3.4.2 
Safety 
Shift Table of Clinical Chemistry Results 
Table 14.3.4.3 
Safety 
Descriptive Summary of Hematology 
Table 14.3.4.4 
Safety 
Shift Table of Hematology Results 
Table 14.3.4.5 
Safety 
Descriptive Summary of Coagulation 
Table 14.3.4.6 
Safety 
Shift Table of Coagulation Results 
Table 14.3.4.7 
Safety 
Descriptive Summary of Urinalysis 
Table 14.3.4.8 
Safety 
Shift Table of Urinalysis Results 
Table 14.3.4.9 
Safety 
Maximum On-Treatment ALT and AST versus Maximum On-Treatment 
Total Bilirubin 
14.3.6 Other Safety Data Summary Tables 
Table 14.3.5.1 
Safety 
Descriptive Summary of Vital Signs 
Table 14.3.5.2 
Safety 
Descriptive Summary of ECG Data 
Table 14.3.5.3 
Safety 
Summary of Overall Evaluation of safety ECG Data 
Table 14.3.5.4 
Safety 
Covid-19 Screening 
Table 14.3.5.5 
Safety 
Summary of Sub-Scores for Total Neuropathy Score-Nurse 
Table 14.3.5.6 
Safety 
Descriptive Summary of Total Neuropathy Score-Nurse 
Table 14.3.5.7 
Safety 
Summary of Motor and Sensory Nerve Conduction Studies 
Table 14.3.5.8 
Safety 
Summary of Strength and Deep Tendon Reflexes 
Table 14.3.5.9 
Safety 
Summary of Local Injection Site Reactions 
Table 14.3.5.10 
Safety 
Summary of Anaphylactic Reactions 
Table 14.3.5.11 
Safety 
Summary of Liver Diagnostic Investigations 
Table 14.3.5.12 
Safety 
Summary of Liver Risk Factors and Lifestyle Events 
Table 14.3.5.13 
Safety 
Summary of Liver Signs and Symptoms 
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Table Number 
Population 
Table Title / Summary 
Table 14.3.5.14 
Safety 
Summary of Infection Diagnostic Investigations 
Table 14.3.5.15 
Safety 
Summary of Infection Risk Factors and Lifestyle Events 
Table 14.3.5.16 
Safety 
Summary of Infection Signs and Symptoms 
Table 14.3.5.17 
Safety 
Summary of Concomitant Medications by ATC Level 2 and Preferred 
Term 
Table 14.3.5.18 
Safety 
Summary of Concomitant Procedures 
Table 14.3.5.19 
Safety 
Anti-Drug Antibody Results and Titre Summary by Timepoint 
Table 14.3.5.20 
Safety 
Descriptive Summary of Anti-Drug Antibody Results and Titre by ADA 
Categories 
 
 
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13.4. Pharmacokinetic/Pharmacodynamic Data 
Table 4: Pharmacokinetic/Pharmacodynamic Data 
Table Number 
Population 
Table Title / Summary 
14.4 Pharmacokinetic and Pharmacodynamic Data Summary Tables 
Table 14.4.1 
PK 
Summary of Serum MEDI7352 Concentrations 
Table 14.4.2 
Safety 
Summary of Serum total NGF Concentrations 
13.5. Planned Listing Descriptions 
The following are planned data and patient/subject data listings for protocol number 
D5680C00002.  
In general, one listing will be produced per eCRF domain. All listings will be sorted by 
treatment, site, and subject number. All calculated variables will be included in the listings. 
In all listings a blank line will be placed between each subject. Within a data listing, if an item 
appears line after line (e.g., repetition of subject number), then only the first occurrence will be 
displayed. 
In data listings, the information for one subject will be kept on one page if at all possible, rather 
than splitting a subject’s information across pages. 
Table 5: Planned Listings 
 
Data Listing Number 
Population 
Data Listing Title / Summary 
16.2 Subject Data Listings 
16.2.1 Subject Discontinuations/Completions 
Listing 16.2.1.1 
Screening 
Subject Disposition 
Listing 16.2.1.2 
Screening 
Assignment to Analysis Populations 
Listing 16.2.1.3 
Safety 
Reason for IP Discontinuation and Withdrawal from the Study 
Listing 16.2.1.4 
Screen Failure 
List of Reasons for Screening Failure 
Listing 16.2.1.5 
Screening 
Visits List and COVID-19 Impact 
16.2.2 Protocol Deviations 
Listing 16.2.2.1 
Screening 
Subjects Not Meeting All Inclusion Criteria or Meeting any 
Exclusion Criteria 
Listing 16.2.2.2 
Safety 
Protocol Deviations 
16.2.3 Randomization 
Listing 16.2.3 
Safety 
Randomization and Treatment Group 
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Data Listing Number 
Population 
Data Listing Title / Summary 
16.2 Subject Data Listings 
16.2.4 Demographic Data and Other Baseline Characteristics 
Listing 16.2.4.1 
Screening 
Demographic and Baseline Characteristics 
Listing 16.2.4.2 
Safety 
Medical History  
Listing 16.2.4.3 
Screening 
Osteoarthritis Characteristics 
16.2.5 Compliance and/or Drug Concentration Data 
Listing 16.2.5.1 
Safety 
Study Drug Administration: Individual Doses 
16.2.6 Individual Efficacy Response Data 
Listing 16.2.6.1 
mITT 
Daily Pain NRS 
Listing 16.2.6.2 
mITT 
Galer NPS 
Listing 16.2.6.3 
mITT 
DSIS 
Listing 16.2.6.4 
mITT 
SF-36 
Listing 16.2.6.5 
mITT 
Rescue Medication Usage 
Listing 16.2.6.6 
mITT 
Patient Global Impression of Change 
16.2.7 Adverse Event Listings (by Patient/Subject) 
Listing 16.2.7.1 
Safety 
Adverse Events  
Listing 16.2.7.2 
Safety 
Treatment Emergent Adverse Events Leading to Study Drug 
Discontinuation 
Listing 16.2.7.3 
Safety 
Treatment Emergent Adverse Events Associated with Abnormal 
Liver 
Listing 16.2.7.4 
Safety 
Joint Related Adverse Events of Special Interest 
Listing 16.2.7.5 
Safety 
Serious and/or Severe Infections 
Listing 16.2.7.6 
Safety 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related 
Reactions Leading to Discontinuation of Study Drug 
16.2.8 Laboratory Values (by Patient/Subject) 
Listing 16.2.8.1 
Safety 
Clinical Chemistry Laboratory Evaluations 
Listing 16.2.8.2 
Safety 
Hematology Laboratory Evaluations 
Listing 16.2.8.3 
Safety 
Coagulation Laboratory Evaluations 
Listing 16.2.8.4 
Safety 
Urinalysis Laboratory Evaluations 
Listing 16.2.8.5 
Safety 
Serology Laboratory Evaluations 
Listing 16.2.8.6 
Safety 
Pregnancy Test Results 
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Data Listing Number 
Population 
Data Listing Title / Summary 
16.2 Subject Data Listings 
Listing 16.2.8.7 
Safety 
Drug Test Results 
Listing 16.2.8.8 
Safety 
COVID-19 Screening 
16.2.9 Other Clinical Observations and Measurements (by Patient/Subject) 
Listing 16.2.9.1 
Safety 
Vital Signs Measurements 
Listing 16.2.9.2 
Safety 
ECG Results 
Listing 16.2.9.3 
Safety 
Physical Examination Results 
Listing 16.2.9.4 
Safety 
Neurological Examination Results 
Listing 16.2.9.5 
Safety 
Total Neuropathy Score-Nurse 
Listing 16.2.9.6 
Safety 
Motor and Sensory Nerve Conduction Studies 
Listing 16.2.9.7 
Safety 
Strength and Deep Tendon Reflexes 
Listing 16.2.9.8 
Safety 
Injection Site Reactions 
Listing 16.2.9.9 
Safety 
Anaphylactic Reactions 
Listing 16.2.9.10 
Safety 
Liver Diagnostic Investigations 
Listing 16.2.9.11 
Safety 
Liver Risk Factors and Lifestyle Events 
Listing 16.2.9.12 
Safety 
Liver Signs and Symptoms 
Listing 16.2.9.13 
Safety 
Infection Diagnostic Investigations 
Listing 16.2.9.14 
Safety 
Infection Risk Factors and Lifestyle Events 
Listing 16.2.9.15 
Safety 
Infection Signs and Symptoms 
Listing 16.2.9.16 
Safety 
Prior and Concomitant Medications 
Listing 16.2.9.17 
Safety 
Prohibited Concomitant Medications 
Listing 16.2.9.18 
Safety 
Concomitant Procedures 
Listing 16.2.9.19 
Safety 
Anti-drug Antibody Test Results 
16.2.10 Pharmacokinetic/Pharmacodynamic Measurements  
Listing 16.2.10.1 
PK 
Serum MEDI7352 Concentrations 
Listing 16.2.10.2 
Safety 
Serum total NGF Concentrations 
 
13.6. Planned Figure Descriptions 
The following are planned summary figures for protocol number D5680C00002. The figure 
numbers and page numbers are place holders only and will be determined when the figures are 
produced. 
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Table 6: Planned Figures 
Figure Number 
Population 
Figure Title/Summary 
Figure 14.2.1.1 
mITT 
Daily Pain NRS: MCP-Mod Dose Response Model 
Figure 14.2.1.2 
mITT 
Daily Pain NRS: Boxplots at Week 12 by Treatment 
Group and Missing Data Handling 
Figure 14.2.1.3 
mITT 
Daily Pain NRS: Boxplots at Week 12 by Treatment 
Group and Co-Medication Subgroup 
Figure 14.2.1.4 
mITT 
Daily Pain NRS: MMRM LS Means (95% Confidence 
Interval) over 12-weeks by Treatment Group (Observed 
Cases) 
Figure 14.3.6.1.1 Safety 
Vital Sign Profiles: Mean (±SD) Systolic Blood Pressure 
over time 
Figure 14.3.6.1.2 Safety 
Vital Sign Profiles: Mean (±SD) Diastolic Blood 
Pressure over time 
Figure 14.3.6.1.3 Safety 
Vital Sign Profiles: Mean (±SD) Heart Rate over time 
Figure 14.3.6.1.4 Safety 
Vital Sign Profiles: Mean (±SD) Respiratory Rate over 
time 
Figure 14.3.6.1.5 Safety 
Vital Sign Profiles: Mean (±SD) Temperature over time 
Figure 14.4.1.1 
PK 
Pharmacokinetics: Line Plot of Geometric Mean (with 
and without gSD) Serum MEDI7352 over time 
Figure 14.4.1.2 
PK 
Pharmacokinetics: Individual Plot of Serum MEDI7352 
Concentrations over time  
Figure 14.4.2.1 
Safety 
Pharmacodynamics: Line Plot of Geometric Mean (with 
and without gSD) Serum total NGF over time 
Figure 14.4.2.2 
Safety 
Pharmacodynamics: Individual Plot of Serum total NGF 
over time 
 
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14. 
Tables, Listing and Figure Shells 
14.1. 
Standard Layout for all Tables, Listings, and Figures 
The following standard layout will be applied to all Tables, Listings, and Figures in support of this study. Note that programming 
notes may be added if appropriate after each table, listing and figure shell. All shells will be provided as a separate document. 
 
 
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Figure 1: Standardized Layout 
Astra Zeneca 
Page xx of xx 
Protocol: D5680C00002 
Version  
 
<Table, Listing, Figure> xx.x.x 
Title of Table, Listing or Figure 
Study Population and if applicable subgroup Description 
____________________________________________________________________________________________________________ 
 
 
Body of Table, Listing or Figure 
 
 
___________________________________________________________________________________________________________ 
Note: If directly Applicable 
Footnote 1  
Footnote 2  
Footnote n  
Footnote n+1 SAS program path and name Executed on ddmmmyyyy at hh:mm on data from ddmmmyyyy  
 
 
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15. 
Appendix: Calculation of Dose to achieve target effects 
Although only one dose-response model type (Emax) is pre-specified in the protocol for the primary analysis, 
 
 
 
Let us assume the R® DoseFinding package original parametrization for these two dose-response model functions below: 
 
 
1. Equations for Target Dose DΔ to achieve a Delta (∆) versus placebo 
Emax: TDΔ= ED50/((Emax/∆) - 1), where ED50 and Emax are estimated from the fitted Emax model 
Exponential: TDΔ= 𝛿*log((∆/E1) +1), where 𝛿 and E1 are estimated from the fitted exponential model 
(The function TD from the DoseFinding package will be used for the above) 
2. Equations for Dose (EDP) to achieve a certain proportion P of the effect of the maximum dose studied versus placebo (See 
DoseFinding manual page 51 where ED is ‘Effective Dose’) 
I 
Journal of Statistical Software 
Name 
f(d, 0 ) 
J0(d, 0• ) 
(*) 
m 
linear 
Eo+8d 
d 
linlog 
Eo + 81og(d+c) 
Jog(d + c) 
C 
quadratic 
Eo + f31d + f32d2 
d + 8d2 if /32 < 0 
8 
emax 
Eo + Emaxd/(EDso + d) 
d/(EDso +d) 
EDso 
l ogistic 
Eo + Emax/ {1 + exp [(EDso - d) /8]} 
1/ {1 + exp [(EDso - d) /8]} 
(EDso, 8) T 
exponential 
E0 + E 1 (exp(d/8) - 1) 
exp(d/8) - 1 
8 
sigEmax 
Eo + Emaxdh /(EDgo + dh) 
d"/(EDgo + dh) 
(EDso, h)T 
betaMod 
Eo + EmaxB(81, 82)(d/ Dl1 (1 - d/ D)62 
B(81 ,82)(d/D)6'(1 - d/D)62 
(81,82f 
D 
Table 1: Dose-response models implemented in the MCPMod package. Column (*) lists for 
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Emax: EDP= (P * ED50*max(doses))/(ED50+(1-P) * max(doses)) = (P* ED50*150)/(ED50+(1-P)*150) 
Exponential: EDP= δ *log((P*exp(max(doses)/ δ) + 1-P)) = δ *log((P*exp(150/ δ) + 1-P)) 
(The function ED from the DoseFinding package will be used for the above) 
3. Equation for Dose (asym EDP) to achieve a certain proportion P of the asymptotic maximum effect (Emax) versus placebo 
Emax: asymptotic EDP= (P*ED50) /(1-P) 
 
Simulation-based CI will be created for each of the above quantities from the mean and covariance matrix of the model parameters, 
assuming multivariate normality. Therefore 10,000 samples from the multivariate distribution will be taken, and for each simulation 
the TD and ED estimates calculated.  The 2.5% and 97.5% percentiles will then form the appropriate 95% two-sided CI. 
 
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   Statistical Analysis Plan 
Sponsor 
AstraZeneca 
Protocol Title: 
A Randomised, Double-Blind, Placebo-Controlled, Dose-
Response Study of the Efficacy and Safety of MEDI7352 in 
Subjects with Painful Diabetic Neuropathy 
Development Phase 
2 
Protocol Number: 
D5680C00002 
Premier Research PCN: 
MEDU177093 
Document Version: 
Final Version 1.1 
Document Date:  
31-Aug-2023 
Approvals 
Role 
Signatures 
Biostatistician 
Print Name: 
 
Biostatistician, Premier Research 
Sign Name: 
 
 
 
 
 
Peer Reviewer 
Print Name: 
 
 Biostatistics, Premier Research 
Sign Name: 
 
 
 
 
 
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Role 
Signatures 
AstraZeneca 
Biostatistician 
Print Name: 
 
Statistical Consultant to AstraZeneca 
Sign Name: 
 
 
 
 
 
AstraZeneca 
Representative 
Print Name: 
 
 
AstraZeneca Neuroscience 
Sign Name: 
 
 
 
 
 
 
 
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Document History 
Version 
Date 
Author 
Description 
0.1 
27-Mar-2019 
 
Draft Version 
0.2 
16-Apr-2021 
 
Draft Version 
0.3 
25-Jun-2021 
 
Draft Version 
0.4 
24-Mar-2023 
 
Draft Version 
0.5 
21-Apr-2023 
 
Draft Version 
0.6 
24-May-2023 
 
Draft Version 
1.0 
12-Jul-2023 
 
Final Version 
1.1 
31-Jul-2023 
 
Final Version 
 
 
 
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Table of Contents 
Approvals................................................................................................................................ 1 
Document History ................................................................................................................... 3 
Table of Contents .................................................................................................................... 4 
List of Tables .......................................................................................................................... 6 
List of Figures ......................................................................................................................... 6 
List of Abbreviations ............................................................................................................... 7 
1.
Overview ................................................................................................................... 11
2.
Study Objectives and Endpoints.................................................................................. 11 
2.1. 
Study Objectives .................................................................................................. 11 
2.1.1. Primary Objective................................................................................................. 11 
2.1.2. Secondary Objectives ........................................................................................... 11 
2.1.3. Exploratory Objectives ......................................................................................... 12 
2.2. 
Study Endpoints ................................................................................................... 12 
2.2.1. Efficacy Endpoints ............................................................................................... 12 
2.2.2. Safety Endpoints .................................................................................................. 13 
2.2.3. Pharmacokinetic/Pharmacodynamic Variable(s) .................................................... 13 
2.2.4. Other Endpoints ................................................................................................... 14 
3.
Overall Study Design and Plan ................................................................................... 14 
3.1. 
Overall Design ..................................................................................................... 14 
3.2. 
Sample Size and Power......................................................................................... 14 
3.3. 
Study Population .................................................................................................. 15 
3.4. 
Treatments Administered ...................................................................................... 16 
3.5. 
Method of Assigning Subjects to Treatment Groups .............................................. 16 
3.6. 
Blinding and Unblinding....................................................................................... 16 
3.7. 
Schedule of Events ............................................................................................... 17 
4.
Statistical Analysis and Reporting............................................................................... 17 
4.1. 
Introduction.......................................................................................................... 17 
4.2. 
Interim Analysis and Data Monitoring................................................................... 18 
5.
Analysis Populations .................................................................................................. 18 
6.
General Issues for Statistical Analysis ......................................................................... 19 
6.1. 
Statistical Definitions and Algorithms ................................................................... 19 
6.1.1. Baseline ............................................................................................................... 19 
6.1.2. Adjustments for Covariates ................................................................................... 19 
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6.1.3. Multiple Comparisons .......................................................................................... 19 
6.1.4. Handling of Dropouts or Missing Data .................................................................. 20 
6.1.5. Analysis Visit Windows ....................................................................................... 20 
6.1.6. Pooling of Sites .................................................................................................... 21 
6.1.7. Efficacy Variables ................................................................................................ 21 
6.1.8. Derived Variables................................................................................................. 23 
6.1.9. Data Adjustments/Handling/Conventions .............................................................. 24 
7. 
Study Patients/Subjects and Demographics ................................................................. 25 
7.1. 
Disposition of Patients/Subjects and Withdrawals .................................................. 25 
7.2. 
Protocol Deviations .............................................................................................. 26 
7.3. 
Demographics and Other Baseline Characteristics ................................................. 26 
7.4. 
Exposure .............................................................................................................. 27 
8. 
Efficacy Analysis ....................................................................................................... 27 
8.1. 
Primary Efficacy Analysis .................................................................................... 27 
8.1.1. Sensitivity Analyses of the Primary Efficacy Endpoint .......................................... 29 
8.2. 
Secondary Efficacy Analysis................................................................................. 29 
8.3. 
Exploratory Efficacy Analysis............................................................................... 30 
9. 
Safety and Tolerability Analysis ................................................................................. 30 
9.1. 
Adverse Events .................................................................................................... 32 
9.1.1. Adverse Events Leading to Discontinuation of IP .................................................. 32 
9.1.2. Deaths and Serious Adverse Events....................................................................... 33 
9.1.3. Drug-Induced Liver Injury .................................................................................... 33 
9.1.4. Infection Risk ....................................................................................................... 33 
9.2. 
COVID-19 Vaccination and Screening .................................................................. 33 
9.3. 
Clinical Laboratory Evaluations ............................................................................ 33 
9.4. 
Vital Signs ........................................................................................................... 34 
9.5. 
Electrocardiograms ............................................................................................... 34 
9.6. 
Physical and Neurological Examination ................................................................ 35 
9.7. 
Total Neuropathy Score-Nurse .............................................................................. 35 
9.8. 
Motor and Sensory Nerve Conduction Studies ....................................................... 35 
9.9. 
Strength and Deep Tendon Reflexes ...................................................................... 35 
9.10. Hypersensitivity/Anaphylactic Reactions, Injection Site or Infusion Reactions ....... 35 
9.11. Prior and Concomitant Medication and Procedures ................................................ 36 
10. 
Changes from Planned Analysis.................................................................................. 37 
11. 
Other Planned Analysis .............................................................................................. 37 
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11.1. Biomarkers........................................................................................................... 37 
11.2. Immunogenicity ................................................................................................... 38 
11.3. Pharmacokinetic Analysis ..................................................................................... 39 
12. 
References ................................................................................................................. 39 
13. 
Tables, Listings, and Figures ...................................................................................... 41 
13.1. Demographic Data................................................................................................ 41 
13.2. Efficacy Data ....................................................................................................... 42 
13.3. Safety Data........................................................................................................... 43 
13.4. Pharmacokinetic/Pharmacodynamic Data .............................................................. 46 
13.5. Planned Listing Descriptions................................................................................. 46 
13.6. Planned Figure Descriptions ................................................................................. 49 
14. 
Tables, Listing and Figure Shells ................................................................................ 51 
14.1. Standard Layout for all Tables, Listings, and Figures ............................................. 51 
15. 
Appendix: Calculation of Dose to achieve target effects .............................................. 53 
 
List of Tables 
Table 1: Demographic Data Summary Tables and Figures ...................................................... 41 
Table 2: Efficacy Data ........................................................................................................... 42 
Table 3: Safety Data .............................................................................................................. 43 
Table 4: Pharmacokinetic/Pharmacodynamic Data.................................................................. 46 
Table 5: Planned Listings....................................................................................................... 46 
Table 6: Planned Figures........................................................................................................ 50 
 
List of Figures 
Figure 1: Standardized Layout ............................................................................................... 52 
 
 
 
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List of Abbreviations 
Abbreviation 
Definition 
ADA 
Anti-Drug Antibody 
AE 
Adverse Event 
AIC 
Akaike Information Criterion 
ALT 
Alanine Aminotransferase 
ANCOVA 
Analysis of Covariance 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
BOCF 
Baseline Observation Carried Forward 
CI 
Confidence Interval 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
Coronavirus Disease 2019 
CSR 
Clinical Study Report 
DSIS 
Daily Sleep Interference Scale 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
ED50, ED90 
The Dose to achieve 50%, 90% of the Maximum Effect. 
EMA 
European Medicines Agency 
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Abbreviation 
Definition 
Emax 
The Model-Based Maximum Treatment Effect Versus Placebo 
ePRO 
Electronic Patient-Reported Outcome System 
FDA 
Food and Drug Administration 
gCV% 
Geometric Coefficient of Variation 
GEE 
Generalized Estimating Equation 
gmean 
Geometric Mean 
gSD 
Geometric Standard Deviation 
HL 
Hy’s Law 
HR 
Heart Rate 
ICH 
International Council for Harmonization  
IP 
Investigational Product 
IV 
Intravenous 
IWRS 
Interactive Web Response System 
LLOQ 
Lower Limit of Quantification 
LOCF 
Last Observation Carried Forward 
LS 
Least Squares 
MCP-mod 
Multiple Comparison Procedure Modelling 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
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Abbreviation 
Definition 
MMRM 
Mixed Effects Models Repeated Measures 
NC 
Not Calculable 
NCA 
Noncompartmental Analysis 
NPS 
Neuropathic Pain Scale 
NQ 
Not Quantifiable 
NRS 
Numeric Rating Scale 
PD 
Pharmacodynamics 
PDN 
Painful Diabetic Neuropathy 
PGIC 
Patient Global Impression of Change 
PHT 
Potential Hy’s Law 
PK 
Pharmacokinetic 
PT 
Preferred Term 
QTcF 
QT Fridericia’s Correction 
RPOA 
Rapidly Progressive Osteoarthritis 
SAE 
Serious Adverse Event 
SAF 
Safety 
SAP 
Statistical Analysis Plan 
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Abbreviation 
Definition 
SAS®  
a Software System Used for Data Analysis 
SDTM 
Study Data Tabulation Model 
SF-36 
36-Item Short Form Health Survey 
SiAP 
Statistical Interim Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TBL 
Total Bilirubin 
TEAE 
Treatment-Emergent Adverse Event 
tNGF 
Total Nerve Growth Factor 
TNSn 
Total Neuropathy Score-Nurse 
ULN 
Upper Limit of Normal 
ULOQ 
Upper Limit of Quantification 
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1. 
Overview 
This statistical analysis plan (SAP) describes the planned analysis and reporting for AstraZeneca 
protocol number D5680C00002 (A Randomised, Double-Blind, Placebo-Controlled, Dose-
Response Study of the Efficacy and Safety of MEDI7352 in Subjects with Painful Diabetic 
Neuropathy), dated 13-Apr-2022 version 7.0. Reference materials for this statistical plan include 
the protocol and the accompanying sample data collection documents. Operational aspects 
related to collection and timing of planned clinical assessments are not repeated in this SAP 
unless relevant to the planned analysis. 
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA), 
and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical 
Trials (ICH, 1998). All work planned and reported for this SAP will follow internationally 
accepted guidelines, published by the American Statistical Association (ASA, 2018) and the 
Royal Statistical Society (RSS, 2014), for ethical statistical practice. 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. 
 
 
 
The statistical plan described hereafter has been developed by blinded study team members prior 
to the Interim Analysis but after the Administrative Analysis has been conducted. It will be 
approved before final unblind, performing inferential or descriptive analysis of hard-locked data 
from AstraZeneca’s study D5680C00002. 
2. 
Study Objectives and Endpoints 
2.1. 
Study Objectives 
2.1.1. Primary Objective 
The primary objective is to assess the efficacy of MEDI7352 versus placebo on chronic pain in 
subjects with painful diabetic neuropathy (PDN) currently taking standard of care medication for 
their PDN pain. 
2.1.2. Secondary Objectives 
The secondary objectives are: 
• To assess the safety and tolerability of MEDI7352 in subjects with PDN 
• To assess the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of 
MEDI7352 in subjects with PDN  
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• To characterise the dose-response relationship of MEDI7352 on chronic pain in subjects 
with PDN 
2.1.3. Exploratory Objectives 
2.2. 
Study Endpoints 
2.2.1. Efficacy Endpoints 
2.2.1.1. 
Primary Efficacy Endpoint 
The primary efficacy endpoint of this study is the change in the weekly average of the average 
daily pain scores from the baseline week to Week 12 of MEDI7352 compared to placebo, as 
measured on an 11-point (0-10) numeric rating scale (NRS). 
The target population is the entire patient population, i.e., the collection of all patients eligible to 
be included in the randomized clinical trial based on prespecified (and duly justified) 
inclusion/exclusion criteria.  
The study was not designed using the Estimand framework. However, the following general 
aspects of an Estimand can be inferred: the Estimand can be generically defined as the true 
between‐treatment difference in the target population endpoint means for the change from 
baseline for the Pain NRS at Week 12, while-on-treatment and regardless of prohibited or rescue 
medication use. 
 
2.2.1.2. 
Secondary Efficacy Endpoint(s) 
The secondary efficacy endpoints of this study include the following:  
• Change in the weekly average of the average daily pain score, as measured on an 11-
point (0-10) NRS, from baseline to Weeks 2, 4, 6, 8, and 10 of treatment and the week 
before the follow-up visit.  
• Percentage of subjects who have achieved ≥30% and ≥50% reductions in the weekly 
average of the average daily pain score from baseline during Weeks 4, 8, and 12 of 
treatment and the week before follow-up. 
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• Change in Galer Neuropathic Pain Scale (NPS) from baseline to Days 28, 56, and 84 of 
treatment and the follow-up visit. 
• Change in Daily Sleep Interference Scale (DSIS) from baseline to Days 28, 56, and 84 of 
treatment and the follow-up visit. 
• Proportion of subjects who have ‘improved’, ‘much improved,’ or ‘very much improved’ 
relative to baseline on the Patient Global Impression of Change (PGIC) on Days 28, 56, 
and 84 of treatment and the follow-up visit. 
• Change in the 36-item Short-Form Health Survey (SF-36) from baseline to Day 84 of 
treatment. 
• Usage of rescue medication (yes/no) from baseline to Week 12 of treatment. 
2.2.1.3. 
Exploratory Efficacy Endpoint(s) 
2.2.2. Safety Endpoints 
The safety endpoints of this study include the following: 
• Adverse events (AEs) and serious adverse events (SAEs) 
• Physical and neurological examinations 
• Neuropathy assessments Total Neuropathy Score-Nurse (TNSn) S 
• Strength (dorsiflexion), and deep tendon reflex (knee and ankle) assessments 
• Vital signs 
• 12 lead digital electrocardiogram (ECGs) 
• Clinical laboratory testing (hematology, chemistry, coagulation, and immunology) 
• Motor and sensory nerve conduction studies 
• Concomitant medications and therapies 
• Injection site reactions and infusion reactions 
2.2.3. Pharmacokinetic/Pharmacodynamic Variable(s) 
The pharmacokinetic (PK) endpoints of the study include the MEDI7352 concentrations 
measurements in serum/plasma.  
The pharmacodynamic (PD) endpoints of the study include total nerve growth factor (tNGF) 
measurements in serum/plasma. 
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2.2.4. Other Endpoints 
The following endpoints will be assessed:  
• Change in the weekly average of the average daily pain scores from the baseline week to 
Week 12, as measured on an 11-point (0-10) NRS, versus dose. 
• 
Immunogenicity (ADA) assessments. 
3. 
Overall Study Design and Plan 
This is a randomised, double-blind, placebo-controlled study of MEDI7352 in subjects with 
moderate to severe chronic PDN persistent for 6 months or longer, not adequately controlled by 
standard of care treatments, caused by type 1 or type 2 diabetes mellitus. The study incorporates 
a screening period of up to 45 days and a 12-week double-blind treatment period during which 
MEDI7352 or placebo will be administered intravenously (IV) on 6 occasions, with each dose 
separated by 14 days. There will be a 6-week follow-up period.  
3.1. 
Overall Design 
3.2. 
Sample Size and Power 
There will be 4 stages in the study: in the first stage, subjects will be randomly assigned to 
placebo or the lowest dose (
) until at least 10 subjects have been recruited. In the second 
stage, up to 30 subjects will be randomly assigned to a placebo or
 of MEDI7352; prior 
to commencing the third stage, the safety and tolerability experience following administration of  
multiple doses of 
 in the Phase 1 study of MEDI7352 will be evaluated. In stage 3 of 
the study, approximately 67 subjects will be randomly assigned to placebo or 
 of  
MEDI7352. The third stage will include an interim analysis to enable decision making for stage 
4 with respect to the sample size and dose allocation ratio. If no changes are made following the 
interim analysis, in stage 4 of the study, approximately 165 eligible subjects will be randomly 
assigned to treatment across 3 dose levels of MEDI7352 (
) or placebo, to 
ensure that approximately 236 subjects are evaluable for the efficacy analysis of stages 2 to 4 
combined. The number of subjects in the fourth stage is currently planned to follow an equal 
treatment allocation to each of the 4 treatment groups. However, the exact number of subjects 
and the allocation to each dose in stage 4 will be determined after the interim analysis. 
There is no formal sample size calculation for stage 1; 10 subjects in stage 1 are considered 
sufficient for the initial assessment of safety. The sample size for stages 2-4 combined was 
determined by a formal power calculation (see below) and the size of stage 3 was defined to 
enable decision making for the stage 4 sample size and dose allocation ratio. 
This study is powered at greater than 80% to detect a statistically significant (1-sided alpha = 
0.025) dose-response relationship when the true Week 12 placebo-corrected change from 
baseline difference at the 
 dose is 1.25 on the 11-point NRS scale (MEDI7352-placebo 
treatment) and the true dose-response follows a hyperbolic Emax relationship, with ED50 within 
the range 1-750 μg/kg. This calculation also assumes: 
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• The true standard deviation (SD) is 2.4, which is based on other studies undertaken with 
pregabalin in PDN (Satoh et al. 2011, Lesser et al. 2004, Rosenstock et al. 2004, Tӧlle et 
al. 2008). 
• The data from stages 2, 3, and 4 are combined so that the number of subjects for the dose-
response analysis is 236 with the total number evaluable for placebo, 
 
 doses equal to 81, 37, 51, and 67, respectively. This is comprised of, assuming an 
overall 10% non-evaluability rate: 
o 28 out of 30 randomised in stage 2; 14 per arm  
o 60 out of 67 randomised in stage 3; 30 per arm, and  
o 148 out of 165 randomised in stage 4; 37 per arm 
• The dose-response hypothesis test is multiplicity adjusted as described by Pinheiro et al. 
2006 in order to control the type 1-error. 
The above calculations were performed using the software R and the R-package ‘DoseFinding’ 
[https://cran.r-project.org/web/packages/DoseFinding/DoseFinding.pdf] with the following 
parameters: 
• Population SD (of change from baseline to week 12) = 2.4  
• Placebo effect = 1 point reduction in NRS and 
 effect = 2.25 reduction from 
baseline, ie, delta= 1.25 
• Linear contrasts were determined from 5 ‘candidate dose’ response models which are all 
Emax models with decreasing potency/increasing ED50: 7.5, 15, 30, 60, 750 μg/kg. The 
5th case is essentially linear in dose. Emax models were chosen following the 
recommendations in a recent meta-analysis of dose response studies by Thomas et al., 
2014. 
• Power was assessed across 16 alternative true dose response curves, 12 Emax with ED50 
ranging from 0.375 to 750 μg/kg, 3 logistic and 1 quadratic, all having a Week 12 
placebo-corrected change from baseline difference at the 
 dose of 1.25. 
The overall withdrawal rate is anticipated to be approximately 10%. However, since the primary 
analysis will use Last Observation Carried Forward (LOCF) for withdrawn subjects, and the SD 
estimate is taken from studies which also used the LOCF approach, the only additional subjects 
recruited will be to account for withdrawals in stages 2, 3, and 4 if withdrawal occurs at, or prior 
to, the Week 2 visit. 
The number of subjects who will agree to participate in the genetic research is unknown. It is 
therefore not possible to establish whether sufficient data will be collected to allow a formal 
statistical evaluation or whether only descriptive statistics will be generated. 
3.3. 
Study Population 
Male or female (postmenopausal or surgically sterile) subjects aged ≥18 to ≤80 years with 
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chronic PDN persistent for 6 months or longer, not adequately controlled by standard of care 
treatments . 
3.4. 
Treatments Administered 
Once randomized, subjects will be dosed with either MEDI7352 or placebo on Day 1, Day 14, 
Day 28, Day 42, Day 56, and Day 70. MEDI7352 or placebo will be administered IV over a 
60-minute period. To maintain the blind, a placebo volume equivalent to the MEDI7352 volume 
will be administered for each dosing. 
3.5. 
Method of Assigning Subjects to Treatment Groups 
The randomisation schedule will be computer generated using a permuted block algorithm 
appropriate to the treatment groups included in each stage and will randomly allocate 
investigational product (IP) to randomisation numbers. The randomisation numbers will be 
assigned sequentially through a central interactive web response system (IWRS) as subjects are 
entered into the study. The randomisation schedule will not be stratified, and study centre will 
not be a blocking factor in the randomisation schedule. 
The randomisation schedule has been prepared by Premier Research before the start of the study. 
No one involved in the study performance will have access to the randomisation schedule before 
official unblinding of treatment assignment. No subject will be randomised into this study more 
than once. 
3.6. 
Blinding and Unblinding 
All subjects, investigators, and study personnel involved in the conduct of the study, including 
data management, will be blinded to treatment assignment with the exception of a specified 
unblinded statistician and programmer from Premier Research who will have access to the 
randomization code, unblinded site monitors and clinical manager from Premier Research, and 
the unblinded pharmacist at each study site. The unblinded study personnel will not participate in 
study procedures or data analysis prior to unblinding of the study data to all study related 
personnel. Unblinded personnel who are not otherwise involved in the study will prepare data for 
review and interim analysis. 
Study personnel will make every effort to safeguard the integrity of the study blind to minimize 
bias in the conduct of the study. Treatment unblinding is discouraged if knowledge of the 
treatment assignment will not materially change the planned management of a medical 
emergency. Unblinding will be permitted in a medical emergency that requires immediate 
knowledge of the subject’s treatment assignment. 
Unblinding should be discussed in advance with the medical monitor if possible. For emergency 
unblinding, study personnel will use the IWRS. Only authorized users will have access to the 
unblinding function in the IWRS, and the IWRS will reveal the treatment information for the 
selected subject only. If the investigator is not able to discuss treatment unblinding in advance, 
then he/she must notify the medical monitor as soon as possible about the unblinding incident 
without revealing the subject’s treatment assignment. The IWRS will also send a blinded 
notification to the clinical team alerting them that a break blind occurred. 
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The investigator or designee must record the date and reason for treatment unblinding on the 
appropriate electronic case report form (eCRF) for that subject. In all cases that are not 
emergencies, the investigator must discuss the event with the medical monitor prior to 
unblinding the subject’s treatment assignment. 
If treatment assignment is unblinded for an individual subject, study personnel will be notified of 
that subject’s treatment assignment without unblinding the treatment assignments for the 
remaining subjects in the study. Thus, the overall study blind will not be compromised. If a 
subject’s treatment assignment is unblinded, he/she will be asked to withdraw from the study. 
The investigator will make this decision after consultation with the medical monitor. 
Overall unblinding will take place at the end of the study only after database lock has been 
achieved. 
3.7. 
Schedule of Events 
Please see the protocol Tables 2-1, 2-2 for a detailed schedule of events. 
4. 
Statistical Analysis and Reporting 
All efficacy and safety statistical analysis will be based on data from stages 1, 2, 3 and 4 
combined, unless specified otherwise. 
4.1. 
Introduction 
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations will primarily use SAS (release 9.4 or higher). The multiple 
comparison and modelling (MCP-Mod) analysis will be performed using R (release 4.2.1 or 
higher) and the DoseFinding package (version 1.0-3 or higher). If a use of other software is 
warranted, the final statistical methodology report will detail what software was used for what 
purposes. 
Continuous (quantitative) variable summaries will include the number of subjects (n) with 
non-missing values, the number of missing values, arithmetic mean, SD, median, 1st, and 3rd 
quartiles (where applicable), minimum, and maximum.  
Categorical (qualitative) variable summaries will include the frequency and percentage of 
subjects who are in the particular category or each possible value. In general, the denominator 
for the percentage calculation will be based upon the total number of subjects in the study 
population for the treatment group, unless otherwise specified. The denominator for by-visit 
displays will be the number of subjects in the relevant study population with non-missing data at 
each visit, unless otherwise specified.  
The minimum and maximum will be reported with the same degree of precision (i.e., the same 
number of decimal places) as the observed data. Measures of location (mean and median) will be 
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reported to 1 degree of precision more than the observed data and measures of spread will be 
reported to 2 degrees of precision more than the observed data. 
For derived data, minimum and maximum will be reported to 2 degrees of precision. Measures 
of location (mean and median) will be reported to 3 degree of precision, and measures of spread 
will be reported to 4 degrees of precision. 
Percentages will be presented to 1 decimal place, unless otherwise specified. 
Unless otherwise indicated, all statistical tests will be conducted at the 0.025 significance level 
using 1-tailed tests, and P values will be reported. For estimation purposes, 2-sided 95% 
confidence intervals (CI) will be presented. 
Total NGF and PK concentration data will be summarized by dose as per the quantitative 
variables and presenting the number (n) of non-missing observations, and the n < lower limit of 
quantification (LLOQ). PD and PK parameters will be summarized by dose and will include the 
arithmetic mean, SD, geometric mean (gmean), gmean ± geometric SD, geometric coefficient of 
variation (gCV%), median, minimum and maximum. 
4.2. 
Interim Analysis and Data Monitoring 
Details of the interim analysis have been included in the Statistical Interim Analysis Plan (SiAP) 
version 1.0 dated 10-Feb-2023. 
5. 
Analysis Populations 
The following analysis populations are planned for this study:  
• Screening Population (Screened): All subjects who provide informed consent and/or 
assent and provide demographic and/or baseline screening assessments, regardless of the 
subject’s randomisation and treatment status in the study. The Screening Set will be 
analysed as randomised, according to planned treatment. 
• Safety Population (SAF): The Safety Population includes all subjects who receive at 
least 1 dose of double-blind study medication. The Safety Set will be analysed according 
to actual treatment. 
• Modified Intent-To-Treat Population (mITT): The modified intent-to-treat population 
will be used for all efficacy analyses and will include all randomised subjects who 
receive at least 1 dose of double-blind study medication and have at least 1 daily NRS 
assessment while receiving double-blind treatment. The mITT Set will be analysed as 
randomised, according to planned treatment. 
• Pharmacokinetic Population (PK): The PK Population will include all subjects for who 
a PK sample was obtained and analysed. The PK Set will be analysed according to actual 
treatment. 
Assignment of subjects to populations will be confirmed at a blinded data review meeting to be 
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held before the study database is locked. 
If a subject is randomised incorrectly or is administered the incorrect IP, analyses of the mITT 
population will be based on the IWRS-assigned treatment whereas all other analyses will be 
based on the actual treatment. 
6. 
General Issues for Statistical Analysis 
6.1. 
Statistical Definitions and Algorithms 
6.1.1. Baseline 
For all safety endpoints, the last observation recorded prior to the first dose of treatment will be 
used as the baseline observation for calculations of change from baseline.  
For pain diary data the baseline period is defined as the seven-day period prior to randomization, 
i.e., Day -7 to Day -1, inclusive. A subject is considered to have an evaluable baseline pain score 
if there are at least 4 days of recorded diary pain scores in the 7-day period.  
6.1.2. Adjustments for Covariates 
In addition to treatment group, the baseline value of the variable undergoing analysis and the 
co-medication type (Anticonvulsant versus Antidepressant) will be included in the analysis of 
covariance (ANCOVA) model as additive covariates. Co-medication type will be determined by 
blinded clinical review of each subject’s medication record at baseline. 
Covariates in the mixed effects models repeated measures (MMRM) and generalized estimating 
equations (GEE) analyses include those specified for the ANCOVA analyses, together with time 
and its interaction with dose group.  
The crossing of co-medication type and median baseline pain score will be used as strata in the 
Cochran-Mantel-Haenszel (CMH) model tests. Assuming two co-medication types, the strata 
will be: 
1) Anticonvulsant (Baseline NRS < Median), 
2) Anticonvulsant (Baseline NRS > Median), 
3) Antidepressant (Baseline NRS < Median), 
 
4) Antidepressant (Baseline NRS > Median).  
Where the median baseline NRS is calculated over all subjects. 
6.1.3. Multiple Comparisons 
A multiple comparison procedure modelling approach (MCP-Mod) on LOCF data will be used 
for primary efficacy endpoints.  
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No adjustments will be made for multiple comparisons outside the MCP-Mod approach.  
6.1.4. Handling of Dropouts or Missing Data 
For the analyses of the primary efficacy endpoints based on the mITT Population, a variety of 
methods will be used to deal with missing data, including:  
• Primary Method: LOCF. 
• Observed cases analysis. 
• Baseline observation carried forward (BOCF) 
Subjects with missing weekly average NRS baseline data (i.e., zero or 1-3 days of diary pain 
scores) will not be included in the efficacy analysis because the primary analysis is change-from-
baseline. If a subject has zero or <3 days of diary pain data in each of the possible post-baseline 
seven day periods ending within the protocol definition of week 12 (day 84 + 3),  then an 
imputed ‘week 12 LOCF’ weekly average NRS pain score will be calculated from the latest 7 
‘non-missing’ entries of the subject’s diary closest to their nominal week 12 visit (i.e., the latest 
7 day period containing at least 4 NRS values), provided that this would qualify as at least ‘week 
2’ according to the windowing outlined in Section 6.1.5.  Otherwise, the week 12 LOCF weekly 
average NRS pain score will be set to missing.   
6.1.5. Analysis Visit Windows 
Statistical analyses will be based on scheduled visits and windows as per Protocol Table 2-1: 
Schedule of Events. If an assessment falls between 2 windows, then the closest visit will be used 
only if an assessment result is not provided within that window. All other visits will be listed only 
as unscheduled visits. For presentation purposes these will be mapped to the visit prior and labeled, 
e.g., Unscheduled Visit 3.1, if Visit 3 was the closest date prior. 
For pain diary data the following analysis periods will be defined:  
• Week Xi: the 7-day period ending within the protocol window Day Yi ± 3 where at least 4 
days out of 7 have recorded diary pain scores. Where several such windows exist the one 
ending closest to day Yi will be selected. If there are two such windows that are equidistant 
from day Yi, then the one with the largest number of diary entries will take precedence. If 
they have the same number of entries, then the later of the two end dates will be chosen. If 
no such window exists, then week Xi will be considered missing for the purposes of weekly 
average scoring.  
Where: 
• X1=2, Y1=14 
• X2=4, Y2=28 
• X3=6, Y3=42 
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• X4=8, Y4=56 
• X5=10, Y5=70 
• X6=12, Y6=84 
• The week before follow-up is defined as the 7-day period prior to the last day of pain diary 
data for subjects completing the study (i.e., entering in the Week 18) where at least 4 days 
out of 7 have recorded diary pain scores.  
6.1.6. Pooling of Sites 
Analysis by investigative site will not be conducted. 
6.1.7. Efficacy Variables 
6.1.7.1. 
Pain Numerical Rating Scale 
Subjects will assess their perceived average neuropathic pain over the previous 24 hours using an 
11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. 
Subjects will be instructed to assess their average daily pain at approximately the same time 
every morning, and to record their response in a subject diary (ePRO). 
6.1.7.2. 
  Neuropathic Pain Scale 
Subjects will assess their neuropathic pain using the Galer NPS. The NPS includes 2 descriptors 
of pain, including intensity and unpleasantness, and 8 descriptors that assess specific qualities of 
neuropathic pain: sharp, hot, dull, cold, sensitive, itchy, deep, and surface pain. Each of these 10 
dimensions has a 0 to 10 NRS in which 0 is equal to no pain and 10 equals the most intense pain. 
There is an additional descriptor about duration and frequency of pain, which has a 1 to 3 NRS. 
In which 1 = I feel a background pain all the time and occasional flare-ups (breakthrough pain) 
some of the time, 2 = I feel a single type of pain all the time, and 3 = I feel a single type of pain 
only sometimes. Other times, I am pain free. 
6.1.7.3. 
Daily Sleep Interference Scale 
Subjects will assess how their neuropathic pain interferes with their sleep using the DSIS. The 
DSIS is an 11-point Likert scale, with 0 indicating that pain did not interfere with sleep and 10 
indicating that pain completely interfered with sleep. The DSIS is completed by subjects once a 
day (upon awakening) to accurately capture variability in sleep interference due to pain on a 
daily basis, thus minimizing recall bias. 
6.1.7.4. 
Patient Global Impression of Change 
Subjects will rate their overall improvement in health status using the PGIC. The PGIC consists 
of a 7-point scale where 1 = “very much improved” and 7 = “very much worse.” Subjects will be 
asked the following question: “How would you rate your overall improvement with treatment 
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during the clinical study?” The response options include the following:  
• Very Much Improved - 1 
• Much Improved - 2 
• Minimally Improved - 3 
• No Change - 4 
• Minimally Worse - 5 
• Much Worse - 6 
• Very Much Worse - 7 
6.1.7.5. 
Short-Form Health Survey 
The subject’s health status and quality of life will be assessed using the SF-36. The SF-36 
assesses 8 health concepts: 1) limitations in physical activities because of health problems; 2) 
limitations in social activities because of physical or emotional problems; 3) limitations in usual 
role activities because of physical health problems; 4) bodily pain; 5) general mental health 
(psychological distress and well-being); 6) limitations in usual role activities because of 
emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The 
items use Likert-type scales with either 5 or 6 points, or 2 or 3 points. Scores will be derived by 
the validated built-in scoring tool. Higher SF-36 scores indicate a better state of health. 
6.1.7.6. 
Rescue Medication Use 
Subjects will record all rescue medications they take for neuropathic pain in a paper diary. This 
will be transcribed in to the eCRF collecting usage, date and time of rescue medication, 
medication administered, dose, frequency and route.  
Subjects will be grouped by the following for rescue medication use: 
• 
Compliant with protocol guidance on permitted therapies 
• 
Non-compliant with protocol guidance on permitted therapies 
A review of medications will be conducted at a blinded data review meeting to be held before the 
study database is locked. 
6.1.7.7. 
 
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6.1.8. Derived Variables 
• Change from baseline = value at current time point – value at baseline.  
• Reference End Date = Date of completion/discontinuation. 
• Study duration = Reference end date – date of first dose of treatment + 1 
• Duration of exposure (days) = min(date of last dose of treatment + 14 days or date of death) 
– date of first dose of treatment + 1. 
• Treatment-emergent AEs (TEAEs) are defined as: 
o AEs with onset at the time of or following the start of treatment with IP, or 
o AEs starting prior to the start of treatment but increasing in severity or relationship 
at the time of, or following, the start of treatment with IP. 
• Average Baseline Pain NRS = the arithmetic average of the ‘non-missing’ daily pain scores 
within the baseline period defined in Section 6.1.1. For example, if a subject has 5 days of 
non-missing pain scores their average will be calculated over 5 days, not the full 7-day 
baseline period. 
• Average Week X Pain NRS = the arithmetic average of the ‘non-missing’ daily pain scores 
within each subject’s specific week X period defined in Section 6.1.5. 
• Average Week 12 Pain NRS (LOCF) = the arithmetic average of the ‘non-missing’ daily 
pain scores within each subject’s specific week 12 period or according to the imputed 
LOCF/BOCF approach defined in Section 6.1.4. 
• Change from Baseline to Week X Pain NRS = for each subject ‘Average Week X Pain 
NRS’ minus ‘Average Baseline Pain NRS’. 
• Change from Baseline to Week 12 Pain NRS (LOCF/BOCF) = for each subject ‘Average 
Week 12 Pain NRS (LOCF)’ minus ‘Average Baseline Pain NRS’. 
• Galer NPS Total Score (ranges from 0 to 100): sum of Pain Intensity, Pain Unpleasantness, 
Pain Sharpness, Pain Hotness, Pain Dullness, Pain Coldness, Pain Sensitivity, Pain Itching, 
Deep Pain Intensity, and Surface Pain Intensity (All in an 11-point NRS). 
• Change from Baseline to Week X Galer NPS Total Score = for each subject ‘Galer NPS 
Total Score’ minus ‘Baseline Galer NPS Total Score’. 
• Total number of days rescue medication was used = End Date of Medication - Start Date 
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of medication + 1. Each day on which rescue medication was used at least once is 
counted. 
• Cumulative consumption (mg) of paracetamol rescue medication use = Total dose of 
rescue medication (mg) consumed during the days in which paracetamol was used. 
• Average daily dose (mg) of paracetamol rescue medication use = Cumulative 
consumption of paracetamol rescue medication (mg) /total number of days paracetamol 
rescue medication was used. 
6.1.9. Data Adjustments/Handling/Conventions 
All collected data will be presented in listings. Data not subject to analysis according to this plan 
will not appear in any tables or graphs but will be included only in the data listings. 
All P values will be displayed in four decimals and rounded using standard scientific notation (e.g., 
0.XXXX). If a P value less than 0.0001 occurs it will be shown in tables as <0.0001. 
AEs and medical histories will be coded using the latest version of the Medical Dictionary for 
Regulatory Activities (MedDRA) thesaurus available at time of programming. 
If partial dates of AEs occur, the convention for replacing missing dates for the purpose of TEAE 
is as follows: if just day is missing then the day assigned is the first day of the month or the date 
of first dose (if in the same month), whichever is later; if just month is missing then the month 
assigned is the month of the first dose, unless that results in a date prior to the first dose in which 
case the month after the first dose is used; and if both month and day are missing then the month 
assigned is the month of the first dose and the day assigned is either the first day of the month or 
the first dose date, whichever is later. 
If partial times occur, the convention is as follows: if the missing time occurs on the day of the 
first dose and both the hour and minute are missing then the time assigned is the time of the first 
dose, otherwise if both the hour and minute are missing and the date is not the date of first dose 
the time assigned is 12:00; if the date is the same as the date of the first dose and only hour is 
missing the hour assigned is 12 or the hour of first dose, whichever is later, and if the date is the 
same as the date of first dose and only the minute is missing the minute assigned is 30 or the 
minute of first dose, whichever is later. Otherwise the hour assigned is 12 if the hour is missing 
and the date is not the same as the date of first dose and the minute assigned is 30 is the the date 
is not the same as the date of first dose. 
These conventions will be applied only to AE onset dates and times with the following 
precaution:  if the missing date and time reflect the date and time of onset of an AE, the modified 
date and time will be constructed to match the first documented date/time post drug 
administration while preserving the order in which the AE was reported in the eCRF. 
In general, for quantitative laboratory values reported as ‘<X’ or ‘≤X’, the LLOQ will be used 
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for analysis (i.e., the value of X will be used in the analysis for lab values reported as ‘<X’ or 
‘≤X’). Similarly, for quantitative laboratory values reported as ‘>X’ or ‘≥X’, the upper limit of 
quantification (ULOQ) will be used for analysis (i.e., the value of X will be used in the analysis 
for lab values reported as ‘>X’ or ‘≥X’). 
For analysis purposes, repeat laboratory test results will not be used unless the original 
laboratory value is missing or indicated as invalid, in which case the first non-missing repeated 
laboratory value will be used for data analysis. 
ADA titre reported as <30 (below the minimum required dilution) is a negative result for the 
presence of ADA. 
For descriptive statistics of serum concentration summaries: 
• 
At a time-point where less than or equal to 50% of the values are not quantifiable (NQ, 
below LLOQ), all NQ values will be set to the LLOQ, and all descriptive statistics will be 
calculated accordingly. 
• 
If more than 50%, but not all, of the concentrations are NQ, the geometric mean, 
geometric mean ± geometric SD and gCV% will be reported as not calculable (NC). The 
maximum value is reported from the individual data, and the minimum and median are 
set as NQ. 
• 
If all concentrations are NQ at a time-point, the geometric mean, minimum, median and 
maximum are reported as NQ and the gCV% and geometric mean ± geometric SD as NC. 
7. 
Study Patients/Subjects and Demographics 
7.1. 
Disposition of Patients/Subjects and Withdrawals 
The total number of subjects for each of the following analysis populations will be presented for 
the Screening Population by randomized treatment group and overall: 
• Screening Population 
• Safety Population 
• mITT Population 
• Included in the mITT population 
▪ Evaluable Week 12 efficacy 
▪ Evaluable LOCF efficacy 
• Not efficacy evaluable 
• PK Population 
For the Screening Population, disposition will include tabulation of: 
• the number of screened subjects 
• the number of re-screened subjects 
• the number of enrolled subjects 
The output will be further presented by treatment group and overall summarising: 
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• the number of randomized subjects 
• the number of subjects who completed study treatment 
• the number of completed subjects 
• the number of subjects withdrawing (discontinued)  
• the reasons for discontinuation from study treatment and withdrawal from the 
study. 
For all categories of subjects by treatment group, percentages will be calculated using the 
number of subjects randomized as the denominator. 
7.2. 
Protocol Deviations 
Major protocol deviations, as determined by a Sponsor blinded review of the data prior to 
database lock and unblinding of the study will be reported in listings.  
The Sponsor or designee will be responsible for producing the final deviation file. This file will 
be finalized prior to database lock, and all information will be included in the SDTM.DV domain 
(deviations domain). 
All protocol deviations will be presented in a data listing, with a flag to indicate if a deviation 
was considered major.  
A summary table by treatment group and overall will be generated based on protocol deviation 
severity (minor/major) and the classification of protocol using the following categories:  
o Inclusion  
o Exclusion  
o Study drug  
o Assessment – safety  
o Assessment– efficacy  
o Lab/endpoint data  
o Visit window  
o Informed consent  
o Prohibited co-medication  
o Overdose/misuse 
o Other 
7.3. 
Demographics and Other Baseline Characteristics 
Descriptive summaries of the demographic and other baseline characteristics will be presented 
for all analysis populations. All demographic and baseline characteristics will be presented both 
overall and by treatment group. 
The following demographic and baseline data will be presented in tables: 
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• Demographics: age, gender, ethnicity, race, height, weight, and body mass index (BMI)  
• For female the number and percentage of women surgically sterile and postmenopausal 
will be described.  
• Diagnosis of osteoarthritis: number of subjects with osteoarthritis diagnosis and area 
affected, clinical significance, radiological investigations, radiological significance, 
Kellgren-Lawrence score. 
The number and percent of subjects reporting various medical histories, grouped by MedDRA 
system organ class (SOC) and preferred term (PT), will be tabulated by treatment group.  
This analysis will be conducted for the Safety Population. 
7.4. 
Exposure 
The following parameters of study drug exposure and compliance will be summarized by 
treatment group for the Safety Population: 
 
• Maximum number of doses administered 
• Total duration of exposure 
• Total (cumulative) dose infused 
In addition, any incomplete infusions will be listed. 
8. 
Efficacy Analysis 
All efficacy variables will be summarized descriptively including number of observations, 
number of missing values, mean, SD, minimum, median, and maximum for continuous variables, 
and frequency of observations in each category and percentage for categorical variables.  
Primary and secondary endpoint efficacy data will be tabulated according to the observed cases, 
LOCF, and BOCF approaches. 
8.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint of this study is the change in the weekly average of the average 
daily pain scores from the baseline week to Week 12 measured on an 11-point (0-10) NRS. 
MCP-Mod approach. The main statistical analysis of the primary efficacy endpoint will use the 
MCP-Mod approach on LOCF data, which is a well-established statistical methodology for 
establishing both the existence of a dose response and modelling the underlying dose-response 
relationship. The modelling step (‘MOD’ step) from the MCP-MOD approach will only be 
conducted if stage 4 is initiated, otherwise there would be insufficient dosing data to fit the non-
linear models. 
There are two steps to MCP-Mod: 
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1. The ‘MCP’ step is a rigorous method to establish presence of a dose response while 
protecting the type I error and, if the dose-response relationship is statistically significant, 
then  
2. The ‘MOD’ step estimates the dose response function and associated model parameters. 
The MCP test will use linear contrasts corresponding to the five candidate models described in 
Section 3.2. The test will use pre-specified model parameters and optimal contrasts for each will 
be generated. The hypotheses are as follows: 
 
Null hypothesis (H0): Optimal contrasts µ ≥0 for all models 
 
Alternative hypothesis (HA): Optimal contrasts µ <0 for at least one model 
where µ is the true event rate. 
The underlying model will be an ANCOVA with dependent variable ‘change from baseline to 
Week 12 (LOCF)’, and independent variables will include: 
• dose group as a factor variable with the placebo group as the reference level 
• baseline score, i.e. baseline weekly average pain (NRS), as a continuous variable 
• co-medication type. 
The random error is assumed to be normally and independently distributed with constant 
variance. The parameter estimates of the difference between each dose group and placebo, least 
square (LS) Means estimates of change from baseline to Week 12 for each dose, standard errors, 
95% unadjusted, ‘Lalonde-type’ asymmetric CI (i.e., lower limit of 1-sided 90% CI and upper 
limit of 1-sided 80% CI), and P values will be presented. 
If the MCP test is statistically significant, then the MOD step will select the most appropriate 
model from hyperbolic Emax, sigmoidal Emax or linear using the ‘Emaxlin’ approach as described by 
Kirby et al (2011). From this model (including the same covariates as the ANCOVA model), 
various estimates will be derived (together with CI) of parameters of interest such as ED50, 
effective dose to achieve 90% of maximum effect (ED90), dose to achieve selected target effects, 
and model estimates of the treatment effect at doses studied (see Appendix in Section 15). 
MMRM: In addition, changes from baseline in continuous endpoints will be compared between 
treatment groups using mixed models repeated measures including terms for: 
• co-medication type (as a factor) 
• treatment (as a factor) 
• time (as a factor) 
• the interaction between treatment and time point 
• and the baseline value of the variable undergoing analysis  
The mixed model for repeated measure will use average of average daily pain score of observed 
data at week 2, 4, 6, 8, 10, and 12. An unstructured covariance matrix will be used to model the 
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within-subject errors. The Kenwards-Roger method will be used to estimate degrees of freedom. 
If this analysis fails to converge, a simpler structure (e.g., first-order ante-dependent or 
heterogeneous compound symmetry structures) will be found using Akaike information criterion 
(AIC). 
The results will be presented using LS Means estimates, corresponding 95% CI for each 
treatment group and timepoint, along with the LS Means of differences with Placebo, standard 
error, 95% CI and p-values. 
The primary efficacy analysis will be based on the mITT population.  
8.1.1. Sensitivity Analyses of the Primary Efficacy Endpoint  
To complement the MCP-MOD outputs, estimates and CI of each pairwise comparison versus 
placebo from the ANCOVA model described in the MCP step will be produced. 
8.2. 
Secondary Efficacy Analysis 
The MMRM model outlined in Section 8.1 will be applied for secondary endpoints using 
observed cases: 
• Change in Galer NPS total score from baseline to Days 28, 56, and 84 of treatment and the 
follow-up visit.   
• Change in DSIS from baseline to Days 28, 56, and 84 of treatment and the follow-up visit. 
• Change in the eight SF-36 parameters from baseline to Day 84 of treatment. 
A GEE approach for binary data will be used for the following dichotomous endpoints: 
• Percentage of subjects who have achieved ≥30% reductions in the weekly average of the 
average daily pain score from baseline during Weeks 4, 8, and 12 of treatment and the week 
before follow-up. 
• Percentage of subjects who have achieved ≥50% reductions in the weekly average of the 
average daily pain score from baseline during Weeks 4, 8, and 12 of treatment and the week 
before follow-up. 
The GEE model specification will include a binomial distribution, a logit link function, and an 
unstructured covariance matrix. If this analysis fails to converge, a simpler structure (e.g. first-
order autoregressive or compound symmetry structures) will be found using AIC. The model will 
include terms for:  
• co-medication type (as a factor) 
• treatment (as a factor) 
• time (as a factor) 
• the interaction between treatment and time  
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A CMH test stratified by the crossing of co-medication subgroup and median baseline pain score 
will also be carried out for the above dichotomous endpoints. The CMH risk difference at Week 
12 will be estimated between the treatment group and placebo. The number and percentage of 
subjects meeting the reduction response will be displayed, along with the risk difference, 95% CI 
and P value.  
The proportion of subjects who have ‘improved’, ‘much improved,’ or ‘very much improved’ 
relative to baseline on the PGIC on Days 28, 56, and 84 of treatment and the follow-up visit will 
be tested using a CMH statistics. 
The efficacy analysis of secondary endpoints will be based on the observed cases and on the 
mITT population.  
Usage of rescue medication (yes/no) will be summarized by dose group for each visit from 
baseline to Week 12 of treatment and over the whole treatment period. The following additional 
variables will be derived and summarised: 
• 
Total number of days rescue medication was used. 
− Each day on which rescue medication was used at least once is counted. 
• 
Cumulative consumption (mg) of paracetamol rescue medication use. 
− Calculated as the total dose of rescue medication (mg). 
• 
Average daily dose (mg) of paracetamol rescue medication use. 
− Calculated as: cumulative consumption of rescue medication (mg)/total number of 
days rescue medication was used. 
8.3. 
Exploratory Efficacy Analysis 
9. 
Safety and Tolerability Analysis 
All safety analyses will be performed on the Safety Population using descriptive statistics. 
Descriptive summaries by treatment group and overall will be produced. No inferential statistical 
tests will be performed.  
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The analysis of safety assessments in this study will include summaries of the following 
categories of safety and tolerability data collected for each patient: 
• Adverse events 
o TEAEs 
o SAEs 
o Significant AEs 
▪ TEAEs leading to discontinuation of IP 
o AEs of Special Interest 
▪ Positively-adjudicated possible or probable rapidly progressive 
osteoarthritis (RPOA), subchondral insufficiency fractures, primary 
osteonecrosis, or pathological fracture 
▪ Infections that meet SAE and/or severe AE criteria   
▪ Anaphylactic reactions or infusion-related reactions that lead to permanent 
discontinuation of administration of IP 
o TEAEs associated with abnormal liver  
o Any deaths 
o Drug induced liver injury 
Clinical laboratory investigations  
• Vital signs 
• Electrocardiograms (ECG) 
• COVID-19 screening 
• Physical and neurological examination 
• Total neuropathy score-nurse 
• Motor and sensory nerve conduction studies 
• Strength and deep tendon reflexes 
• Hypersensitivity /Anaphylactic reactions 
• Injection site or infusion reactions 
• Liver diagnostic investigations, risk factors, signs and symptoms. 
• Infection diagnostic investigations, risk factors, signs and symptoms. 
• Prior and concomitant medications and therapies 
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9.1. 
Adverse Events 
A summary table by treatment group will present the number and percent of subjects reporting: 
• Any AEs 
• Non-serious AEs occurring in more than 5% of subjects 
• Any TEAEs 
• Any SAEs 
• Any TEAEs possibley related to study drug 
• Any TEAEs leading to discontinuation of IP 
• Any SAEs possibley related to study drug 
• Life-threatenings SAEs 
• SAEs resulting in death 
Summaries of the incidence of TEAEs will be displayed by treatment group, by ADA status, by 
severity and by: 
• SOC and PT 
• SOC, PT, and maximum severity (mild, moderate, severe) 
• SOC, PT, and maximum causality (not related, possibly related) to the study drug 
In the summaries showing severity and relationship to study drug the event with the maximum 
severity or strongest relationship will be reported. If a particular event is missing the severity 
and/or relationship, then the strongest possible severity or relationship will be assumed for 
analysis (severity = severe, relationship = related). 
In the case of multiple occurrences of the same AE within the same subject, each subject will 
only be counted once for each level of summarization.  
All AEs will be presented in a by-treatment and by-subject listing, detailing the verbatim term 
given by the Investigator, the PT, SOC, onset date and time, end date and time, severity, 
outcome, relationship to study drug, action taken with study drug, other action taken, 
seriousness, and criteria for seriousness.  
9.1.1. Adverse Events Leading to Discontinuation of IP 
A summary of incidence rates (frequencies and percentages) of TEAEs leading to 
discontinuation of IP, by treatment group, SOC, and PT will be prepared. The table will also be 
produced separately by maximum severity and maximum causality. 
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A data listing of TEAEs leading to discontinuation of IP will also be provided, displaying details 
of the event(s) captured on the rCRF. 
9.1.2. Deaths and Serious Adverse Events 
Any deaths that occur during the study and serious adverse events will be listed. 
A summary of incidence rates (frequencies and percentages) of SAEs by treatment group, SOC, 
and PT will be prepared. The table will also be produced separately for life-threatening SAEs, 
for SAEs with outcome death and for SAEs by relationship to study medication. 
9.1.3. Drug-Induced Liver Injury 
A summary of incidence rates of TEAEs associated with abnormal liver by treatment group, 
SOC, and PT will be prepared.  
The type and the results of the liver diagnostic investigation performed will be tabulated by 
treatment group.  
The number and percentage of subjects within each type of liver risk factors and style events will 
be tabulated by treatment group. Liver signs and symptoms will be presented in the same way. 
9.1.4. Infection Risk 
A summary of incidence rates of infections that meet SAE or severe AE criteria by treatment 
group, SOC, and PT will be prepared.  
The type and the results of infection diagnostic investigation performed will be tabulated by 
treatment group.  
The number and percentage of subjects within each type of infection risk factors and style events 
will be tabulated by treatment group. Infection signs and symptoms will be presented in the same 
way. 
9.2. 
COVID-19 Vaccination and Screening 
The number and percentage of fully vaccinated subjects at baseline will be summarized by 
treatment group. 
The symptoms, tests, and results from coronavirus disease 2019 (COVID-19) screening will be 
tabulated for each visit by treatment group. 
COVID-19 vaccination, signs, symptoms and impact will be presented in listings. 
9.3. 
Clinical Laboratory Evaluations 
Absolute values and changes from baseline will be summarized using descriptive statistics by 
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treatment group and visit for chemistry, hematology, coagulation, and urinalysis tests. 
The number of subjects with clinical laboratory values (chemistry, hematology, coagulation, and 
urinalysis) categorized as below, within, or above normal ranges (or as either normal or 
abnormal for urinalysis variables that do not have quantitative ranges) and whether they are 
clinically significant or not will be tabulated for each clinical laboratory analyte by treatment 
group and visit. A shift table showing change from baseline in range categories for each clinical 
laboratory analyte will be produced by treatment group and by visit.  
The number of subjects with values for Aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN), and with values for total bilirubin 
(TBL) ≥ 2 × ULN will be summarized in AST, ALT vs. TBL shift tables to identify Potential 
Hy’s Law (PHL) and Hy’s Law (HL) cases by treatment group. 
Diagnostic immunology, urine pregnancy, and urine drug tests will be presented in by-subject 
listings only. 
All laboratory values will be displayed in the data listings and those that are outside the normal 
range will be flagged, along with corresponding normal ranges. 
9.4. 
Vital Signs 
Descriptive summaries of actual values and changes from baseline by treatment group, visit and 
time point will be presented for: 
• Supine heart rate 
• Supine systolic blood pressure 
• Supine diastolic blood pressure 
• Respiratory rate 
• Body temperature 
• Standing heart rate 
• Standing systolic blood pressure 
• Standing diastolic blood pressure 
Height, weight, and BMI will be presented at baseline only.  
9.5. 
Electrocardiograms 
The number and percentage of subjects with normal, abnormal not clinically significant, and 
abnormal clinically significant ECG results will be summarized by treatment group and by visit. 
If applicable (digital ECGs), descriptive summaries will be presented by treatment group, visit 
and time point (for Day 1 only) for ECG measures of PR, QRS, QT, RR intervals and for the 
calculated variables QTcF and HR for each treatment group and time point.  
Heart rate (HR) and Fridericia’s correction (QTcF) will be derived as follows: 
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Heart Rate (HR) 
𝐻𝑅= 103 60
𝑅𝑅𝑚𝑠𝑒𝑐
 
Fridericia’s Correction 
(QTcF) 
3
sec
RR
QT
QTc
m
f =
sec 
9.6. 
Physical and Neurological Examination 
The physical and neurological examination findings will be presented in listings.  
9.7. 
Total Neuropathy Score-Nurse 
Descriptive summaries of the TNSn will be presented by treatment groups and by visit. 
Additionally, the number and percentage of subjects within each category (0, 1, 2, 3, and 4) for 
each sub-score (sensory symptom, motor symptom, autonomic symptom, pin sensibility, 
vibration sensibility) will be summarized by treatment group and by visit. 
9.8. 
Motor and Sensory Nerve Conduction Studies 
Amplitude, peak latency, conduction velocity, and duration of nerve action potentials will be 
summarized by treatment group and visit for each location and evaluation type. The number of 
subjects with normal and abnormal evaluation will be tabulated by treatment group and by visit.  
9.9. 
Strength and Deep Tendon Reflexes 
The number and percentage of subjects within each category of the ankle dorsiflexion strength 
and the deep tendon reflexes will be tabulated by treatment group and by visit . 
9.10. Hypersensitivity/Anaphylactic Reactions, Injection Site or Infusion Reactions 
The type and symptoms of hypersensitivity/ anaphylactic reactions will be tabulated by treatment 
group.  
Injection site reactions will be tabulated describing the severity of pain, tenderness, 
erythema/redness, and induration/swelling by treatment group and by visit. 
Anaphylactic reactions and infusion related reactions will be summarized in line with AEs, 
displayed by treatment group and by: 
• SOC and PT 
• SOC, PT, and maximum severity (mild, moderate, severe) 
Hypersensitivity/anaphylactic and infusion related reactions will also be presented in a by-
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treatment and by-subject listings, detailing type of reaction, severity grade for symptom with 
highest severity and onset time for hypersensitivity/anaphylactic reactions, and assessment result 
for injection site or infusion related reactions.  
9.11. Prior and Concomitant Medication and Procedures 
Prior medications will be presented separately from concomitant medications.  
Medications will be coded using the latest version of the WHO Drug Dictionary. 
Medications that started before first dose of study medication will be considered prior, whether 
they were stopped before first dose of study medication or not.  
A concomitant medication is defined as any medication continuing or starting after first dose of 
study medication. This includes medications which start before first dose of study medication 
and continue while on-treatment, and medications that started after first dose of study 
medication. 
The frequency and percentage of concomitant medications will be summarized by Anatomical 
Therapeutic Chemical (ATC) class 2 and preferred name by treatment groups, unless otherwise 
specified.  
In listings, all medications will be displayed. 
If the start/stop dates of a medication are partially or completely missing, then the medication 
will be assumed to be concomitant if it cannot be definitely shown from the start/stop dates that 
it was not administered while on-treatment (from first exposure to treatment till last dose of 
study medication + 14 exposure days). Missing dates will not be replaced.  
Thus, the following approach will be taken for exclusion from concomitant medications because 
of discontinuation before start of treatment:  
• If the stop day is missing but the month is complete, then the medication will be excluded 
from concomitant medications only if the stop month is before the month of the first dose 
of study medication.  
• If the stop day and month are missing but the year is complete, then the medication will 
be excluded from concomitant medications only if the stop year is before the year of the 
first dose of study medication.  
• If the stop date is completely missing, then the medication will not be excluded.  
For concomitant medication exclusion (because of the late start after the end of the treatment 
period):  
• If the start day is missing but the month is complete, then the medication will be excluded 
from concomitant medications only if the start month is after the last month of the 
treatment period.  
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• If the start day and month are missing but the year is complete, then the medication will 
be excluded from concomitant medications only if the start year is after the year of the 
treatment period.  
• If the start date is completely missing, then the medication will not be excluded. 
A similar approach will be used for summarizing concomitant procedures. 
10. 
Changes from Planned Analysis 
The PK endpoints involving derivation of PK parameters for each dose and for each subject will 
be conducted by a population PK analysis of the data as part of a pooled data analysis instead of 
by a noncompartmental analysis (NCA). This will be documented in the CSR as a change in 
planned analysis. The pooled data analysis will be described in a separate modelling analysis 
plan. As a result, description of TLFs related to PK parameters are removed from this SAP. 
 
Additional analyses with pooled site as a covariate are not going to be conducted and as such, 
they are removed from this SAP. 
 
It was planned to have a supplementary analysis to the primary using an adaptive MCP-MOD 
method. In this analysis, stages 2+3 and stage 4 were going to be analysed separately and the 
results combined using an inverse-normal P value combination function (with weights related to 
the original planned sample sizes). This supplementary analysis is removed from this SAP. 
 
The Cochran-Mantel-Haenszel test for the non-binary categorical endpoints has been extended to 
include the secondary endpoint of pain response. 
 
The definition of TEAE from the protocol has been changed in this SAP, eliminating the 
condition for the AE onset not being more than 30 days after the last administration of IP to be 
regarded as a TEAE. The change in the definition of TEAE has been made upon Sponsor 
request, to enable transparency, adequate safety reporting and oversight of safety profile/risks. 
11. 
Other Planned Analysis 
11.1. 
 
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11.2. Immunogenicity 
Blood samples will be collected for assessment of ADA levels. Anti-Drug Antibody response 
during the entire study period and at each study assessment will be summarised according to 
ADA category and titre value for the Safety population with evaluable ADA results. A listing of 
the ADA test results will be produced.  
For immunogenicity analysis, the presence of detectable (i.e., positive) ADAs against 
MEDI7352 will be reported. ADA results from each sample are reported as either positive or 
negative. In addition, the ADA titer result will be reported for samples confirmed positive for the 
presence of ADAs. A participant is defined as being ADA-positive if a positive ADA result is 
available at any time, including baseline and all post-baseline measurements, otherwise ADA 
negative. 
The following ADA categories will be determined: 
• ADA positive if a collected sample is tested positive at any time during the study, 
including baseline and/or post-baseline. (The percentage of these participants in a 
population is known as ADA prevalence). 
• Treatment-emergent ADA positive (TE-ADA+): A positive post-baseline result and 
either of the following statements holds: 
o Baseline is ADA negative and at least one post-baseline assessment is ADA 
positive. This is called treatment-induced ADA positive. 
o Baseline is ADA positive, and the baseline titre is boosted by greater than the 
variability of the assay (i.e., ≥X-fold increase, commonly 4-fold) at ≥1 post-
baseline timepoint. This is called treatment-boosted ADA positive. 
(The percentage of these participants in a population is known as ADA incidence) 
• Only baseline positive if a collected sample is tested positive at baseline. 
• Non-Treatment-emergent ADA positive (non-TE-ADA+): Participants who are ADA 
positive but not fulfilling the conditions for TE-ADA+. 
• Treatment-emergent Persistently ADA positive: ADA negative at baseline and having at 
least 2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between 
first and last positive, or an ADA positive result at the last available post-baseline 
assessment. 
• Treatment-emergent Transiently ADA positive: ADA negative at baseline and at least 
one post-baseline ADA positive measurement and not fulfilling the conditions for 
persistently positive 
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•
ADA positive post-baseline and positive at baseline.
11.3.  Pharmacokinetic Analysis 
Pharmacokinetic concentration data will be summarized using descriptive statistics by dose and 
treatment visit overall and by ADA status (positive/negative) presenting the number (n) of non-
missing observations, and the n < LLOQ. A figure of geometric mean (with and without gSD) 
serum MEDI7352 concentration over time by treatment group will be generated (overall and by 
ADA status (positive/negative)). Additionally, pharmacokinetic concentration data will be listed 
and presented graphically as spaghetti plots of individual participant profiles by treatment group 
and ADA status (positive/negative). 
12.
References
1. ICH (1998) ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials E9; 
1998. https://database.ich.org/sites/default/files/E9_Guideline.pdf
2. ASA. (2018) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April 2018. http://www.amstat.org/about/ethicalguidelines.cfm
3. RSS. (2014) The Royal Statistical Society: Code of Conduct, 2014.
http://www.rss.org.uk/Images/PDF/join-us/RSS-Code-of-Conduct-2014.pdf.
4. Satoh J, Yagihashi S, Baba M, Suzuki M, Arakawa A, Yoshiyama T. Efficacy and safety 
evaluation of pregabalin treatment over 52 weeks in patients with diabetic neuropathic pain 
extended after a double-blind placebo-controlled trial. J Diabetes Investig. 2011;2(6):457-463. 
Doi: 10.1111/j.2040-1124.2011.00122.x.
5. Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful 
diabetic neuropathy: a randomized controlled trial. Neurology. 2004;63(11):2104-2110.
6. Rosenstock J, Tuchman M, LaMoreaux L, Sharma U. Pregabalin for the treatment of painful 
diabetic 
peripheral neuropathy: a 
double-blind, placebo-controlled trial. 
Pain. 
2004;110(3):628-638.
7. Tӧlle T, Freynhagen R, Versavel M, Trostmann U, Young JP Jr. Pregabalin for relief of 
neuropathic pain associated with diabetic neuropathy: a randomized, double-blind study. Eur 
J Pain. 2008;12(2):203-213.
8. Pinheiro J, Bornkamp B, Bretz F. Design and analysis of dose-finding studies combining 
multiple comparisons and modelling procedures. J Biopharm Stat. 2006;16(5):639-656. Doi: 
10.1080/10543400600860428.
9. Thomas N, Sweeney K, Somayaji V. Meta-analysis of clinical dose–response in a large drug 
development 
portfolio. 
Stat 
Biopharm 
Res. 
2014;6(4):302-317. 
Doi: 
10.1080/19466315.2014.924876.
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10. Kirby S, Brain P, Jones B. Fitting E(max) models to clinical trial dose-response data. Pharma Stat. 
2011;10(2):143-149. Doi: 10.1002/pst.432.  
 
 
 
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13. 
Tables, Listings, and Figures 
All listings, tables, and graphs will have a header showing the sponsor company name and 
protocol and a footer showing the version of SAS, the file name and path, and the source of the 
data (eCRF page or listing number). 
The following are planned summary tables for protocol number D5680C00002. The table 
numbers and page numbers are place holders only and will be determined when the tables are 
produced. 
 
13.1. Demographic Data 
Table 1: Demographic Data Summary Tables and Figures 
Table Number 
Population 
Table Title/Summary 
Table 14.1.2 
Screening 
Subject Disposition 
Table 14.1.3 
Screen Failure 
Summary of Reasons for Screening Failure 
Table 14.1.4.1 
Screening 
Demographics and Baseline Characteristics 
Table 14.1.4.2 
Safety 
Demographics and Baseline Characteristics 
Table 14.1.4.3 
mITT 
Demographics and Baseline Characteristics 
Table 14.1.4.4 
PK 
Demographics and Baseline Characteristics 
Table 14.1.5.1 
Screening 
Osteoarthritis Characteristics 
Table 14.1.5.2 
Safety 
Osteoarthritis Characteristics 
Table 14.1.5.3 
mITT 
Osteoarthritis Characteristics 
Table 14.1.5.4 
PK 
Osteoarthritis Characteristics 
Table 14.1.6 
Safety 
Medical History by System Organ Class and Preferred Term 
Table 14.1.7 
Safety 
Prior Medications by ATC Class and Preferred Name 
Table 14.1.8 
Safety 
Protocol Deviations 
Table 14.1.9 
Safety 
Overall Study Drug Exposure 
 
 
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13.2. Efficacy Data 
Table 2: Efficacy Data 
Table Number 
Population 
Table Title / Summary 
Table 14.2.1.1.1 mITT 
Daily Pain NRS: Summary Statistics (Observed Cases) 
Table 14.2.1.1.2 mITT 
Daily Pain NRS: Summary Statistics (LOCF) 
Table 14.2.1.1.3 mITT 
Daily Pain NRS: Summary Statistics (BOCF) 
Table 14.2.1.2.1 mITT 
Daily Pain NRS: Primary MCP-Mod Analysis (LOCF) 
Table 14.2.1.2.2 mITT 
Statistical Analysis of CFB to Week 12 Daily Pain NRS: Primary ANCOVA 
Analysis (LOCF) 
Table 14.2.1.3.1 mITT 
Statistical Analysis of CFB Daily Pain NRS: MMRM Analysis. (Observed 
Cases) 
Table 14.2.1.3.2 mITT 
Daily Pain NRS: Sensitivity of Primary MCP-Mod Analysis (BOCF) 
Table 14.2.2.1 
mITT 
Galer NPS: Summary Statistics (Observed Cases) 
Table 14.2.2.2 
mITT 
Galer NPS: MMRM Analysis (Observed Cases) 
Table 14.2.3.1 
mITT 
DSIS: Summary Statistics (Observed Cases) 
Table 14.2.3.2 
mITT 
DSIS: MMRM Analysis (Observed Cases) 
Table 14.2.4.1 
mITT 
SF-36: Summary Statistics (Observed Cases) 
Table 14.2.4.2 
mITT 
SF-36: MMRM Analysis (Observed Cases) 
Table 14.2.5.1 
mITT 
Rescue Medication Use: Summary Statistics 
Table 14.2.6.1 
mITT 
Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel-Haenszel 
(Observed Cases) 
Table 14.2.6.2 
mITT 
Daily Pain NRS Responder Analysis (≥30%): GEE Analysis (Observed 
Cases) 
Table 14.2.7.1 
mITT 
Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel-Haenszel 
(Observed Cases) 
Table 14.2.7.2 
mITT 
Daily Pain NRS Responder Analysis (≥50%): GEE Analysis (Observed 
Cases) 
Table 14.2.8.1 
mITT 
Patient Global Impression of Change: Summary Statistics 
Table 14.2.8.2 
mITT 
Patient Global Impression of Change: Cochran-Mantel-Haenszel 
 
 
 
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13.3. Safety Data 
Table 3: Safety Data 
Table Number 
Population 
Table Title / Summary 
14.3.1 Displays of Adverse Events 
Table 14.3.1.1 
Safety 
Summary of Overall Adverse Events 
Table 14.3.1.2 
Safety 
Treatment Emergent Adverse Events by System Organ Class and 
Preferred Term 
Table 14.3.1.3 
Safety 
Treatment Emergent Adverse Events by Severity, System Organ Class 
and Preferred Term 
Table 14.3.1.4 
Safety 
Treatment Emergent Adverse Events by Relationship to Study 
Medication, System Organ Class and Preferred Term 
Table 14.3.1.5 
Safety 
Treatment Emergent Adverse Events by ADA Status Category, System 
Organ Class and Preferred Term 
Table 14.3.1.6 
Safety 
Treatment Emergent Adverse Events Leading to Discontinuation of 
Study drug by System Organ Class and Preferred Term 
Table 14.3.1.7 
Safety 
Non-Serious Adverse Events Occurring in More than 5% of Subjects by 
System Organ Class and Preferred Term 
Table 14.3.1.8 
Safety 
Treatment Emergent Adverse Events Occurring in More than 5% of 
Subjects by Preferred Term 
Table 14.3.1.9 
Safety 
Treatment Emergent Adverse Events by Preferred Term 
14.3.2 Summary of Deaths, Other Serious and Significant Adverse Events 
Table 14.3.2.1.1 Safety 
Serious Adverse Events by System Organ Class and Preferred Term 
Table 14.3.2.1.2 Safety 
Life-Threatening Serious Adverse Events by System Organ Class and 
Preferred Term 
Table 14.3.2.1.3 Safety 
Serious Adverse Events with Outcome Death by System Organ Class and 
Preferred Term 
Table 14.3.2.1.4 Safety 
Serious Adverse Events by Relationship to Study Medication, System 
Organ Class and Preferred Term 
14.3.2.2 Displays of Significant Adverse Events and Adverse Events of Special Interest 
Table 14.3.2.2.1 Safety 
Treatment Emergent Adverse Events Associated with Abnormal Liver by 
System Organ Class and Preferred Term 
Table 14.3.2.2.2 Safety  
Potential Joint Related Adverse Events of Special Interest by System 
Organ Class and Preferred Term  
Table 14.3.2.2.3 Safety 
Serious and/or severe Infections by System Organ Class and Preferred 
Term 
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Protocol Number D5680C00002  
 
PCN Number MEDU177093 
 
AD-ST-33.06 Effective date: 12-Nov-2020 
Version 1.1    |    Date 31-Aug-2023      |    AD-PR-109.02 Effective date: 17-Aug-2020 
 Page 44 of 54 
 
 
Table Number 
Population 
Table Title / Summary 
Table 14.3.2.2.4 Safety 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions 
Leading to Discontinuation of IP by System Organ Class and Preferred 
Term 
14.3.3 Narratives of Deaths and Other Serious Adverse Events 
Table 14.3.3.1 
Safety 
Listing of Serious Adverse Events 
Table 14.3.3.2 
Safety 
Listing of Deaths 
14.3.4 Laboratory Data Summary Tables 
Table 14.3.4.1 
Safety 
Descriptive Summary of Clinical Chemistry 
Table 14.3.4.2 
Safety 
Shift Table of Clinical Chemistry Results 
Table 14.3.4.3 
Safety 
Descriptive Summary of Hematology 
Table 14.3.4.4 
Safety 
Shift Table of Hematology Results 
Table 14.3.4.5 
Safety 
Descriptive Summary of Coagulation 
Table 14.3.4.6 
Safety 
Shift Table of Coagulation Results 
Table 14.3.4.7 
Safety 
Descriptive Summary of Urinalysis 
Table 14.3.4.8 
Safety 
Shift Table of Urinalysis Results 
Table 14.3.4.9 
Safety 
Maximum On-Treatment ALT and AST versus Maximum On-Treatment 
Total Bilirubin 
14.3.6 Other Safety Data Summary Tables 
Table 14.3.5.1 
Safety 
Descriptive Summary of Vital Signs 
Table 14.3.5.2 
Safety 
Descriptive Summary of ECG Digital Data 
Table 14.3.5.3 
Safety 
Summary of Overall Evaluation of Safety ECG Data 
Table 14.3.5.4 
Safety 
Covid-19 Screening 
Table 14.3.5.5 
Safety 
Summary of Sub-Scores for Total Neuropathy Score-Nurse 
Table 14.3.5.6 
Safety 
Descriptive Summary of Total Neuropathy Score-Nurse 
Table 14.3.5.7 
Safety 
Summary of Motor and Sensory Nerve Conduction Studies 
Table 14.3.5.8 
Safety 
Summary of Strength and Deep Tendon Reflexes 
Table 14.3.5.9 
Safety 
Summary of Local Injection Site Reactions 
Table 14.3.5.10 Safety 
Summary of Anaphylactic Reactions 
Table 14.3.5.11 Safety 
Summary of Liver Diagnostic Investigations 
Table 14.3.5.12 Safety 
Summary of Liver Risk Factors and Lifestyle Events 
Table 14.3.5.13 Safety 
Summary of Liver Signs and Symptoms 
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Table Number 
Population 
Table Title / Summary 
Table 14.3.5.14 Safety 
Summary of Infection Diagnostic Investigations 
Table 14.3.5.15 Safety 
Summary of Infection Risk Factors and Lifestyle Events 
Table 14.3.5.16 Safety 
Summary of Infection Signs and Symptoms 
Table 14.3.5.17 Safety 
Summary of Concomitant Medications by ATC Level 2 and Preferred 
Term 
Table 14.3.5.18 Safety 
Summary of Concomitant Procedures 
Table 14.3.5.19 Safety 
Anti-Drug Antibody Results and Titre Summary by Timepoint 
Table 14.3.5.20 Safety 
Descriptive Summary of Anti-Drug Antibody Results and Titre by ADA 
Categories 
 
 
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13.4. Pharmacokinetic/Pharmacodynamic Data 
Table 4: Pharmacokinetic/Pharmacodynamic Data 
Table Number 
Population 
Table Title / Summary 
14.4 Pharmacokinetic and Pharmacodynamic Data Summary Tables 
Table 14.4.1 
PK 
Summary of Serum MEDI7352 Concentrations 
Table 14.4.2 
Safety 
Summary of Serum total NGF Concentrations 
13.5. Planned Listing Descriptions 
The following are planned data and patient/subject data listings for protocol number 
D5680C00002.  
In general, one listing will be produced per eCRF domain. All listings will be sorted by 
treatment, site, and subject number. All calculated variables will be included in the listings. 
In all listings a blank line will be placed between each subject. Within a data listing, if an item 
appears line after line (e.g., repetition of subject number), then only the first occurrence will be 
displayed. 
In data listings, the information for one subject will be kept on one page if at all possible, rather 
than splitting a subject’s information across pages. 
Table 5: Planned Listings 
 
Data Listing Number 
Population 
Data Listing Title / Summary 
16.2 Subject Data Listings 
16.2.1 Subject Discontinuations/Completions 
Listing 16.2.1.1 
Screening 
Subject Disposition 
Listing 16.2.1.2 
Screening 
Assignment to Analysis Populations 
Listing 16.2.1.3 
Safety 
Reason for IP Discontinuation and Withdrawal from the Study 
Listing 16.2.1.4 
Screen Failure 
List of Reasons for Screening Failure 
Listing 16.2.1.5 
Screening 
Visits List and COVID-19 Impact 
16.2.2 Protocol Deviations 
Listing 16.2.2.1 
Screening 
Subjects Not Meeting All Inclusion Criteria or Meeting any 
Exclusion Criteria 
Listing 16.2.2.2 
Safety 
Protocol Deviations 
16.2.3 Randomization 
Listing 16.2.3 
Safety 
Randomization and Treatment Group 
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Data Listing Number 
Population 
Data Listing Title / Summary 
16.2 Subject Data Listings 
16.2.4 Demographic Data and Other Baseline Characteristics 
Listing 16.2.4.1 
Screening 
Demographic and Baseline Characteristics 
Listing 16.2.4.2 
Safety 
Medical History  
Listing 16.2.4.3 
Screening 
Osteoarthritis Characteristics 
16.2.5 Compliance and/or Drug Concentration Data 
Listing 16.2.5.1 
Safety 
Study Drug Administration: Individual Doses 
16.2.6 Individual Efficacy Response Data 
Listing 16.2.6.1 
mITT 
Daily Pain NRS 
Listing 16.2.6.2 
mITT 
Galer NPS 
Listing 16.2.6.3 
mITT 
DSIS 
Listing 16.2.6.4 
mITT 
SF-36 
Listing 16.2.6.5 
mITT 
Rescue Medication Usage 
Listing 16.2.6.6 
mITT 
Patient Global Impression of Change 
16.2.7 Adverse Event Listings (by Patient/Subject) 
Listing 16.2.7.1 
Safety 
Adverse Events  
Listing 16.2.7.2 
Safety 
Treatment Emergent Adverse Events Leading to Study Drug 
Discontinuation 
Listing 16.2.7.3 
Safety 
Treatment Emergent Adverse Events Associated with Abnormal 
Liver 
Listing 16.2.7.4 
Safety 
Joint Related Adverse Events of Special Interest 
Listing 16.2.7.5 
Safety 
Serious and/or Severe Infections 
Listing 16.2.7.6 
Safety 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related 
Reactions Leading to Discontinuation of Study Drug 
16.2.8 Laboratory Values (by Patient/Subject) 
Listing 16.2.8.1 
Safety 
Clinical Chemistry Laboratory Evaluations 
Listing 16.2.8.2 
Safety 
Hematology Laboratory Evaluations 
Listing 16.2.8.3 
Safety 
Coagulation Laboratory Evaluations 
Listing 16.2.8.4 
Safety 
Urinalysis Laboratory Evaluations 
Listing 16.2.8.5 
Safety 
Serology Laboratory Evaluations 
Listing 16.2.8.6 
Safety 
Pregnancy Test Results 
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Data Listing Number 
Population 
Data Listing Title / Summary 
16.2 Subject Data Listings 
Listing 16.2.8.7 
Safety 
Drug Test Results 
Listing 16.2.8.8 
Safety 
COVID-19 Screening 
16.2.9 Other Clinical Observations and Measurements (by Patient/Subject) 
Listing 16.2.9.1 
Safety 
Vital Signs Measurements 
Listing 16.2.9.2.1 
Safety 
12-Lead Digital ECG Results 
Listing 16.2.9.2.2 
Safety 
12-Lead Safety ECG Results 
Listing 16.2.9.3 
Safety 
Physical Examination Results 
Listing 16.2.9.4 
Safety 
Neurological Examination Results 
Listing 16.2.9.5 
Safety 
Total Neuropathy Score-Nurse 
Listing 16.2.9.6 
Safety 
Motor and Sensory Nerve Conduction Studies 
Listing 16.2.9.7 
Safety 
Strength and Deep Tendon Reflexes 
Listing 16.2.9.8 
Safety 
Injection Site Reactions 
Listing 16.2.9.9 
Safety 
Anaphylactic Reactions 
Listing 16.2.9.10 
Safety 
Liver Diagnostic Investigations 
Listing 16.2.9.11 
Safety 
Liver Risk Factors and Lifestyle Events 
Listing 16.2.9.12 
Safety 
Liver Signs and Symptoms 
Listing 16.2.9.13 
Safety 
Infection Diagnostic Investigations 
Listing 16.2.9.14 
Safety 
Infection Risk Factors and Lifestyle Events 
Listing 16.2.9.15 
Safety 
Infection Signs and Symptoms 
Listing 16.2.9.16 
Safety 
Prior and Concomitant Medications 
Listing 16.2.9.17 
Safety 
Prohibited Concomitant Medications 
Listing 16.2.9.18 
Safety 
Concomitant Procedures 
Listing 16.2.9.19 
Safety 
Anti-drug Antibody Test Results 
16.2.10 Pharmacokinetic/Pharmacodynamic Measurements  
Listing 16.2.10.1 
PK 
Serum MEDI7352 Concentrations 
Listing 16.2.10.2 
Safety 
Serum total NGF Concentrations 
 
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13.6. Planned Figure Descriptions 
The following are planned summary figures for protocol number D5680C00002. The figure 
numbers and page numbers are place holders only and will be determined when the figures are 
produced. 
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Table 6: Planned Figures 
Figure Number 
Population 
Figure Title/Summary 
Figure 14.2.1.1 
mITT 
Daily Pain NRS: MCP-Mod Dose Response Model 
Figure 14.2.1.2 
mITT 
Daily Pain NRS: Boxplots at Week 12 by Treatment 
Group and Missing Data Handling 
Figure 14.2.1.3 
mITT 
Daily Pain NRS: Boxplots at Week 12 by Treatment 
Group and Co-Medication Subgroup 
Figure 14.2.1.4 
mITT 
Daily Pain NRS: MMRM LS Means (95% Confidence 
Interval) over 12-weeks by Treatment Group (Observed 
Cases) 
Figure 14.3.6.1.1 Safety 
Vital Sign Profiles: Mean (±SD) Systolic Blood Pressure 
over time 
Figure 14.3.6.1.2 Safety 
Vital Sign Profiles: Mean (±SD) Diastolic Blood 
Pressure over time 
Figure 14.3.6.1.3 Safety 
Vital Sign Profiles: Mean (±SD) Heart Rate over time 
Figure 14.3.6.1.4 Safety 
Vital Sign Profiles: Mean (±SD) Respiratory Rate over 
time 
Figure 14.3.6.1.5 Safety 
Vital Sign Profiles: Mean (±SD) Temperature over time 
Figure 14.4.1.1 
PK 
Pharmacokinetics: Line Plot of Geometric Mean (with 
and without gSD) Serum MEDI7352 over time 
Figure 14.4.1.2 
PK 
Pharmacokinetics: Individual Plot of Serum MEDI7352 
Concentrations over time  
Figure 14.4.2.1 
Safety 
Pharmacodynamics: Line Plot of Geometric Mean (with 
and without gSD) Serum total NGF over time 
Figure 14.4.2.2 
Safety 
Pharmacodynamics: Individual Plot of Serum total NGF 
over time 
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Version 1.1    |    Date 31-Aug-2023      |    AD-PR-109.02 Effective date: 17-Aug-2020 
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14. 
Tables, Listing and Figure Shells 
14.1. 
Standard Layout for all Tables, Listings, and Figures 
The following standard layout will be applied to all Tables, Listings, and Figures in support of this study. Note that programming 
notes may be added if appropriate after each table, listing and figure shell. All shells will be provided as a separate document. 
 
 
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Figure 1: Standardized Layout 
Astra Zeneca 
Page xx of xx 
Protocol: D5680C00002 
Version  
 
<Table, Listing, Figure> xx.x.x 
Title of Table, Listing or Figure 
Study Population and if applicable subgroup Description 
____________________________________________________________________________________________________________ 
 
 
Body of Table, Listing or Figure 
 
 
___________________________________________________________________________________________________________ 
Note: If directly Applicable 
Footnote 1  
Footnote 2  
Footnote n  
Footnote n+1 SAS program path and name Executed on ddmmmyyyy at hh:mm on data from ddmmmyyyy  
 
 
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15. 
Appendix: Calculation of Dose to achieve target effects 
Although only one dose-response model type (Emax) is pre-specified in the protocol for the primary analysis, 
 
 
 
Let us assume the R® DoseFinding package original parametrization for these two dose-response model functions below: 
 
 
1. Equations for Target Dose DΔ to achieve a Delta (∆) versus placebo 
Emax: TDΔ= ED50/((Emax/∆) - 1), where ED50 and Emax are estimated from the fitted Emax model 
Exponential: TDΔ= 𝛿*log((∆/E1) +1), where 𝛿 and E1 are estimated from the fitted exponential model 
(The function TD from the DoseFinding package will be used for the above) 
2. Equations for Dose (EDP) to achieve a certain proportion P of the effect of the maximum dose studied versus placebo (See 
DoseFinding manual page 51 where ED is ‘Effective Dose’) 
I 
Journal of Statistical Software 
Name 
f(d, 0 ) 
J0(d, 0• ) 
(*) 
m 
linear 
Eo+8d 
d 
linlog 
Eo + 81og(d+c) 
Jog(d + c) 
C 
quadratic 
Eo + f31d + f32d2 
d + 8d2 if /32 < 0 
8 
emax 
Eo + Emaxd/(EDso + d) 
d/(EDso +d) 
EDso 
l ogistic 
Eo + Emax/ {1 + exp [(EDso - d) /8]} 
1/ {1 + exp [(EDso - d) /8]} 
(EDso, 8) T 
exponential 
E0 + E 1 (exp(d/8) - 1) 
exp(d/8) - 1 
8 
sigEmax 
Eo + Emaxdh /(EDgo + dh) 
d"/(EDgo + dh) 
(EDso, h)T 
betaMod 
Eo + EmaxB(81, 82)(d/ Dl1 (1 - d/ D)62 
B(81 ,82)(d/D)6'(1 - d/D)62 
(81,82f 
D 
Table 1: Dose-response models implemented in the MCPMod package. Column (*) lists for 
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 Page 54 of 54 
 
 
Emax: EDP= (P * ED50*max(doses))/(ED50+(1-P) * max(doses)) = (P* ED50*150)/(ED50+(1-P)*150) 
Exponential: EDP= δ *log((P*exp(max(doses)/ δ) + 1-P)) = δ *log((P*exp(150/ δ) + 1-P)) 
(The function ED from the DoseFinding package will be used for the above) 
3. Equation for Dose (asym EDP) to achieve a certain proportion P of the asymptotic maximum effect (Emax) versus placebo 
Emax: asymptotic EDP= (P*ED50) /(1-P) 
 
Simulation-based CI will be created for each of the above quantities from the mean and covariance matrix of the model parameters, 
assuming multivariate normality. Therefore 10,000 samples from the multivariate distribution will be taken, and for each simulation 
the TD and ED estimates calculated.  The 2.5% and 97.5% percentiles will then form the appropriate 95% two -sided CI. 
 
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Sponsor: 
AstraZeneca 
Protocol Title 
A Randomised, Double-Blind, Placebo-Controlled, Dose-
Response Study of the Efficacy and Safety of MEDI7352 in 
Subjects with Painful Diabetic Neuropathy 
Development Phase  
2 
Protocol Numbers: 
D5680C00002 
Premier Research PCNs: 
MEDU177093 
Document Version: 
Final Version 1.0 
Document Date:  
12-Jul-2023 
Document History 
Version 
Date 
Author 
Description 
0.1 
24-Mar-2023 
 
Draft Version 
0.2 
21-Apr-2023 
 
Draft Version 
0.3 
24-May-2023 
 
Draft Version 
0.4 
20-Jun-2023 
 
Draft Version 
 
 
 
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PPD
PPD
PPD
PPD


 
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Tables, Listings, and Figures Conventions 
All listings, tables, and graphs will have a header showing the sponsor company name, protocol 
and version of delivery and a footer showing the version of SAS, the file name and path, and the 
source of the data (listing number). 
The following reporting conventions will be adopted for the presentation of study data. These 
conventions will enhance the review process and help to standardize the presentation with common 
notations. 
General Reporting Conventions 
• All tables and data listings will be developed in landscape orientation. 
• Specialized text styles, such as bolding, italics, borders, shading, and superscripted and 
subscripted text will not be used in tables, figures, and data listings unless they add 
significant value to the table, figure, or data listing.  
• Only standard keyboard characters should be used in tables and data listings. Special 
characters, such as nonprintable control characters, printer-specific characters, or font 
specific characters, will not be used on a table, figure, or data listing. 
• Adverse events with missing MedDRA coding will have their system organ class preferred 
term presented as “Not Coded” and the Preferred Term presented as verbatim in the tables. 
The “Not Coded” frequencies will be sorted to the end of the tables. This will only be 
applicable for any deliveries sent before database lock (e.g., for dry runs). 
• Programming notes may be inserted into the shells, these notes will not appear in the final 
output. 
 
Population Summary Conventions 
• Population sizes may be presented for each classification factor as totals in the column 
header as (N=xx), where appropriate.  
• All population summaries for categorical variables will include all categories that were 
planned and for which the participants may have had a response. 
• All population summaries for continuous variables will include: n, mean, SD, median, 
quartiles, minimum, and maximum. Other summaries (e.g., number missing, geometric 
mean, 95% CIs, and coefficient of variation [CV] or % CV) may be used as appropriate. 
The precision of the maximum and minimum will match the maximum precision in the 
observed data and 2 decimals for derived data unless specifically mentioned in the 
corresponding shell. The mean and median will have 1 additional decimal place. The SD 
will have 2 additional decimal places. For derived data, minimum and maximum will be 
reported to 2 degrees of precision. Measures of location (mean and median) will be reported 
to 3 degree of precision, and measures of spread will be reported to 4 degrees of precision. 
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• 
All percentages are rounded and reported to a single decimal point (xx.x%). Exceptions 
are 0 and 100 that will be displayed as 0 and 100% respectively. 
Planned Tables, Figures and Listings  
• The table and listing numbers are place holders only and will be determined when the 
outputs are produced. 
• In all listings a blank line will be placed between each participant. Within a data listing, if 
an item appears line after line (e.g., repetition of participant number), then only the first 
occurrence will be displayed. 
• In data listings, the information for 1 participant will be kept on 1 page, if possible, rather 
than splitting a Subjects’s information across pages. 
 
 
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Planned Table Descriptions and Shells 
Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.1.2 - - Screening Population 
U 
Table 14.1.3 - Summary of Reasons for Screening Failure - Screen Failure Population 
U 
Table 14.1.4.1 - Demographics and Baseline Characteristics - Screening Population 
U 
Table 14.1.4.2 - Demographics and Baseline Characteristics - Safety Population 
R 
Table 14.1.4.3 - Demographics and Baseline Characteristics - mITT Population 
R 
Table 14.1.4.4 - Demographics and Baseline Characteristics - PK Population 
R 
Table 14.1.5.1 - Osteoarthritis Characteristics - Screening Population 
U 
Table 14.1.5.2 - Osteoarthritis Characteristics - Safety Population 
R 
Table 14.1.5.3 - Osteoarthritis Characteristics - mITT Population 
R 
Table 14.1.5.4 - Osteoarthritis Characteristics - PK Population 
R 
Table 14.1.6 - Medical History by System Organ Class and Preferred Term - Safety Population 
U 
Table 14.1.7 - Prior Medications by ATC Level 2 and Preferred Name - Safety Population 
U 
Table 14.1.8 - Protocol Deviations - Safety Population 
U 
Table 14.1.9 - Overall Study Drug Exposure - Safety Population 
U 
Table 14.2.1.1.1 - Daily Pain NRS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.1.1.2 - Daily Pain NRS: Summary Statistics (LOCF) - mITT Population 
R 
Table 14.2.1.1.3 - Daily Pain NRS: Summary Statistics (BOCF) - mITT Population 
R 
Table 14.2.1.2.1 - Daily Pain NRS: Primary MCP-Mod Analysis (LOCF) - mITT Population 
U 
Table 14.2.1.2.2 - Statistical Analysis of CFB to Week 12 Daily Pain NRS: Primary ANCOVA 
Analysis (LOCF) - mITT Population 
U 
Table 14.2.1.3.1 - Statistical Analysis of CFB Daily Pain NRS: MMRM Analysis. (Observed 
Cases) - mITT Population 
U 
Table 14.2.1.3.2 - Daily Pain NRS: Sensitivity of Primary MCP-Mod Analysis (BOCF) - mITT 
Population 
R 
Table 14.2.2.1 - Galer NPS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.2.2 - Galer NPS: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.3.1 - DSIS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.3.2 - DSIS: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.4.1 - SF-36: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.4.2 - SF-36: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.5.1 - Rescue Medication Use: Summary Statistics - mITT Population 
U 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.2.6.1 - Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel Haenszel 
(Observed Cases) - mITT Population 
U 
Table 14.2.6.2 - Daily Pain NRS Responder Analysis (≥30%): GEE Analysis (Observed Cases) 
- mITT Population 
U 
Table 14.2.7.1 - Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel Haenszel 
(Observed Cases) - mITT Population 
R 
Table 14.2.7.2 - Daily Pain NRS Responder Analysis (≥50%): GEE Analysis (Observed Cases) 
- mITT Population 
R 
Table 14.2.8.1 - Patient Global Impression of Change: Summary Statistics - mITT Population 
U 
Table 14.2.8.2 - Patient Global Impression of Change: Cochran-Mantel Haenszel - mITT 
Population 
U 
 
U 
Table 14.3.1.1 - Summary of Overall Adverse Events - Safety Population 
U 
Table 14.3.1.2 - Treatment Emergent of Adverse Events by System Organ Class and Preferred 
Term - Safety Population 
U 
Table 14.3.1.3 - Treatment Emergent of Adverse Events by Severity, System Organ Class and 
Preferred Term - Safety Population 
U 
Table 14.3.1.4 - Treatment Emergent Adverse Events by Relationship to Study Medication, 
System Organ Class and Preferred Term - Safety Population 
U 
Table 14.3.1.5 - Treatment Emergent Adverse Events by ADA Status Category, System Organ 
Class and Preferred Term - Safety Population 
U 
Table 14.3.1.6 - Treatment Emergent Adverse Events Leading to Discontinuation of Study drug 
by System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.1.7 - Non-Serious Adverse Events Occurring in More than 5% of Subjects by 
System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.1.8 - Treatment Emergent Adverse Events Occurring in More than 5% of Subjects 
by Preferred Term - Safety Population 
R 
Table 14.3.1.9 - Treatment Emergent Adverse Events by Preferred Term - Safety Population 
R 
Table 14.3.2.1.1 - Serious Adverse Events by System Organ Class and Preferred Term - Safety 
Population 
R 
Table 14.3.2.1.2 - Life-Threatening Serious Adverse Events by System Organ Class and 
Preferred Term - Safety Population  
R 
Table 14.3.2.1.2 - Serious Adverse Events with Outcome Death by System Organ Class and 
Preferred Term - Safety Population 
R 
Table 14.3.2.1.4 - Serious Adverse Events by Relationship to Study Medication, System Organ 
Class and Preferred Term - Safety Population 
R 
Table 14.3.3.1 - Listing of Serious Adverse Events - Safety Population 
U 
Table 14.3.3.2 - Listing of Deaths - Safety Population 
U 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.3.2.2.1 - Treatment Emergent Adverse Events Associated with Abnormal Liver by 
System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.2.2.2 - Potential Joint Related Adverse Events of Special Interest by System Organ 
Class and Preferred Term - Safety Population 
R 
 Table 14.3.2.2.3 - Serious and/or severe Infections by System Organ Class and Preferred Term 
- Safety Population 
R 
Table 14.3.2.2.4 - Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions 
Leading to Discontinuation of IP by System Organ Class and Preferred Term - Safety 
Population 
R 
Table 14.3.4.1 - Descriptive Summary of Clinical Chemistry - Safety Population 
U 
Table 14.3.4.2 - Shift Table of Clinical Chemistry Results - Safety Population 
U 
Table 14.3.4.3 - Descriptive Summary of Hematology - Safety Population 
R 
Table 14.3.4.4 - Shift Table of Hematology Results - Safety Population 
R 
Table 14.3.4.5 - Descriptive Summary of Coagulation - Safety Population 
R 
Table 14.3.4.6 - Shift Table of Coagulation Results - Safety Population 
R 
Table 14.3.4.7 - Descriptive Summary of Urinalysis - Safety Population 
U 
Table 14.3.4.8 - Shift Table of Urinalysis Results - Safety Population 
R 
Table 14.3.4.9 - Maximum On-Treatment ALT and AST versus Maximum On-Treatment Total Bilirubin - Safety 
Population 
U 
Table 14.3.5.1 - Descriptive Summary of Vital Signs - Safety Population 
U 
Table 14.3.5.2 - Descriptive Summary of ECG Data - Safety Population 
U 
Table 14.3.5.3 - Summary of Overall Evaluation of safety ECG Data - Safety Population 
U 
Table 14.3.5.4 - Covid-19 Screening - Safety Population 
U 
Table 14.3.5.5 - Summary of Sub-Scores for Total Neuropathy Score-Nurse - Safety Population 
U 
Table 14.3.5.6 - Descriptive Summary of Total Neuropathy Score-Nurse - Safety Population 
U 
Table 14.3.5.7 - Summary of Motor and Sensory Nerve Conduction Studies - Safety Population 
U 
Table 14.3.5.8 - Summary of Strength and Deep Tendon Reflexes - Safety Population 
U 
Table 14.3.5.9 - Summary of Local Injection Site Reactions - Safety Population 
U 
Table 14.3.5.10 - Summary of Hypersensitivity/Anaphylactic Reactions - Safety Population 
U 
Table 14.3.5.11 - Summary of Liver Diagnostic Investigations - Safety Population 
U 
Table 14.3.5.12 - Summary of Liver Risk Factors and Lifestyle Events - Safety Population 
U 
Table 14.3.5.13 - Summary of Liver Signs and Symptoms - Safety Population 
U 
Table 14.3.5.14 - Summary of Infection Diagnostic Investigations - Safety Population 
U 
Table 14.3.5.15 - Summary of Infection Risk Factors and Lifestyle Events - Safety Population 
U 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.3.5.16 - Summary of Infection Signs and Symptoms - Safety Population 
U 
Table 14.3.5.17 - Summary of Concomitant Medications by ATC Level 2 and Preferred Name - 
Safety Population 
R 
Table 14.3.5.18 - Summary of Concomitant Procedures - Safety Population 
R 
Table 14.3.5.19 - Anti-Drug Antibody Results and Titre Summary by Timepoint - Safety 
Population 
U 
Table 14.3.5.20 - Descriptive Summary of Anti-Drug Antibody Results and Titre by ADA 
Categories - Safety Population 
U 
Table 14.4.1 - Summary of Serum MEDI7352 Concentrations - PK Population 
U 
Table 14.4.2 - Summary of Serum total NGF Concentrations - PD Population 
U 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table Change Log 
Output 
Number 
Date of 
Change 
Change Made 
By (initials) 
Description/Rationale 
 
 
 
 
 
 
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1. Demographic Data 
Table 14.1.2 
Subject Disposition  
Screening Population 
 
Placebo 
MEDI7352 
Total 
Status 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Screening Population [1] 
 
 
 
 
xx (100%) 
  Enrolled Subjects 
 
 
 
 
xx (xx.x %) 
  Re-screened Subjects 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
Randomized Subjects  
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
Safety Population [2] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
mITT Population [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evaluable Week 12 Efficacy  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evaluable LOCF Efficacy [4] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not Efficacy Evaluable 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
PK Population [5] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Completed Study Treatment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Discontinued Study Treatment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Reason for Discontinuation: 
 
 
 
 
 
   Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lack of Efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lost to Follow-up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Non-compliance with Study Drug 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Physician Decision 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pregnancy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Progressive Disease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Protocol Violation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Study Terminated by Sponsor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Technical Problems 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Withdrawal by Subject 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
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Completed Study  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Withdrawn from the Study 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Reason for Discontinuation: 
 
 
 
 
 
   Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lack of Efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lost to Follow-up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 = Coronavirus disease 2019; LOCF = Last Observation Carried Forward; mITT = modified intent-to-treat; N = number of subjects per treatment 
group; PK = pharmacokinetic. 
Note: Percentages are n/Number of subjects randomized*100 as displayed in column header N, except for the screened, enrolled, re-screened and randomized, 
where n/Number of Screening subjects*100. 
[1] The Screening Population includes all subjects who provide informed consent and provide demographic and/or baseline screening assessments. 
[2] The Safety Population includes all subjects who receive at least 1 dose of double-blind study medication. 
[3] The mITT Population includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
[4] Subjects in the mITT Population with LOCF applied for missing efficacy data at week 12, 
[5] The PK Population includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
 
Reference Listings: 16.2.1.1, 16.2.1.2, 16.2.1.3, 
 
 
Programming Notes:  
• 
Display only reasons for early discontinuation with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
  
 
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Table 14.1.3 
Summary of Reasons for Screening Failure 
Screen Failure Population 
 
Total 
 
(N=xx) 
 
 
Number of Subjects Who Don’t Meet Inclusion/Exclusion Criteria 
xx (xx.x%) 
  Reason 1 
xx (xx.x%) 
  Reason 2 
xx (xx.x%)  
  Reason 3 
xx (xx.x%) 
  Reason 4 
xx (xx.x%)  
 
 
N = number of subjects. 
Note:  subject can be counted in more than one criterion. 
Reference Listing 16.2.1.4 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.1.4.1 
Demographics and Baseline Characteristics 
Screening Population 
 
Variable 
Placebo 
MEDI7352 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Age (years) [1] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Age Category 
 
 
 
 
 
   ≥18 - <65 years 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   ≥65 years 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Gender 
 
 
 
 
 
   Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
   Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Race 
 
 
 
 
 
   American Indian or Alaska Native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Black or African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Native Hawaiian or Other Pacific Islander 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Not Specified 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Screening Height (cm) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
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Screening Weight (kg)  
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Screening BMI (kg/m²) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Female characteristics [2] 
 
 
 
 
 
   Surgically sterile 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Postmenopausal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Fully vaccinated for COVID-19 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
BMI = Body Mass Index; COVID-19 = Coronavirus disease 2019; n = number of subjects by treatment group with collected parameter; N = number of 
subjects per treatment group; SD = standard deviation. 
[1] Age was calculated as age at time of consent. 
[2] Percentages are n/Number of Female subjects from Analysis Population*100 
Reference Listing: 16.2.4.1 
 
Programming Notes: 
• 
If a variable is between 2 pages, start the variable in the second page. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
 will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.1.4.2 
Demographics and Baseline Characteristics 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.4.3 
Demographics and Baseline Characteristics 
mITT Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.4.4 
Demographics and Baseline Characteristics 
PK Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.1.5.1 
Osteoarthritis Characteristics 
Screening Population 
 
Placebo 
MEDI7352 
Total 
Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
Subjects diagnosed with Osteoarthritis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Joint(s)/Area(s) affected: 
 
 
 
 
 
   Shoulder 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Elbow 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hip 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Knee 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ankle 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Spine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hands 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Feet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Osteoarthritis clinically significant 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Radiologic investigations conducted [1] 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Plain radiography 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     MRI 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Joint(s)/Area(s) investigated: 
 
 
 
 
 
   Shoulder 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Elbow 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hip 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Knee 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ankle 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Spine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
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   Hands 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Feet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Osteoarthritis radiologically significant 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Kellgren-Lawrence score reported 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 0  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No/Not applicable 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Radiologic Scoring System Used? 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
MRI = magnetic resonance imaging; N = number of subjects per treatment group. 
[1] Subjects who reported more than one radiologic investigation within each category were only counted once. 
Reference Listing: 16.2.4.3 
 
Programming Notes: 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
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Table 14.1.5.2 
Osteoarthritis Characteristics 
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.5.3 
Osteoarthritis Characteristics 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.5.4 
Osteoarthritis Characteristics 
PK Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
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Table 14.1.6 
Medical History by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xxx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xxx) 
 
 
 
 
 
 
Any Medical History 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   … 
… 
… 
… 
… 
… 
 
 
 
 
 
 
System Organ Class n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Note: All medical history terms were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 26.0. At each level of summarization 
(system organ class or preferred term), subjects having more than one medical history term were counted only once. System organ class and preferred terms 
are sorted in descending order of frequency of Total column, and alphabetically if same frequency. 
 
Reference Listing: 16.2.4.2 
 
Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Sort SOC and PT (within SOC) in descending order of frequency in the Total column.  Sort alphabetically in case of ties. 
• 
Uncoded Medical History Events 
o 
When there are uncoded Medical History Events in the database, the events will be summarized with SOC and PT set to [Not Coded]. The [Not 
Coded] will be sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.1.7  
Prior Medications by ATC Class and Preferred Name 
Safety Population 
 
ATC Class [1] 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Subjects with at Least One Prior 
Medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC Level 2 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC Level 2 n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC = Anatomical Therapeutic Class; N = number of subjects per treatment group. 
[1] ATC Class is defined as ATC Level 2. 
Note: Prior medications are defined as medications that started before first dose of study, whether they were stopped before first dose of study medication or 
not. All prior medications are coded using WHO drug dictionary version vMar2023. At each level of summarization (ATC Level 2 or Preferred Name), 
subjects who reported more than one prior medication were only counted once. ATC Level 2 and Preferred Term are sorted in in descending order of 
frequency of total, and alphabetically if same frequency.  
Reference Listing: 16.2.9.16 
 
Programming Notes: 
• 
If uncoded ATC Level or Preferred Name, please put them as [Not Coded] 
• 
ATC and Preferred Name texts should be in proper case in table. 
• 
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 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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Table 14.1.8 
Protocol Deviations 
Safety Population 
 
 
Placebo 
MEDI7352 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Subjects With Any Important Protocol 
Deviation/Violation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Protocol Deviation Type 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 5 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 6 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
………….. 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Notes: Percentages are n/Number of subjects by treatment group*100. 
Subjects with one or more deviations within a type of protocol deviation were counted only once. 
 
Reference Listing 16.2.2.1 
 
Programming Notes: 
• 
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 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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2. 
Exposure and Compliance 
Table 14.1.9 
Overall Study Drug Exposure 
Safety Population 
 
Placebo 
MEDI7352 
Total 
Category/ Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Maximum Number of Doses Administered [1] 
 
 
 
 
 
1 Dose 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3 Doses 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
4 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
5 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
6 Doses 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
 
 
Total Duration of Exposure (days) [2] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Total (cumulative) dose infused (mL) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
n = number of subjects by treatment group with collected parameter; N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; 
Q3 = third quartile. 
[1] Subjects are counted once for each level of dose administered. 
[2] Duration of exposure (days) = min(date of last dose of treatment + 14 days or date of death) – date of first dose of treatment + 1. 
Reference Listing: 16.2.5.1 
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Programming Notes: 
• 
Add all categories even if count is 0. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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3. 
Primary Efficacy Analysis 
Table 14.2.1.1.1 
Daily Pain NRS: Summary Statistics (Observed Cases) 
mITT Population 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; DPS = Daily Pain Score; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per 
treatment group; NRS = Numeric Rating Scale; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are weekly averages of the average daily pain scores on an 11-point (0-10) NRS and CFB for the same variable. 
[1] Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e., Day -7 to Day -1, inclusive.  
Reference Listing: 16.2.6.1 
 
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Programming Notes: 
• 
Include all observed data (Not the LOCF) on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, 12 and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.1.1.2 
Daily Pain NRS: Summary Statistics (LOCF) 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.2.1.1.1. 
• 
Include all observed and LOCF data on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and 12 
• 
Add abbreviation in footnote: LOCF = Last Observation Carried Forward. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
Table 14.2.1.1.3 
Daily Pain NRS: Summary Statistics (BOCF) 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.2.1.1.1. 
• 
Include all observed and BOCF data on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and 12 
• 
Add abbreviation in footnote: BOCF = Baseline Observation Carried Forward. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
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Table 14.2.1.2.1 
Daily Pain NRS: Primary MCP-Mod Analysis (LOCF) 
mITT Population 
‘MCP’ step 
Model 
        Contrast [1] 
 
 
 
t value 
1-sided adjusted P-value [2] 
Hyperbolic Emax 
 
 
 
 
 
        ED50 = 7.5 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 15 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 30 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 60 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 750 
 
 
 
xx.xx 
0.xxxx 
 
 
 
 
 
 
Exponential 
 
 
 
 
 
        δ = 100 
 
 
 
xx.xx 
0.xxxx 
        δ = 200 
 
 
 
xx.xx 
0.xxxx 
CFB = Change from Baseline; LOCF = Last Observation Carried Forward; MCP = Multiple Comparisons; Procedure; NRS = Numeric rating scale. 
[1] ED50 = Effective Dose giving half of the asymptotic maximum effect. 
[2] Multiplicity Adjusted P-value 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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‘MOD’ step [3] 
Selected Model xxxxxxxxxx 
Parameter 
Estimate 
95% CI of Estimate [6] 
ED50 
xx.x 
[ x.xx to x.xx ] 
ED90 [4] 
xx.x 
[ x.xx to x.xx ] 
Asymptotic ED90 [5] 
xx.x 
[ x.xx to x.xx ] 
Dose to achieve target (-1.25) effect 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 5 mcg 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 50 mcg 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 150 mcg 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 450 mcg 
xx.x 
[ x.xx to x.xx ] 
CI: Confidence Interval; LOCF = Last Observation Carried Forward; MCP = Multiple Comparisons; Procedure; MOD = Modelling; NRS = Numeric rating 
scale. 
[3] Results from the ‘MOD’ step will only be available in case any of the MCP tests is statistically significant. 
[4] ED90 = Effective Dose giving 90% of the effect of the maximum dose studied. 
[5] Asymptotic ED90 = Effective Dose giving 90% of the asymptotic maximum effect. 
[6] 2.5% and 97.5% quantiles taken from 100000 samples from the multivariate normal distribution for model fitted estimates and its covariance matrix. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
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Table 14.2.1.2.2 
Statistical Analysis of CFB to Week 12 Daily Pain NRS: Primary ANCOVA Analysis (LOCF)  
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
[ x.xx to x.xx ] 
 
 
Co-Medication Type 
 
 
2 
 
 
 
0.xxxx 
Baseline pain NRS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
Active 5 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 150 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 450 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard 
deviation 
xx.xx 
 
 
 
 
 
 
ANCOVA = analysis of covariance; CFB = Change from Baseline; 
CL = Confidence limits; LOCF = Last Observation Carried Forward; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: ANCOVA by dose using NRS baseline value and co-medication as covariates, with CFB to Week 12 (LOCF) 
as dependent variable. 
 
Least Square Means 
Treatment 
Number of Subjects 
LS mean [3] 
95% CI of LS mean 
Active 450 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LOCF = Last Observation Carried Forward; LS = least square; NRS = Numeric rating scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average pain NRS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.1 
 
 
 
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Programming Notes: 
• 
Concomitant co-medication Type indicated for Painful Diabetic Neuropathy: either anticonvulsant class (pregabalin or gabapentin) or antidepressant 
class (duloxetine, venlafaxine, or amitriptyline). 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.1.3.1 
Statistical Analysis of CFB Daily Pain NRS: MMRM Analysis. (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
1 
 
 
 
0.xxxx 
Week 
 
 
7 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
21 
 
 
 
0.xxxx 
Baseline pain NRS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
Active 5 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 150 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 450 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard 
deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM = Mixed Model for Repeated Measures; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, NRS baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: week xxxxx 
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
Active 450 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 450 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square; NRS = Numeric rating scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average pain NRS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
Include LSmeans and difference in Lsmean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.1.3.2 
Daily Pain NRS: Sensitivity of Primary MCP-Mod Analysis (BOCF) 
mITT Population  
 
Programming Notes: 
• 
Same shell as Table 14.2.1.2.1, substituting “LOCF = Last Observation Carried Forward” by “BOCF = Baseline Observation Carried Forward”. 
• 
The MCP-MOD approach will only be performed if stage 4 is initiated, otherwise there would be insufficient dosing data to fit the non-linear models. 
 
 
 
 
 
 
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4. 
Secondary Efficacy Analysis 
Table 14.2.2.1 
Galer NPS: Summary Statistics (Observed Cases)  
mITT Population 
Parameter: xxxxx 
 
 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
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For Pain Duration Frequency  
 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   I feel a background pain all of the time and occasional flare-ups 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   I feel a single type of pain all the time 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   feel a single type of pain only sometimes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NPS = 
Neuropathic Pain Scale; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are Pain Intensity, Unpleasantness, and Descriptor scores on an 11-point (0-10) NRS, and Pain Duration/Frequency on a 3-point NRS (1-3), 
plus CFB for the same variables. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.6.2 
 
Programming Notes: 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Repeat for the Parameters: Pain intensity, Pain Unpleasantness, Pain Sharpness, Pain Hotness, Pain Dullness, Pain Coldness, Pain Sensitivity, Pain 
Itching, Deep Pain Intensity, Surface Pain Intensity (All in an 11-point NRS), and Pain Duration/Frequency (in a 3-point NRS). 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.2.2 
Galer NPS: MMRM Analysis (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-Medication type 
 
 
1 
 
 
 
0.xxxx 
Week 
 
 
4 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
12 
 
 
 
0.xxxx 
Baseline NPS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
Active 5 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 150 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 450 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard 
deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; NPS = Neuropathic Pain Scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, NPS baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: week: xxxx  
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
Active 450 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 450 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square; NPS = Neuropathic Pain Scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline NPS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.2 
 
Programming Notes: 
• 
Include Lsmeans and difference in Lsmean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Analysis is done for Galer NPS Total Score. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.3.1 
DSIS: Summary Statistics (Observed Cases) 
mITT Population  
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; DSIS = Daily Sleep Interference; n = number of subjects by treatment group at each visit for the parameter; N = number of 
subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are weekly averages of the average daily sleep interference scores on an 11-point (0-10) NRS and CFB for the same variable. 
[1] Baseline is defined as the average of the ‘non-missing’ DSIS within the seven-day period prior to randomization i.e., Day -7 to Day -1, inclusive. 
Reference Listing: 16.2.6.3 
 
 
 
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Programming Notes: 
• 
Include all observed data on weekly averages of the average daily Sleep Interference score for Baseline, Week 4, 8, 12, and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.3.2 
DSIS: MMRM Analysis (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
1 
 
 
 
0.xxxx 
Week 
 
 
4 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
12 
 
 
 
0.xxxx 
Baseline DSIS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
Active 5 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 150 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 450 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard 
deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; DSIS = Daily Sleep Interference. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, DSIS baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: week xxxx 
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
Active 450 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 450 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average DSIS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
Include LS means and difference in LS mean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Include all observed data on weekly average DSIS for Baseline, Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.4.1 
SF-36: Summary Statistics (Observed Cases) 
mITT Population  
Parameter: xxxxx 
 
 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 12 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
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When parameter is “Change in general Health” 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   Much better now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Somewhat better now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   About the same as one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Somewhat worse now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Much worse now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NRS = 
numeric rating scale; SD = standard deviation; SF-36 = 36-Item Short-Form Health Survey; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are derived SF-36 scores and Change in General Health on a 5-point NRS (1-5), plus CFB for the same variables. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.6.4 
 
Programming Notes: 
• 
Include all observed data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Vitality 
(Energy/fatigue), Emotional well-being, Social functioning, Pain and General Health (from 0 to 100), Physical Health Summary, Mental Health 
Summary, and Change in general Health (in a 5-point NRS). 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
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Table 14.2.4.2 
SF-36: MMRM Analysis (Observed Cases) 
mITT Population 
 
Model parameter estimates: xxxxxxxx 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
xx 
 
 
 
0.xxxx 
Week 
 
 
1 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
3 
 
 
 
0.xxxx 
Baseline SF-36 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
Active 5 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 150 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Active 450 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard 
deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; SF-36 = 36-Item Short-Form Health Survey. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, SF-36 baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
 
 
 
 
 
 
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Least Square Means: xxxxxxxx / week xxxx 
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
Active 450 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 450 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 150 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
Active 5 mcg - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline SF-36 parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.4 
 
Programming Notes: 
• 
Include Lsmeans and difference in Lsmean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Include all observed data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Vitality 
(Energy/fatigue), Emotional well-being, Social functioning, Pain and General Health. Add parameter name after ‘Model parameter estimates:’ and after 
‘Least Square Means:’ 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.5.1 
Rescue Medication Use: Summary Statistics 
mITT Population 
 
Variable   
Placebo 
MEDI7352 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
Number of subjects taking any 
rescue medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Number of subjects taking any 
permitted rescue medication  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Total number of days rescue 
medication was used [1] 
 
 
 
 
 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Cumulative consumption of 
Paracetamol Rescue Medication 
(mg) [2] 
 
 
 
 
 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Paracetamol Rescue Medication 
Average Daily Dose (mg) [3] 
 
 
 
 
 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
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Number of subjects taking any 
prohibited rescue medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Each day on which permitted rescue medication was used at least once is counted. 
[2] Calculated as the total dose of paracetamol rescue medication (mg). 
[3] Calculated as: cumulative consumption of paracetamol rescue medication (mg) /total number of days rescue medication was used. 
 
Reference Listing: 16.2.6.5 
 
 
Programming Notes: 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
• 
Refer to  
 
 
 
 
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Table 14.2.6.1 
Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel Haenszel (Observed Cases) 
mITT Population 
Cochran-Mantel-Haenszel Test 
Visit/ 
    Category 
Number of  
Subjects (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Week 4 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Week 8 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Week 12 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Week 18 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata. 
[2] P-value < 0.05 indicates a significant association between number of subjects with >=30% decrease from Baseline and treatment across strata. 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 4, 8, 12, 18. 
 
 
 
 
 
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Table 14.2.6.2 
Daily Pain NRS Responder Analysis (≥30%): GEE Analysis (Observed Cases)  
mITT Population 
 
Model parameter estimates 
Parameter 
Estimate 
Z value 
Degrees of freedom 
Standard Error 
2-sided 95% CL 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
Co-medication type 
 
 
xx 
 
 
0.xxxx 
Week 
 
 
4 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
0.xxxx 
Treatment*Week 
 
 
12 
 
 
0.xxxx 
Active 5 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
Active 150 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
Active 450 mcg vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
Dispersion 
xx.xx 
 
 
 
 
 
CL = Confidence limits; GEE: Generalized Estimation Equations; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: GEE using Time, Treatment, Treatment*Time and Co-medication type as covariates, with dependent binary 
variable indicating whether weekly average pain NRS has >=30% decrease from Baseline. 
 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
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Table 14.2.7.1 
Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel Haenszel (Observed Cases) 
mITT Population 
 
Cochran-Mantel-Haenszel Test 
Visit/ 
    Category 
Number of  
Subjects (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Week 4 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Week 8 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Week 12 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Week 18 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata. 
[2] P-value < 0.05 indicates a significant association between number of subjects with >=50% decrease from Baseline and treatment across strata. 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 4, 8, 12, and 18. 
 
 
  
 
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Table 14.2.7.2 
Daily Pain NRS Responder Analysis (≥50%): GEE Analysis (Observed Cases) 
mITT Population 
 
Programming notes: 
• 
Same shell as Table 14.2.6.3. Change footnote in [2] as: “p-value is derived from the following model: GEE using Time, Treatment, Treatment*Time 
and Co-medication type as covariates, with dependent binary variable indicating whether weekly average pain NRS has >=50% decrease from 
Baseline”. 
• 
Include all observed data for Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.2.8.1 
Patient Global Impression of Change: Summary Statistics 
mITT Population 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   Number of PGIC Responders 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Very Much Improved   
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Much Improved 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Minimally Improved 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      No change 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Minimally Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Much Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Very Much Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 8 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group; PGIC = Patient Global Impression of Change. 
Note: Percentages for Number of subjects in the different improvement categories relative to baseline are n/Number of Subjects by treatment group at each 
visit *100. 
 
Reference Listing: 16.2.6.6 
 
Programming notes: 
• 
Include all observed data on PGIC scores for Week 4, 8, 12 and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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Table 14.2.8.2 
Patient Global Impression of Change: Cochran-Mantel Haenszel  
mITT Population 
 
Cochran-Mantel-Haenszel Test 
Visit/ 
    Category 
Number of  
Patients (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Week 4 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
   Much Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
   Very Much improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Week 8 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
   Much Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
   Very Much improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Week 12 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
   Much Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
   Very Much improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
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Week 18 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
   Much Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
   Very Much improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata. 
[2] P-value < 0.05 indicates a significant association between improvement relative to Baseline and treatment across strata. 
Reference Listing: 16.2.6.6 
 
Programming Notes: 
• 
Include all observed data on PGIC scores for Week 4, 8, 12 and 18. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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5. 
Exploratory Efficacy Analyses 
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6. 
Safety and Tolerability 
6.1. 
Displays of Adverse Events 
Table 14.3.1.1 
Summary of Overall Adverse Events  
Safety Population 
 
 
Placebo 
MEDI7352 
Total 
Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with any AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE possibly related 
to IP [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE leading to 
Discontinuation of IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE related to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Mild related to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Moderate related 
to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Severe related to 
IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE leading to Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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AE = adverse event; IP = Investigational product, N = number of subjects per treatment group; SAE = serious adverse event; TEAE = treatment emergent 
adverse event. 
[1] Possibly related is defined as with reasonable possibility that the AE was caused by the IP, as assessed by investigator 
Note: Subjects who reported more than one adverse event within each category were only counted once. A TEAE is defined as an adverse event with an onset 
at the time of or following the start of treatment with IP.  
Reference Listing: 16.2.7.1, 16.2.7.2, 16.2.7.3, 16.2.7.4 
 
Programming Notes: 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.3.1.2 
Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
Placebo 
MEDI7352 
Total 
    Preferred Term 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each SOC/PT 
category; N = number of subjects per treatment group; IP = investigational product; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-
emergent adverse event. 
Note: Results are n (n/N * 100) then the total number of events.  
A TEAE is defined as AE with an onset at the time of or following the start of treatment with IP.  
Aes were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT.  
Aes are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency.  
Reference Listing: 16.2.7.1 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.3 
Treatment Emergent Adverse Events by Severity, System Organ Class and Preferred Term 
Safety Population 
System Organ Class 
 
 
 
 
 
 
   Preferred Term 
Placebo 
MEDI7352 
Total 
      Severity 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Subjects with at Least One TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
   Preferred Term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; ; n = number of subjects within each 
SOC/PT/Severity category; N = number of subjects per treatment group; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-emergent 
adverse event. 
Note: Results are n (n/N * 100).  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
Aes were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT at the maximum severity.  
Aes are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency. 
Reference Listing 16.2.7.1 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Present only severity categories with at least one subject. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.4 
Treatment Emergent Adverse Events by Relationship to Study Medication, System Organ Class and Preferred Term 
Safety Population 
System Organ Class 
 
 
 
 
 
 
   Preferred Term 
Placebo 
MEDI7352 
Total 
      Relatedness 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Subjects with at Least One TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
   Preferred Term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities;  n = number of subjects within each 
SOC/PT/Relatedness category; N = number of subjects per treatment group; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-emergent 
adverse event. 
[1] Related is defined as reasonable possibility that the AE was caused by investigational product, as assessed by the investigator. 
Note: Results are n (n/N *100).  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
Aes were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT for the most related AE.  
Aes are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency. 
Reference Listing 16.2.7.1 
 
 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Present only severity categories with at least one subject. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.5 
Treatment Emergent Adverse Events by ADA Status Category, System Organ Class and Preferred Term 
Safety Population 
Treatment: xxxxxxx 
 
 
 
 
 
System Organ Class 
ADA 
Negative  
ADA Positive 
TE-ADA 
Positive 
Non-TE-
ADA Positive 
TE 
Persistently 
ADA Positive 
TE 
Transiently 
ADA Positive 
Post-Baseline 
and Baseline 
Positive 
Only Baseline 
Positive 
    Preferred Term 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
AE = adverse event; ADA = Anti-Drug Antibodies; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; ; n = number of 
subjects within each SOC/PT category; N = number of subjects per ADA status category; PT = Preferred Term; SOC = System Organ Class; TEAE = 
treatment-emergent adverse event. 
ADA categories are defined in the Statistical Analysis Plan. 
Note: Results are n (n/N *100) then the total number of events.  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
Aes were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT.  
Table is sorted by international order for SOC, and alphabetically for PT. 
Reference Listing: 16.2.7.1 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Repeat for Placebo, 
 and Overall. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A table for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.1.6 
Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by System Organ Class and Preferred Term  
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One TEAE leading to IP discontinuation”. 
• 
Update Reference Listing to 16.2.7.2. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.1.7 
Non-Serious Adverse Events Occurring in More than 5% of Subjects by System Organ Class and Preferred Term 
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One Non-Serious AE” and remove references to TEAEs. 
• 
Update Reference Listing  to 16.2.7.1. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.3.1.8 
Treatment Emergent Adverse Events Occurring in More than 5% of Subjects by Preferred Term  
Safety Population 
 
Placebo 
MEDI7352 
Total 
    Preferred Term 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
… 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each PT category; 
N = number of subjects per treatment group; PT = Preferred Term; TEAE = treatment-emergent adverse event. 
Note: Results are n (n/Number of subjects in the Safety population within each PT*100) then the total number of events.  
A TEAE is defined as AE with an onset at the time of or following the start of treatment with IP.  
Aes were coded using MedDRA version 26.0. Subjects are counted once for each PT.  
Aes are displayed by descending frequency of PT based on ‘All MEDI7352’ column, and alphabetically for PT of same frequency.  
Reference Listing: 16.2.7.1 
 
Programming Notes: 
• 
PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as Not Coded [PT]”, and sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.3.1.9 
Treatment Emergent Adverse Events by Preferred Term  
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.8. 
• 
Display all TEAEs, not only the most common. 
• 
PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as Not Coded [PT]”, and sorted at the end of the table. 
• 
A column for 
 dosing 
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.2. 
Summary of Deaths and Other Serious Adverse Events 
 
Table 14.3.2.1.1 
Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One SAE”, add “SAE = Serious Adverse Event” to 
abbreviations, and remove references to TEAEs. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
Table 14.3.2.1.2 
Life-Threatening Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One Life-Threatening SAE”, add “SAE = Serious Adverse 
Event” to abbreviations, and remove references to TEAEs. 
• 
Add “Note: Life-threatening SAEs as judged by the investigator”. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated 
 
 
 
 
 
 
 
 
 
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Table 14.3.2.1.3 
Serious Adverse Events with Outcome Death by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One SAE with Outcome Death”, add “SAE = Serious Adverse 
Event” to abbreviations, and remove references to TEAEs. 
• 
Change footnote for “Reference Table 14.3.3.2”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
Table 14.3.2.1.4 
Serious Adverse Events by Relationship to Study Medication, System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.4. Change first row to be “Number of subjects with at Least One SAE”, add “SAE = Serious Adverse Event” to 
abbreviations, and remove references to TEAEs. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.3.1 
Listing of Serious Adverse Events 
Safety Population 
Subject ID/ 
Treatment Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date/Time 
(Study Day)/ 
   End Date/Time 
(Study Day) 
Severity/ 
   Relationship 
Outcome/ 
      Action Taken/ 
           Therapy? 
 
SAE Leading 
to Study DC? TEAE?  
Serious 
Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/
HH:MM (X)/ 
DDMMMYYYY/
HH:MM (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
     XXXXXXXXXX/ 
                         Yes 
No 
No  
XX 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXXXX 
 
DDMMMYYYY/
HH:MM (X)/ 
DDMONYYYY
/HH:MM (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
   XXXXXXXXXX/ 
                        No 
Yes 
XX 
XX / 
XXX 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMONYYYY/
HH:MM (X)/ 
   Ongoing 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXXXX/N
o 
No 
XX 
XX / 
XXX 
 
DC = discontinuation; ID = identification; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; SAE = serious adverse event; 
TEAE = treatment emergent adverse event. 
Note: Study Day = date of interest – date of first infusion. A TEAE is defined as an adverse event with an onset at the time of or following the start of treatment 
with IP. 
SAEs were coded using MedDRA version 26.0 
 
 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e., no AEs occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment ID/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g.. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.3.2 
Listing of Deaths 
Safety Population 
Subject ID/ 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date/Time 
(Study Day)/ 
   End Date/Time 
(Study Day) 
Severity/ 
   Relationship 
Outcome/ 
      Action Taken/ 
           Therapy? 
AE 
Leading 
to IP DC? TEAE?  
 Serious 
 Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/H
H:MM (X)/ 
   
DDMMMYYYY/H
H:MM (X) 
XXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
  XXXXXXXXXX/ 
                     Yes 
No 
No  
XX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXXXX 
 
DDMMMYYYY/H
H:MM (X)/ 
   
DDMMMYYYY/H
H:MM (X) 
XXXXXXXX/ 
XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXXX/No 
Yes 
XX 
XX / XXX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMMMYYYY/H
H:MM (X)/ 
   Ongoing 
XXXXXXXX/ 
XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXX/ 
                No 
No 
XX 
XX / XXX 
 
DC = discontinuation; ID = identification; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; TEAE = treatment emergent 
adverse event. 
Note: Study Day = date of interest – date of first infusion. A TEAE is defined as an adverse event with an onset at the time of or following the start of treatment 
with IP. 
AEs were coded using MedDRA version 26.0 
 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e., no AEs occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.3. 
Displays of Significant Adverse Events and Adverse Events of Special Interest 
 
 
Table 14.3.2.2.1 
Treatment Emergent Adverse Events Associated with Abnormal Liver by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at least One TEAE Associated with Abnormal Liver”. Remove references to TEAEs 
in footnote. 
• 
Update Reference Listing to 16.2.7.3. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
Table 14.3.2.2.2 
Potential joint Related Adverse Events of Special Interest by System Organ Class and Preferred Term  
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at least One Potential Joint Related AESI” 
• 
Add abbreviation for AESI = Adverse Event of Special Interest. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.4 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
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Table 14.3.2.2.3 
Serious and/or severe Infections by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One SAE or Severe AE Related to Infection”. Add “SAE = Serious Adverse 
Event” to abbreviations. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.5. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.2.2.4 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of IP by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One Anaphylactic Reaction, Hypersensitivity or Infusion-Related Reactions 
Leading to Discontinuation of IP”. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.6. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
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6.4. 
Laboratory Data 
 
Table 14.3.4.1 
Descriptive Summary of Clinical Chemistry 
Safety Population 
Parameter: xxxxx (unit) 
Visit/ 
    Statistic 
Placebo 
MEDI7352 
 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
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Day 1 CFB 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically Significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects 
per treatment group; NCS = not clinically significant; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages are n/Number of subjects by treatment group at each visit*100.  
Reference Listing: 16.2.8.1 
 
Programming Notes: 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Albumin, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), 
Bicarbonate, Calcium, Chloride, Creatinine, High-Sensitivity C-Reactive Protein (hs-CRP), Estimated Glomerular Filtration Rate (eGFR by Cockcroft - 
Gault), Serum Glucose, Lactate Dehydrogenase (LDH), Potassium, Sodium, Total Bilirubin, Total Protein, Blood Urea Nitrogen (BUN), Uric Acid. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.2 
Shift Table of Clinical Chemistry Results 
Safety Population 
Parameter (Unit)/ 
    Visit  
        Post-Baseline 
        Grade    
Baseline Grade [1] 
Placebo 
 (N=xxx) 
MEDI7352, 
 
 (N=xxx) 
Low 
Normal 
High 
Missing 
Total 
Low 
Normal 
High 
Missing 
Total 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX (Unit) 
 
 
 
 
 
 
 
 
 
 
    Week x 
 
 
 
 
 
 
 
 
 
 
        Low 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        High 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Missing 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Total 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     Week x 
 
 
 
 
 
 
 
 
 
 
        Low 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        High 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Missing 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Total 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects within each category; N = number of subjects per treatment group. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Percentages are n/Number of subjects by treatment group at each visit for the parameter*100. 
Reference Listing 16.2.8.1 
Programming Notes: 
• 
Repeat above in new pages for MEDI7352, 
, MEDI7352, 
 and All MEDI7352. 
• 
Repeat the above for 
 dosing only if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.5.1. 
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Table 14.3.4.3 
Descriptive Summary of Hematology 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.5.1 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Absolute basophil count, absolute eosinophil count, absolute lymphocytes count, Absolute Monocyte Count, 
Absolute Neutrophil Count, Basophils %, Eosinophils %, Hematocrit (HCT), Hemoglobin (HGB), hemoglobin A1C (HgbA1C), Lymphocytes %, mean 
corpuscular hemoglobin (MHC), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), Monocytes %, Neutrophils 
%, Platelets, Red blood cell count (RBC), Red Cell Distribution Width, white blood cell Count (WBC). 
• 
Update Reference listing to 16.2.8.2. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.4.4 
Shift Table of Hematology Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.5.2 
• 
Repeat the shell for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.5.3. 
• 
Update Reference listing to 16.2.8.2 
 
 
 
 
 
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Table 14.3.4.5 
Descriptive Summary of Coagulation 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.5.1 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Activated Partial Thromboplastin Clotting Time (APTT), Fibrinogen, International normalized ratio (INR), 
Prothrombin Time (PT). 
• 
Update Reference listing to 16.2.8.3. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.4.6 
Shift Table of Coagulation Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.5.2 
• 
Repeat for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.5.4. 
• 
Update Reference listing to 16.2.8.3. 
 
 
 
 
 
 
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Table 14.3.4.7 
Descriptive Summary of Urinalysis 
Safety Population 
Parameter: xxxxx (unit) 
Visit/ 
    Statistic 
Placebo 
MEDI7352 
 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 CFB 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
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… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for all visits for Parameters: Specific 
Gravity and pH 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
       n 
xx 
xx 
xx 
xx 
xx 
xx 
       Negative 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
       Positive 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
If Positive, Specify [2] 
 
 
 
 
 
 
   100 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   250 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   500 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   >= 1000 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
       n 
xx 
xx 
xx 
xx 
xx 
xx 
       Negative 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
       Positive 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for all visits for Parameters: Blood, 
Glucose, Ketones and Protein 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects 
per treatment group; NCS = not clinically significant; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
[2] Percentages are n/Number of Subjects with a Positive Result*100. 
Note: Percentages are n/Number of subjects by treatment group at each visit*100.  
Reference Listing: 16.2.8.4 
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Programming Notes: 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Blood Urine, Glucose, Ketones, pH, Protein, Specific Gravity. 
• 
Categories for If Positive, Specify: 
o 
Blood, Urine: Trace, Small, Moderate. 
o 
Glucose: 100 mg/dL, 250 mg/dL, 500 mg/dL, >= 1000 mg/dL. 
o 
Ketones: Trace, 15 mg/dL. 
o 
Protein: Trace, 30 mg/dL, 100 mg/dL. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.8 
Shift Table of Urinalysis Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.5.2 
• 
Repeat for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit.  
• 
Present parameters in the same order as in Table 14.3.5.3. 
• 
Update Reference listing to 16.2.8.4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.9 
Maximum On-Treatment ALT and AST versus Maximum On-Treatment Total Bilirubin 
Safety Population 
 
  
  
  
Total Bilirubin 
 
 
 
<2 x ULN 
>=2 x ULN 
Group 
Nobs 
 
n (%) 
n (%) 
Placebo 
 
  
  
  
N=xxx 
xxx 
ALT 
 
 
 
 
<3 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=3 - <5 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=5 - <10 x ULN 
0 
0 
 
 
>=10 x ULN 
0 
0 
 
 
 
 
 
 
AST 
 
 
 
 
<3 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=3 - <5 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=5 - <10 x ULN 
0 
0 
 
 
>=10 x ULN 
0 
0 
… 
 
 
 
Repeat for: 
 All MEDI7352 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; IP = investigational product; n = number of subjects per category; N = number of 
subjects per treatment group; Nobs = number of subjects per treatment group with at least one post-baseline assessment on treatment; ULN = upper limit of 
normal.  
Note: On-treatment assessments include assessments on or after the date of first dose of IP. Baseline is defined as the last observation recorded prior to the 
first dose of treatment. 
Percentages are based on Nobs. 
Reference Listing: 16.2.8.1 
 
 
 
 
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Programming Notes: 
• 
Per Protocol, the elevations of ALT or AST and Total Bilirubin do not have to occur at the same time or within a specified time frame. That is the reason 
why the table is presented by Subject instead of by visit. So, if for example, one subject has ALT >=3 - <5 x ULN at Day 1, and TBL >=2 x ULN at 
Week 18, n in that cell will increase by one. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.5. 
Other Safety Data  
 
Table 14.3.5.1 
Descriptive Summary of Vital Signs 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 15 Minutes Post-
Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 15 Minutes Post-
Dose CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; SD = 
standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. Reference Listing: 16.2.9.1 
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Programming Notes: 
• 
Repeat for Supine Heart Rate, Supine Systolic Blood Pressure, Supine Diastolic Blood Pressure, Respiratory Rate, Body Temperature, Standing Heart 
Rate, Standing Systolic Blood Pressure, Standing Diastolic Blood Pressure. 
• 
After Week 2 (inclusive), Supine measure are taken in sitting position. We will consider them as supine (in resting position) for calculating Change from 
Baseline (always at supine position). 
• 
Include the following timepoints: Baseline, Day 1: 5 Minutes Post-Dose, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 
Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion 
Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 
8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, 
Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Note that Body Tº, and standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.2 
Descriptive Summary of ECG Data 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; SD = 
standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are averages of the 3 replicates taken for each parameter and timepoint, and CFB for the same variables.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.9.2 
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Programming Notes: 
• 
Repeat for PR, QRS, QT, RR, HR (Heart Rate) and QTcF taken from external data. 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, Week 12, 
and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.3 
Summary of Overall Evaluation of Safety ECG Data 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NCS = Not 
clinically significant. 
Note: Data are taken as the most conservative from the 3 replicates taken by timepoint. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.9.2 
 
 
Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, Week 12, 
and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
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Table 14.3.5.4 
Covid-19 Screening 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
Subjects Screened for COVID-19 Symptoms 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
COVID-19 Symptoms Screened: 
 
 
 
 
 
 
   Fever 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sore Throat 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Loss of Taste 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Loss of Smell 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Body Temperature Check 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Subjects with COVID-19 Swab Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with COVID-19 Antibody Testing 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Confirmed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Suspected 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Subjects with COVID-19 Antigen Testing 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment 
group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Percentages are n/Number of subjects by treatment group at each visit*100. 
Reference Listing: 16.2.8.8 
 
 
Programming Notes: 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.5 
Summary of Sub-Scores for Total Neuropathy Score-Nurse 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
Subjects performing TNSn 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Sensory Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Motor Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Autonomic Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Pin Sensibility Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
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Vibration Sensibility Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 xx (xx.x%) 
 xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 N = number of subjects per treatment group; TNSn = Total Neuropathy Score-Nurse.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages for subjects performing TNSn are n/Number of subjects by treatment group at each visit*100. Percentages for each Score are n/Number of 
subjects by treatment group at each visit without missing score*100 
Reference Listing: 16.2.9.5 
 
Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12 and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.6 
Descriptive Summary of Total Neuropathy Score-Nurse 
Safety Population 
Score: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1 CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
TNSn = Total Neuropathy Score-Nurse; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment 
group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. Reference Listing: 16.2.9.5 
Programming Notes: 
- Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12 and Week 18.  
- Include the following scores: Sensory Symptom Score, Motor Symptom Score, Autonomic Symptom Score, Pin Sensibility Score, Vibration Sensibility Score, 
and TNSn Total. 
- A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.3.5.7 
Summary of Motor and Sensory Nerve Conduction Studies 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Week 18 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Week 18 CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Evaluation Result 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abnormal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Week 18 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abnormal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; SD = 
standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages are number of subjects by treatment group at each visit for each category /Number of subjects by treatment group for each visit*100 
Reference Listing: 16.2.9.6 
 
Programming Notes: 
• 
Repeat for the following Parameters: Lower Limb - right side/Motor evaluation/Amplitude, Lower Limb - right side/Sensory evaluation/Amplitude, 
Lower Limb - left side/ Motor evaluation/Amplitude, Lower Limb - left side/ Sensory evaluation/Amplitude, Upper Limb - right side /Motor 
evaluation/Amplitude, Upper Limb - right side/ Sensory evaluation/Amplitude, Upper Limb - left side/ Motor evaluation/Amplitude, Upper Limb - left 
side /Sensory evaluation/Amplitude. (Repeat the same combination of Location - Laterality/Evaluation for Peak Latency, Conduction Velocity, 
Duration of action Potential). 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.8 
Summary of Strength and Deep Tendon Reflexes 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
Subjects performing SDTR assessment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Ankle Dorsiflexion Strength 
 
 
 
 
 
 
   0 - Normal Power 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 - Mild Weakness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 - Moderate Weakness   
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 - Severe Weakness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 - Paralysis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Deep Tendon Reflexes 
 
 
 
 
 
 
   0 - Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 - Ankle reflex reduced 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 - Ankle reflex absent 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 - Ankle reflex absent and knee reflex 
reduced 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 - All reflexes (both ankle and knee) 
absent 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects by treatment group at each visit for each category; N = number of subjects per treatment group; SDTR = strength and deep tendon 
reflexes. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages for each Score are n/Number of subjects by treatment group at each visit*100 
Reference Listing: 16.2.9.7 
Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12, and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
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Table 14.3.5.9 
Summary of Local Injection Site Reactions 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
       Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Day 1: 15 Minutes after 
Start of Infusion 
 
 
 
 
 
 
    Subjects with injection 
Site Assessed  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Pain 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Tenderness 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Erythema/ Redness 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
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Induration/ Swelling 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects by treatment group at each visit for each category; N = number of subjects per treatment group. 
Note: Percentages for each Score are n/Number of subjects by treatment group at each visit*100 
Reference Listing: 16.2.9.8 
 
Programming Notes: 
• 
Include the following timepoints: Day 1: 15 Minutes after Start of Infusion, Day 1: 30 Minutes after Start of Infusion, Day 1: 45 Minutes after Start of 
Infusion, Day 1: 60 Minutes after Start of Infusion, Day 1: 2 hours after Start of Infusion, Day 1: 4 hours after Start of Infusion, Week 2, Week 4, Week 
6, Week, 8, Week 10, Week 12, and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.10 
Summary of Hypersensitivity/Anaphylactic Reactions 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with any 
Hypersensitivity/   
Anaphylaxis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Highest Severity Grade 
 
 
 
 
 
 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Type of Reaction 
 
 
 
 
 
 
   Urticaria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pruritus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Flushing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Swollen Lips, Tongue, 
Uvula and/or Vulva 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Wheeze-Bronchospasm 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Stridor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hypoxia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hypotension 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Crampy Abdominal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Diarrhoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.9 
 
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Programming Notes: 
• 
Display only Type of reaction with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.11 
Summary of Liver Diagnostic Investigations 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Diagnostics 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Type of Diagnostic Investigation 
 
 
 
 
 
 
   Ultrasound 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   CT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   MRI/MRCP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Flushing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   ERCP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   X-Ray 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening for 
Acetaminophen/Paracetamol 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening for Ethanol 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening, Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Specialist Consulted 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis A 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis B 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis C 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis D 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis E 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Serology for Cytomegalovirus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Epstein Barr Virus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Autoimmune Serology 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT = Computerized tomography; ERCP = Endoscopic retrograde cholangiopancreatography; MRI = Magnetic resonance imaging; MRCP = Magnetic 
resonance cholangiopancreatography; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.10 
 
 
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Programming Notes: 
• 
Display only Diagnostic Investigations with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.12 
Summary of Liver Risk Factors and Lifestyle Events 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Risk Factors 
Assessed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Liver Risk Factor 
 
 
 
 
 
 
   Alcohol Abuse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Increased Alcohol Consumption    
within 1 Month of Reported Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   IV Drug Abuse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tattoo 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Acupuncture 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sexually Transmitted Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Toxic/Chemical Agent Exposure 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Travel (Areas at Risk in the Last Year) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pregnancy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Parenteral Nutrition 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Excessive Physical Exercise 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Changes Diet/Fasting Episodes/Weight 
Loss Diet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Previous Drug Reaction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Blood Transfusion 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Patient Exposed to Anyone with 
Jaundice in the Last Month 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   History of Hypotension 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
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   Low Blood Pressure at Time of Event 
of Liver Injury and/or Abnormal Liver 
Laboratory Value 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   History of Liver Disease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV = intravenous; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.10 
 
 
 
Programming Notes: 
• 
Display only Liver Risk Factor with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.13 
Summary of Liver Signs and Symptoms 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Signs/Symptoms 
Assessed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Liver Sign/Symptom 
 
 
 
 
 
 
   Anorexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Asthenia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pyrexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pruritus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Jaundice  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Arthralgia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abdominal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abdominal Tenderness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Nausea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mucosal Inflammation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Purpura 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hepatomegaly 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Splenomegaly 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Lymphadenopathy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ascites 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Confusional State 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Coma 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Upper Quadrant Tenderness 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Biliary Obstruction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Eosinophilia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dark Urine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.12 
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• 
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Table 14.3.5.14 
Summary of Infection Diagnostic Investigations 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Diagnostic 
Investigations 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Method 
 
 
 
 
 
 
   Microscopy, Culture and Sensitivity 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serological Tests 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Nucleic Acid Based Tests 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   X-Ray 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.13 
 
 
 
Programming Notes: 
• 
Display only Methods with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.15 
Summary of Infection Risk Factors and Lifestyle Events 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Risk Factor Occurred 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Infection risk factor 
 
 
 
 
 
 
   Extensive Burns within the Last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tattoo, Piercing or Acupuncture within the 
last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sexually Transmitted Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Travel to Areas at Risk of Tuberculosis or 
Tropical Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Infections Related to Travel 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Blood Transfusion (within the Last Year) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Exposure to Nosocomial Pathogens within the 
Last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Contact History with Infection Source 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Previous BCG Immunization 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evidence of BCG Scar 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tuberculin Skin or Quantiferon Test Confirms 
     Previous Exposure or Immunity to 
Tuberculosis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
BCG = Bacillus Calmette-Guerin; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.14 
Programming Notes: 
• 
Display only infection risk factors with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.3.5.16 
Summary of Infection Signs and Symptoms 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Sign/Symptom 
Occurred 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Infection Sign/Symptoms 
 
 
 
 
 
 
   Pyrexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Headache 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Confusional State 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Convulsion 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rhinitis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Oropharyngeal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Productive Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Haemoptysis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Wheezing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pleuritic Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Diarrhoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Genital Discharge 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Haematuria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dysuria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hepatosplenomegaly 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Jaundice 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lymphadenopathy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
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   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Petechial 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Vesicular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Macular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Papular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Urticaria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Erythema 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Blanching 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Splinter Haemorrhages 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Night sweats 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Chills 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Myalgia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Weight Decrease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.15 
 
 
Programming Notes: 
• 
Display only infection Signs/Symptoms with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.17 
Summary of Concomitant Medications by ATC Level 2 and Preferred Name 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.1.7. 
• 
Change footnote Note by: “Note: Concomitant medications are defined as medications continuing or starting on or after first dose of study medication. 
All concomitant medications are coded using WHO drug dictionary version vMar2023. At each level of summarization (ATC Level 2 or Preferred 
Name), subjects who reported more than one concomitant medication were only counted once. ATC Level 2 and Preferred Name are sorted in in 
descending order of frequency of total, and alphabetically if same frequency”. 
• 
If uncoded ATC Level or Preferred Name, please put them as [Not Coded] 
• 
ATC and Preferred Name texts should be in proper case in table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.18 
Summary of Concomitant Procedures 
Safety Population 
System Organ Class 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xxx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xxx) 
 
 
 
 
 
 
Any Concomitant Procedure 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   … 
… 
… 
… 
… 
… 
 
 
 
 
 
 
System Organ Class n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Note: All Procedure terms were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 26.0. At each level of summarization 
(system organ class or preferred term), subjects having more than one Procedure term were counted only once. System organ class and preferred terms are 
sorted in descending order of frequency of Total column, and alphabetically if same frequency. 
 
Reference Listing: 16.2.9.18 
 
Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Sort SOC and PT (within SOC) in descending order of frequency in the Total column.  Sort alphabetically in case of ties. 
• 
Uncoded Procedure events 
o 
When there are uncoded Procedure Events in the database, the events will be summarized with SOC and PT set to [Not Coded]. The [Not 
Coded] will be sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.3.5.19 
Anti-Drug Antibody Results and Titre Summary by Timepoint 
Safety Population 
 
Placebo 
MEDI7352 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n [2] 
xx 
xx 
xx 
xx 
xx 
ADA Positive: n (%) [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
   n [2] 
xx 
xx 
xx 
xx 
xx 
ADA Positive: n (%) [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
… 
 
 
 
 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
[2] Number of subjects with at least one ADA assessment at the specific visit. 
[3] Number of subjects with a positive result at the specific visit. The denominator for all percentages is the number of subjects with an ADA result for each 
visit. 
Reference Listing: 16.2.9.19 
Programming Notes: 
• 
Keep in mind that in this table ‘Total’ column does not include placebo. 
• 
Repeat for all scheduled post-baseline visits. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.3.5.20 
Descriptive Summary of Anti-Drug Antibody Results and Titre by ADA Categories  
Safety Population 
 
Placebo 
MEDI7352 
ADA Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
 
 
 
 
 
ADA positive at baseline and/or post-baseline (ADA 
prevalence) 
 
 
 
 
 
   n/Nobs (%) [1] [2] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
TE-ADA positive (ADA incidence) [5] 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Treatment Induced ADA Positive 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
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Treatment-Boosted ADA Positive 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Non-TE-ADA Positive 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Both baseline and post-baseline positive 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Only baseline positive 
 
 
 
 
 
   n/Nobs (%) [1] [4] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
TE-persistently ADA positive [6] 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
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TE-transiently ADA positive [7] 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; N = number of subjects per treatment group; TE-ADA = Treatment Emergent ADA; SD = standard deviation; Q1 = first 
quartile; Q3 = third quartile. 
[1] n represents the number of subjects satisfying the conditions of the specified ADA category  
[2] Nobs represents the number of subjects with any ADA result at baseline and/or post-baseline. 
[3] Nobs represents the number of subjects with an ADA result at baseline and at least one post-baseline ADA assessment. 
[4] Nobs represents the number of subjects with an ADA result at baseline. 
[5] TE-ADA positive is defined as either ADA negative at baseline and post-baseline ADA positive (Treatment Induced ADA Positive), or as ADA positive at 
baseline with pre-existing titre boosted during the study period (Treatment Induced ADA Positive). ADA incidence is the proportion of TE-ADA+ subjects in 
a population. 
[6] ADA negative at baseline and having at least 2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between first and last positive, or an 
ADA positive result at the last available post-baseline assessment. 
[7] ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. 
Reference Listing: 16.2.9.19 
 
 
Programming Notes: 
• 
If a participant has more than 1 non-missing titre during the study, the maximum titre for each participant is summarized. 
• 
Only present summary statistics if titre is available. 
• 
If no positive results for a particular block of the table, then the summary statistics for the titres for that particular block would not appear. 
• 
It is assumed that participants with a missing baseline ADA result are ADA negative at baseline. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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7. 
Pharmacokinetic/Pharmacodynamic Data  
Table 14.4.1 
Summary of Serum MEDI7352 Concentrations 
PK Population 
ADA Status: xxxxxxxxxx 
 
 
MEDI7352 
Visit/ 
    Statistic 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
Baseline [1] 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   gMean ± gSD 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
   gCV% 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Week 2 
xx (xx) 
xx (xx) 
xx (xx) 
   n (n < LLOQ) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Mean (SD) 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
   gMean ± gSD 
xx.x 
xx.x 
xx.x 
   gCV% 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Median 
xx, xx 
xx, xx 
xx, xx 
   Min, Max 
 
 
 
 
 
 
 
Week 4 
xx (xx) 
xx (xx) 
xx (xx) 
   n (n < LLOQ) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Mean (SD) 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
   gMean ± gSD 
xx.x 
xx.x 
xx.x 
   gCV% 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Median 
xx, xx 
xx, xx 
xx, xx 
   Min, Max 
 
 
 
 
 
 
 
… 
 
 
 
gCV% = Geometric Coefficient of Variation (%); gMean = Geometric Mean; gSD = Geometric SD; LLOQ = Lower Limit of Quantification; n = number of 
subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.10.1 
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Programming Notes: 
• 
Include the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 
10: 8 Hours after Infusion, Week 10 + 24 hours/ Pre-Dose, Week 11/ Pre-Dose, Week 10 + 14 Days/Pre-Dose; Week 18. 
• 
Repeat the table for ‘ADA Positive’, ‘ADA Negative’ and ‘Overall'. 
• 
Any values reported as NRR (not reportable) or NS (missing) will be excluded from the summary tables. 
• 
At a time point where less than or equal to 50% of the concentration values are NQ (below LLOQ), all NQ values will be set to the LLOQ, and all 
descriptive statistics will be calculated accordingly. 
• 
At a time point where more than 50% (but not all) of the values are NQ, the gmean, gmean ± gSD and gCV% will be set to NC. The maximum value 
will be reported from the individual data, and the minimum and median will be set to NQ. 
• 
If all concentrations are NQ at a time point, no descriptive statistics will be calculated for that time point. The gmean, minimum, median and maximum 
will be reported as NQ and the gCV% and gmean ± gSD as NC. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.4.2 
Summary of Serum total NGF Concentrations 
Safety Population 
ADA Status: xxxxxxxxxx 
 
 
 
Placebo 
MEDI7352 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
Baseline [1] 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   gMean ± gSD 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Week 2 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   gMean ± gSD 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Week 4 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   gMean ± gSD 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
 x.xx to x.xx 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
gCV% = Geometric Coefficient of Variation (%); gMean = Geometric Mean; gSD = Geometric SD; LLOQ = Lower Limit of Quantification; n = number of 
subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NGF = Nerve-Growth Factor. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Reference Listing: 16.2.10.3 
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Programming Notes: 
• 
Repeat for ADA Status: “ADA Positive”, “ADA Negative” and “Overall”.  
• 
Include the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 
10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Planned Listing Descriptions and Shells 
Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
Listing 16.2.1.1 - Subject Disposition - Screening Population 
U 
Listing 16.2.1.2 - Assignment to Analysis Populations - Screening Population 
U 
Listing 16.2.1.3 - Reason for IP Discontinuation and Withdrawal from the Study - Safety Population 
U 
Listing 16.2.1.4 - List of Reasons for Screening Failure - Screen Failure Population 
U 
Listing 16.2.1.5 - Subject Visits and COVID-19 Impact - Screening Population 
U 
Listing 16.2.2.1 - Subjects Not Meeting All Inclusion Criteria or Meeting any Exclusion Criteria - Screening Population 
U 
Listing 16.2.2.2 - Protocol Deviations - Safety Population 
U 
Listing 16.2.3 - Randomization and Treatment Group - Safety Population
U 
Listing 16.2.4.1 - Demographic and Baseline Characteristics - Screening Population 
U 
Listing 16.2.4.2 - Medical History - Safety Population 
U 
Listing 16.2.4.3 - Osteoarthritis Characteristics - Screening Population 
U 
Listing 16.2.5.1 - Study Drug Administration: Individual Doses - Safety Population 
U 
Listing 16.2.6.1 - Daily Pain NRS - mITT Population 
U 
Listing 16.2.6.2 - Galer NPS - mITT Population 
U 
Listing 16.2.6.3 - DSIS - mITT Population 
U 
Listing 16.2.6.4 - SF-36 - mITT Population 
U 
Listing 16.2.6.5 - Rescue Medication Usage - mITT Population 
R 
Listing 16.2.6.6 - Patient Global Impression of Change - mITT Population 
U 
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Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
 
U 
Listing 16.2.7.1 - Adverse Events - Safety Population 
U 
Listing 16.2.7.2 - Treatment Emergent Adverse Events Leading to Study Drug DiscontinuationError! Reference source not found. - Safety 
Population 
R 
Listing 16.2.7.3 - Treatment Emergent Adverse Events Associated with Abnormal Liver - Safety Population 
R 
Listing 16.2.7.4 - Joint Related Adverse Events of Special Interest - Safety Population 
R 
Listing 16.2.7.5 - Serious and/or Severe Infections - Safety Population 
R 
Listing 16.2.7.6 - Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of Study Drug - 
Safety Population 
R 
Listing 16.2.8.1 - Clinical Chemistry Laboratory Evaluations - Safety Population 
U 
Listing 16.2.8.2 - Hematology Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.3 - Coagulation Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.4 - Urinalysis Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.5 - Serology Laboratory Evaluations - Safety Population 
U 
Listing 16.2.8.6 - Pregnancy Test Results - Safety Population 
U 
Listing 16.2.8.7 - Drug Test Results - Safety Population 
U 
Listing 16.2.8.8 - COVID-19 Screening and Vaccination - Safety Population 
U 
Listing 16.2.9.1 - Vital Signs Measurements - Safety Population 
U 
Listing 16.2.9.2 - ECG Results - Safety Population 
U 
Listing 16.2.9.3 - Physical Examination Results - Safety Population 
U 
Listing 16.2.9.4 - Neurological Examination Results - Safety Population 
U 
Listing 16.2.9.5 - Total Neuropathy Score-Nurse - Safety Population 
U 
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Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
Listing 16.2.9.6 - Motor and Sensory Nerve Conduction Studies - Safety Population 
U 
Listing 16.2.9.7 - Strength and Deep Tendon Reflexes - Safety Population 
U 
Listing 16.2.9.8 - Injection Site Reactions - Safety Population 
U 
Listing 16.2.9.9 - Hypersensitivity/Anaphylactic Reactions - Safety Population 
U 
Listing 16.2.9.10 - Liver Diagnostic Investigations - Safety Population 
U 
Listing 16.2.9.11 - Liver Risk Factors and Lifestyle Events - Safety Population 
U 
Listing 16.2.9.12 - Liver Signs and Symptoms - Safety Population 
U 
Listing 16.2.9.13 - Infection Diagnostic Investigations - Safety Population 
U 
Listing 16.2.9.14 - Infection Risk Factors and Lifestyle Events - Safety Population 
U 
Listing 16.2.9.15 - Infection Signs and Symptoms - Safety Population 
U 
Listing 16.2.9.16 - Prior and Concomitant Medications - Safety Population 
U 
Listing 16.2.9.17 - Prohibited Concomitant Medications - Safety Population 
R 
Listing 16.2.9.18 - Concomitant Procedures - Safety Population 
R 
Listing 16.2.9.19 - Anti-drug Antibody Test Results - Safety Population 
U 
Listing 16.2.10.1 - Serum MEDI7352 Concentrations - PK Population 
U 
Listing 16.2.10.2 - Serum total NGF Concentrations - PD Population 
U 
 
 
 
 
 
 
 
 
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Listing Change Log: 
Output 
Number 
Date of 
Change 
Change 
Made By 
(initials) 
Description/Rationale 
 
 
 
 
 
 
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Listing 16.2.1.1 
Subject Disposition  
Screening Population  
 
Subject 
ID 
Re-screened?/ 
Previous 
Subject ID 
Treatment 
Arm 
Re-consent/ 
Date/Time of Initial IC/ 
Initial Protocol Version 
Date/Time of 
Informed Consent 
Protocol 
Version at 
consent/ 
Re-consent 
Consent for 
 
sample? /Date of 
Consent 
Consent for 
COVID-19 Safety 
Measures /Date of 
Consent 
Current 
Protocol 
version 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
Yes/ XXXX 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
Yes / 
DDMMMYYYY/hh:mm 
/ XXXX 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
No 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
No 
No 
XXXXX 
 
 
 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; IC = Informed Consent; 
 
. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
 
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Listing 16.2.1.2 
Assignment to Analysis Populations 
Screening Population  
Subject ID 
Treatment 
Arm 
Screened [1] 
Randomized 
SAF [2] 
mITT [3] 
PK [4] 
Reason to Exclude from 
Safety [5] 
Reason to Exclude from 
mITT [6] 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
No 
No 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
No 
No 
No 
XXX 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
No 
No 
XXX/ XXX 
XXX/ XXX 
 
 
 
 
 
 
 
 
 
mITT = Modified Intent-To-Treat Population Set; NRS = numeric rating scale; PK = pharmacokinetics; SAF = Safety Population Set. 
[1] The Screening Population includes all subjects who provide informed consent and provide demographic and/or baseline screening assessments. 
[2] The Safety Population includes all subjects who receive at least 1 dose of double-blind study medication. 
[3] The mITT Population includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
[4] The PK Population includes all subjects for who a pharmacokinetic sample was obtained and analysed. 
[5] Major deviation reason/s to exclude from Safety Population for randomized subject. 
[6] Major deviation reason/s to exclude from mITT Population for randomized subject. 
 
 
Programming Notes: 
• 
If there is more than one major deviation, please concatenate with “/” 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
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Listing 16.2.1.3 
Reason for IP Discontinuation and Withdrawal from the Study 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
Study 
Completion 
Status 
IP 
Discontinuation/ 
Study 
Withdrawal 
Completion/ 
Discontinuation 
Date/Time (Study Day) 
Date of Last Dose 
Primary 
Reason for 
DC/ 
Withdrawal 
Blind Broken? / 
Date/Time / 
Reason 
Reason for 
breaking 
the Blind 
Study 
Duration 
 
 
 
 
 
 
 
 
 
XXXXXX
/XXXX 
Discontinued 
Early 
IP 
Discontinuation  
DDMMMYYYY/hh:mm 
(XX) 
 
XXXXXX
X 
Yes /  
DDMMMYYYY
/hh:mm 
XXXXXX 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX
/XXXX 
Discontinued 
Early  
IP 
Discontinuation  
DDMMMYYYY/hh:mm 
(XX) 
 
XXXXXX
X 
No 
 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX
/XXXX 
Completed 
 
DDMMMYYYY/hh:mm 
(XX) 
DDMMMYYYY 
 
No 
 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX
/XXXX 
Discontinued 
Early  
Study 
Withdrawal 
DDMMMYYYY/hh:mm 
 
Other: 
XXXXXX
X 
No 
 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX
/XXXX 
Completed 
 
DDMMMYYYY/hh:mm 
(XX) 
DDMMMYYYY 
 
No 
 
XX 
 
 
 
 
 
 
 
 
 
DC = Discontinuation; IP = Investigational product.  
[1] Any withdrawal from the study before last IP dose (Week 10) is considered an IP discontinuation. 
Note: Study Day is calculated relative to the date of first dose. Study Duration = Reference end date – date of first dose of treatment + 1. 
 
Programming Notes: 
• 
If reason for non-completion is Other, concatenate the specify text as follows: “Other: XXXXXXXXX”.  
• 
If reason for non-completion is adverse event, concatenate with AE line number as follows: “Adverse event number X”.  
• 
For Physician decision, screen-fail and withdrawal by subject, please provide explanation if presented on the logic “Physician decision: XXX”.  
• 
Sort by Treatment Arm/ Subject ID. 
 
 
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Listing 16.2.1.4  
List of Reasons for Screening Failure 
Screen Failure Population 
 
Subject ID 
Treatment Arm 
Screen failure Date 
Date/Time 
Primary Reason for Screen Failure 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY/hh:mm 
XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY/hh:mm 
XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY/hh:mm 
 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY/hh:mm 
Other: XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY/hh:mm 
 
 
 
 
 
 
 
Programming Notes: 
• 
If reason for non-completion is Other, concatenate the “Primary Reason for Screen Failure” text as follows: “Other: XXXXXXXXX”.  
• 
Sort by Subject ID. 
 
 
 
 
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Listing 16.2.1.5 
Visits List and COVID-19 Impact 
Screening Population 
 
Subject ID/ 
Treatment 
Arm 
Visit 
Name 
Visit Date 
(Study 
Day) 
Is COVID-
19 
Pandemic 
Ongoing? 
Impacted 
by 
COVID-19 
Was visit 
performed? / 
Visit Type 
Visit 
Performe
d Via 
VS Data 
provided? / 
Assessments 
Missed? 
IP dosing 
missed due to 
COVID-19 / 
Details 
End of 
Treatment 
linked to 
COVID-19 
Subject 
discontinued 
due to 
COVID-19? / 
Details 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
Yes 
 
Yes 
Yes/ 
Delayed 
On site 
Y/  
Efficacy 
Y/ XXXX 
Other: XXXX 
Y/ XXXX 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
Yes 
 
No 
Yes 
 
N/ Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
No 
 
Yes 
Yes 
Video 
N/  
Efficacy, 
Safety 
Y/ Other: 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
No 
 
No 
No / Missed 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; IP = Investigational Product; VS = Vital Signs. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
• 
Visit Type: Missed, Abbreviated, Delayed. 
• 
Visit Performed Via: Video, Phone, On Site Other: xxxxxx. 
• 
Details on IP dosing missed: Treatment on hold due to Sponsor Decision, Subject infected with COVID-19, Subject decision, Other: xxxxxx. 
• 
End of treatment, reason if due to COVID: Subject infected with COVID-19, Subject decision, Travel restrictions, Site closed, Study delayed/cancelled, 
Other: xxxxxx. 
• 
Details on Subjects discontinuing due to COVID-19: Subject infected with COVID-19, Subject decision, End of Treatment due to Sponsor, Other: xxxxxx. 
• 
Sort by Treatment Arm/ Subject ID. 
 
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Listing 16.2.2.1 
Subjects Not Meeting All Inclusion Criteria or Meeting any Exclusion Criteria 
Screening Population 
Subject ID 
Treatment Arm 
Enrolled 
Randomized 
Inclusion or 
Exclusion 
Criteria 
Number 
Criteria Label 
 
 
 
 
 
 
 
XXXXXX 
Screen Failure 
Yes 
No 
Inclusion 
XX 
XXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
Yes 
No 
Exclusion 
XX 
XXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
Programming Notes: 
 
• 
Sort by Subject ID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.2.2 
Protocol Deviations 
Safety Population 
 
Subject ID Treatment Arm Analysis Population 
Event Date (Study Day) Event Type 
Description 
Category 
Covid-
19 
Related? 
 
 
 
 
 
XXXXXX 
XXXX 
Screened\RND\SAF\
mITT 
DDMMMYYYY (XX) 
XXXXXXXXXXX 
XXXXXXX 
Non-
important 
Y 
 
 
XXXXXXXXXXXXXX 
XXXXXXXXXXXXXXX Important 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (XX) 
XXXXXXXXXXXX 
XXXXXXXXXXXXXXX
XXX 
XXXXX 
 
 
XXXXXXXXXXXXXXXX XXXXXXXXXXX 
XXXXX 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (XX) 
XXXXXXXXXXXX 
XXXXXXXXXXXXXXX
XXX 
XXXXX 
COVID-19 = Coronavirus disease 2019; mITT = Modified Intent-To-Treat Population; RND = Randomized Subjects; SAF = Safety Population. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
o 
The structure of this listing may change depending on the information in the protocol deviations file. In the analysis population column, include only the 
analysis population where subject is included in. 
o 
Sort by Treatment Arm/ Subject ID. If date is present in file, add a column for date of event and sort by date. If no date is present, sort by category with 
non-important first and then important. 
o 
Event Type: Inclusion Criteria, Exclusion Criteria, Study Drug, Assessment − Safety, Assessment − Efficacy, Lab/endpoint data, Visit Window, 
Informed Consent, Prohibited Co-Medication, Overdose/Misuse, Other. 
 
 
 
 
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Listing 16.2.3 
Randomization and Treatment group 
Safety Population 
 
Subject ID 
Treatment Arm 
Randomization Stage 
Randomization Treatment 
Randomization Date / Time 
(Study Day) 
Randomization 
Number 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 1 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 3 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 2 
Placebo 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 2 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 3 
Placebo 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.4.1 
Demographic and Baseline Characteristics 
Screening Population 
Subject 
ID 
Treatment 
Arm 
Birth Date 
Age 
(years) 
Sex 
Surgically sterile?/ 
Postmenopausal? [1] 
Ethnicity 
Race 
Weight 
(kg) 
Height 
(cm) 
BMI 
(kg/m²) 
Fully 
vaccinated 
for COVID-
19? 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
XXX 
DDMMMYYY 
XX 
XX 
 
XXXXX 
XXXX 
XX.X 
XX.X 
XX.X 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
XXX 
--MMMYYY 
XX 
XX 
No/ Yes 
XXXXX 
XXXX 
XX.X 
XX.X 
XX.X 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 = Coronavirus disease 2019. 
Note: Height and weight are the values at Screening.  
[1] Age was calculated as age at time of consent. 
[2] For Female Subject Only. 
 
 
 
 
Programming Notes: 
o 
Sort by Treatment Arm/ Subject ID 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.4.2 
Medical History 
Safety Population 
 
 
System Organ Class/ 
 
 
 
  Preferred Term/ 
Start Date (Study Day)/ 
 Subject ID 
Treatment Arm 
    Verbatim Term 
   End Date (Study Day)/ 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
     XXXXXXXXXXXXX 
MMMYYYY (X)/ 
   Ongoing 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
     XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   Ongoing 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
 
 
 
 
 
 
 
 
MedDRA = Medical Dictionary for Regulatory Activities.  
Note: Study Day is calculated relative to the date of first dose. 
Medical History were coded using MedDRA version 26.0.  
Only subjects with medical history recorded are listed. 
 
Programming Notes: 
 
• 
SOC & PT text should be in proper case in listing. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date of medical event. 
 
 
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Listing 16.2.4.3 
Osteoarthritis Characteristics 
Screening Population 
 
Subject ID 
Treatment 
Arm 
Subject with 
OA? / Joint/ 
Area affected 
Is OA 
considered 
CS? 
Radiological 
Investigations 
Conducted? / Details 
Joint Area 
Investigated 
Is OA 
considered 
RS? 
K-L Score 
Reported 
Radiologic Scoring 
System / Details/  
Result 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Y / Shoulder 
Y 
Y/ Other: XXXXXX 
Shoulder 
Y 
Grade 3 
XXXXXX/ 
         XXXXXX/ 
   XX 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Y / Ankle 
N 
Y / MRI 
Ankle 
N 
N 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CS = Clinically Significant; K-L = Kellgren-Lawrence; OA = Osteoarthritis; RS = Radiologically Significant. 
. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.5.1 
Study Drug Administration: Individual Doses 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
Visit 
Name 
Start 
Date/ 
Time 
(Study 
Day) 
End 
Date/ 
Time 
(Study 
Day) 
Was 
Infusion 
Performed?/ 
Infusion 
Volume 
(mL)[1]/ 
Reason not 
Performed 
Actually 
Administered 
Volume (mL) 
[2] 
If 
Difference 
between 
[1] and [2] 
Volume, 
Reason 
Any 
Injection 
Site 
Reactions? 
Any 
Infusion 
Related 
Reactions  
Infusion 
Rate 
(mL/ 
hour) 
Rate Change 
Justification 
Reason 
for 
Infusion 
Rate 
Change 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
DDMM
MYYYY
/hh:mm 
(X) 
DDMM
MYYYY
/hh:mm 
(X) 
Y/  
XX 
XX 
 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
DDMM
MYYYY
/hh:mm 
(X) 
DDMM
MYYYY
/hh:mm 
(X) 
Y/  
XX 
XX 
XXXXX 
Y 
Y 
xx.x 
XXXXX 
XXXXX
XX 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
 
 
N/  
XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date. 
• 
Rate Change Justification: Increased, Decreased, Interrupted. 
 
 
 
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Listing 16.2.6.1 
Daily Pain NRS 
mITT Population 
 
Subject ID 
Treatment Arm 
Study Visit [1] 
Subject Diary (ePRO) Date / Study Day 
Baseline Flag [2] 
DPS 
 
 
 
 
 
 
XXXXXX 
XXXX 
Baseline 
DDMMMYYYY/ (-7) 
Y 
X 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-6) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-2) 
Y 
XX 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-1) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY/ (13) 
 
XX 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY/ (14) 
 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
XXXXXX 
XXXX 
Baseline 
DDMMMYYYY/ (-7) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
DPS = Daily Pain Score; ePRO = Electronic Patient-Reported Outcome; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘DPS’ are average daily pain scores on an 11-point (0-10) NRS. Study Day is calculated relative to the date of first dose. 
[1] Study Visit is defined as the 7-day period ending within the protocol window Day ± 3, where at least 4 days out of 7 have recorded diary pain scores. 
[2] Baseline is defined as the 7-day period prior to randomization i.e., Day -7 to Day -1, inclusive. A subject is considered to have an evaluable baseline pain 
score if there are at least 5 days of recorded diary pain scores in the 7-day period. 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Subject Diary Date. 
• 
Display all measurement per Subject, starting on the Study Day = -7. 
• 
Display Study Visit for days involved in weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and 12 
• 
Flag Baseline records only when there is at least 5 days of recorded diary pain scores in the 7-day Baseline period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.6.2 
Galer NPS 
mITT Population 
Subject ID 
Treatment Arm 
Parameter 
Study Visit 
Collection Date / Study 
Day 
Baseline Flag [1] 
NPS 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Pain intensity 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
Week 4 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
XX 
 
 
 
 
 
 
 
 
 
 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
XX 
 
 
 
 
 
 
 
 
 
XXXX 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Pain intensity 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
XXXX 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
NPS = Neuropathic Pain Scale; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘NPS’ are Pain Intensity, Unpleasantness, and Descriptor scores on an 11-point (0-10) NRS, and Pain Duration/Frequency on a 3-
point NRS (1-3).  
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter /Collection Date. 
• 
Keep Parameter sorting from the last bullet point in this programming notes. 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Repeat for the Parameters: Pain intensity, Pain Unpleasantness, Pain Sharpness, Pain Hotness, Pain Dullness, Pain Coldness, Pain Sensitivity, Pain 
Itching, Deep Pain Intensity, Surface Pain Intensity (All in an 11-point NRS), and Pain Duration/Frequency (in a 3-point NRS). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.6.3 
DSIS 
mITT Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.6.1. 
• 
Update footnote as:  
DSIS = Daily Sleep Interference Scale; ePRO = Electronic Patient-Reported Outcome; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘DSIS’ are average daily Sleep Interference scores on an 11-point (0-10) NRS. Study Day is calculated relative to the date 
of the day of first dose. 
[1] Study Visit is defined as the seven-day period ending within the protocol window Day ± 3. 
[2] Baseline is defined as the seven-day period prior to randomization i.e., Day -7 to Day -1,. 
• 
Sort by Treatment Arm/ Subject ID / Subject Diary Date. 
• 
Display all measurement per Subject, starting on the Study Day = -7. 
• 
Display Study Visit for days involved in weekly averages of the average Sleep interference scores for Baseline, Week 4, 8, 12, and 18. 
• 
Flag Baseline records only when there is at least 5 days of recorded diary Sleep interference scores in the 7-day Baseline period. 
 
 
 
 
 
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Listing 16.2.6.4 
SF-36 
mITT Population 
Subject ID 
Treatment 
Arm 
Parameter 
Item 
Number 
Item name 
Study Visit 
Collection Date / Study 
Day 
Baseline 
Flag [1] 
SF-36 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Physical 
functioning 
3 
Vigorous 
Activities 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
Moderate 
Activities 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
- 
Total 
Baseline 
DDMMMYYYY/ (X) 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Role 
limitations 
due to 
physical 
health 
13 
Cut Amount 
of Time 
Spent on 
Work/Act 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
… 
… 
.. 
… 
 
 
 
 
 
 
 
 
 
… 
 
… 
… 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
SF-36 = 36-Item Short-Form Health Survey; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘SF-36’ are derived SF-36 scores and Change in General Health on a 5-point NRS (1-5).  
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Item /Collection Date. 
• 
Keep Parameter sorting from the last bullet point in this programming notes. 
• 
Include all data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical functioning (items 3, 4, 5, 6, 7, 8, 9, 10, 11, 12), Role limitations due to physical health (items: 13, 14, 15, 16), Role 
limitations due to emotional problems (items: 17, 18, 19), Vitality (Energy/fatigue) (items: 23, 27, 29, 31), Emotional well-being (items: 24, 25, 26, 28, 
30), Social functioning (20, 32), Pain (items: 21, 22) and General Health (items: 1, 33, 34, 35, 36), all with values ranging from 0 to 100. Change in 
general Health (in a 5-point NRS, item: 2). 
 
 
 
 
 
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Listing 16.2.6.5 
Rescue Medication Usage 
mITT Population 
 Subject 
ID 
Treatment Arm 
ATC Class (Level 2)/ 
   Preferred Name/ 
      Verbatim Term 
Primary 
Indication 
Start Date (Study Day)/ 
   End Date (Study Day) 
Dose 
(unit) 
Route 
Frequency 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
--MMMYYYY (-XX)/ 
   DDMMMYYYY (-X) 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
  XXXXXXXXX/ 
   XXXXXXXXXXXXXXX/ 
      XXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
--MMMYYYY (-X)/ 
   Ongoing 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
XXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
DDMMMYYYY (X)/ 
   DDMMMYYYY 
(XX) 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ATC = anatomical therapeutic chemical. 
Note: Study Day is calculated relative to the date of first dose. 
Medications were coded using WHO drug dictionary version vMar2023. 
 
 
Programming Notes: 
• 
ATC & Preferred Name text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications 
 
 
 
 
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Listing 16.2.6.6 
Patient Global Impression of Change 
mITT Population 
Subject ID 
Treatment Arm 
Study Visit 
Collection Date / Study Day 
PGIC 
 
 
 
 
 
XXXXXX 
XXXX 
Week 4 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
XXXXXX 
XXXX 
Week 4 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
… 
… 
… 
 
 
 
 
 
PGIC =Patient Global Impression of Change. 
Note: Data shown in column ‘PGIC’ are Subjects ratings about overall improvement in health status. 
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include all observed data on PGIC scores for Week 4, 8, 12, and 18. 
 
 
 
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Listing 16.2.7.1 
Adverse Events 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date/Time 
(Study Day)/ 
   End Date/Time 
(Study Day) 
Severity/ 
Relationship 
Outcome/ 
      Action Taken/ 
           Therapy? 
AE Leading 
to Study DC? 
TEAE 
Serious/ 
Serious 
Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMMMYYYY/HH:
MM (X)/ 
DDMMMYYYY/HH:
MM (X) 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                       Yes 
No 
Yes 
  
No 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMMMYYYY/HH:
MM (X)/ 
DDMONYYYY/HH:
MM (X) 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                     No 
Yes 
No 
Yes / XXX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMONYYYY/HH:
MM (X)/ 
   Ongoing 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                   No 
No 
No  
Yes / XXX 
 
AE = adverse event; DC = discontinuation; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; SAE = serious adverse event; 
TEAE = treatment emergent adverse event. 
Note: Study Day is calculated relative to the date of first dose. A TEAE is defined as an AE with an onset at the time of or following the start of treatment with 
IP. 
AEs were coded using MedDRA version 26.0 
 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e, no AEs occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT 
abbreviations should be added in this case in footnote. 
 
 
 
Listing 16.2.7.2 
Treatment Emergent Adverse Events Leading to Study Drug Discontinuation 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update listing deleting seventh and eight columns 
 
 
Listing 16.2.7.3 
Treatment Emergent Adverse Events Associated with Abnormal Liver 
Safety Population 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update listing deleting eighth column. 
 
 
 
 
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Listing 16.2.7.4 
Joint Related Adverse Events of Special Interest 
Safety Population 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
 
 
Listing 16.2.7.5 
Serious and/or Severe Infections 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
 
 
Listing 16.2.7.6 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of Study Drug  
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update listing by deleting seventh column. 
 
 
 
 
 
 
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Listing 16.2.8.1 
Clinical Chemistry Laboratory Evaluations 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Parameter 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Original 
Result 
(Unit) 
Standard 
Results 
(unit) 
Reference 
Range 
[1] 
 
 
 
 
Baseline 
Flag 
 
 
 
 
CFB 
Results 
Assessment 
/ Reason 
CS 
Lab ID 
Number 
Fasting 
Status 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Chemistry 
panel 
XXXXXX 
 
 
 
 
 
 
ND: xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Albumin 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
Y 
 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-NCS 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically significant; H = High; L = Low; NCS = not clinically significant; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
 [1] Reference range is used to identify potentially clinically significant laboratory values. 
 
Programming Notes: 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Chemistry panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Albumin, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), 
Bicarbonate, Calcium, Chloride, Creatinine, High-Sensitivity C-Reactive Protein (hs-CRP), Estimated Glomerular Filtration Rate (eGFR by Cockcroft - 
Gault), Serum Glucose, Lactate Dehydrogenase (LDH), Potassium, Sodium, Total Bilirubin, Total Protein, Blood Urea Nitrogen (BUN), Uric Acid. 
 
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Listing 16.2.8.2 
Hematology Laboratory Evaluations 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.8.1. 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Hematology panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Absolute basophil count, absolute eosinophil count, absolute lymphocytes count, Absolute Monocyte Count, 
Absolute Neutrophil Count, Basophils %, Eosinophils %, Hematocrit (HCT), Hemoglobin (HGB), hemoglobin A1C (HgbA1C), Lymphocytes %, mean 
corpuscular hemoglobin (MHC), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), Monocytes %, Neutrophils 
%, Platelets, Red blood cell count (RBC), Red Cell Distribution Width, white blood cell Count (WBC). 
 
 
Listing 16.2.8.3 
Coagulation Laboratory Evaluations 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.8.1. 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Coagulation panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Activated Partial Thromboplastin Clotting Time (APTT), Fibrinogen, International normalized ratio (INR), 
Prothrombin Time (PT). 
 
 
 
 
 
 
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Listing 16.2.8.4 
Urinalysis Laboratory Evaluations 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Parameter 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Original 
Result 
(Unit) 
Standard 
Results 
(unit) 
Reference 
Range 
[1] 
 
 
 
 
Baseline 
Flag 
 
 
 
 
CFB 
Results 
Assessment 
/ Reason 
CS 
Lab ID 
Number 
Fasting 
Status 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
Urinalysis 
panel 
XXXXXX 
 
 
 
 
 
 
ND: xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
pH/ 
Specific 
Gravity 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
Y 
 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-NCS 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
Urine/ 
Glucose/ 
Ketones/ 
Protein 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Trace 
 
 
Y 
 
H-NCS 
XXXXXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
100 
(mg/dL) 
100 
(mg/dL) 
 
 
 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Negative 
 
 
 
 
 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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CFB = change from baseline; CS = clinically significant; H = High; L = Low; NCS = not clinically significant; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
 [1] Reference range is used to identify potentially clinically significant laboratory values. 
 
 
Programming Notes: 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Urinalysis panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Blood Urine, Glucose, Ketones, pH, Protein, Specific Gravity. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.5 
Serology Laboratory Evaluations 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Was 
Serology 
Test 
Collected? 
Date/Time of 
Collection 
(Study Day) 
Test (Unit) [1] 
Result 
Lab ID 
Number 
Fasting 
Status 
Reason not 
collected 
Comments 
 
 
 
 
 
 
 
 
 
 
XXXX 
XXXX 
Yes 
DDMMMYYY
Y/HH:MM (X) 
Hepatitis B Ag 
Negative 
XXXX 
Y 
 
XXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis C Ab 
Positive 
XXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1/ -2 Ag 
Not Done 
XXXX 
Y 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Quantiferon 
Gold Plus NIL 
X.XX (IU/mL) 
XXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Ab = antibody; Ag = antigen; HIV = human immunodeficiency virus; TB = tuberculosis. 
Note: Study Day is calculated relative to the date of first dose. 
[1] if Applicable 
 
Programming Notes: 
 
• 
Sort by Treatment Arm/ Subject ID / Date of collection / Test. 
• 
Keep parameter sorting from the last bullet point below 
• 
Sort Parameters in the following Order: Hepatitis B Antigen, Hepatitis C Virus Antigen, Hepatitis C Virus Antibody, HIV-1/ -2 Antigen, Quantiferon 
Gold Plus NIL, Quantiferon Gold Plus TB, Quantiferon Gold Plus Mitogen minus NIL, Quantiferon Gold Plus TB1 minus NIL, Quantiferon Gold Plus 
TB2 minus NIL 
 
 
 
 
 
 
 
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Listing 16.2.8.6 
Pregnancy Test Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Was a Urine pregnancy test 
performed? 
Date/Time Performed (Study Day) 
If not, Reason 
Result 
xxxxx 
xxxx 
xxxxx 
Xxxx 
Ddmmmyyyy/ hh:mm (XX) 
xxxx 
xxxx 
 
 
xxxxx 
Xxxx 
Ddmmmyyyy/ hh:mm (XX) 
Other: xxxx 
xxxx 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.7 
Drug Test Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Was Drug Test 
Performed? 
Date/ Time Assessment 
(Study Day) 
Result 
Findings 
Reason Test 
not Performed 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
DDMMMYYYY/ HH:MM 
(XX) 
Negative 
Negative 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
DDMMMYYYY/ HH:MM 
(XX) 
Positive 
Cocaine /  
Opiates 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Concatenate all findings by “/” 
• 
Sort by Treatment Arm/ Subject ID / Date of assessment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.8 
COVID-19 Screening 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
COVID-19 Sx 
Screening?/Date
/ Time (Study 
Day) 
Sx 
Body Tº 
Check?/ Date/ 
Time (Study 
Day) 
Body Tº 
(Unit) 
COVID-19 
swab?/ Date/ 
Time (Study 
Day) 
Swab 
result 
COVID-19 Ab 
testing?/ Date/ 
Time (Study 
Day) 
 
Ab 
testing 
results 
COVID-19 
Ag testing?/ 
Date/ Time 
(Study Day) 
Ag 
testing 
results 
xxxxx/ 
xxxx 
xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XXX/ 
XXX 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XX (XX) 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy
/ hh:mm (XX) 
Xxxx 
 
xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XXX 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XX (XX) 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy
/ hh:mm (XX) 
Xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
Ab = Antibody; Ag = Antigen; COVID-19 = Coronavirus disease 2019; Sx = Symptoms; Tº = Temperature. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Concatenate all Symptoms by “/” 
• 
Sort by Treatment Arm/ Subject ID / Date of assessment 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.1 
Vital Signs Measurements 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Parameter 
Study 
Visit 
Position [1] / 
 Tº Method 
Date/Time of 
Collection 
(Study Day) 
Original Result 
(Unit) 
 
Baseline Flag 
CFB 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Body 
Temperature 
XXXXXX 
XXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX (XX) 
Y 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX (XX) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Resting 
Heat Rate 
Screening 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
 
 
 
 
Day 1: 
Pre-Dose 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
Y 
XX 
 
 
 
XXXXXX 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
XX 
 
 
 
XXXXXX 
Sitting 
 
ND 
 
 
 
 
 
XXXXXX 
Sitting 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
XX 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
[1] Resting position measurements encompass Sitting and Supine position measurements.  
 
 
 
 
 
 
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter (Order in the second bullet point)/ Date time of collection. 
• 
Repeat for Resting Heart Rate, Resting Systolic Blood Pressure, Resting Diastolic Blood Pressure, Respiratory Rate, Body Temperature, Standing Heart 
Rate, Standing Systolic Blood Pressure, Standing Diastolic Blood Pressure. 
• 
After Week 2 (inclusive), Supine measure are taken in sitting position. We will consider them as supine (in resting position) for calculating Change from 
Baseline (always at supine position). 
• 
Include the following timepoints: Screening, Baseline (Day 1: Pre-Dose), Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 
Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion 
Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 
8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, 
Week 11, Week 12, Week 18.   
• 
Note that Body Tº, and standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.2 
ECG Results 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
 
ECG Date / Time 
(Study Day) 
Tracing 
ECG Result/ 
Comment 
PR 
Interval 
(msaec) 
QRS 
duration 
(msec) 
QT 
Interval 
(msec) 
Heart 
Rate 
(bpm) 
QTcF 
Interval 
(msec) 
Reason 
Not 
Done 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
Day 1: Pre-Dose 
DDMMMYYYY / 
HH:MM (XX) 
1 
Abnormal CS/ 
xxxx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
2 
Abnormal CS/ 
xxxx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
3 
Abnormal NCS/ 
xxxx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
 
DDMMMYYYY/ 
HH:MM (XX) 
1 
Normal 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
2 
Normal 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
3 
Normal 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant; ECG = electrocardiogram; NCS = Not clinically significant 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Date time of collection / Tracing 
• 
Include the following timepoints: Day 1: Pre-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, 
Week 12, and Week 18. 
 
 
 
 
 
 
 
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Listing 16.2.9.3 
Physical Examination Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Examination 
Type 
Exam Date/ Time 
(Study Day) 
Body System 
Result / Change 
from previous 
assessment [1] 
If Abnormal, 
findings / 
Specify 
Changes [2] 
Reason Not 
Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
Complete 
DDMMMYYYY 
/ HH:MM (XX) 
Head, Neck and 
Thyroid 
Normal 
 
 
 
 
 
 
 
Ears, Eyes, Nose 
and Throat 
Abnormal CS 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
Targeted 
DDMMMYYYY 
/ HH:MM (XX) 
Ears, Eyes, Nose 
and Throat 
XXXXXXXXXX 
XXXXXXXX 
 
 
 
 
 
 
  
 
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant 
Note: Study Day is calculated relative to the date of first dose. 
[1] For targeted examination type: Change from previous assessment. 
[2] For targeted examination type: Specify Changes. 
 
 
Programming Notes: 
• 
Keep sorting from eCRF: Head, Neck and Thyroid/ Ears, Eyes, Nose and Throat/ Chest (including breasts)/ Lungs / Heart / Lymph Nodes / Abdomen / 
Hepatic / Gastrointestinal / Anorectal / Genitourinary/ Skin / Musculoskeletal/Extremities / Neurological / Other. 
• 
Complete Physical examination only at Screening, Week 12, 18 (it can also be unscheduled). 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Body system 
 
 
 
 
 
 
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Listing 16.2.9.4 
Neurological Examination Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Exam Date/ Time 
(Study Day) 
Body System 
Result  
If Abnormal, 
findings 
Reason Not 
Done 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
DDMMMYYYY / 
HH:MM (XX) 
Mental Status 
Normal 
 
 
 
 
 
 
Cranial Nerves 
Abnormal CS 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY / 
HH:MM (XX) 
Cranial Nerves 
XXXXXXXXXX 
XXXXXXXX 
 
 
 
 
 
  
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Keep sorting from eCRF: Mental status/ Cranial Nerves/ Motor Function/ Reflexes / Sensation and Propioception / Coordination / Other. 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Body system 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.5 
Total Neuropathy Score-Nurse 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Visit 
Date/ Time of 
collection 
(Study Day) 
Sensory 
Symptom 
Score 
(0−4) 
Motor 
Symptom 
Score 
(0−4) 
Autonomic 
Symptom 
Score (0−4) 
Pin 
Sensibility 
Score 
(0−4) 
Vibration 
Sensibility 
Score 
(0−4) 
TNSn Total 
(0−20) 
Reason Not Done 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Screening 
DDMMMYYYY 
/ HH:MM (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY 
/ HH:MM (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY 
/ HH:MM (XX) 
ND 
ND 
ND 
ND 
ND 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
ND = Not Done; TNSn = Total Neuropathy Score-Nurse. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.6 
Motor and Sensory Nerve Conduction Studies 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
 
Date / Time of 
Collection 
(Study Day) 
Location / 
Evaluation 
Was 
Evaluation 
Preformed
? / Nerve 
Amplitude 
(Motor = 
mV; sensory 
= microV) / 
Range 
Peak 
Latency 
(msec) / 
Range 
Conduction 
velocity 
(msec) / 
Range 
Duration 
of action 
potential 
(msec) / 
Range 
Evaluation 
Result 
If 
Abnormal, 
Specify 
Significant 
Changes 
from 
Baseline? / 
if Yes, 
Specify 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
Screening 
DDMMMYY
YY / HH:MM 
(XX) 
Lower Limb 
- right side/  
         Motor 
evaluation 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
NA 
 
 
 
XXXXXX/    
XXXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Normal 
 
NA 
 
 
 
XXXXXX/   
XXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 18 
 
DDMMMYY
YY/ HH:MM 
(XX) 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
N 
 
 
 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Normal 
 
N 
 
 
 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
Y/  
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
NA = Not Applicable 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Location - Evaluation 
• 
Keep sorting from eCRF: Lower Limb - right side/Motor evaluation, Lower Limb - right side/Sensory evaluation, Lower Limb - left side/ Motor evaluation, 
Lower Limb - left side/ Sensory evaluation, Upper Limb - right side /Motor evaluation, Upper Limb - right side/ Sensory evaluation, Upper Limb - left 
side/ Motor evaluation, Upper Limb - left side /Sensory evaluation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.7 
Strength and Deep Tendon Reflexes 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Date/ Time of 
collection 
(Study Day) 
Ankle Dorsiflexion 
Strength 
Deep Tendon Reflexes 
Reason Not Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY / 
HH:MM (XX) 
ND 
 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
ND = Not Done. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.8 
Injection Site Reactions 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Visit 
Date/ Time of Assessment 
(Study Day) 
Pain 
Tenderness 
Erythema/redness 
Induration/
swelling 
Reason Not Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Day 1: 15 
Minutes 
after Start of 
Infusion 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1: 30 
Minutes 
after Start of 
Infusion 
DDMMMYYYY / 
HH:MM (XX) 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY / 
HH:MM (XX) 
ND 
ND 
ND 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
ND = Not Done. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
• 
Include the following timepoints: Day 1: 15 Minutes after Start of Infusion, Day 1: 30 Minutes after Start of Infusion, Day 1: 45 Minutes after Start of 
Infusion, Day 1: 60 Minutes after Start of Infusion, Day 1: 2 hours after Start of Infusion, Day 1: 4 hours after Start of Infusion, Week 2, Week 4, Week 
6, Week, 8, Week 10, Week 12, and Week 18.  
 
 
 
 
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Listing 16.2.9.9 
Hypersensitivity/Anaphylactic Reactions 
Safety Population 
Subject 
ID 
Treatment 
Arm 
AE ID 
Number 
Onset Date/Time (Study Day)/ 
   Resolution Date/Time (Study 
Day) 
Type of 
Reaction 
Severity grade for 
the Symptom 
with Highest 
Severity 
Onset Time 
for Highest 
Severity 
Leading to IP 
Discontinuation? 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMMMYYYY/HH:MM (X) 
XXXX 
XXXX 
/HH:MM 
Yes 
 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMONYYYY/HH:MM (X) 
XXXXX 
 
 
No 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMONYYYY/HH:MM (X) 
XXXXX 
XXXX 
/HH:MM 
No 
 
 
 
 
 
 
 
 
AE = Adverse Event. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Onset Date/Time / Resolution Date/Time / Reaction Type. 
• 
Keep sorting from eCRF: Urticaria, Pruritus, Rash, Flushing, Swollen lips, tongue, uvula and/or vulva, Dyspnoea, Wheeze-bronchospasm, Stridor, 
Hypoxia, Hypotension, Crampy abdominal pain, Vomiting, Diarrhoea, Other. 
 
 
 
 
 
 
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Listing 16.2.9.10 
Liver Diagnostic Investigations 
Safety Population 
Subject ID 
Treatment 
Arm 
Potential Hy's 
Law Case 
Number 
Liver Diagnostic Investigation 
Date (Study Day) 
Liver Diagnostic 
Investigation 
Liver Diagnostic 
Investigation 
Results 
Comments 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X) 
 
XXXX 
XXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY (X) 
 
XXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X) 
 
XXXXX 
XXXXX 
 
 
 
CT = Computerized tomography; ERCP = Endoscopic retrograde cholangiopancreatography; MRI = Magnetic resonance imaging; MRCP = Magnetic 
resonance cholangiopancreatography. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Diagnostic Date / Liver Diagnostic Investigation. 
• 
Keep sorting from eCRF: Ultrasound, CT, MRI/MRCP, ERCP, Liver Biopsy, X-Ray, Tox Screening for Acetaminophen/Paracetamol, Tox Screening for 
Ethanol, Tox Screening, Other, Specialist (e.g. Hepatologist) Consulted, Serology for Hepatitis A, Serology for Hepatitis B, Serology for Hepatitis C, 
Serology for Hepatitis D, Serology for Hepatitis E, for Cytomegalovirus (CMV), Serology for Epstein Barr Virus (EBV), Autoimmune Serology, Other. 
 
 
 
 
 
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Listing 16.2.9.11 
Liver Risk Factors and Lifestyle Events 
Safety Population 
Subject ID 
Treatment 
Arm 
Potential 
Hy's Law 
Case 
Number 
Assessment Date 
(Study Day) 
 
Liver Risk Factor Start Date 
(Study Day)/ 
Liver Risk Factor Stop Date 
(Study Day) 
Liver Risk 
Factor / 
Reference 
Period 
Liver Risk 
Factor Details 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/  
       DDMMMYYYY (X) 
XXXX/ 
   XXX 
XXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/  
         DDMMMYYYY (X) 
XXXXX/  
   XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/ 
      Ongoing  
XXXXX/ 
   XXX 
XXXXX 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Assessment Date / Liver Risk Factor Start Date / Stop Date / Liver Risk Factor. 
• 
Keep sorting from eCRF: Alcohol Abuse, Increased Alcohol Consumption within 1 Month of Reported Event, IV Drug Abuse, Tattoo, Acupuncture, 
Sexually Transmitted Diseases, Toxic/Chemical Agent Exposure, Travel (Areas at Risk in the Last Year), Pregnancy, Parenteral Nutrition, Excessive 
Physical Exercise, Changes Diet/Fasting Episodes/Weight Loss Diet, Previous Drug Reaction (Associated with an Elevation of Liver Tests), Blood 
Transfusion, Subject Exposed to Anyone with Jaundice in the Last Month, History of Hypotension, Low Blood Pressure at Time of Event of Liver Injury 
and/or Abnormal Liver Laboratory Value, History of Liver Disease, Other. 
• 
Concatenate comments with “/”. 
 
 
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Listing 16.2.9.12 
Liver Signs and Symptoms 
Safety Population 
Subject ID 
Treatment Arm 
Potential Hy's 
Law Case Number 
Start Date (Study Day)/ 
Stop Date (Study Day) 
Liver Sign/ 
Symptom 
Intermittent 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X)/  
       DDMMMYYYY (X) 
XXXX 
 
N 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY (X)/  
         DDMMMYYYY (X) 
XXXXX 
  
N 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X)/ 
      Ongoing  
XXXXX 
 
Y 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Liver Sign/Symptom. 
• 
Keep sorting from eCRF: Anorexia, Asthenia, Pyrexia, Pruritus, Jaundice, Arthralgia, Abdominal Pain, Abdominal Tenderness, Nausea, Vomiting, Rash, 
Mucosal Inflammation, Purpura, Hepatomegaly, Splenomegaly, Lymphadenopathy, Ascites, Confusional State, Coma, Upper Quadrant Tenderness, 
Biliary Obstruction, Eosinophilia, Dark Urine, Other. 
• 
If Rash, Lymphadenopathy or Other, Concatenate Symptom with Comment as: “Rash: xxxxxx”. “Lymphadenopathy: xxxxxx”, “Other: xxxxxxxx” 
 
 
 
 
 
 
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Listing 16.2.9.13 
Infection Diagnostic Investigations 
Safety Population 
Subject ID 
Treatment Arm 
AE ID 
Number 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Method 
Examination 
performed 
Test Result 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
XXXXX 
 
 
AE = adverse event. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Method. 
• 
Keep sorting from eCRF: Microscopy, Culture and Sensitivity, Serological Tests, Nucleic Acid Based Tests, X-Ray, Other. 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.14 
Infection Risk Factors and Lifestyle Events 
Safety Population 
Subject ID 
Treatment 
Arm 
AE ID 
Number 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Infection Risk 
Factor 
Infection Risk 
Occurrence 
Comments 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
Ongoing 
 
 
AE = adverse event; BCG = Bacillus Calmette–Guérin. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Infection Risk Factor. 
• 
Keep sorting from eCRF: Extensive Burns within the Last Year (Thermal Burn), Tattoo, Piercing or Acupuncture within the Last Year, Sexually 
Transmitted Diseases, Travel to Areas at Risk of Tuberculosis or Tropical Diseases, Infections Related to Travel (e.g. Tuberculosis and Tropical Diseases), 
Blood Transfusion (within the Last Year), Exposure to Nosocomial Pathogens within the Last Year, Contact History with Infection Source, Previous BCG 
Immunization, Evidence of BCG Scar, Tuberculin Skin or Quantiferon Test Confirms Previous Exposure or Immunity to Tuberculosis. 
• 
Fill Comment column if Infection risk factor test  = Unknown Previous BCG Immunization, not done, known Sexually Transmitted Disease reference 
Period, or Infection risk factor specifications. 
 
 
 
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Listing 16.2.9.15 
Infection Signs and Symptoms 
Safety Population 
Subject ID 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Clinical 
Event 
Infection 
Sign/Symptom 
Occurrence 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM 
(X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM 
(X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
Ongoing 
 
 
AE = adverse event. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Clinical Event. 
• 
Keep sorting from eCRF: Pyrexia, Headache, Confusional State, Convulsion, Rhinitis, Oropharyngeal Pain, Cough, Productive Cough, Haemoptysis, 
Wheezing, Dyspnoea, Pleuritic Pain, Vomiting, Diarrhoea, Genital Discharge, Haematuria, Dysuria, Hepatosplenomegaly, Jaundice, Lymphadenopathy, 
Rash, Night sweats, Chills, Myalgia, Weight Decrease. 
• 
Fill Comment column if Maximum Tº (Unit) available for Pyrexia, or if site for Rash or Lymphadenopathy is known.  
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Listing 16.2.9.16 
Prior and Concomitant Medications 
Safety Population 
 Subject 
ID/ 
Treatment 
Arm 
Prior/ 
Concomitant 
[1] 
ATC Class (Level 2)/ 
   Preferred Name/ 
      Verbatim Term 
 
 
 
 
Given 
for/as 
Primary 
Indication 
Start Date (Study 
Day)/ 
   End Date (Study 
Day) 
Dose (unit) 
Route 
Frequency 
 
 
 
 
 
 
 
 
 
XXXXXX
/ XXXX 
Prior 
XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXX 
Medical 
History 
XXXXXXX 
--MMMYYYY     
(-XX)/ 
  DDMMMYYYY 
(-X) 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
Both 
  XXXXXXXXX/ 
   XXXXXXXXXXXXXXX/ 
      XXXXXXXXXXX 
Prophylaxis 
XXXXXXX 
--MMMYYYY     
(-X)/ 
   Ongoing 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
Concomitant 
XXXXXXXXX/ 
   XXXXXXXXXXXXXX/    
XXXXXXXXXXXXXXXXX 
Adverse 
event 
XXXXXXX 
DDMMMYYYY 
(X)/ 
  DDMMMYYYY 
(XX) 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ATC = anatomical therapeutic chemical; WHO-DDE = World Health Organization-Drug Dictionary Enhanced. 
Note: Study Day is calculated relative to the date of first dose. 
Medications were coded using WHO-DDE version vMar2018. 
[1] Prior medications are defined as medications that started before first dose of study, whether they were stopped before first dose of study medication or not. 
Concomitant medications are defined as medications starting on or after first dose of study medication Both indicates medication that was started before the 
day of first dose and continued after. 
 
 
 
 
 
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Programming Notes: 
• 
ATC & Preferred Name text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by Treatment ID/ Subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.17 
Prohibited Concomitant Medications 
Safety Population 
 
Programming Notes: 
• 
Same Shell as Listing 16.2.9.16.  
• 
Display prohibited prior and concomitant medications provided by the Medical Coder: 
• 
Prohibited concomitant medications:  
o 
NSAIDs analgesic therapies (with acetylsalicylic acid with doses >= 325 mg/day). 
o 
COX-2 analgesic therapies. 
o 
Immunotherapeutics. 
o 
Live viral or attenuated bacterial vaccines. 
o 
Oral, IV, intramuscular, or any other parenteral (other than oral) steroids (inhaled or topical steroids are permitted). 
o 
Biologic therapeutic agents. 
• 
Prohibited prior and/or concomitant medications: 
o 
Anti-NGF therapies. 
o 
Anti-TNF therapies. 
• 
ATC & PN text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications) 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.18 
Concomitant Procedures 
Safety Population 
Subject 
ID 
Treatment 
Arm 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date (Study Day)/ 
   End Date (Study Day) 
Reason for Procedure 
Reason (derived verbatim 
term) 
If Reason is Other, 
Specify 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
XXXXXXXXX/ 
 XXXXXXXX 
XXXXXXXXXX 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMMMYYYY (X)/ 
   Ongoing 
OTHER 
OTHER 
 
XXXXXXXXXXX 
 
 
MedDRA = Medical Dictionary for Regulatory Activities. 
Note: Study Day is calculated relative to the date of first dose. All Procedure terms were coded using the MedDRA version 26.0. Concomitant Procedures are 
defined as medications continuing or starting on or after first dose of study medication.  
 
Programming Notes: 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
 
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Listing 16.2.9.19 
Anti-drug Antibody Test Results 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Screening  
Status Result 
ADA Titer  
Confirmatory 
Status result 
Lab ID 
Number 
Comments 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Positive 
XX 
Positive 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Positive 
XX 
Positive 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Negative 
XX 
Negative 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Missing 
 
NRR 
XXXXXXX 
XXXX 
 
 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; NA = Not Applicable; NRR = Not Reportable Result; QNS = Quantity Not Sufficient. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
ADA titre reported as <30 (below the minimum required dilution) is a negative result for the presence of ADA. 
• 
Include Following timepoints: Screening, Weeks 2, 4, 8, 10, 12, 18. 
 
 
 
 
 
 
 
 
 
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Listing 16.2.10.1 
Serum MEDI7352 Concentrations 
PK Population 
Subject 
ID 
Treatment 
Arm 
Parameter 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Result  
(ng/mL) 
Lab ID Number 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
MEDI7352 
Concentration 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
NRR 
XXXXXXX 
XXXX 
 
 
 
 
 
 
 
 
NA = Not Applicable; NRR = Not Reportable Result. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 10: 8 Hours 
after Infusion, Week 10 + 24 hours: after Week 10/ Pre-Dose, Week 11: after Week 10/ Pre-Dose, Week 10 + 14 Days: after Week 10/ Pre-Dose, Week 
18. 
 
 
 
 
 
 
 
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Listing 16.2.10.2 
Serum total NGF Concentrations 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Parameter 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Result  
(pg/mL) 
Lab ID Number 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
tNGF 
Concentration 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
NS 
XXXXXXX 
XXXX 
 
 
 
 
 
 
 
 
BLLOQ = Below the Lowest Limit of Quantitation; NA = Not Applicable; ND = Not Detected; NS = No Value due to Insufficient Volume or No Sample 
Received; SAT = Greater than the Top of the Standard Curve; tNGF = total Nerve-Growth Factor. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 10: 8 Hours 
after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18. 
 
 
 
 
 
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Planned Figure Descriptions and Shells 
Number        Title       Population 
Unique (U) or 
Repeated (R) 
Figure 14.2.1.1 - Daily Pain NRS: MCP-Mod Dose Response Model - mITT Population 
U 
Figure 14.2.1.2 - Daily Pain NRS: Boxplots at Week 12 by Treatment Group and Missing Data Handling - mITT Population 
U 
Figure 14.2.1.3 - Daily Pain NRS: Boxplots at Week 12 by Treatment Group and Co-Medication Subgroup - mITT Population 
R 
Figure 14.2.1.4 - Daily Pain NRS: MMRM LS Means (95% Confidence Interval) over 12-weeks by Treatment Group (Observed Cases) - 
mITT Population 
U 
Figure 14.3.6.1.1 - Vital Sign Profiles: Mean (±SD) Systolic Blood Pressure over time - Safety Population 
U 
Figure 14.3.6.1.2 - Vital Sign Profiles: Mean (±SD) Diastolic Blood Pressure over time - Safety Population 
R 
Figure 14.3.6.1.3 - Vital Sign Profiles: Mean (±SD) Heart Rate over time - Safety Population 
R 
Figure 14.3.6.1.4 - Vital Sign Profiles: Mean (±SD) Respiratory Rate over time - Safety Population 
R 
Figure 14.3.6.1.5 - Vital Sign Profiles: Mean (±SD) Temperature over time - Safety Population 
R 
Figure 14.4.1.1 - Pharmacokinetics: Line Plot of Geometric Mean (with and without gSD) Serum MEDI7352 over time - PK Population 
R 
Figure 14.4.1.2 - Pharmacokinetics: Individual Plot of Serum MEDI7352 Concentrations over time - PK Population 
U 
Figure 14.4.2.1 - Pharmacodynamics: Line Plot of Geometric Mean (with and without gSD) total NGF over time - Safety Population 
R 
Figure 14.4.2.2 - Pharmacodynamics: Individual Plot of Serum total NGF over time - Safety Population 
R 
 
 
 
 
 
 
 
 
 
 
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Figures Change Log 
Output 
Number 
Date of 
Change 
Change 
Made By 
(initials) 
Description/Rationale 
 
 
 
 
 
 
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Figure 14.2.1.1 
Daily Pain NRS: MCP-Mod Dose Response Model 
mITT Population 
 
CI = Confidence Interval; CFB = Change from Baseline; DPS = Daily Pain Score; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive. Envelope depicts 95% CI of mean dose-response. Added dots are actual doses ± 95% CI.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
I 
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(U 
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I 
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Weekly Average to Week 12 Daily Pain NRS CFB, 
Emax dose-response model 
I 
I 
I 
I • 
100 
200 
300 
Dose (µg/kg) 
Hyperbolic Emax 
Eo = -0.21 
Emax = -5.54 
ED50 = 197.56 
400 
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Programming Notes: 
• 
Insert the following text as legend: “Weekly Average to Week 12 Daily Pain NRS CFB, xxxx dose-response model”, with ‘xxxx’ as the selected dose-
response model (e.g., Hyperbolic Emax). 
• 
Dose (µg/kg) in x axis and Daily Pain NRS CFB in y axis. 
• 
Add model parameter values as an inset plot. For e.g., Sigmoid Emax; E0 = xxx, Emax = xxx, ED50 = xxx, λ = xxx. 
• 
The MCP-MOD approach will only be performed if stage 4 is initiated, otherwise there would be insufficient dosing data to fit the non-linear models. 
 
 
 
 
 
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Figure 14.2.1.2 
Daily Pain NRS: Boxplots at Week 12 by Treatment Group and Missing Data Handling 
mITT Population 
 
 
BOCF = Baseline Observation Carried Forward; CFB = Change from Baseline; DPS = Daily Pain Score; LOCF = Last Observation 
Carried Forward; NRS = Numeric Rating Scale; OBS = Observed Cases. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
 
I 
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0 
5 
Dose (~tg/kg) 
150 
450 
Data 
OBS 
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LOCF 
BOCF 
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Programming Notes: 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS”. 
• 
Dose (µg/kg) and Observed/LOCF/BOCF in x axis and Daily Pain NRS CFB in y axis. 
• 
A level for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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Figure 14.2.1.3 
Daily Pain NRS: Boxplots at Week 12 by Treatment Group and Co-Medication Subgroup 
mITT Population 
 
 
CFB = Change from Baseline; DPS = Daily Pain Score; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.2 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS”. 
• 
Dose (µg/kg) in x axis, Anticonvulsant/ Antidepressant/ Both/ None in right side Co-medication labels, and Daily Pain NRS CFB in y axis. 
• 
A level for 
 dosing (between 
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.2.1.4 
Daily Pain NRS: MMRM LS Means (95% Confidence Interval) over 12-weeks by Treatment Group (Observed Cases) 
mITT Population 
 
CFB = Change from Baseline; CI = Confidence Interval; DPS = Daily Pain Score; LS = Least Square; MMRM = Mixed Model for 
Repeated Measures; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
I 
...- -
0 
-
m 
LL 
...-
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{Y z 
N 
-
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I 
-
0 
'I" -
Ii) -
I 
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·-• ·- 0 
···•··· 5 
_..__ 150 
--
450 
4 
Weekly Average CFB to Week 12 
Daily Pain NRS ± 95% Cl 
6 
8 
Week 
10 
12 
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Programming Notes: 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS ± 95% CI”. 
• 
Week in x axis and Daily Pain NRS CFB in y axis. 
• 
Include a profile for each dose treatment group. 
• 
Include the following timepoints: Week 2, 4, 6, 8, 10, and 12. 
• 
Extract data for this figure from the MMRM of CFB Daily Pain NRS with Observed Cases. 
• 
A profile for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Figure 14.3.6.1.1 
Vital Sign Profiles: Mean (±SD) Systolic Blood Pressure over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; SBP = Systolic Blood Pressure; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = Week 
11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average SBP ± Standard Deviation”. 
• 
Study Visit in x axis and Systolic Blood Pressure (mmHg) in y axis. 
• 
Include a profile for Resting SBP and another for Standing SBP. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.3.6.1.2 
Vital Sign Profiles: Mean (±SD) Diastolic Blood Pressure over time 
Safety Population 
 
 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; DBP = Diastolic Blood Pressure; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = 
Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average DBP ± Standard Deviation”. 
• 
Study Visit in x axis and Diastolic Blood Pressure (mmHg) in y axis. 
• 
Include a profile for Resting DBP and another for Standing DBP. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated) 
 
 
 
 
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Figure 14.3.6.1.3 
Vital Sign Profiles: Mean (±SD) Heart Rate over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; HR = Heart Rate; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = Week 11; W12 = 
Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average HR ± Standard Deviation”. 
• 
Study Visit in x axis and Heart Rate (Beats/min) in y axis. 
• 
Include a profile for Resting HR and another for Standing HR. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.3.6.1.4 
Vital Sign Profiles: Mean (±SD) Respiratory Rate over time 
Safety Population 
 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 4H PD = 4 hours Post-Dose; 5M PD = 
5 minutes after Infusion Completion; BASE = Baseline; D1 = Day 1; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; 
W10 = Week 10; W11 = Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average Respiratory Rate ± Standard Deviation”. 
• 
Study Visit in x axis and Respiratory Rate (Breaths/min) in y axis. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-
Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-
Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 
minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Make one plot with 4 profiles (one for each treatment group). 
• 
A profile for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Figure 14.3.6.1.5 
Vital Sign Profiles: Mean (±SD) Temperature over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 2H PD = 2 Hours Post-Dose; 4H PD = 4 hours Post-Dose; 5M PD = 5 minutes after Infusion 
Completion; BASE = Baseline; D1 = Day 1; T° = Temperature; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = 
Week 10; W11 = Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average Body Tº ± Standard Deviation”. 
• 
Study Visit in x axis and Body Temperature (ºC) in y axis. 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 
5 minutes after Infusion Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after 
Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion 
Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Make one plot with 4 profiles (one for each treatment group). 
• 
A plot for 
 dosing 
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
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Figure 14.4.1.1 
Pharmacokinetics: Line Plot of Geometric Mean (with and without gSD) Serum MEDI7352 Concentrations over time  
PK Population 
 
 
ADA = Antidrug Antibodies; gMean = Geometric Mean. 
PK Population = includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.1 
 
 
I 
Geometric Mean serum MEDl7352 ± Geometric Standard Deviation 
Overall 
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Overall 
50 
50 
Study Visn (days) 
Study Visn (days) 
100 
100 
Treatment 
-
150 
-•· 450 
Treatment 
-
150 
- • · 450 
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Programming Notes: 
• 
Insert the following text as upper legend: “Geometric Mean serum MEDI7352 ± Geometric Standard Deviation” for the linear plot, and “Geometric 
Mean serum MEDI7352” for the semi-log plot. Below legend, add legend for ADA status: “Overall”, “ADA Positive”, “ADA Negative”. 
• 
Insert legend with different point symbols and colors for each treatment group (
) for the Overall plot, and a legend with different point 
symbols and colors for each ADA status (ADA+, ADA-) for each treatment group plot by ADA status. 
• 
Study Visit in x axis and Serum MEDI7352 concentration (ng/mL) in y axis (in linear and log10 scale, for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10: Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 10 + 14 days, Week 18.   
• 
Make one overall plot by treatment group, and a plot for each treatment group by ADA status for a total of 4 plots. 
• 
A line for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Figure 14.4.1.2 
Pharmacokinetics: Individual Plot of Serum MEDI7352 Concentrations over time  
PK Population 
 
ADA = Antidrug Antibodies. 
PK Population = includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.1 
 
I 
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MEDl7352 Concentration by Subject, Treatment Group, and ADA Status 
450 11g/kg 
50 
Study Vis~ (days) 
MEDl7352 Concentration by Subject, Treatment Group, and ADA Status 
450 11g/kg 
50 
Study Visit (days) 
100 
100 
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ADA_Status 
NegatiVe 
-
Positive 
ADA_Status 
Negative 
-
Positive 
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Final 1.0    |    12-Jul-2023    |     
 Page 203 of 205 
 
 
Programming Notes: 
• 
Insert the following text as upper legend: “MEDI7352 Concentration by Subject, Treatment group, and ADA status”. Below legend, add legend for 
Treatment Group: 
 
• 
Insert legend with different colors for each ADA status (Positive/ Negative). 
• 
Time (days) in x axis and Serum MEDI7352 concentration (ng/mL) in y axis (in linear and log10 scale, for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 10 + 14 days, Week 18.   
• 
Make one plot for each Treatment group (
), for a total of 3 plots. 
• 
Plots for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Figure 14.4.2.1 
Pharmacodynamics Line Plot of Geometric Mean (with and without gSD) Serum total NGF over time  
Safety Population 
 
 
ADA = Antidrug Antibodies; gMean = Geometric Mean; NGF = Nerve-Growth Factor. 
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.3 
 
 
Programming Notes: 
• 
Same shell as Figure 14.4.1.1 
• 
Insert the following text as upper legend: “Geometric Mean total NGF ± Geometric Standard Deviation” for the linear plot, and “Geometric Mean total 
NGF” for the semi-log plot. Below legend, add legend for ADA status: “Overall”, “ADA Positive”, “ADA Negative”. 
• 
Insert legend with different point symbols and colors for each treatment group (Placebo, 
) for the Overall plot, and a legend with 
different point symbols and colors for each ADA status (ADA+, ADA-) for each treatment group plot by ADA status. 
• 
Study Visit in x axis and Serum tNGF (pg/mL) in y axis (in linear and log10 scale for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10: Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12, Week 18.   
• 
Make one overall plot by treatment group, and a plot for each treatment group by ADA status for a total of 5 plots . 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
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Figure 14.4.2.2 
Pharmacodynamics: Individual Plot of Serum total NGF over time  
Safety Population 
ADA = Antidrug Antibodies; NGF = Nerve-Growth Factor. 
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.3 
 
 
Programming Notes: 
• 
Same shell as Figure 14.4.1.2 
• 
Insert the following text as legend: “Total NGF by Subject, Treatment group, and ADA status”. Below legend, add legend for Treatment Group: 
 
. 
• 
Insert legend with different colors for each ADA status (Positive/ Negative). 
• 
Time (days) in x axis and Serum tNGF concentration (pg/mL) in y axis (in linear and log10 scale for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18.   
• 
Make one plot for each Treatment group (
 Placebo), for a total of 4 plots . 
• 
Plots for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Sponsor: 
AstraZeneca 
Protocol Title 
A Randomised, Double-Blind, Placebo-Controlled, Dose-
Response Study of the Efficacy and Safety of MEDI7352 in 
Subjects with Painful Diabetic Neuropathy 
Development Phase  
2 
Protocol Numbers: 
D5680C00002 
Premier Research PCNs: 
MEDU177093 
Document Version: 
Final Version 1.1 
Document Date:  
31-Aug-2023 
Document History 
Version 
Date 
Author 
Description 
0.1 
24-Mar-2023 
 
Draft Version 
0.2 
21-Apr-2023 
 
Draft Version 
0.3 
24-May-2023 
 
Draft Version 
1 
12-Jul-2023 
 
Final Version 
 
 
 
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Tables, Listings, and Figures Conventions 
All listings, tables, and graphs will have a header showing the sponsor company name, protocol 
and version of delivery and a footer showing the version of SAS, the file name and path, and the 
source of the data (listing number). 
The following reporting conventions will be adopted for the presentation of study data. These 
conventions will enhance the review process and help to standardize the presentation with common 
notations. 
General Reporting Conventions 
• All tables and data listings will be developed in landscape orientation. 
• Specialized text styles, such as bolding, italics, borders, shading, and superscripted and 
subscripted text will not be used in tables, figures, and data listings unless they add 
significant value to the table, figure, or data listing.  
• Only standard keyboard characters should be used in tables and data listings. Special 
characters, such as nonprintable control characters, printer-specific characters, or font 
specific characters, will not be used on a table, figure, or data listing. 
• Adverse events with missing MedDRA coding will have their system organ class preferred 
term presented as “Not Coded” and the Preferred Term presented as verbatim in the tables. 
The “Not Coded” frequencies will be sorted to the end of the tables. This will only be 
applicable for any deliveries sent before database lock (e.g., for dry runs). 
• Programming notes may be inserted into the shells, these notes will not appear in the final 
output. 
 
Population Summary Conventions 
• Population sizes may be presented for each classification factor as totals in the column 
header as (N=xx), where appropriate.  
• All population summaries for categorical variables will include all categories that were 
planned and for which the participants may have had a response. 
• All population summaries for continuous variables will include: n, mean, SD, median, 
quartiles, minimum, and maximum. Other summaries (e.g., number missing, geometric 
mean, 95% CIs, and coefficient of variation [CV] or % CV) may be used as appropriate. 
The precision of the maximum and minimum will match the maximum precision in the 
observed data and 2 decimals for derived data unless specifically mentioned in the 
corresponding shell. The mean and median will have 1 additional decimal place. The SD 
will have 2 additional decimal places. For derived data, minimum and maximum will be 
reported to 2 degrees of precision. Measures of location (mean and median) will be reported 
to 3 degree of precision, and measures of spread will be reported to 4 degrees of precision. 
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• 
All percentages are rounded and reported to a single decimal point (xx.x%). Exceptions 
are 0 and 100 that will be displayed as 0 and 100% respectively. 
Planned Tables, Figures and Listings  
• The table and listing numbers are place holders only and will be determined when the 
outputs are produced. 
• In all listings a blank line will be placed between each participant. Within a data listing, if 
an item appears line after line (e.g., repetition of participant number), then only the first 
occurrence will be displayed. 
• In data listings, the information for 1 participant will be kept on 1 page, if possible, rather 
than splitting a Subjects’s information across pages. 
 
 
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Planned Table Descriptions and Shells 
Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.1.2 - - Screening Population 
U 
Table 14.1.3 - Summary of Reasons for Screening Failure - Screen Failure Population 
U 
Table 14.1.4.1 - Demographics and Baseline Characteristics - Screening Population 
U 
Table 14.1.4.2 - Demographics and Baseline Characteristics - Safety Population 
R 
Table 14.1.4.3 - Demographics and Baseline Characteristics - mITT Population 
R 
Table 14.1.4.4 - Demographics and Baseline Characteristics - PK Population 
R 
Table 14.1.5.1 - Osteoarthritis Characteristics - Screening Population 
U 
Table 14.1.5.2 - Osteoarthritis Characteristics - Safety Population 
R 
Table 14.1.5.3 - Osteoarthritis Characteristics - mITT Population 
R 
Table 14.1.5.4 - Osteoarthritis Characteristics - PK Population 
R 
Table 14.1.6 - Medical History by System Organ Class and Preferred Term - Safety Population 
U 
Table 14.1.7 - Prior Medications by ATC Level 2 and Preferred Name - Safety Population 
U 
Table 14.1.8 - Protocol Deviations - Safety Population 
U 
Table 14.1.9 - Overall Study Drug Exposure - Safety Population  
U 
Table 14.2.1.1.1 - Daily Pain NRS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.1.1.2 - Daily Pain NRS: Summary Statistics (LOCF)Error! Reference source not 
found.- mITT Population 
R 
Table 14.2.1.1.3 - Daily Pain NRS: Summary Statistics (BOCF) - mITT Population 
R 
Table 14.2.1.2.1 - Daily Pain NRS: Primary MCP-Mod Analysis (LOCF) - mITT Population 
U 
Table 14.2.1.2.2 - Statistical Analysis of CFB to Week 12 Daily Pain NRS: Primary ANCOVA 
Analysis (LOCF) - mITT Population 
U 
Table 14.2.1.3.1 - Statistical Analysis of CFB Daily Pain NRS: MMRM Analysis. (Observed 
Cases) - mITT Population 
U 
Table 14.2.1.3.2 - Daily Pain NRS: Sensitivity of Primary MCP-Mod Analysis (BOCF) - mITT 
Population 
R 
Table 14.2.2.1 - Galer NPS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.2.2 - Galer NPS: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.3.1 - DSIS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.3.2 - DSIS: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.4.1 - SF-36: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.4.2 - SF-36: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.5.1 - Rescue Medication Use: Summary Statistics - mITT Population 
U 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.2.6.1 - Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel Haenszel 
(Observed Cases) - mITT Population 
U 
Table 14.2.6.2 - Daily Pain NRS Responder Analysis (≥30%): GEE Analysis (Observed Cases) 
- mITT Population 
U 
Table 14.2.7.1 - Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel Haenszel 
(Observed Cases) - mITT Population 
R 
Table 14.2.7.2 - Daily Pain NRS Responder Analysis (≥50%): GEE Analysis (Observed Cases) 
- mITT Population 
R 
Table 14.2.8.1 - Patient Global Impression of Change: Summary Statistics - mITT Population 
U 
Table 14.2.8.2 - Patient Global Impression of Change: Cochran-Mantel Haenszel - mITT 
Population 
U 
 
U 
Table 14.3.1.1 - Summary of Overall Adverse Events - Safety Population 
U 
Table 14.3.1.2 - Treatment Emergent of Adverse Events by System Organ Class and Preferred 
Term - Safety Population 
U 
Table 14.3.1.3 - Treatment Emergent of Adverse Events by Severity, System Organ Class and 
Preferred Term - Safety Population 
U 
Table 14.3.1.4 - Treatment Emergent Adverse Events by Relationship to Study Medication, 
System Organ Class and Preferred Term - Safety Population 
U 
Table 14.3.1.5 - Treatment Emergent Adverse Events by ADA Status Category, System Organ 
Class and Preferred Term - Safety Population 
U 
Table 14.3.1.6 - Treatment Emergent Adverse Events Leading to Discontinuation of Study drug 
by System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.1.7 - Non-Serious Adverse Events Occurring in More than 5% of Subjects by 
System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.1.8 - Treatment Emergent Adverse Events Occurring in More than 5% of Subjects 
by Preferred Term - Safety Population 
R 
Table 14.3.1.9 - Treatment Emergent Adverse Events by Preferred Term - Safety Population 
R 
Table 14.3.2.1.1 - Serious Adverse Events by System Organ Class and Preferred Term - Safety 
Population 
R 
Table 14.3.2.1.2 - Life-Threatening Serious Adverse Events by System Organ Class and 
Preferred Term - Safety Population  
R 
Table 14.3.2.1.3 - Serious Adverse Events with Outcome Death by System Organ Class and 
Preferred Term - Safety Population 
R 
Table 14.3.2.1.4 - Serious Adverse Events by Relationship to Study Medication, System Organ 
Class and Preferred Term - Safety Population 
R 
Table 14.3.3.1 - Listing of Serious Adverse Events - Safety Population 
U 
Table 14.3.3.2 - Listing of Deaths - Safety Population 
U 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.3.2.2.1 - Treatment Emergent Adverse Events Associated with Abnormal Liver by 
System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.2.2.2 - Potential Joint Related Adverse Events of Special Interest by System Organ 
Class and Preferred Term - Safety Population 
R 
 Table 14.3.2.2.3 - Serious and/or severe Infections by System Organ Class and Preferred Term 
- Safety Population 
R 
Table 14.3.2.2.4 - Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions 
Leading to Discontinuation of IP by System Organ Class and Preferred Term - Safety 
Population 
R 
Table 14.3.4.1 - Descriptive Summary of Clinical Chemistry - Safety Population 
U 
Table 14.3.4.2 - Shift Table of Clinical Chemistry Results - Safety Population 
U 
Table 14.3.4.3 - Descriptive Summary of Hematology - Safety Population 
R 
Table 14.3.4.4 - Shift Table of Hematology Results - Safety Population 
R 
Table 14.3.4.5 - Descriptive Summary of Coagulation - Safety Population 
R 
Table 14.3.4.6 - Shift Table of Coagulation Results - Safety Population 
R 
Table 14.3.4.7 - Descriptive Summary of Urinalysis - Safety Population 
U 
Table 14.3.4.8 - Shift Table of Urinalysis Results - Safety Population 
R 
Table 14.3.4.9 - Maximum On-Treatment ALT and AST versus Maximum On-Treatment Total 
Bilirubin - Safety Population 
U 
Table 14.3.5.1 - Descriptive Summary of Vital Signs - Safety Population 
U 
Table 14.3.5.2 - Descriptive Summary of Digital ECG Data - Safety Population 
U 
Table 14.3.5.3 - Summary of Overall Evaluation of safety ECG Data - Safety Population 
U 
Table 14.3.5.4 - Covid-19 Screening - Safety Population 
U 
Table 14.3.5.5 - Summary of Sub-Scores for Total Neuropathy Score-Nurse - Safety Population 
U 
Table 14.3.5.6 - Descriptive Summary of Total Neuropathy Score-Nurse - Safety Population 
U 
Table 14.3.5.7 - Summary of Motor and Sensory Nerve Conduction Studies - Safety Population 
U 
Table 14.3.5.8 - Summary of Strength and Deep Tendon Reflexes - Safety Population 
U 
Table 14.3.5.9 - Summary of Local Injection Site Reactions - Safety Population 
U 
Table 14.3.5.10 - Summary of Hypersensitivity/Anaphylactic Reactions - Safety Population 
U 
Table 14.3.5.11 - Summary of Liver Diagnostic Investigations - Safety Population 
U 
Table 14.3.5.12 - Summary of Liver Risk Factors and Lifestyle Events - Safety Population 
U 
Table 14.3.5.13 - Summary of Liver Signs and Symptoms - Safety Population 
U 
Table 14.3.5.14 - Summary of Infection Diagnostic Investigations - Safety Population 
U 
Table 14.3.5.15 - Summary of Infection Risk Factors and Lifestyle Events - Safety Population 
U 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.3.5.16 - Summary of Infection Signs and Symptoms - Safety Population 
U 
Table 14.3.5.17 - Summary of Concomitant Medications by ATC Level 2 and Preferred Name - 
Safety Population 
R 
Table 14.3.5.18 - Summary of Concomitant Procedures - Safety Population 
R 
Table 14.3.5.19 - Anti-Drug Antibody Results and Titre Summary by Timepoint - Safety 
Population 
U 
Table 14.3.5.20 - Descriptive Summary of Anti-Drug Antibody Results and Titre by ADA 
Categories - Safety Population 
U 
Table 14.4.1 - Summary of Serum MEDI7352 Concentrations - PK Population 
U 
Table 14.4.2 - Summary of Serum total NGF Concentrations - PD Population 
U 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table Change Log 
Output 
Number 
Date of 
Change 
Change Made 
By (initials) 
Description/Rationale 
 
 
 
 
 
 
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1. Demographic Data 
Table 14.1.2 
Subject Disposition  
Screening Population 
 
Placebo 
MEDI7352 
Total 
Status 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Screening Population [1] 
 
 
 
 
xx (100%) 
  Screen Failures 
 
 
 
 
xx (xx.x %) 
  Enrolled Subjects 
 
 
 
 
xx (xx.x %) 
  Re-screened Subjects 
 
 
 
 
xx (xx.x %) 
 
 
 
 
 
 
Randomized Subjects  
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
Randomized and Not Treated Subjects 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
    Reason for Discontinuation 
 
 
 
 
 
        Adverse Event 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
        Other 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
Safety Population [2] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
mITT Population [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evaluable Week 12 Efficacy  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evaluable LOCF Efficacy [4] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not Efficacy Evaluable 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
PK Population [5] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Completed Study Treatment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Discontinued Study Treatment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Reason for Discontinuation: 
 
 
 
 
 
   Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lack of Efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lost to Follow-up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Non-compliance with Study Drug 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Physician Decision 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pregnancy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Progressive Disease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Protocol Violation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
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   Study Terminated by Sponsor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Technical Problems 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Withdrawal by Subject 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sponsor Decision 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Completed Study  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Withdrawn from the Study 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Reason for Discontinuation: 
 
 
 
 
 
   Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lack of Efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lost to Follow-up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 = Coronavirus disease 2019; LOCF = Last Observation Carried Forward; mITT = modified intent-to-treat; N = number of subjects per treatment 
group; PK = pharmacokinetic. 
Note: Percentages are n/Number of subjects randomized*100 as displayed in column header N, except for the screened, enrolled  and re-screened where 
n/Number of Screening subjects*100, and for the randomized, where n/Number of Enrolled subjects*100. 
Re-screened subjects are a subset of the Screening population. 
[1] The Screening Population includes all subjects who provide informed consent and provide demographic and/or baseline screening assessments. 
[2] The Safety Population includes all subjects who receive at least 1 dose of double-blind study medication. 
[3] The mITT Population includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
[4] Subjects in the mITT Population with LOCF applied for missing efficacy data at week 12, 
[5] The PK Population includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
 
Reference Listings: 16.2.1.1, 16.2.1.2, 16.2.1.3, 
 
 
Programming Notes:  
• 
Display only reasons for early discontinuation with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
  
 
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Table 14.1.3 
Summary of Reasons for Screening Failure 
Screen Failure Population 
 
Total 
 
(N=xx) 
 
 
Number of Subjects Who Don’t Meet Inclusion/Exclusion Criteria  
xx (xx.x%) 
 
 
  IC 01: Xxxxxxxxxxxx 
xx (xx.x%) 
 
 
  IC 02: Xxxxxxxxxxxx 
xx (xx.x%)  
 
 
… 
 
 
 
  EC 01: Xxxxxxxxxxxx 
xx (xx.x%) 
 
 
  EC 02: Xxxxxxxxxxxx 
xx (xx.x%)  
 
 
  … 
 
 
 
Number of Subjects Who are Screen Failure for other Reason than Eligibility Criteria 
xx (xx.x%) 
 
 
EC = exclusion criteria; IC = inclusion criteria; N = number of subjects. 
Note:  subject can be counted in more than one criterion. 
Reference Listing 16.2.1.4 
 
 
 
 
 
 
 
 
 
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Table 14.1.4.1 
Demographics and Baseline Characteristics 
Screening Population 
 
Variable 
Placebo 
MEDI7352 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Age (years) [1] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Age Category 
 
 
 
 
 
   ≥18 - <65 years 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   ≥65 years 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Gender 
 
 
 
 
 
   Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
   Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Race 
 
 
 
 
 
   American Indian or Alaska Native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Black or African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Native Hawaiian or Other Pacific Islander 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Not Specified 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Screening Height (cm) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
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Screening Weight (kg)  
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Screening BMI (kg/m²) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Female characteristics [2] 
 
 
 
 
 
   Surgically sterile 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Postmenopausal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Fully vaccinated for COVID-19 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
BMI = Body Mass Index; COVID-19 = Coronavirus disease 2019; n = number of subjects by treatment group with collected parameter; N = number of 
subjects per treatment group; SD = standard deviation. 
Note: The Screening Population includes all subjects who provide informed consent and provide demographic and/or baseline screening assessments. 
[1] Age was calculated as age at time of consent. 
[2] Percentages are n/Number of Female subjects from Analysis Population*100 
Reference Listing: 16.2.4.1 
 
Programming Notes: 
• 
If a variable is between 2 pages, start the variable in the second page. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.1.4.2 
Demographics and Baseline Characteristics 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.4.3 
Demographics and Baseline Characteristics 
mITT Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.4.4 
Demographics and Baseline Characteristics 
PK Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.1.5.1 
Osteoarthritis Characteristics 
Screening Population 
 
Placebo 
MEDI7352 
Total 
Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
Subjects diagnosed with Osteoarthritis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Joint(s)/Area(s) affected: 
 
 
 
 
 
   Shoulder 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Elbow 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hip 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Knee 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ankle 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Spine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hands 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Feet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Osteoarthritis clinically significant 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Radiologic investigations conducted [1] 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Plain radiography 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     MRI 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Joint(s)/Area(s) investigated: 
 
 
 
 
 
   Shoulder 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Elbow 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hip 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Knee 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ankle 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Spine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
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   Hands 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Feet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Osteoarthritis radiologically significant 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Kellgren-Lawrence score reported 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 0  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No/Not applicable 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Radiologic Scoring System Used? 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
MRI = magnetic resonance imaging; N = number of subjects per treatment group. 
[1] Subjects who reported more than one radiologic investigation within each category were only counted once. 
Reference Listing: 16.2.4.3 
 
Programming Notes: 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
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Table 14.1.5.2 
Osteoarthritis Characteristics 
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.5.3 
Osteoarthritis Characteristics 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.5.4 
Osteoarthritis Characteristics 
PK Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
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Table 14.1.6 
Medical History by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xxx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xxx) 
 
 
 
 
 
 
Any Medical History 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   … 
… 
… 
… 
… 
… 
 
 
 
 
 
 
System Organ Class n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Note: All medical history terms were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 26.0. At each level of summarization 
(system organ class or preferred term), subjects having more than one medical history term were counted only once. System organ class and preferred terms 
are sorted in descending order of frequency of Total column, and alphabetically if same frequency. 
 
Reference Listing: 16.2.4.2 
 
Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Sort SOC and PT (within SOC) in descending order of frequency in the Total column.  Sort alphabetically in case of ties. 
• 
Uncoded Medical History Events 
o When there are uncoded Medical History Events in the database, the events will be summarized with SOC and PT set to [Not Coded]. The [Not 
Coded] will be sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.1.7  
Prior Medications by ATC Class and Preferred Name 
Safety Population 
 
ATC Class [1] 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Subjects with at Least One Prior 
Medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC Level 2 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC Level 2 n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC = Anatomical Therapeutic Class; N = number of subjects per treatment group. 
[1] ATC Class is defined as ATC Level 2. 
Note: Prior medications are defined as medications that started before first dose of study, whether they were stopped before first dose of study medication or 
not. All prior medications are coded using WHO drug dictionary version vMar2023. At each level of summarization (ATC Level 2 or Preferred Name), 
subjects who reported more than one prior medication were only counted once. ATC Level 2 and Preferred Term are sorted in descending order of frequency 
of total, and alphabetically if same frequency.  
Reference Listing: 16.2.9.16 
 
Programming Notes: 
• 
If uncoded ATC Level or Preferred Name, please put them as [Not Coded] 
• 
ATC and Preferred Name texts should be in proper case in table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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Table 14.1.8  
Protocol Deviations 
Safety Population 
 
 
Placebo 
MEDI7352 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Subjects With Any Important Protocol 
Deviation/Violation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Protocol Deviation Type 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 5 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 6 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
………….. 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Notes: Percentages are n/Number of subjects by treatment group*100. 
Subjects with one or more deviations within a type of protocol deviation were counted only once. 
 
Reference Listing 16.2.2.1 
 
Programming Notes: 
• 
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 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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2. 
Exposure and Compliance 
Table 14.1.9 
Overall Study Drug Exposure 
Safety Population 
 
Placebo 
MEDI7352 
Total 
Category/ Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Maximum Number of Doses Administered [1] 
 
 
 
 
 
1 Dose 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3 Doses 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
4 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
5 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
6 Doses 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
 
 
Total Duration of Exposure (days) [2] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Total (cumulative) IP volume infused (mL) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
n = number of subjects by treatment group with collected parameter; N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; 
Q3 = third quartile. 
[1] Subjects are counted once for each level of dose administered. 
[2] Duration of exposure (days) = min(date of last dose of treatment + 14 days or date of death) – date of first dose of treatment + 1. 
Reference Listing: 16.2.5.1 
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Programming Notes: 
• 
Add all categories even if count is 0. 
• 
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 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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3. 
Primary Efficacy Analysis 
Table 14.2.1.1.1 
Daily Pain NRS: Summary Statistics (Observed Cases) 
mITT Population 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; DPS = Daily Pain Score; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per 
treatment group; NRS = Numeric Rating Scale; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are weekly averages of the average daily pain scores on an 11-point (0-10) NRS and CFB for the same variable. Total N for the mITT 
population = 106 at Week 2 as Subject 
 has < 4 days of diary pain data on that visit, completing the following visits till Week 12. 
[1] Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e., Day -7 to Day -1, inclusive.  
Reference Listing: 16.2.6.1 
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Programming Notes: 
• 
Include all observed data (Not the LOCF) on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, 12 and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.1.1.2 
Daily Pain NRS: Summary Statistics (LOCF) 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.2.1.1.1. 
• 
Include all observed and LOCF data on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and  12 
• 
Add abbreviation in footnote: LOCF = Last Observation Carried Forward. 
• 
Add the following note in footnote: “LOCF applied to Week 12 only”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
Table 14.2.1.1.3 
Daily Pain NRS: Summary Statistics (BOCF) 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.2.1.1.1. 
• 
Include all observed and BOCF data on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and 12 
• 
Add abbreviation in footnote: BOCF = Baseline Observation Carried Forward. 
• 
Add the following note in footnote: “BOCF applied to Week 12 only”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
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Table 14.2.1.2.1 
Daily Pain NRS: Primary MCP-Mod Analysis (LOCF) 
mITT Population 
‘MCP’ step 
Model 
        Contrast [1] 
 
 
 
t value 
1-sided adjusted P-value [2] 
Hyperbolic Emax 
 
 
 
 
 
        ED50 = 7.5 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 15 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 30 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 60 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 750 
 
 
 
xx.xx 
0.xxxx 
 
 
 
 
 
 
Exponential 
 
 
 
 
 
        δ = 100 
 
 
 
xx.xx 
0.xxxx 
        δ = 200 
 
 
 
xx.xx 
0.xxxx 
 
 
 
 
 
 
Overall MCP test 
 
 
 
xx.xx 
0.xxxx 
 
 
 
 
 
 
CFB = Change from Baseline; LOCF = Last Observation Carried Forward; MCP = Multiple Comparisons; Procedure; NRS = Numeric rating scale. 
[1] ED50 = Effective Dose giving half of the asymptotic maximum effect. 
[2] Multiplicity Adjusted P-value. 
 
 
 
 
 
 
 
 
 
 
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‘MOD’ step [3] 
Selected Model xxxxxxxxxx 
Parameter 
Estimate 
95% CI of Estimate [6] 
ED50 
xx.x 
[ x.xx to x.xx ] 
ED90 [4] 
xx.x 
[ x.xx to x.xx ] 
Asymptotic ED90 [5] 
xx.x 
[ x.xx to x.xx ] 
Dose to achieve target (-1.25) effect 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 
 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 
 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 
 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 
 
xx.x 
[ x.xx to x.xx ] 
CI: Confidence Interval; LOCF = Last Observation Carried Forward; MCP = Multiple Comparisons; Procedure; MOD = Modelling; NRS = Numeric rating 
scale. 
[3] Results from the ‘MOD’ step will only be available in case any of the MCP tests is statistically significa nt. 
[4] ED90 = Effective Dose giving 90% of the effect of the maximum dose studied. 
[5] Asymptotic ED90 = Effective Dose giving 90% of the asymptotic maximum effect. 
[6] 2.5% and 97.5% quantiles taken from 100000 samples from the multivariate normal distribution for model fitted estimates and its covariance matrix. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
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Table 14.2.1.2.2 
Statistical Analysis of CFB to Week 12 Daily Pain NRS: Primary ANCOVA Analysis (LOCF)  
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
[ x.xx to x.xx ] 
 
 
Co-Medication Type 
 
 
3 
 
 
 
0.xxxx 
Baseline pain NRS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
ANCOVA = analysis of covariance; CFB = Change from Baseline; 
CL = Confidence limits; LOCF = Last Observation Carried Forward; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: ANCOVA by dose using NRS baseline value and co-medication as covariates, with CFB to Week 12 (LOCF) 
as dependent variable. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means 
Treatment 
Number of Subjects 
LS mean [3] 
95% CI of LS mean 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LOCF = Last Observation Carried Forward; LS = least square; NRS = Numeric rating scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average pain NRS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.1 
 
 
 
Programming Notes: 
• 
Concomitant co-medication Type indicated for Painful Diabetic Neuropathy: either anticonvulsant class (pregabalin or gabapentin) or antidepressant 
class (duloxetine, venlafaxine, or amitriptyline). 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.1.3.1 
Statistical Analysis of CFB Daily Pain NRS: MMRM Analysis. (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
3 
 
 
 
0.xxxx 
Week 
 
 
6 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
18 
 
 
 
0.xxxx 
Baseline pain NRS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 1
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM = Mixed Model for Repeated Measures; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, NRS baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
Note: model was fitted using an unstructured covariance structure. Estimates for difference vs Placebo at Week 12. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: Week xxxxx 
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
- Placebo 
 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square; NRS = Numeric rating scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average pain NRS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
Include LSmeans and difference in LSmean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.1.3.2 
Daily Pain NRS: Sensitivity of Primary MCP-Mod Analysis (BOCF) 
mITT Population  
 
Programming Notes: 
• 
Same shell as Table 14.2.1.2.1, substituting “LOCF = Last Observation Carried Forward” by “BOCF = Baseline Observation Carried Forward”. 
• 
The MCP-MOD approach will only be performed if stage 4 is initiated, otherwise there would be insufficient dosing data to fit the non-linear models. 
 
 
 
 
 
 
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4. 
Secondary Efficacy Analysis 
Table 14.2.2.1 
Galer NPS: Summary Statistics (Observed Cases)  
mITT Population 
Parameter: xxxxx 
 
 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
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For Pain Duration Frequency  
 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   I feel a background pain all of the time and occasional flare-ups 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   I feel a single type of pain all the time 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   feel a single type of pain only sometimes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NPS = 
Neuropathic Pain Scale; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are Pain Intensity, Unpleasantness, and Descriptor scores on an 11-point (0-10) NRS, and Pain Duration/Frequency on a 3-point NRS (1-3), 
plus CFB for the same variables. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.6.2 
 
Programming Notes: 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Repeat for the Parameters: Pain intensity, Pain Unpleasantness, Pain Sharpness, Pain Hotness, Pain Dullness, Pain Coldness, Pain Sensitivity, Pain 
Itching, Deep Pain Intensity, Surface Pain Intensity (All in an 11-point NRS), Galer NPS Total Score (ranging from 0 to 100), and Pain 
Duration/Frequency (in a 3-point NRS). 
• 
A column for 
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) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.2.2 
Galer NPS: MMRM Analysis (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-Medication type 
 
 
3 
 
 
 
0.xxxx 
Week 
 
 
3 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
9 
 
 
 
0.xxxx 
Baseline NPS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; NPS = Neuropathic Pain Scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, NPS baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
Note: model was fitted using an unstructured covariance structure. 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: Week: xxxx  
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square; NPS = Neuropathic Pain Scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline NPS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.2 
 
Programming Notes: 
• 
Include LSmeans and difference in LSmean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Analysis is done for Galer NPS Total Score. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.3.1 
DSIS: Summary Statistics (Observed Cases) 
mITT Population  
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; DSIS = Daily Sleep Interference; n = number of subjects by treatment group at each visit for the parameter; N = number of 
subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are weekly averages of the average daily sleep interference scores on an 11-point (0-10) NRS and CFB for the same variable. 
[1] Baseline is defined as the average of the ‘non-missing’ DSIS within the seven-day period prior to randomization i.e., Day -7 to Day -1, inclusive. 
Reference Listing: 16.2.6.3 
 
 
 
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Programming Notes: 
• 
Include all observed data on weekly averages of the average daily Sleep Interference score for Baseline, Week 4, 8, 12, and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.3.2 
DSIS: MMRM Analysis (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
3 
 
 
 
0.xxxx 
Week 
 
 
3 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
9 
 
 
 
0.xxxx 
Baseline DSIS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; DSIS = Daily Sleep Interference. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, DSIS baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
Note: model was fitted using an unstructured covariance structure. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: Week xxxx 
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average DSIS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.3 
 
Programming Notes: 
• 
Include LS means and difference in LS mean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Include all observed data on weekly average DSIS for Baseline, Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.4.1 
SF-36: Summary Statistics (Observed Cases) 
mITT Population  
Parameter: xxxxx 
 
 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 12 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
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When parameter is “Change in general Health” 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   Much better now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Somewhat better now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   About the same as one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Somewhat worse now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Much worse now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NRS = 
numeric rating scale; SD = standard deviation; SF-36 = 36-Item Short-Form Health Survey; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are derived SF-36 scores and Change in General Health on a 5-point NRS (1-5), plus CFB for the same variables. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.6.4 
 
Programming Notes: 
• 
Include all observed data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Vitality 
(Energy/fatigue), Emotional well-being, Social functioning, Pain and General Health (from 0 to 100), Physical Health Summary, Mental Health 
Summary, and Change in general Health (in a 5-point NRS). 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.2.4.2 
SF-36: MMRM Analysis (Observed Cases) 
mITT Population 
 
Model parameter estimates: xxxxxxxx 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
3 
 
 
 
0.xxxx 
Week 
 
 
1 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
3 
 
 
 
0.xxxx 
Baseline SF-36 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; SF-36 = 36-Item Short-Form Health Survey. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Treatment, SF-36 baseline value, and Co-medication type as covariates, with CFB as dependent 
variable. 
Note: model was fitted using an unstructured covariance structure. 
 
 
 
 
 
 
 
 
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Least Square Means: xxxxxxxx  
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline SF-36 parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.4 
 
Programming Notes: 
• 
Include LSmeans and difference in LSmean with Placebo.. 
• 
Include all observed data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical Health Summary, and Mental Health Summary Add parameter name after ‘Model parameter estimates:’ and after 
‘Least Square Means:’ 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.5.1 
Rescue Medication Use: Summary Statistics 
mITT Population 
 
Variable   
Placebo 
MEDI7352 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
Number of subjects taking any 
rescue medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Number of subjects taking any 
permitted rescue medication  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Total number of days rescue 
medication was used [1] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Cumulative consumption of 
Paracetamol Rescue Medication 
(mg) [2] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Paracetamol Rescue Medication 
Average Daily Dose (mg) [3] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
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Number of subjects taking any 
prohibited rescue medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Each day on which permitted rescue medication was used at least once is counted. 
[2] Calculated as the total dose of paracetamol rescue medication (mg). 
[3] Calculated as: cumulative consumption of paracetamol rescue medication (mg) /total number of days rescue medication was used. 
 
Reference Listing: 16.2.6.5 
 
 
Programming Notes: 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
• 
Refer to  
 
 
 
 
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Table 14.2.6.1 
Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel Haenszel (Observed Cases) 
mITT Population 
Cochran-Mantel-Haenszel Test 
Treatment/ 
    Category 
Number of  
Subjects (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Placebo (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
 
 
 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata of MEDI7352 dose - Placebo. 
[2] P-value < 0.05 indicates a significant association between number of subjects with >=30% decrease from Baseline and treatment across strata. 
Note: a separate CMH test is performed for each dose versus placebo at Week 12. 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 12. 
 
 
 
 
 
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Table 14.2.6.2 
Daily Pain NRS Responder Analysis (≥30%): GEE Analysis (Observed Cases)  
mITT Population 
 
Model parameter estimates 
Parameter 
Estimate 
Z value 
Degrees of freedom 
Standard Error 
2-sided 95% CL 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
Co-medication type 
 
 
3 
 
 
0.xxxx 
Week 
 
 
3 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
0.xxxx 
Treatment*Week 
 
 
9 
 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
Dispersion 
xx.xx 
 
 
 
 
 
CL = Confidence limits; GEE: Generalized Estimation Equations; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: GEE using Time, Treatment, Treatment*Time and Co-medication type as covariates, with dependent binary 
variable indicating whether weekly average pain NRS has >=30% decrease from Baseline. 
Note: model was fitted using a first-order autoregressive covariance structure. Estimates for MEDI7352 dose vs placebo and for 2-sided 95% CL displayed in 
odds ratio scale. 
 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
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Table 14.2.7.1 
Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel Haenszel (Observed Cases) 
mITT Population 
 
Cochran-Mantel-Haenszel Test 
Treatment/ 
    Category 
Number of  
Subjects (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Placebo (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
 
 
 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata of MEDI7352 dose - Placebo. 
[2] P-value < 0.05 indicates a significant association between number of subjects with >=50% decrease from Baseline and treatment across strata. 
Note: a separate CMH test is performed for each dose versus placebo at Week 12. 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 12. 
 
 
 
 
 
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Table 14.2.7.2 
Daily Pain NRS Responder Analysis (≥50%): GEE Analysis (Observed Cases) 
mITT Population 
 
Programming notes: 
• 
Same shell as Table 14.2.6.2. Change footnote in [2] as: “p-value is derived from the following model: GEE using Time, Treatment, Treatment*Time 
and Co-medication type as covariates, with dependent binary variable indicating whether weekly average pain NRS has >=50% decrease from Baseline. 
Note: model was fitted using an unstructured covariance structure, with 'MEDI7352
' and 'MEDI7352
 treatment groups, together with 
co-medication categories (both types at the same time and none) dropped from the analysis to make the generalized Hessian matrix  positive definite. 
Estimates for MEDI7352 dose vs placebo and for 2-sided 95% CL displayed in odds ratio scale.”. 
• 
Include all observed data for Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.2.8.1 
Patient Global Impression of Change: Summary Statistics 
mITT Population 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   Number of PGIC Responders 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Very Much Improved   
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Much Improved 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Minimally Improved 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      No change 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Minimally Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Much Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Very Much Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 8 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group; PGIC = Patient Global Impression of Change. 
Note: Percentages for Number of subjects in the different improvement categories relative to baseline are n/Number of Subject s by treatment group at each 
visit *100. 
 
Reference Listing: 16.2.6.6 
 
Programming notes: 
• 
Include all observed data on PGIC scores for Week 4, 8, 12 and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.8.2 
Patient Global Impression of Change: Cochran-Mantel Haenszel  
mITT Population 
 
Cochran-Mantel-Haenszel Test: MEDI7352 xxx μg/kg vs Placebo 
Visit/ 
    Category 
Number of  
Patients (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Placebo, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Placebo, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 8 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Placebo, Week 12 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
 
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Placebo, Week 18 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata of MEDI7352 dose - Placebo. 
[2] P-value < 0.05 indicates a significant association between improvement relative to Baseline and treatment across strata. 
Note: median Baseline Pain NRS was calculated from subjects having valid NRS data on at least one of the above four post-baseline visits. Note: a separate 
CMH test is performed for each dose versus placebo. 
Reference Listing: 16.2.6.6 
 
Programming Notes: 
• 
Include all observed data on PGIC scores for Week 4, 8, 12 and 18. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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5. 
Exploratory Efficacy Analyses 
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6. 
Safety and Tolerability 
6.1. 
Displays of Adverse Events 
Table 14.3.1.1 
Summary of Overall Adverse Events  
Safety Population 
 
 
Placebo 
MEDI7352 
Total 
Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with any AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE possibly related 
to IP [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE leading to 
Discontinuation of IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE related to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Mild related to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Moderate related 
to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Severe related to 
IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE leading to Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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AE = adverse event; IP = Investigational product, N = number of subjects per treatment group; SAE = serious adverse event; TEAE = treatment emergent 
adverse event. 
[1] Possibly related is defined as with reasonable possibility that the AE was caused by the IP, as assessed by investigator. 
Note: Subjects who reported more than one adverse event within each category were only counted once. A TEAE is defined as an adverse event with an onset 
at the time of or following the start of treatment with IP. For TEAEs categorized by severity, subjects were counted at the maximum severity. 
Reference Listing: 16.2.7.1, 16.2.7.2, 16.2.7.3, 16.2.7.4 
 
Programming Notes: 
• 
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Table 14.3.1.2 
Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
Placebo 
MEDI7352 
Total 
    Preferred Term 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
All MEDI7352 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each SOC/PT 
category; N = number of subjects per treatment group; IP = investigational product; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-
emergent adverse event. 
Note: Results are n (n/N * 100) m is number of events.  
A TEAE is defined as AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT.  
AEs are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency.  
Reference Listing: 16.2.7.1 
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• 
SOC and PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. 
• 
A column for 
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) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.3 
Treatment Emergent Adverse Events by Severity, System Organ Class and Preferred Term 
Safety Population 
System Organ Class 
 
 
 
 
 
 
   Preferred Term 
Placebo 
MEDI7352 
Total 
      Severity 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Subjects with at Least One TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
   Preferred Term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each 
SOC/PT/Severity category; N = number of subjects per treatment group; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-emergent 
adverse event. 
Note: Results are n (n/N * 100).  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT at the maximum severity.  
AEs are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency. 
Reference Listing 16.2.7.1 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Present only severity categories with at least one subject. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.4 
Treatment Emergent Adverse Events by Relationship to Study Medication, System Organ Class and Preferred Term  
Safety Population 
System Organ Class 
 
 
 
 
 
 
   Preferred Term 
Placebo 
MEDI7352 
Total 
      Relatedness 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Subjects with at Least One TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
   Preferred Term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each 
SOC/PT/Relatedness category; N = number of subjects per treatment group; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-emergent 
adverse event. 
[1] Related is defined as reasonable possibility that the AE was caused by investigational product, as assessed by the investigator. If investigator's assessment 
is missing the event is judged as related. 
Note: Results are n (n/N *100).  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT for the most related AE.  
AEs are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency. 
Reference Listing 16.2.7.1 
 
 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Present only severity categories with at least one subject. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.5 
Treatment Emergent Adverse Events by ADA Status Category, System Organ Class and Preferred Term 
Safety Population 
Treatment: xxxxxxx 
 
 
 
 
 
System Organ Class 
ADA 
Negative  
ADA Positive 
TE-ADA + 
Non-TE-
ADA + 
TE 
Persistently 
ADA + 
TE 
Transiently 
ADA + 
Post-Baseline 
and Baseline 
Positive 
Only Baseline 
Positive 
    Preferred Term 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
 
 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 3 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
 
AE = adverse event; ADA = Anti-Drug Antibodies; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of 
subjects within each SOC/PT category; N = number of subjects per ADA status category; PT = Preferred Term; SOC = System Organ Class; TE-ADA + = 
Treatment emergent ADA positive; TEAE = treatment-emergent adverse event. 
ADA categories are defined in the Statistical Analysis Plan. 
Note: Results are n (n/N *100) m is number of events.  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT.  
Table is sorted by international order for SOC, and alphabetically for PT. 
Reference Listing: 16.2.7.1 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Repeat for Placebo, 
 and Overall. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A table for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.1.6 
Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by System Organ Class and Preferred Term  
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One TEAE leading to IP discontinuation”. 
• 
Update Reference Listing to 16.2.7.2. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.1.7 
Non-Serious Adverse Events Occurring in More than 5% of Subjects by System Organ Class and Preferred Term  
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One Non-Serious TEAEAE”. 
• 
Update footnote adding: “The 5% threshold for an AE to be displayed is taken from the Total column.” 
• 
Update Reference Listing  to 16.2.7.1. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
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Table 14.3.1.8 
Treatment Emergent Adverse Events Occurring in More than 5% of Subjects by Preferred Term   
Safety Population 
 
Placebo 
MEDI7352 
Total 
    Preferred Term 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
All MEDI7352 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
… 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each PT category; 
N = number of subjects per treatment group; PT = Preferred Term; TEAE = treatment-emergent adverse event. 
Note: Results are n (n/Number of subjects in the Safety population within each PT*100) m is number of events.  
A TEAE is defined as AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each PT.  
AEs are displayed by descending frequency of PT based on ‘All MEDI7352’ column, and alphabetically for PT of same frequency.  
The 5% threshold for a TEAE to be displayed is taken from the Total column. 
Reference Listing: 16.2.7.1 
 
Programming Notes: 
• 
PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as “Not Coded [PT]” and sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.3.1.9 
Treatment Emergent Adverse Events by Preferred Term  
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.8. 
• 
Display all TEAEs, not only the most common. 
• 
PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as Not Coded [PT]”, and sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.2. 
Summary of Deaths and Other Serious Adverse Events 
 
Table 14.3.2.1.1 
Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One Treatment Emergent SAE”, add “SAE = Serious Adverse 
Event” to abbreviations. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
Table 14.3.2.1.2 
Life-Threatening Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One Life-Threatening SAE”, add “SAE = Serious Adverse 
Event” to abbreviations. 
• 
Add “Note: Life-threatening SAEs as judged by the investigator”. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated  
 
 
 
 
 
 
 
 
 
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Table 14.3.2.1.3 
Serious Adverse Events with Outcome Death by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One SAE with Outcome Death”, add “SAE = Serious Adverse 
Event” to abbreviations. 
• 
Change footnote for “Reference Table 14.3.3.2”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated . 
 
 
 
 
Table 14.3.2.1.4 
Serious Adverse Events by Relationship to Study Medication, System Organ Class and Preferred Term  
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.4. Change first row to be “Number of subjects with at Least One Treatment Emergent SAE”, add “SAE = Serious Adverse 
Event” to abbreviations. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.3.1 
Listing of Serious Adverse Events 
Safety Population 
Subject ID/ 
Treatment Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
AE Start Date/Time 
(Study Day)/ 
   End Date/Time (Study 
Day) 
Severity/ 
   Relationship [1] 
Outcome/ 
  Action Taken with IP/ 
    Therapy taken for this AE? 
 
SAE 
Leading 
to Study 
DC? 
TEAE? 
Serious? /
Serious 
Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:M
M (X)/ 
DDMMMYYYY/HH:M
M (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
     XXXXXXXXXX/ 
                         Yes 
No 
No  
XX 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXXXX 
 
DDMMMYYYY/HH:M
M (X)/ 
DDMONYYYY/HH:
MM (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
   XXXXXXXXXX/ 
                        No 
Yes 
XX 
XX / 
XXX 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMONYYYY/HH:M
M (X)/ 
   Ongoing 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXXXX/No 
No 
XX 
XX / 
XXX 
 
DC = discontinuation; ID = identification; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; SAE = serious adverse event; 
TEAE = treatment emergent adverse event. 
[1] Reasonable possibility AE caused by IP as assessed by the investigator. 
Note: Study Day = date of interest – date of first infusion. A TEAE is defined as an adverse event with an onset at the time of or following the start of treatment 
with IP. 
SAEs were coded using MedDRA version 26.0 
 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e, no AEs occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment ID/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g.. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.3.2 
Listing of Deaths 
Safety Population 
Subject ID/ 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date/Time 
(Study Day)/ 
   End Date/Time 
(Study Day) 
Severity/ 
   Relationship 
Outcome/ 
      Action Taken/ 
           Therapy? 
AE 
Leading 
to IP DC? TEAE?  
Serious? / 
 Serious 
 Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/H
H:MM (X)/ 
   
DDMMMYYYY/H
H:MM (X) 
XXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
  XXXXXXXXXX/ 
                     Yes 
No 
No  
XX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXXXX 
 
DDMMMYYYY/H
H:MM (X)/ 
   
DDMMMYYYY/H
H:MM (X) 
XXXXXXXX/ 
XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXXX/No 
Yes 
XX 
XX / XXX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMMMYYYY/H
H:MM (X)/ 
   Ongoing 
XXXXXXXX/ 
XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXX/ 
                No 
No 
XX 
XX / XXX 
 
DC = discontinuation; ID = identification; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; TEAE = treatment emergent 
adverse event. 
Note: Study Day = date of interest – date of first infusion. A TEAE is defined as an adverse event with an onset at the time of or following the start of treatment 
with IP. 
AEs were coded using MedDRA version 26.0 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e, no Aes occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.3. 
Displays of Significant Adverse Events and Adverse Events of Special Interest 
 
 
Table 14.3.2.2.1 
Treatment Emergent Adverse Events Associated with Abnormal Liver by System Organ Class and Preferred Term  
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at least One TEAE Associated with Abnormal Liver”. 
• 
Update Reference Listing to 16.2.7.3. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
Table 14.3.2.2.2 
Potential joint Related Adverse Events of Special Interest by System Organ Class and Preferred Term  
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at least One Potential Joint Related AESI” 
• 
Add abbreviation for AESI = Adverse Event of Special Interest. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.4 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
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Table 14.3.2.2.3 
Serious and/or severe Infections by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One SAE or Severe AE Related to Infection”. Add “SAE = Serious Adverse 
Event” to abbreviations. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.5. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.2.2.4 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of IP by System Organ Class and Preferred Term 
Safety Population 
System Organ Class 
Placebo 
MEDI7352 
Total 
    Preferred Term 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
All MEDI7352 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
 
 
 
 
 
 
 
Subjects with at Least 
One Anaphylactic 
Reaction, 
Hypersensitivity or 
Infusion-Related 
Reactions Leading to 
Discontinuation of IP 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Subjects with at Least 
One Anaphylactic 
Reaction, 
Hypersensitivity or 
Infusion-Related 
Reactions Not Leading to 
Discontinuation of IP [1] 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each SOC/PT 
category; N = number of subjects per treatment group; IP = investigational product; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-
emergent adverse event. 
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[1] Anaphylactic reactions, hypersensitivity or infusion-related reactions not leading to discontinuation of IP were included in table as they were categorized as 
AE of special interest under Protocol Amendment 4 (V5.0). Definition for AE of special interest changed from Amendment 6 (V6.0) onwards, including 
anaphylactic reactions, hypersensitivity or infusion-related reactions leading to permanent discontinuation of IP.. 
Note: Results are n (n/N * 100) m is number of events.  
A TEAE is defined as AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT.  
AEs are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency.  
Reference Listing: 16.2.7.6 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One Anaphylactic Reaction, Hypersensitivity or Infusion-Related Reactions 
Leading to Discontinuation of IP”. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.6. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.4. 
Laboratory Data 
 
Table 14.3.4.1 
Descriptive Summary of Clinical Chemistry 
Safety Population 
Parameter: xxxxx (unit) 
Visit/ 
    Statistic 
Placebo 
MEDI7352 
 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
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Day 1 CFB 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically Significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects 
per treatment group; NCS = not clinically significant; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages are n/Number of subjects with not missing data by treatment group at each visit*100.  
Reference Listing: 16.2.8.1 
 
Programming Notes: 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Albumin, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), 
Bicarbonate, Calcium, Chloride, Creatinine, High-Sensitivity C-Reactive Protein (hs-CRP), Estimated Glomerular Filtration Rate (eGFR by Cockcroft - 
Gault), Serum Glucose, Lactate Dehydrogenase (LDH), Potassium, Sodium, Total Bilirubin, Total Protein, Blood Urea Nitrogen (BUN), Uric Acid. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.2 
Shift Table of Clinical Chemistry Results 
Safety Population 
Parameter (Unit)/ 
    Visit  
        Post-Baseline 
        Grade    
Baseline Grade [1] 
Placebo 
 (N=xxx) 
MEDI7352, 5 µg/kg 
 (N=xxx) 
Low 
Normal 
High 
Missing 
Total 
Low 
Normal 
High 
Missing 
Total 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX (Unit) 
 
 
 
 
 
 
 
 
 
 
    Week x 
 
 
 
 
 
 
 
 
 
 
        Low 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        High 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Missing 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Total 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     Week x 
 
 
 
 
 
 
 
 
 
 
        Low 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        High 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Missing 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Total 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects within each category; N = number of subjects per treatment group. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Percentages are n/Number of subjects by treatment group at each visit for the parameter*100. 
Reference Listing 16.2.8.1 
Programming Notes: 
• 
Repeat above in new pages for MEDI7352, 
 MEDI7352, 
 and All MEDI7352. 
• 
Repeat the above for 
 dosing only if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.4.1. 
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Table 14.3.4.3 
Descriptive Summary of Hematology 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.1 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Absolute basophil count, absolute eosinophil count, absolute lymphocytes count, Absolute Monocyte Count, 
Absolute Neutrophil Count, Basophils %, Eosinophils %, Hematocrit (HCT), Hemoglobin (HGB), hemoglobin A1C (HgbA1C), Lymphocytes %, mean 
corpuscular hemoglobin (MHC), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), Monocytes %, Neutrophils 
%, Platelets, Red blood cell count (RBC), Red Cell Distribution Width, white blood cell Count (WBC). 
• 
Update Reference listing to 16.2.8.2. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.4.4 
Shift Table of Hematology Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.2 
• 
Repeat the shell for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.4.3. 
• 
Update Reference listing to 16.2.8.2 
 
 
 
 
 
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Table 14.3.4.5 
Descriptive Summary of Coagulation 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.1 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Activated Partial Thromboplastin Clotting Time (APTT), Fibrinogen, International normalized ratio (INR), 
Prothrombin Time (PT). 
• 
Update Reference listing to 16.2.8.3. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.4.6 
Shift Table of Coagulation Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.2 
• 
Repeat for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.4.5. 
• 
Update Reference listing to 16.2.8.3. 
 
 
 
 
 
 
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Table 14.3.4.7 
Descriptive Summary of Urinalysis 
Safety Population 
Parameter: xxxxx (unit) 
Visit/ 
    Statistic 
Placebo 
MEDI7352 
 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 CFB 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
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… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for all visits for Parameters: Specific 
Gravity and pH 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
       n 
xx 
xx 
xx 
xx 
xx 
xx 
       Negative 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
       Positive 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
If Positive, Specify [2] 
 
 
 
 
 
 
   100 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   250 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   500 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   >= 1000 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
       n 
xx 
xx 
xx 
xx 
xx 
xx 
       Negative 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
       Positive 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for all visits for Parameters: Blood, 
Glucose, Ketones and Protein 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects 
per treatment group; NCS = not clinically significant; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
[2] Percentages are n/Number of Subjects with a Positive Result*100. 
Note: Percentages are n/Number of subjects with not missing data by treatment group at each visit*100.  
Reference Listing: 16.2.8.4 
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Programming Notes: 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Blood Urine, Glucose, Ketones, pH, Protein, Specific Gravity. 
• 
Categories for If Positive, Specify: 
o Blood, Urine: Trace, Small, Moderate. 
o Glucose: 100 mg/dL, 250 mg/dL, 500 mg/dL, >= 1000 mg/dL. 
o Ketones: Trace, 15 mg/dL, 40 mg/dL. 
o Protein: Trace, 30 mg/dL, 100 mg/dL, 300 mg/dL. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.8 
Shift Table of Urinalysis Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.2 
• 
Repeat for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit.  
• 
Present parameters in the same order as in Table 14.3.4.7. 
• 
Update Reference listing to 16.2.8.4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.9 
Maximum On-Treatment ALT and AST versus Maximum On-Treatment Total Bilirubin 
Safety Population 
 
  
  
  
Total Bilirubin 
 
 
 
<2 x ULN 
>=2 x ULN 
Group 
Nobs 
 
n (%) 
n (%) 
Placebo 
 
  
  
  
N=xxx 
xxx 
ALT 
 
 
 
 
<3 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=3 - <5 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=5 - <10 x ULN 
0 
0 
 
 
>=10 x ULN 
0 
0 
 
 
 
 
 
xxx 
AST 
 
 
 
 
<3 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=3 - <5 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=5 - <10 x ULN 
0 
0 
 
 
>=10 x ULN 
0 
0 
… 
 
 
 
 
Repeat for: 
 All MEDI7352 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; IP = investigational product; n = number of subjects per category; N = number of 
subjects per treatment group; Nobs = number of subjects per treatment group with at least one post-baseline assessment on treatment; ULN = upper limit of 
normal.  
Note: On-treatment assessments include assessments on or after the date of first dose of IP. Baseline is defined as the last observation recorded prior to the 
first dose of treatment. 
Percentages are based on Nobs. 
Reference Listing: 16.2.8.1 
 
 
 
 
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Programming Notes: 
• 
Per Protocol, the elevations of ALT or AST and Total Bilirubin do not have to occur at the same time or within a specified time frame. That is the reason 
why the table is presented by Subject instead of by visit. So, if for example, one subject has ALT >=3 - <5 x ULN at Day 1, and TBL >=2 x ULN at 
Week 18, n in that cell will increase by one. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.5. 
Other Safety Data  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.1 
Descriptive Summary of Vital Signs 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 15 Minutes Post-
Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 15 Minutes Post-
Dose CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
CFB = Change from Baseline; eCRF = Electronic Case Report Form; n = number of subjects by treatment group at each visit for the parameter; N = number 
of subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Note: ‘Day 1: 5 minutes after Infusion Completion’ time point was only applied to subjects enrolled in Stage 1, with data collected under eCRF versions 4.0 
(11DEC2018) or older.  
Reference Listing: 16.2.9.1 
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Programming Notes: 
• 
Repeat for Supine Heart Rate, Supine Systolic Blood Pressure, Supine Diastolic Blood Pressure, Respiratory Rate, Body Temperature, Standing Heart 
Rate, Standing Systolic Blood Pressure, Standing Diastolic Blood Pressure. 
• 
After Week 2 (inclusive), Supine measure are taken in sitting position. We will consider them as supine (in resting position) for calculating Change from 
Baseline (always at supine position). 
• 
Include the following timepoints: Baseline, Day 1: 5 Minutes Post-Dose, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 
Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion 
Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 
8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, 
Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Note that Body Tº, and standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.2 
Descriptive Summary of Digital ECG Data 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group ; SD = 
standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are averages of the 3 replicates taken for each parameter and timepoint, and CFB for the same variables.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.9.2.1 
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Programming Notes: 
• 
Repeat for PR, QRS, QT, RR, HR (Heart Rate) and QTcF taken from external data. 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, Week 12, 
and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.3 
Summary of Overall Evaluation of Safety ECG Data 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NCS = Not 
clinically significant. 
Note: Data are taken as the most conservative from the 3 replicates taken by timepoint. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.9.2.2 
 
 
Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, Week 12, 
and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
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Table 14.3.5.4 
Covid-19 Screening 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
Subjects Screened for COVID-19 Symptoms 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
COVID-19 Symptoms Screened: 
 
 
 
 
 
 
   Fever 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sore Throat 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Loss of Taste 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Loss of Smell 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Body Temperature Check 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Subjects with COVID-19 Swab Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with COVID-19 Antibody Testing 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Confirmed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Suspected 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Subjects with COVID-19 Antigen Testing 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment 
group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Percentages are n/Number of subjects by treatment group at each visit*100. 
Reference Listing: 16.2.8.8 
 
 
Programming Notes: 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.5 
Summary of Sub-Scores for Total Neuropathy Score-Nurse 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
Subjects performing TNSn 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Sensory Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Motor Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Autonomic Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Pin Sensibility Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
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Vibration Sensibility Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 xx (xx.x%) 
 xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 N = number of subjects per treatment group; TNSn = Total Neuropathy Score-Nurse.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages for subjects performing TNSn are n/Number of subjects by treatment group at each visit*100. Percentages for each Score are n/Number of 
subjects by treatment group at each visit without missing score*100 
Reference Listing: 16.2.9.5 
 
Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12 and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.6 
Descriptive Summary of Total Neuropathy Score-Nurse 
Safety Population 
Score: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1 CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
TNSn = Total Neuropathy Score-Nurse; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment 
group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. Reference Listing: 16.2.9.5 
Programming Notes: 
- Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12 and Week 18.  
- Include the following scores: Sensory Symptom Score, Motor Symptom Score, Autonomic Symptom Score, Pin Sensibility Score, Vibration Sensibility Score, 
and TNSn Total. 
- A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.3.5.7 
Summary of Motor and Sensory Nerve Conduction Studies 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Week 18 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Week 18 CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Evaluation Result 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abnormal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Week 18 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abnormal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group;  SD = 
standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages are number of subjects by treatment group at each visit for each category /Number of subjects with not missing data by treatment group for 
each visit*100 
Reference Listing: 16.2.9.6 
 
Programming Notes: 
• 
Repeat for the following Parameters: Lower Limb - right side/Motor evaluation/Amplitude, Lower Limb - right side/Sensory evaluation/Amplitude, 
Lower Limb - left side/ Motor evaluation/Amplitude, Lower Limb - left side/ Sensory evaluation/Amplitude, Upper Limb - right side /Motor 
evaluation/Amplitude, Upper Limb - right side/ Sensory evaluation/Amplitude, Upper Limb - left side/ Motor evaluation/Amplitude, Upper Limb - left 
side /Sensory evaluation/Amplitude. (Repeat the same combination of Location - Laterality/Evaluation for Peak Latency, Conduction Velocity, 
Duration of action Potential). 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
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Table 14.3.5.8 
Summary of Strength and Deep Tendon Reflexes 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
Subjects performing SDTR assessment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Ankle Dorsiflexion Strength 
 
 
 
 
 
 
   0 - Normal Power 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 - Mild Weakness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 - Moderate Weakness   
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 - Severe Weakness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 - Paralysis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Deep Tendon Reflexes 
 
 
 
 
 
 
   0 - Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 - Ankle reflex reduced 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 - Ankle reflex absent 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 - Ankle reflex absent and knee reflex 
reduced 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 - All reflexes (both ankle and knee) 
absent 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects by treatment group at each visit for each category; N = number of subjects per treatment group; SDTR = strength and deep tendon 
reflexes. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages for each Score are n/Number of subjects by treatment group at each visit*100  
Reference Listing: 16.2.9.7 
Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12, and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
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Table 14.3.5.9 
Summary of Local Injection Site Reactions 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
       Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Day 1: 15 Minutes after 
Start of Infusion 
 
 
 
 
 
 
    Subjects with injection 
Site Assessed  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Pain 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Tenderness 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Erythema/ Redness 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
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Induration/ Swelling 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects by treatment group at each visit for each category; N = number of subjects per treatment group. 
Note: Percentages for each Score are n/Number of subjects by treatment group at each visit*100  
Reference Listing: 16.2.9.8 
 
Programming Notes: 
• 
Include the following timepoints: Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour Post-Dose, 
Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12, and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.10 
Summary of Hypersensitivity/Anaphylactic Reactions 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with any 
Hypersensitivity/   
Anaphylaxis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Highest Severity Grade 
 
 
 
 
 
 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Type of Reaction 
 
 
 
 
 
 
   Urticaria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pruritus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Flushing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Swollen Lips, Tongue, 
Uvula and/or Vulva 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Wheeze-Bronchospasm 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Stridor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hypoxia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hypotension 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Crampy Abdominal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Diarrhoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.9 
 
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Programming Notes: 
• 
Display only Type of reaction with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.11 
Summary of Liver Diagnostic Investigations 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Diagnostics 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Type of Diagnostic Investigation 
 
 
 
 
 
 
   Ultrasound 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   CT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   MRI/MRCP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Flushing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   ERCP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   X-Ray 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening for 
Acetaminophen/Paracetamol 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening for Ethanol 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening, Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Specialist Consulted 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis A 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis B 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis C 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis D 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis E 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Serology for Cytomegalovirus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Epstein Barr Virus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Autoimmune Serology 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT = Computerized tomography; ERCP = Endoscopic retrograde cholangiopancreatography; MRI = Magnetic resonance imaging; MRCP = Magnetic 
resonance cholangiopancreatography; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.10 
 
 
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Programming Notes: 
• 
Display only Diagnostic Investigations with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.12 
Summary of Liver Risk Factors and Lifestyle Events 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Risk Factors 
Assessed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Liver Risk Factor 
 
 
 
 
 
 
   Alcohol Abuse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Increased Alcohol Consumption    
within 1 Month of Reported Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   IV Drug Abuse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tattoo 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Acupuncture 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sexually Transmitted Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Toxic/Chemical Agent Exposure 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Travel (Areas at Risk in the Last Year) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pregnancy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Parenteral Nutrition 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Excessive Physical Exercise 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Changes Diet/Fasting Episodes/Weight 
Loss Diet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Previous Drug Reaction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Blood Transfusion 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Patient Exposed to Anyone with 
Jaundice in the Last Month 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   History of Hypotension 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
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   Low Blood Pressure at Time of Event 
of Liver Injury and/or Abnormal Liver 
Laboratory Value 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   History of Liver Disease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV = intravenous; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.10 
 
 
 
Programming Notes: 
• 
Display only Liver Risk Factor with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.13 
Summary of Liver Signs and Symptoms 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Signs/Symptoms 
Assessed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Liver Sign/Symptom 
 
 
 
 
 
 
   Anorexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Asthenia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pyrexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pruritus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Jaundice  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Arthralgia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abdominal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abdominal Tenderness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Nausea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mucosal Inflammation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Purpura 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hepatomegaly 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Splenomegaly 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Lymphadenopathy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ascites 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Confusional State 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Coma 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Upper Quadrant Tenderness 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Biliary Obstruction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Eosinophilia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dark Urine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.12 
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• 
Display only Liver Signs/Symptoms with non-missing value. 
• 
A column for 
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) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.14 
Summary of Infection Diagnostic Investigations 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Diagnostic 
Investigations 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Method 
 
 
 
 
 
 
   Microscopy, Culture and Sensitivity 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serological Tests 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Nucleic Acid Based Tests 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   X-Ray 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.13 
 
 
 
Programming Notes: 
• 
Display only Methods with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.15 
Summary of Infection Risk Factors and Lifestyle Events 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Risk Factor Occurred 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Infection risk factor 
 
 
 
 
 
 
   Extensive Burns within the Last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tattoo, Piercing or Acupuncture within the 
last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sexually Transmitted Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Travel to Areas at Risk of Tuberculosis or 
Tropical Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Infections Related to Travel 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Blood Transfusion (within the Last Year) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Exposure to Nosocomial Pathogens within the 
Last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Contact History with Infection Source 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Previous BCG Immunization 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evidence of BCG Scar 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tuberculin Skin or Quantiferon Test Confirms 
     Previous Exposure or Immunity to 
Tuberculosis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
BCG = Bacillus Calmette-Guerin; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.14 
Programming Notes: 
• 
Display only infection risk factors with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.3.5.16 
Summary of Infection Signs and Symptoms 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Sign/Symptom 
Occurred 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Infection Sign/Symptoms 
 
 
 
 
 
 
   Pyrexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Headache 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Confusional State 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Convulsion 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rhinitis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Oropharyngeal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Productive Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Haemoptysis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Wheezing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pleuritic Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Diarrhoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Genital Discharge 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Haematuria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dysuria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hepatosplenomegaly 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Jaundice 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lymphadenopathy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
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   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Petechial 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Vesicular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Macular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Papular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Urticaria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Erythema 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Blanching 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Splinter Haemorrhages 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Night sweats 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Chills 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Myalgia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Weight Decrease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.15 
 
 
Programming Notes: 
• 
Display only infection Signs/Symptoms with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.17 
Summary of Concomitant Medications by ATC Level 2 and Preferred Name 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.1.7. 
• 
Change footnote Note by: “Note: Concomitant medications are defined as medications continuing or starting on or after first dose of study medication. 
All concomitant medications are coded using WHO drug dictionary version vMar2023. At each level of summarization (ATC Level 2 or Preferred 
Name), subjects who reported more than one concomitant medication were only counted once. ATC Level 2 and Preferred Name are sorted in in 
descending order of frequency of total, and alphabetically if same frequency”. 
• 
If uncoded ATC Level or Preferred Name, please put them as [Not Coded] 
• 
ATC and Preferred Name texts should be in proper case in table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.18 
Summary of Concomitant Procedures 
Safety Population 
System Organ Class 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xxx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xxx) 
 
 
 
 
 
 
Any Concomitant Procedure 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   … 
… 
… 
… 
… 
… 
 
 
 
 
 
 
System Organ Class n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
N = number of subjects per treatment group; PT = Preferred Term; SOC = System Organ Class. 
Note: All Procedure terms were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 2 6.0. At each level of summarization 
(system organ class or preferred term), subjects having more than one Procedure term were counted only once. System organ class and preferred terms are 
sorted in descending order of frequency of Total column, and alphabetically if same frequency. 
When there are uncoded Procedure Events in the database, the events will be summarized with SOC and PT set to [Not Coded]. The [Not Coded] are sorted at 
the end of the table. 
 
Reference Listing: 16.2.9.18 
 
Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Sort SOC and PT (within SOC) in descending order of frequency in the Total column.  Sort alphabetically in case of ties. 
• 
Uncoded Procedure events 
o When there are uncoded Procedure Events in the database, the events will be summarized with SOC and PT set to [Not Coded]. The [Not 
Coded] will be sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
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Table 14.3.5.19 
Anti-Drug Antibody Results and Titre Summary by Timepoint 
Safety Population 
 
Placebo 
MEDI7352 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n [2] 
xx 
xx 
xx 
xx 
xx 
ADA Positive: n (%) [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
   n [2] 
xx 
xx 
xx 
xx 
xx 
ADA Positive: n (%) [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
… 
 
 
 
 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
[2] Number of subjects with at least one ADA assessment at the specific visit. 
[3] Number of subjects with a positive result at the specific visit. The denominator for all percentages is the number of subjects with an ADA result for each 
visit. 
Reference Listing: 16.2.9.19 
Programming Notes: 
• 
Keep in mind that in this table ‘Total’ column does not include placebo. 
• 
Repeat for all scheduled post-baseline visits. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.3.5.20 
Descriptive Summary of Anti-Drug Antibody Results and Titre by ADA Categories  
Safety Population 
 
Placebo 
MEDI7352 
ADA Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
 
 
 
 
 
ADA positive at baseline and/or post-baseline (ADA 
prevalence) 
 
 
 
 
 
   n/Nobs (%) [1] [2] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
TE-ADA positive (ADA incidence) [5] 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Treatment Induced ADA Positive 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
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Treatment-Boosted ADA Positive 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Non-TE-ADA Positive [6] 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Both baseline and post-baseline positive 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Only baseline positive 
 
 
 
 
 
   n/Nobs (%) [1] [4] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
TE-persistently ADA positive [7] 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
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TE-transiently ADA positive [8] 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; N = number of subjects per treatment group; TE-ADA = Treatment Emergent ADA; SD = standard deviation; Q1 = first 
quartile; Q3 = third quartile. 
[1] n represents the number of subjects satisfying the conditions of the specified ADA category  
[2] Nobs represents the number of subjects with any ADA result at baseline and/or post-baseline. 
[3] Nobs represents the number of subjects with an ADA result at baseline and at least one post-baseline ADA assessment. 
[4] Nobs represents the number of subjects with an ADA result at baseline. 
[5] TE-ADA positive is defined as either ADA negative at baseline and post-baseline ADA positive (Treatment Induced ADA Positive), or as ADA positive at 
baseline with pre-existing titre boosted by 4-fold or greater during the study period (Treatment Induced ADA Positive). ADA incidence is the proportion of 
TE-ADA+ subjects in a population. 
[6] ADA post-baseline positive but not fulfilling the conditions for TE-ADA+ 
[7] ADA negative at baseline and having at least 2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between first and last positive, or an 
ADA positive result at the last available post-baseline assessment. 
[8] ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. 
Reference Listing: 16.2.9.19 
 
 
Programming Notes: 
• 
If a participant has more than 1 non-missing titre during the study, the maximum titre for each participant is summarized. 
• 
Only present summary statistics if titre is available. 
• 
If no positive results for a particular block of the table, then the summary statistics for the titres for that particular block would not appear. 
• 
It is assumed that participants with a missing baseline ADA result are ADA negative at baseline. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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7. 
Pharmacokinetic/Pharmacodynamic Data  
Table 14.4.1 
Summary of Serum MEDI7352 Concentrations 
PK Population 
ADA Status: xxxxxxxxxx 
 
 
MEDI7352 
Visit/ 
    Statistic 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
Baseline [1] 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
   gCV% 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Week 2 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
   gCV% 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Week 4 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
   gCV% 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
… 
 
 
 
gCV% = Geometric Coefficient of Variation (%); gMean = Geometric Mean; gSD = Geometric SD; LLOQ = Lower Limit of Quantification; n = number of 
subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NC =not calculable; NQ = not quantifiable. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.10.1 
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Programming Notes: 
• 
Include the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 
10: 8 Hours after Infusion, Week 10 + 24 hours/ Pre-Dose, Week 11/ Pre-Dose, Week 10 + 14 Days/Pre-Dose; Week 18. 
• 
Repeat the table for ‘ADA Positive’, ‘ADA Negative’ and ‘Overall'. 
• 
Any values reported as NRR (not reportable) or NS (missing) will be excluded from the summary tables. 
• 
At a time point where less than or equal to 50% of the concentration values are NQ (below LLOQ), all NQ values will be set to the LLOQ, and all 
descriptive statistics will be calculated accordingly. 
• 
At a time point where more than 50% (but not all) of the values are NQ, the gmean, gmean ± gSD and gCV% will be set to NC. Th e maximum value 
will be reported from the individual data, and the minimum and median will be set to NQ. 
• 
If all concentrations are NQ at a time point, no descriptive statistics will be calculated for that time point. The gmean, minimum, median and maximum 
will be reported as NQ and the gCV% and gmean ± gSD as NC. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.4.2 
Summary of Serum total NGF Concentrations 
Safety Population 
ADA Status: xxxxxxxxxx 
 
 
 
Placebo 
MEDI7352 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
Baseline [1] 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Week 2 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Week 4 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
… 
 
 
 
 
 
 
 
 
 
gCV% = Geometric Coefficient of Variation (%); gMean = Geometric Mean; gSD = Geometric SD; LLOQ = Lower Limit of Quantification;  n = number of 
subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; ; NC =not calculable; NGF = Nerve-Growth Factor; 
NQ = not quantifiable. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Reference Listing: 16.2.10.3 
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Programming Notes: 
• 
Repeat for ADA Status: “ADA Positive”, “ADA Negative” and “Overall”.  
• 
Include the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 
10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Planned Listing Descriptions and Shells 
Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
Listing 16.2.1.1 - Subject Disposition - Screening Population 
U 
Listing 16.2.1.2 - Assignment to Analysis Populations - Screening Population 
U 
Listing 16.2.1.3 - Reason for IP Discontinuation and Withdrawal from the Study - Safety Population 
U 
Listing 16.2.1.4 - List of Reasons for Screening Failure - Screen Failure Population 
U 
Listing 16.2.1.5 - Subject Visits and COVID-19 Impact - Screening Population 
U 
Listing 16.2.2.1 - Subjects Not Meeting All Inclusion Criteria or Meeting any Exclusion Criteria  - Screening Population 
U 
Listing 16.2.2.2 - Protocol Deviations - Safety Population Error! Reference source not found.Error! Reference source not found.Error! 
Reference source not found.Error! Reference source not found.Error! Reference source not found. 
U 
Listing 16.2.3 - Randomization and Treatment Group - Safety Population Error! Reference source not found.Error! Reference source 
not found.Error! Reference source not found.Error! Reference source not found.Error! Reference source not found. 
U 
Listing 16.2.4.1 - Demographic and Baseline Characteristics - Screening Population 
U 
Listing 16.2.4.2 - Medical History - Safety Population 
U 
Listing 16.2.4.3 - Osteoarthritis Characteristics - Screening Population 
U 
Listing 16.2.5.1 - Study Drug Administration: Individual Doses - Safety Population 
U 
Listing 16.2.6.1 - Daily Pain NRS - mITT Population 
U 
Listing 16.2.6.2 - Error! Reference source not found. Galer NPS - mITT Population 
U 
Listing 16.2.6.3 - DSIS - mITT Population 
U 
Listing 16.2.6.4 - SF-36 - mITT Population 
U 
Listing 16.2.6.5 - Rescue Medication Usage - mITT Population 
R 
Listing 16.2.6.6 - Patient Global Impression of Change - mITT Population 
U 
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Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
 
U 
Listing 16.2.7.1 - Adverse Events - Safety Population 
U 
Listing 16.2.7.2 - Treatment Emergent Adverse Events Leading to Study Drug DiscontinuationError! Reference source not found. - Safety 
Population 
R 
Listing 16.2.7.3 - Treatment Emergent Adverse Events Associated with Abnormal Liver - Safety Population 
R 
Listing 16.2.7.4 - Joint Related Adverse Events of Special Interest - Safety Population 
R 
Listing 16.2.7.5 - Serious and/or Severe Infections - Safety Population 
R 
Listing 16.2.7.6 - Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of Study Drug - Safety Population 
R 
Listing 16.2.8.1 - Clinical Chemistry Laboratory Evaluations - Safety Population 
U 
Listing 16.2.8.2 - Hematology Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.3 - Coagulation Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.4 - Urinalysis Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.5 - Serology Laboratory Evaluations - Safety Population 
U 
Listing 16.2.8.6 - Pregnancy Test Results - Safety Population 
U 
Listing 16.2.8.7 - Drug Test Results - Safety Population 
U 
Listing 16.2.8.8 - COVID-19 Screening and Vaccination - Safety Population 
U 
Listing 16.2.9.1 - Vital Signs Measurements - Safety Population 
U 
Listing 16.2.9.2.1 - 12-Lead Digital ECG Results - Safety Population  
U 
Listing 16.2.9.2.2 - 12-Lead Safety ECG Results - Safety Population 
U 
Listing 16.2.9.3 - Physical Examination Results - Safety Population 
U 
Listing 16.2.9.4 - Neurological Examination Results - Safety Population 
U 
Listing 16.2.9.5 - Total Neuropathy Score-Nurse - Safety Population 
U 
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Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
Listing 16.2.9.6 - Motor and Sensory Nerve Conduction Studies - Safety Population 
U 
Listing 16.2.9.7 - Strength and Deep Tendon Reflexes - Safety Population 
U 
Listing 16.2.9.8 - Injection Site Reactions - Safety Population 
U 
Listing 16.2.9.9 - Hypersensitivity/Anaphylactic Reactions - Safety Population 
U 
Listing 16.2.9.10 - Liver Diagnostic Investigations - Safety Population 
U 
Listing 16.2.9.11 - Liver Risk Factors and Lifestyle Events - Safety Population 
U 
Listing 16.2.9.12 - Liver Signs and Symptoms - Safety Population 
U 
Listing 16.2.9.13 - Infection Diagnostic Investigations - Safety Population 
U 
Listing 16.2.9.14 - Infection Risk Factors and Lifestyle Events - Safety Population 
U 
Listing 16.2.9.15 - Infection Signs and Symptoms - Safety Population 
U 
Listing 16.2.9.16 - Prior and Concomitant Medications - Safety Population 
U 
Listing 16.2.9.17 - Prohibited Concomitant Medications - Safety Population 
R 
Listing 16.2.9.18 - Concomitant Procedures - Safety Population 
R 
Listing 16.2.9.19 - Anti-drug Antibody Test Results - Safety Population 
U 
Listing 16.2.10.1 - Serum MEDI7352 Concentrations - PK Population 
U 
Listing 16.2.10.2 - Serum total NGF Concentrations - PD Population 
U 
 
 
 
 
 
 
 
 
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Listing Change Log: 
Output 
Number 
Date of 
Change 
Change 
Made By 
(initials) 
Description/Rationale 
 
 
 
 
 
 
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Listing 16.2.1.1 
Subject Disposition  
Screening Population  
 
Subject 
ID 
Re-screened?/ 
Previous 
Subject ID 
Treatment 
Arm 
Re-consent/ 
Date/Time of Initial IC/ 
Initial Protocol Version 
Date/Time of 
Informed Consent 
Protocol 
Version at 
consent/ 
Re-consent 
Consent for 
 
sample? /Date of 
Consent 
Consent for 
COVID-19 Safety 
Measures /Date of 
Consent 
Current 
Protocol 
version 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
Yes/ XXXX 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
Yes / 
DDMMMYYYY/hh:mm 
/ XXXX 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
No 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
No 
No 
XXXXX 
 
 
 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; IC = Informed Consent; 
 
. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
 
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Listing 16.2.1.2 
Assignment to Analysis Populations 
Screening Population  
Subject ID 
Treatment 
Arm 
Screened [1] 
Randomized 
SAF [2] 
mITT [3] 
PK [4] 
Reason to Exclude from 
Safety [5] 
Reason to Exclude from 
mITT [6] 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
No 
No 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
No 
No 
No 
XXX 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
No 
No 
XXX/ XXX 
XXX/ XXX 
 
 
 
 
 
 
 
 
 
mITT = Modified Intent-To-Treat Population Set; NRS = numeric rating scale; PK = pharmacokinetics; SAF = Safety Population Set. 
[1] The Screening Population includes all subjects who provide informed consent and provide demographic and/or baseline screening assessments. 
[2] The Safety Population includes all subjects who receive at least 1 dose of double-blind study medication. 
[3] The mITT Population includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
[4] The PK Population includes all subjects for who a pharmacokinetic sample was obtained and analysed. 
[5] Major deviation reason/s to exclude from Safety Population for randomized subject. 
[6] Major deviation reason/s to exclude from mITT Population for randomized subject. 
 
 
Programming Notes: 
• 
If there is more than one major deviation, please concatenate with “/” 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
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Listing 16.2.1.3 
Reason for IP Discontinuation and Withdrawal from the Study 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
IP 
Discontinuation 
[1]/ Study 
Withdrawal 
Completion/ 
Discontinuation 
Date (Study Day) 
Date of Last Dose 
Number of 
doses 
Primary 
Reason for 
DC/ 
Withdrawal 
Blind Broken? / 
Date/Time / 
Reason 
Reason for 
breaking 
the Blind 
Study 
Duratio
n 
 
 
 
 
 
 
 
 
 
XXXXXX/
XXXX 
IP 
Discontinuation  
DDMMMYYYY(XX) 
DDMMMYYYY 
XX 
XXXXXX
X 
Yes /  
DDMMMYYYY/
hh:mm 
XXXXXX 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX/
XXXX 
IP 
Discontinuation  
DDMMMYYYY (XX) 
DDMMMYYYY 
XX 
XXXXXX
X 
No 
 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX/
XXXX 
Study 
Withdrawal 
DDMMMYYYY (XX) 
DDMMMYYYY 
XX 
Other: 
XXXXXX
X 
No 
 
XX 
 
 
 
 
 
 
 
 
 
DC = Discontinuation; IP = Investigational product.  
[1] Any withdrawal from the study before last IP dose (Week 10) is considered an IP discontinuation. 
Note: Study Day is calculated relative to the date of first dose. Study Duration = Reference end date – date of first dose of treatment + 1. 
 
Programming Notes: 
• 
If reason for non-completion is Other, concatenate the specify text as follows: “Other: XXXXXXXXX”.  
• 
If reason for non-completion is adverse event, concatenate with AE line number as follows: “Adverse event number X”.  
• 
For Physician decision, screen-fail and withdrawal by subject, please provide explanation if presented on the logic “Physician decision: XXX”.  
• 
Do not include subjects who completed the study. 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
 
 
 
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Listing 16.2.1.4  
List of Reasons for Screening Failure 
Screen Failure Population 
 
Subject ID 
Treatment Arm 
Screen failure Date 
Primary Reason for Screen Failure 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
Other: XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
 
 
 
 
 
 
 
Programming Notes: 
• 
If reason for non-completion is Other, concatenate the “Primary Reason for Screen Failure” text as follows: “Other: XXXXXXXXX”.  
• 
Sort by Subject ID. 
 
 
 
 
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Listing 16.2.1.5 
Visits List and COVID-19 Impact 
Screening Population 
 
Subject ID/ 
Treatment 
Arm 
Visit 
Name 
Visit Date 
(Study 
Day) 
Is COVID-
19 
Pandemic 
Ongoing? 
Impacted 
by 
COVID-19 
Was visit 
performed? / 
Visit Type 
Visit 
Performe
d Via 
VS Data 
provided? / 
Assessments 
Missed? 
IP dosing 
missed due to 
COVID-19 / 
Details 
End of 
Treatment 
linked to 
COVID-19 
Subject 
discontinued 
due to 
COVID-19? / 
Details 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
Yes 
 
Yes 
Yes/ 
Delayed 
On site 
Y/  
Efficacy 
Y/ XXXX 
Other: XXXX 
Y/ XXXX 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
Yes 
 
No 
Yes 
 
N/ Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
No 
 
Yes 
Yes 
Video 
N/  
Efficacy, 
Safety 
Y/ Other: 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
No 
 
No 
No / Missed 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; IP = Investigational Product; VS = Vital Signs. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
• 
Visit Type: Missed, Abbreviated, Delayed. 
• 
Visit Performed Via: Video, Phone, On Site Other: xxxxxx. 
• 
Details on IP dosing missed: Treatment on hold due to Sponsor Decision, Subject infected with COVID-19, Subject decision, Other: xxxxxx. 
• 
End of treatment, reason if due to COVID: Subject infected with COVID-19, Subject decision, Travel restrictions, Site closed, Study delayed/cancelled, 
Other: xxxxxx. 
• 
Details on Subjects discontinuing due to COVID-19: Subject infected with COVID-19, Subject decision, End of Treatment due to Sponsor, Other: xxxxxx. 
• 
Sort by Treatment Arm/ Subject ID/ Visit Date. 
 
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Listing 16.2.2.1 
Subjects Not Meeting All Inclusion Criteria or Meeting any Exclusion Criteria 
Screening Population 
Subject ID 
Treatment Arm 
Enrolled 
Randomized 
Inclusion or 
Exclusion 
Criteria 
Number 
Criteria Label 
 
 
 
 
 
 
 
XXXXXX 
Screen Failure 
Yes 
No 
Inclusion 
XX 
XXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
Yes 
No 
Exclusion 
XX 
XXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
Programming Notes: 
 
• 
Sort by Subject ID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.2.2 
Protocol Deviations 
Safety Population 
 
Subject ID Treatment Arm Analysis Population Event Date (Study Day) Event Type 
Description 
Category 
Covid-
19 
Related? 
 
 
 
 
 
XXXXXX 
XXXX 
Screened\RND\SAF\
mITT 
DDMMMYYYY (XX) 
XXXXXXXXXXX 
XXXXXXX 
Non-
important 
Y 
 
 
XXXXXXXXXXXXXX 
XXXXXXXXXXXXXXX Important 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (XX) 
XXXXXXXXXXXX 
XXXXXXXXXXXXXXX
XXX 
XXXXX 
 
 
XXXXXXXXXXXXXXXX XXXXXXXXXXX 
XXXXX 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (XX) 
XXXXXXXXXXXX 
XXXXXXXXXXXXXXX
XXX 
XXXXX 
COVID-19 = Coronavirus disease 2019; mITT = Modified Intent-To-Treat Population; RND = Randomized Subjects; SAF = Safety Population. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
o The structure of this listing may change depending on the information in the protocol deviations file. In the analysis population column, include only the 
analysis population where subject is included in. 
o 
Sort by Treatment Arm/ Subject ID. If date is present in file, add a column for date of event and sort by date. If no date is present, sort by category with 
non-important first and then important. 
o 
Event Type: Inclusion Criteria, Exclusion Criteria, Study Drug, Assessment − Safety, Assessment − Efficacy, Lab/endpoint data, Visit Window, 
Informed Consent, Prohibited Co-Medication, Overdose/Misuse, Other. 
 
 
 
 
 
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Listing 16.2.3 
Randomization and Treatment group 
Safety Population 
 
Subject ID 
Treatment Arm 
Randomization Stage 
Randomization Treatment 
Randomization Date / Time 
(Study Day) 
Randomization 
Number 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 1 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 3 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 2 
Placebo 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 2 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 3 
Placebo 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.4.1 
Demographic and Baseline Characteristics 
Screening Population 
Subject 
ID 
Treatment 
Arm 
Birth Date 
Age 
(years) 
[1] 
Sex 
Surgically sterile?/ 
Postmenopausal? [2] 
Ethnicity 
Race 
Weight 
(kg) 
Height 
(cm) 
BMI 
(kg/m²) 
Fully 
vaccinated 
for COVID-
19? 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
XXX 
DDMMMYYY 
XX 
XX 
 
XXXXX 
XXXX 
XX.X 
XX.X 
XX.X 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
XXX 
--MMMYYY 
XX 
XX 
No/ Yes 
XXXXX 
XXXX 
XX.X 
XX.X 
XX.X 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 = Coronavirus disease 2019. 
Note: Height and weight are the values at Screening.  
[1] Age was calculated as age at time of consent. 
[2] For Female Subject Only. 
 
 
 
 
Programming Notes: 
o 
Sort by Treatment Arm/ Subject ID 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.4.2 
Medical History 
Safety Population 
 
 
System Organ Class/ 
 
 
 
  Preferred Term/ 
Start Date (Study Day)/ 
 Subject ID 
Treatment Arm 
    Verbatim Term 
   End Date (Study Day)/ 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
     XXXXXXXXXXXXX 
MMMYYYY (X)/ 
   Ongoing 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
     XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   Ongoing 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
 
 
 
 
 
 
 
 
MedDRA = Medical Dictionary for Regulatory Activities.  
Note: Study Day is calculated relative to the date of first dose. 
Medical History were coded using MedDRA version 26.0.  
Only subjects with medical history recorded are listed. 
 
Programming Notes: 
 
• 
SOC & PT text should be in proper case in listing. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date of medical event. 
 
 
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Listing 16.2.4.3 
Osteoarthritis Characteristics 
Screening Population 
 
Subject ID 
Treatment 
Arm 
Subject with 
OA? / Joint/ 
Area affected 
Is OA 
considered 
CS? 
Radiological 
Investigations 
Conducted? / Details 
Joint Area 
Investigated 
Is OA 
considered 
RS? 
K-L Score 
Reported 
Radiologic Scoring 
System / Details/  
Result 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Y / Shoulder 
Y 
Y/ Other: XXXXXX 
Shoulder 
Y 
Grade 3 
XXXXXX/ 
         XXXXXX/ 
   XX 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Y / Ankle 
N 
Y / MRI 
Ankle 
N 
N 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CS = Clinically Significant; K-L = Kellgren-Lawrence; OA = Osteoarthritis; RS = Radiologically Significant. 
. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.5.1 
Study Drug Administration: Individual Doses 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
Visit 
Name 
Start 
Date/ 
Time 
(Study 
Day) 
End 
Date/ 
Time 
(Study 
Day) 
Was 
Infusion 
Performed?/ 
Infusion 
Volume 
(mL)[1]/ 
Reason not 
Performed 
Actually 
Administered 
Volume (mL) 
[2] 
If 
Difference 
between 
[1] and [2] 
Volume, 
Reason 
Any 
Injection 
Site 
Reactions? 
Any 
Infusion 
Related 
Reactions  
Infusion 
Rate 
(mL/ 
hour) 
Rate Change 
Justification 
Reason 
for 
Infusion 
Rate 
Change 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
DDMM
MYYYY
/hh:mm 
(X) 
DDMM
MYYYY
/hh:mm 
(X) 
Y/  
XX 
XX 
 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
DDMM
MYYYY
/hh:mm 
(X) 
DDMM
MYYYY
/hh:mm 
(X) 
Y/  
XX 
XX 
XXXXX 
Y 
Y 
xx.x 
XXXXX 
XXXXX
XX 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
 
 
N/  
XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date. 
• 
Rate Change Justification: Increased, Decreased, Interrupted. 
 
 
 
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Listing 16.2.6.1 
Daily Pain NRS 
mITT Population 
 
Subject ID 
Treatment Arm 
Study Visit [1] 
Subject Diary (ePRO) Date / Study Day Baseline Flag [2] 
DPS 
 
 
 
 
 
 
XXXXXX 
XXXX 
Baseline 
DDMMMYYYY/ (-7) 
Y 
X 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-6) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-2) 
Y 
XX 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-1) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY/ (13) 
 
XX 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY/ (14) 
 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
XXXXXX 
XXXX 
Baseline 
DDMMMYYYY/ (-7) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
DPS = Daily Pain Score; ePRO = Electronic Patient-Reported Outcome; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘DPS’ are average daily pain scores on an 11-point (0-10) NRS. Study Day is calculated relative to the date of first dose. 
[1] Study Visit is defined as the 7-day period ending within the protocol window Day ± 3, where at least 4 days out of 7 have recorded diary pain scores. 
[2] Baseline is defined as the 7-day period prior to randomization i.e., Day -7 to Day -1, inclusive. A subject is considered to have an evaluable baseline pain 
score if there are at least 4 days of recorded diary pain scores in the 7-day period. 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Subject Diary Date. 
• 
Display all measurement per Subject, starting on the Study Day = -7. 
• 
Display Study Visit for days involved in weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and 12 
• 
Flag Baseline records only when there is at least 5 days of recorded diary pain scores in the 7-day Baseline period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.6.2 
Galer NPS 
mITT Population 
Subject ID 
Treatment Arm 
Parameter 
Study Visit 
Collection Date / Study 
Day 
Baseline Flag [1] 
NPS 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Pain intensity 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
Week 4 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
XX 
 
 
 
 
 
 
 
 
 
 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
XX 
 
 
 
 
 
 
 
 
 
XXXX 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Pain intensity 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
XXXX 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
NPS = Neuropathic Pain Scale; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘NPS’ are Pain Intensity, Unpleasantness, and Descriptor scores on an 11-point (0-10) NRS, and Pain Duration/Frequency on a 3-
point NRS (1-3).  
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter /Collection Date. 
• 
Keep Parameter sorting from the last bullet point in this programming notes. 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Repeat for the Parameters: Pain intensity, Pain Unpleasantness, Pain Sharpness, Pain Hotness, Pain Dullness, Pain Coldness, Pain Sensitivity, Pain 
Itching, Deep Pain Intensity, Surface Pain Intensity (All in an 11-point NRS), and Pain Duration/Frequency (in a 3-point NRS). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.6.3 
DSIS 
mITT Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.6.1. 
• 
Update footnote as:  
DSIS = Daily Sleep Interference Scale; ePRO = Electronic Patient-Reported Outcome; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘DSIS’ are daily Sleep Interference scores on an 11-point (0-10) NRS. Study Day is calculated relative to the date of the 
day of first dose. 
[1] Study Visit is defined as the seven-day period ending within the protocol window Day ± 3. 
[2] Baseline is defined as the seven-day period prior to randomization i.e., Day -7 to Day -1,. 
• 
Sort by Treatment Arm/ Subject ID / Subject Diary Date. 
• 
Display all measurement per Subject, starting on the Study Day = -7. 
• 
Display Study Visit for days involved in weekly averages of the average Sleep interference scores for Baseline, Week 4, 8, 12 , and 18. 
 
 
 
 
 
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Listing 16.2.6.4 
SF-36 
mITT Population 
Subject ID 
Treatment 
Arm 
Parameter 
Item 
Number 
Item name 
Study Visit 
Collection Date / Study 
Day 
Baseline 
Flag [1] 
SF-36 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Physical 
functioning 
3 
Vigorous 
Activities 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
Moderate 
Activities 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
- 
Total 
Baseline 
DDMMMYYYY/ (X) 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Role 
limitations 
due to 
physical 
health 
13 
Cut Amount 
of Time 
Spent on 
Work/Act 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
… 
… 
.. 
… 
 
 
 
 
 
 
 
 
 
… 
 
… 
… 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
SF-36 = 36-Item Short-Form Health Survey; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘SF-36’ are derived SF-36 scores and Change in General Health on a 5-point NRS (1-5).  
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Item /Collection Date. 
• 
Keep Parameter sorting from the last bullet point in this programming notes. 
• 
Include all data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical functioning (items 3, 4, 5, 6, 7, 8, 9, 10, 11, 12), Role limitations due to physical health (items: 13, 14, 15, 16), Role 
limitations due to emotional problems (items: 17, 18, 19), Vitality (Energy/fatigue) (items: 23, 27, 29, 31), Emotional well-being (items: 24, 25, 26, 28, 
30), Social functioning (20, 32), Pain (items: 21, 22) and General Health (items: 1, 33, 34, 35, 36), all with values ranging from 0 to 100. Change in 
general Health (in a 5-point NRS, item: 2). 
 
 
 
 
 
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Listing 16.2.6.5 
Rescue Medication Usage 
mITT Population 
 Subject 
ID 
Treatment Arm 
ATC Class (Level 2)/ 
   Preferred Name/ 
      Verbatim Term 
Primary 
Indication 
Start Date (Study Day)/ 
   End Date (Study Day) 
Dose 
(unit) 
Route 
Frequency 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
--MMMYYYY (-XX)/ 
   DDMMMYYYY (-X) 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
  XXXXXXXXX/ 
   XXXXXXXXXXXXXXX/ 
      XXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
--MMMYYYY (-X)/ 
   Ongoing 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
XXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
DDMMMYYYY (X)/ 
   DDMMMYYYY 
(XX) 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ATC = anatomical therapeutic chemical. 
Note: Study Day is calculated relative to the date of first dose. 
Medications were coded using WHO drug dictionary version vMar2023. 
 
 
Programming Notes: 
• 
ATC & Preferred Name text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications 
 
 
 
 
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Listing 16.2.6.6 
Patient Global Impression of Change 
mITT Population 
Subject ID 
Treatment Arm 
Study Visit 
Collection Date / Study Day 
PGIC 
 
 
 
 
 
XXXXXX 
XXXX 
Week 4 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
XXXXXX 
XXXX 
Week 4 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
… 
… 
… 
 
 
 
 
 
PGIC =Patient Global Impression of Change. 
Note: Data shown in column ‘PGIC’ are Subjects ratings about overall improvement in health status. 
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include all observed data on PGIC scores for Week 4, 8, 12, and 18. 
 
 
 
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Listing 16.2.7.1 
Adverse Events 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
AE Start Date/Time 
(Study Day)/ 
   End Date/Time 
(Study Day) 
Severity/ 
Relationship 
[1] 
Outcome/ 
      Action Taken with IP/ 
           Therapy taken for this AE? 
AE Leading 
to Study DC? 
TEAE 
Serious? / 
Serious 
Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMMMYYYY/HH:
MM (X)/ 
DDMMMYYYY/HH:
MM (X) 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                       Yes 
No 
Yes 
  
No 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMMMYYYY/HH:
MM (X)/ 
DDMONYYYY/HH:
MM (X) 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                     No 
Yes 
No 
Yes / XXX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMONYYYY/HH:
MM (X)/ 
   Ongoing 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                   No 
No 
No  
Yes / XXX 
 
AE = adverse event; DC = discontinuation; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; SAE = serious adverse event; 
TEAE = treatment emergent adverse event. 
[1] Reasonable possibility AE caused by IP as assessed by the investigator . 
Note: Study Day is calculated relative to the date of first dose. A TEAE is defined as an AE with an onset at the time of or following the start of treatment with 
IP. 
AEs were coded using MedDRA version 26.0 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e, no AEs occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically by SOC /PT if same date for two events). 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT 
abbreviations should be added in this case in footnote. 
 
 
 
Listing 16.2.7.2 
Treatment Emergent Adverse Events Leading to Study Drug Discontinuation 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update listing deleting seventh and eight columns 
 
 
Listing 16.2.7.3 
Treatment Emergent Adverse Events Associated with Abnormal Liver 
Safety Population 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update listing deleting 8th column. 
 
 
 
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Listing 16.2.7.4 
Joint Related Adverse Events of Special Interest 
Safety Population 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
 
 
Listing 16.2.7.5 
Serious and/or Severe Infections 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
 
 
Listing 16.2.7.6 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of Study Drug  
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update footnote: Anaphylactic reactions, hypersensitivity or infusion-related reactions not leading to discontinuation of IP were included in listing as 
they were categorized as AE of special interest under Protocol Amendment 4 (V5.0). Definition for AE of special interest changed from Amendment 6 
(V6.0) onwards, including anaphylactic reactions, hypersensitivity or infusion-related reactions leading to permanent discontinuation of IP. 
 
 
 
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Listing 16.2.8.1 
Clinical Chemistry Laboratory Evaluations 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Parameter 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Original 
Result 
(Unit) 
Standard 
Results 
(unit) 
Reference 
Range 
[1] 
 
 
 
 
Baseline 
Flag 
 
 
 
 
CFB 
Results 
Assessment 
/ Reason 
CS 
Lab ID 
Number 
Fasting 
Status 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Chemistry 
panel 
XXXXXX 
 
 
 
 
 
 
ND: xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Albumin 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
Y 
 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-NCS 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically significant; H = High; L = Low; NCS = not clinically significant; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
 [1] Reference range is used to identify potentially clinica lly significant laboratory values. 
 
Programming Notes: 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Chemistry panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Albumin, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), 
Bicarbonate, Calcium, Chloride, Creatinine, High-Sensitivity C-Reactive Protein (hs-CRP), Estimated Glomerular Filtration Rate (eGFR by Cockcroft - 
Gault), Serum Glucose, Lactate Dehydrogenase (LDH), Potassium, Sodium, Total Bilirubin, Total Protein, Blood Urea Nitrogen (BUN), Uric Acid. 
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Listing 16.2.8.2 
Hematology Laboratory Evaluations 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.8.1. 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Hematology panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Absolute basophil count, absolute eosinophil count, absolute lymphocytes count, Absolute Monocyte Count, 
Absolute Neutrophil Count, Basophils %, Eosinophils %, Hematocrit (HCT), Hemoglobin (HGB), hemoglobin A1C (HgbA1C), Lymphocytes %, mean 
corpuscular hemoglobin (MHC), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), Monocytes %, Neutrophils 
%, Platelets, Red blood cell count (RBC), Red Cell Distribution Width, white blood cell Count (WBC). 
 
 
Listing 16.2.8.3 
Coagulation Laboratory Evaluations 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.8.1. 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Coagulation panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Activated Partial Thromboplastin Clotting Time (APTT), Fibrinogen, International normalized ratio (INR), 
Prothrombin Time (PT). 
 
 
 
 
 
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Listing 16.2.8.4 
Urinalysis Laboratory Evaluations 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Parameter 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Original 
Result 
(Unit) 
Standard 
Results 
(unit) 
Reference 
Range 
[1] 
 
 
 
 
Baseline 
Flag 
 
 
 
 
CFB 
Results 
Assessment 
/ Reason 
CS 
Lab ID 
Number 
Fasting 
Status 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
Urinalysis 
panel 
XXXXXX 
 
 
 
 
 
 
ND: xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
pH/ 
Specific 
Gravity 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
Y 
 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-NCS 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
Urine/ 
Glucose/ 
Ketones/ 
Protein 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Trace 
 
 
Y 
 
H-NCS 
XXXXXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
100 
(mg/dL) 
100 
(mg/dL) 
 
 
 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Negative 
 
 
 
 
 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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CFB = change from baseline; CS = clinically significant; H = High; L = Low; NCS = not clinically significant; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
 [1] Reference range is used to identify potentially clinically significant laboratory values. 
 
 
Programming Notes: 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Urinalysis panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Blood Urine, Glucose, Ketones, pH, Protein, Specific Gravity. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.5 
Serology Laboratory Evaluations 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Was 
Serology 
Test 
Collected? 
Date/Time of 
Collection 
(Study Day) 
Test (Unit) [1] 
Result 
Lab ID 
Number 
Fasting 
Status 
Reason not 
collected 
Comments 
 
 
 
 
 
 
 
 
 
 
XXXX 
XXXX 
Yes 
DDMMMYYY
Y/HH:MM (X) 
Hepatitis B Ag 
Negative 
XXXX 
Y 
 
XXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis C Ab 
Positive 
XXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1/ -2 Ag 
Not Done 
XXXX 
Y 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Quantiferon 
Gold Plus NIL 
X.XX (IU/mL) 
XXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Ab = antibody; Ag = antigen; HIV = human immunodeficiency virus; TB = tuberculosis. 
Note: Study Day is calculated relative to the date of first dose. 
[1] if Applicable 
 
Programming Notes: 
 
• 
Sort by Treatment Arm/ Subject ID / Date of collection / Test. 
• 
Keep parameter sorting from the last bullet point below 
• 
Sort Parameters in the following Order: Hepatitis B Antigen, Hepatitis C Virus Antigen, Hepatitis C Virus Antibody, HIV-1/ -2 Antigen, Quantiferon 
Gold Plus NIL, Quantiferon Gold Plus TB, Quantiferon Gold Plus Mitogen minus NIL, Quantiferon Gold Plus TB1 m inus NIL, Quantiferon Gold Plus 
TB2 minus NIL 
 
 
 
 
 
 
 
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Listing 16.2.8.6 
Pregnancy Test Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Was a Urine pregnancy test 
performed? 
Date/Time Performed (Study Day) 
If not, Reason 
Result 
xxxxx 
xxxx 
xxxxx 
Xxxx 
Ddmmmyyyy/ hh:mm (XX) 
xxxx 
xxxx 
 
 
xxxxx 
Xxxx 
Ddmmmyyyy/ hh:mm (XX) 
Other: xxxx 
xxxx 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.7 
Drug Test Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Was Drug Test 
Performed? 
Date/ Time Assessment 
(Study Day) 
Result 
Findings 
Reason Test 
not Performed 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
DDMMMYYYY/ HH:MM 
(XX) 
Negative 
Negative 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
DDMMMYYYY/ HH:MM 
(XX) 
Positive 
Cocaine /  
Opiates 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Concatenate all findings by “/” 
• 
Sort by Treatment Arm/ Subject ID / Date of assessment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.8 
COVID-19 Screening 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
COVID-19 Sx 
Screening?/Date
/ Time (Study 
Day) 
Sx 
Body Tº 
Check?/ Date/ 
Time (Study 
Day) 
Body Tº 
(Unit) 
COVID-19 
swab?/ Date/ 
Time (Study 
Day) 
Swab 
result 
COVID-19 Ab 
testing?/ Date/ 
Time (Study 
Day) 
 
Ab 
testing 
results 
COVID-19 
Ag testing?/ 
Date/ Time 
(Study Day) 
Ag 
testing 
results 
xxxxx/ 
xxxx 
xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XXX/ 
XXX 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XX (XX) 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy
/ hh:mm (XX) 
Xxxx 
 
xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XXX 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XX (XX) 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy
/ hh:mm (XX) 
Xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
Ab = Antibody; Ag = Antigen; COVID-19 = Coronavirus disease 2019; Sx = Symptoms; Tº = Temperature. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Concatenate all Symptoms by “/” 
• 
Sort by Treatment Arm/ Subject ID / Date of assessment 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.1 
Vital Signs Measurements 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Parameter 
Study 
Visit 
Position [1] / 
 Tº Method 
Date/Time of 
Collection 
(Study Day) 
Original Result 
(Unit) 
 
Baseline Flag 
CFB 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Body 
Temperature 
XXXXXX 
XXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX (XX) 
Y 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX (XX) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Resting 
Heat Rate 
Screening 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
 
 
 
 
Day 1: 
Pre-Dose 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
Y 
XX 
 
 
 
XXXXXX 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
XX 
 
 
 
XXXXXX 
Sitting 
 
ND 
 
 
 
 
 
XXXXXX 
Sitting 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
XX 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; eCRF = Electronic Case Report Form; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
‘Day 1: 5 minutes after Infusion Completion’ time point was only applied to subjects enrolled in Stage 1, with data collected under eCRF versions 4.0 
(11DEC2018) or older. 
[1] Resting position measurements encompass Sitting and Supine position measurements.  
 
 
 
 
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter (Order in the second bullet point)/ Date time of collection. 
• 
Repeat for Resting Heart Rate, Resting Systolic Blood Pressure, Resting Diastolic Blood Pressure, Respiratory Rate, Body Temperature, Standing Heart 
Rate, Standing Systolic Blood Pressure, Standing Diastolic Blood Pressure. 
• 
After Week 2 (inclusive), Supine measure are taken in sitting position. We will consider them as supine (in resting position) for calculating Change from 
Baseline (always at supine position). 
• 
Include the following timepoints: Screening, Baseline (Day 1: Pre-Dose), Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 
Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion 
Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 
8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, 
Week 11, Week 12, Week 18.   
• 
Note that Body Tº, and standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.2.1 
12-Lead Digital ECG Results 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Visit 
 
ECG Date / Time 
(Study Day) 
Tracin
g 
PR Interval 
(msec) 
QRS 
duration  
(msec) 
QT 
Interval  
(msec) 
RR 
interval 
(bpm) 
Heart Rate 
(beats/min) 
QTcF 
Interval  
(msec) 
Findings 
Reason 
Not 
Done 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
Day 1: 
Pre-Dose 
DDMMMYYYY 
/ HH:MM (XX) 
1 
xx 
xx 
xx 
xx 
xx 
xx 
xx: 
xxxxx 
 
 
 
 
2 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
3 
xx 
xx 
xx 
xx 
xx 
xx 
xx: 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
 
DDMMMYYYY/ 
HH:MM (XX)  
1 
xx 
xx 
xx 
xx 
xx 
xx 
xx: 
xxxxx 
 
 
 
 
2 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
3 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant; ECG = electrocardiogram; NCS = Not clinically significant 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Date time of collection / Tracing. 
• 
For Findings, concatenate test name with test result for category “FINDINGS”.  
• 
Include the following timepoints: Day 1: Pre-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, 
Week 12, and Week 18. 
 
 
 
 
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00Listing 16.2.9.2.2 
12-Lead Safety ECG Results 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
 
ECG Date / Time 
(Study Day) 
Tracing 
ECG Result/ 
Comment 
PR Interval 
(msec) 
QRS duration  
(msec) 
QTcF 
Interval  
(msec) 
Reason 
Not Done 
 
 
 
 
 
 
 
 
 
XXXXX 
Day 1: Pre-
Dose 
DDMMMYYYY / 
HH:MM (XX) 
1 
Abnormal CS/ xxxx 
xx 
xx 
xx 
 
 
 
 
2 
Abnormal CS/ xxxx 
xx 
xx 
xx 
 
 
 
 
3 
Abnormal NCS/ 
xxxx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
 
DDMMMYYYY/ 
HH:MM (XX) 
1 
Normal 
xx 
xx 
xx 
 
 
 
 
2 
Normal 
xx 
xx 
xx 
 
 
 
 
3 
Normal 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant; ECG = electrocardiogram; NCS = Not clinically significant 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Date time of collection / Tracing. 
• 
Include the following timepoints: Screening, Day 1: Pre-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, 
Week, 8, Week 12, and Week 18. 
 
 
 
 
 
 
 
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Listing 16.2.9.3 
Physical Examination Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Examination 
Type 
Exam Date/ Time 
(Study Day) 
Body System 
Result / Change 
from previous 
assessment [1] 
If Abnormal, 
findings / 
Specify 
Changes [2] 
Reason Not 
Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
Complete 
DDMMMYYYY 
/ HH:MM (XX) 
Head, Neck and 
Thyroid 
Normal 
 
 
 
 
 
 
 
Ears, Eyes, Nose 
and Throat 
Abnormal CS 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
Targeted 
DDMMMYYYY 
/ HH:MM (XX) 
Ears, Eyes, Nose 
and Throat 
XXXXXXXXXX 
XXXXXXXX 
 
 
 
 
 
 
  
 
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant 
Note: Study Day is calculated relative to the date of first dose. 
[1] For targeted examination type: Change from previous assessment. 
[2] For targeted examination type: Specify Changes. 
 
 
Programming Notes: 
• 
Keep sorting from eCRF: Head, Neck and Thyroid/ Ears, Eyes, Nose and Throat/ Chest (including breasts)/ Lungs / Heart / Lymph Nodes / Abdomen / 
Hepatic / Gastrointestinal / Anorectal / Genitourinary/ Skin / Musculoskeletal/Extremities / Neurological / Other. 
• 
Complete Physical examination only at Screening, Week 12, 18 (it can also be unscheduled). 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Body system 
 
 
 
 
 
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Listing 16.2.9.4 
Neurological Examination Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Exam Date/ Time 
(Study Day) 
Body System 
Result  
If Abnormal, 
findings 
Reason Not 
Done 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
DDMMMYYYY / 
HH:MM (XX) 
Mental Status 
Normal 
 
 
 
 
 
 
Cranial Nerves 
Abnormal CS 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY / 
HH:MM (XX) 
Cranial Nerves 
XXXXXXXXXX 
XXXXXXXX 
 
 
 
 
 
  
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Keep sorting from eCRF: Mental status/ Cranial Nerves/ Motor Function/ Reflexes / Sensation and Propioception / Coordination / Other. 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Body system 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.5 
Total Neuropathy Score-Nurse 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Visit 
Date/ Time of 
collection 
(Study Day) 
Sensory 
Symptom 
Score 
(0−4) 
Motor 
Symptom 
Score 
(0−4) 
Autonomic 
Symptom 
Score (0−4) 
Pin 
Sensibility 
Score 
(0−4) 
Vibration 
Sensibility 
Score 
(0−4) 
TNSn Total 
(0−20) 
Reason Not Done 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Screening 
DDMMMYYYY 
/ HH:MM (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY 
/ HH:MM (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY 
/ HH:MM (XX) 
ND 
ND 
ND 
ND 
ND 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
ND = Not Done; TNSn = Total Neuropathy Score-Nurse. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.6 
Motor and Sensory Nerve Conduction Studies 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
 
Date / Time of 
Collection 
(Study Day) 
Location / 
Evaluation 
Was 
Evaluation 
Preformed
? / Nerve 
Amplitude 
(Motor = 
mV; sensory 
= microV) / 
Range 
Peak 
Latency 
(msec) / 
Range 
Conduction 
velocity 
(msec) / 
Range 
Duration 
of action 
potential 
(msec) / 
Range 
Evaluation 
Result 
If 
Abnormal, 
Specify/ 
Reason 
Not Done 
Significant 
Changes 
from 
Baseline? / 
if Yes, 
Specify 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
Screening 
DDMMMYY
YY / HH:MM 
(XX) 
Lower Limb 
- Right Side/  
         Motor 
Evaluation 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
NA 
 
 
 
XXXXXX/    
XXXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Normal 
 
NA 
 
 
 
XXXXXX/   
XXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 18 
 
DDMMMYY
YY/ HH:MM 
(XX) 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
N 
 
 
 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Normal 
 
N 
 
 
 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
Y/  
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
NA = Not Applicable 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Location - Evaluation 
• 
Keep sorting from eCRF: Lower Limb - right side/Motor evaluation, Lower Limb - right side/Sensory evaluation, Lower Limb - left side/ Motor evaluation, 
Lower Limb - left side/ Sensory evaluation, Upper Limb - right side /Motor evaluation, Upper Limb - right side/ Sensory evaluation, Upper Limb - left 
side/ Motor evaluation, Upper Limb - left side /Sensory evaluation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.7 
Strength and Deep Tendon Reflexes 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Date/ Time of 
collection 
(Study Day) 
Ankle Dorsiflexion 
Strength 
Deep Tendon Reflexes 
Reason Not Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY / 
HH:MM (XX) 
ND 
 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
ND = Not Done. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.8 
Injection Site Reactions 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Visit 
Date/ Time of Assessment 
(Study Day) 
Pain 
Tenderness 
Erythema/redness 
Induration/
swelling 
Reason Not Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Day 1: 15 
Minutes 
after Start of 
Infusion 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1: 30 
Minutes 
after Start of 
Infusion 
DDMMMYYYY / 
HH:MM (XX) 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY / 
HH:MM (XX) 
ND 
ND 
ND 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
ND = Not Done. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
• 
Include the following timepoints: Day 1: 15 Minutes after Start of Infusion, Day 1: 30 Minutes after Start of Infusion, Day 1: 45 Minutes after Start of 
Infusion, Day 1: 60 Minutes after Start of Infusion, Day 1: 2 hours after Start of Infusion, Day 1: 4 hours after Start of Infusion, Week 2, Week 4, Week 
6, Week, 8, Week 10, Week 12, and Week 18.  
 
 
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Listing 16.2.9.9 
Hypersensitivity/Anaphylactic Reactions 
Safety Population 
Subject 
ID 
Treatment 
Arm 
AE ID 
Number 
Onset Date/Time (Study Day)/ 
   Resolution Date/Time (Study 
Day) 
Type of 
Reaction 
Severity grade for 
the Symptom 
with Highest 
Severity 
Onset Time 
for Highest 
Severity 
Leading to IP 
Discontinuation? 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMMMYYYY/HH:MM (X) 
XXXX 
XXXX 
/HH:MM 
Yes 
 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMONYYYY/HH:MM (X) 
XXXXX 
 
 
No 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMONYYYY/HH:MM (X) 
XXXXX 
XXXX 
/HH:MM 
No 
 
 
 
 
 
 
 
 
AE = Adverse Event. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Onset Date/Time / Resolution Date/Time / Reaction Type. 
• 
Keep sorting from eCRF: Urticaria, Pruritus, Rash, Flushing, Swollen lips, tongue, uvula and/or vulva, Dyspnoea, Wheeze-bronchospasm, Stridor, 
Hypoxia, Hypotension, Crampy abdominal pain, Vomiting, Diarrhoea, Other. 
 
 
 
 
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Listing 16.2.9.10 
Liver Diagnostic Investigations 
Safety Population 
Subject ID 
Treatment 
Arm 
Potential Hy's 
Law Case 
Number 
Liver Diagnostic Investigation 
Date (Study Day) 
Liver Diagnostic 
Investigation 
Liver Diagnostic 
Investigation 
Results 
Comments 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X) 
 
XXXX 
XXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY (X) 
 
XXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X) 
 
XXXXX 
XXXXX 
 
 
 
CT = Computerized tomography; ERCP = Endoscopic retrograde cholangiopancreatography; MRI = Magnetic resonance imaging; MRCP = Magnetic 
resonance cholangiopancreatography. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Diagnostic Date / Liver Diagnostic Investigation. 
• 
Keep sorting from eCRF: Ultrasound, CT, MRI/MRCP, ERCP, Liver Biopsy, X-Ray, Tox Screening for Acetaminophen/Paracetamol, Tox Screening for 
Ethanol, Tox Screening, Other, Specialist (e.g. Hepatologist) Consulted, Serology for Hepatitis A, Serology for Hepatitis B, Serology for Hepatitis C, 
Serology for Hepatitis D, Serology for Hepatitis E, for Cytomegalovirus (CMV), Serology for Epstein Barr Virus (EBV), Autoimmune Serology, Other. 
 
 
 
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Listing 16.2.9.11 
Liver Risk Factors and Lifestyle Events 
Safety Population 
Subject ID 
Treatment 
Arm 
Potential 
Hy's Law 
Case 
Number 
Assessment Date 
(Study Day) 
 
Liver Risk Factor Start Date 
(Study Day)/ 
Liver Risk Factor Stop Date 
(Study Day) 
Liver Risk 
Factor / 
Reference 
Period 
Liver Risk 
Factor Details 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/  
       DDMMMYYYY (X) 
XXXX/ 
   XXX 
XXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/  
         DDMMMYYYY (X) 
XXXXX/  
   XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/ 
      Ongoing  
XXXXX/ 
   XXX 
XXXXX 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Assessment Date / Liver Risk Factor Start Date / Stop Date / Liver Risk Factor. 
• 
Keep sorting from eCRF: Alcohol Abuse, Increased Alcohol Consumption within 1 Month of Reported Event, IV Drug Abuse, Tattoo, Acupuncture, 
Sexually Transmitted Diseases, Toxic/Chemical Agent Exposure, Travel (Areas at Risk in the Last Year), Pregnancy, Parenteral Nutrition, Excessive 
Physical Exercise, Changes Diet/Fasting Episodes/Weight Loss Diet, Previous Drug Reaction (Associated with an Elevation of Liver Tests), Blood 
Transfusion, Subject Exposed to Anyone with Jaundice in the Last Month, History of Hypotension, Low Blood Pressure at Time of Event of Liver Injury 
and/or Abnormal Liver Laboratory Value, History of Liver Disease, Other. 
• 
Concatenate comments with “/”. 
 
 
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Listing 16.2.9.12 
Liver Signs and Symptoms 
Safety Population 
Subject ID 
Treatment Arm 
Potential Hy's 
Law Case Number 
Start Date (Study Day)/ 
Stop Date (Study Day) 
Liver Sign/ 
Symptom 
Intermittent 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X)/  
       DDMMMYYYY (X) 
XXXX 
 
N 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY (X)/  
         DDMMMYYYY (X) 
XXXXX 
  
N 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X)/ 
      Ongoing  
XXXXX 
 
Y 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Liver Sign/Symptom. 
• 
Keep sorting from eCRF: Anorexia, Asthenia, Pyrexia, Pruritus, Jaundice, Arthralgia, Abdominal Pain, Abdominal Tenderness, Nausea, Vomiting, Rash, 
Mucosal Inflammation, Purpura, Hepatomegaly, Splenomegaly, Lymphadenopathy, Ascites, Confusional State, Coma, Upper Quadrant Tenderness, 
Biliary Obstruction, Eosinophilia, Dark Urine, Other. 
• 
If Rash, Lymphadenopathy or Other, Concatenate Symptom with Comment as: “Rash: xxxxxx”. “Lymphadenopathy: xxxxxx”, “Other: xxxxxxxx” 
 
 
 
 
 
 
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Listing 16.2.9.13 
Infection Diagnostic Investigations 
Safety Population 
Subject ID 
Treatment Arm 
AE ID 
Number 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Method 
Examination 
performed 
Test Result 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
XXXXX 
 
 
AE = adverse event. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Method. 
• 
Keep sorting from eCRF: Microscopy, Culture and Sensitivity, Serological Tests, Nucleic Acid Based Tests, X-Ray, Other. 
 
 
 
 
 
 
 
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Listing 16.2.9.14 
Infection Risk Factors and Lifestyle Events 
Safety Population 
Subject ID 
Treatment 
Arm 
AE ID 
Number 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Infection Risk 
Factor 
Infection Risk 
Occurrence 
Comments 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
Ongoing 
 
 
AE = adverse event; BCG = Bacillus Calmette–Guérin. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Infection Risk Factor. 
• 
Keep sorting from eCRF: Extensive Burns within the Last Year (Thermal Burn), Tattoo, Piercing or Acupuncture within the Last Year, Sexually 
Transmitted Diseases, Travel to Areas at Risk of Tuberculosis or Tropical Diseases, Infections Related to Travel (e.g. Tuberculosis and Tropical Diseases), 
Blood Transfusion (within the Last Year), Exposure to Nosocomial Pathogens within the Last Year, Contact History with Infection Source, Previous BCG 
Immunization, Evidence of BCG Scar, Tuberculin Skin or Quantiferon Test Confirms Previous Exposure or Immunity to Tuberculosis. 
• 
Fill Comment column if Infection risk factor test = Unknown Previous BCG Immunization, not done, known Sexually Transmitted Disease reference 
Period, or Infection risk factor specifications. 
 
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Listing 16.2.9.15 
Infection Signs and Symptoms 
Safety Population 
Subject ID 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Clinical 
Event 
Infection 
Sign/Symptom 
Occurrence 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM 
(X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM 
(X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
Ongoing 
 
 
AE = adverse event. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Clinical Event. 
• 
Keep sorting from eCRF: Pyrexia, Headache, Confusional State, Convulsion, Rhinitis, Oropharyngeal Pain, Cough, Productive Cough, Haemoptysis, 
Wheezing, Dyspnoea, Pleuritic Pain, Vomiting, Diarrhoea, Genital Discharge, Haematuria, Dysuria, Hepatosplenomegaly, Jaundice, Lymphadenopathy, 
Rash, Night sweats, Chills, Myalgia, Weight Decrease. 
• 
Fill Comment column if Maximum Tº (Unit) available for Pyrexia, or if site for Rash or Lymphadenopathy is known.  
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Listing 16.2.9.16 
Prior and Concomitant Medications 
Safety Population 
 Subject 
ID/ 
Treatment 
Arm 
Prior/ 
Concomitant 
[1] 
ATC Class (Level 2)/ 
   Preferred Name/ 
      Verbatim Term 
 
 
 
 
Given 
for/as 
Primary 
Indication 
Start Date (Study 
Day)/ 
   End Date (Study 
Day) 
Dose (unit) 
Route 
Frequency 
 
 
 
 
 
 
 
 
 
XXXXXX
/ XXXX 
Prior 
XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXX 
Medical 
History 
XXXXXXX 
--MMMYYYY     
(-XX)/ 
  DDMMMYYYY 
(-X) 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
Both 
  XXXXXXXXX/ 
   XXXXXXXXXXXXXXX/ 
      XXXXXXXXXXX 
Prophylaxis XXXXXXX 
--MMMYYYY     
(-X)/ 
   Ongoing 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
Concomitant XXXXXXXXX/ 
   XXXXXXXXXXXXXX/    
XXXXXXXXXXXXXXXXX 
Adverse 
event 
XXXXXXX 
DDMMMYYYY 
(X)/ 
  DDMMMYYYY 
(XX) 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ATC = anatomical therapeutic chemical; WHO-DDE = World Health Organization-Drug Dictionary Enhanced. 
Note: Study Day is calculated relative to the date of first dose. 
Medications were coded using WHO-DDE version vMar2023. 
[1] Prior medications are defined as medications that started before first dose of study, whether they were stopped before first dose of study medication or not. 
Concomitant medications are defined as medications starting on or after first dose of study medication Both indicates medication that was started before the 
day of first dose and continued after. 
 
 
 
 
 
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Programming Notes: 
• 
ATC & Preferred Name text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by Treatment ID/ Subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.17 
Prohibited Concomitant Medications 
Safety Population 
 
Programming Notes: 
• 
Same Shell as Listing 16.2.9.16.  
• 
Display prohibited prior and concomitant medications provided by the Medical Coder: 
• 
Prohibited concomitant medications:  
o NSAIDs analgesic therapies (with acetylsalicylic acid with doses >= 325 mg/day). 
o COX-2 analgesic therapies. 
o Immunotherapeutics. 
o Live viral or attenuated bacterial vaccines. 
o Oral, IV, intramuscular, or any other parenteral (other than oral) steroids (inhaled or topical steroids are permitted). 
o Biologic therapeutic agents. 
• 
Prohibited prior and/or concomitant medications: 
o Anti-NGF therapies. 
o Anti-TNF therapies. 
• 
ATC & PN text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications) 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.18 
Concomitant Procedures 
Safety Population 
Subject 
ID 
Treatment 
Arm 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date (Study Day)/ 
   End Date (Study Day) 
Reason for Procedure 
Reason (derived verbatim 
term) 
If Reason is Other, 
Specify 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
XXXXXXXXX/ 
 XXXXXXXX 
XXXXXXXXXX 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMMMYYYY (X)/ 
   Ongoing 
OTHER 
OTHER 
 
XXXXXXXXXXX 
 
 
MedDRA = Medical Dictionary for Regulatory Activities. 
Note: Study Day is calculated relative to the date of first dose. All Procedure terms were coded using the MedDRA version 26.0. Concomitant Procedures are 
defined as medications continuing or starting on or after first dose of study medication.  
 
Programming Notes: 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
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Listing 16.2.9.19 
Anti-drug Antibody Test Results 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Screening  
Status Result 
Confirmatory 
Status result 
ADA Titer 
Lab ID 
Number 
Comments 
 
 
 
 
 
 
 
 
 
XXXXX XXXX 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Positive 
Positive 
xx 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Positive 
Positive 
xx 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Negative 
Negative 
xx 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Missing 
Not 
Reportable 
Result 
NRR 
XXXXXXX 
XXXX 
 
 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; NA = Not Applicable; NRR = Not Reportable Result; QNS = Quantity Not Sufficient. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
ADA titre reported as <30 (below the minimum required dilution) is a negative result for the presence of ADA. 
• 
Include Following timepoints: Screening, Weeks 2, 4, 8, 10, 12, 18. 
 
 
 
 
 
 
 
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Listing 16.2.10.1 
Serum MEDI7352 Concentrations 
PK Population 
Subject 
ID 
Treatment 
Arm 
Study 
Visit 
PK Blood 
Sample 
Collected? / 
Reason Not 
Collected 
Date/Time of 
Collection 
(Study Day) 
MEDI7352 
Concentration 
(ng/mL) 
Lab ID Number 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXX 
Yes 
 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
XXXXXX 
Yes 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
XXXXXX 
Yes 
DDMMMYYYY/ 
HH:MM (X) 
NRR 
XXXXXXX 
XXXX 
 
 
XXXXXX 
No / 
XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
NA = Not Applicable; NRR = Not Reportable Result. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 10: 8 Hours 
after Infusion, Week 10 + 24 hours: after Week 10/ Pre-Dose, Week 11: after Week 10/ Pre-Dose, Week 10 + 14 Days: after Week 10/ Pre-Dose, Week 
18. 
 
 
 
 
 
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Listing 16.2.10.2 
Serum total NGF Concentrations 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Study 
Visit 
PD Blood Sample 
Collected? / 
Reason Not 
Collected 
Date/Time of 
Collection 
(Study Day) 
Total NGF 
Concentration 
(pg/mL)  
Lab ID Number 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXX 
Yes 
 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
XXXXXX 
Yes 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
XXXXXX 
Yes 
DDMMMYYYY/ 
HH:MM (X) 
NS 
XXXXXXX 
XXXX 
 
 
XXXXXX 
No / 
XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
BLLOQ = Below the Lowest Limit of Quantitation; NA = Not Applicable; ND = Not Detected; NS = No Value due to Insufficient Volume or No Sample 
Received; PD: Pharmacodynamic; SAT = Greater than the Top of the Standard Curve; tNGF = total Nerve-Growth Factor. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 10: 8 Hours 
after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18. 
 
 
 
 
 
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Planned Figure Descriptions and Shells 
Number        Title       Population 
Unique (U) or 
Repeated (R) 
Figure 14.2.1.1 - Daily Pain NRS: MCP-Mod Dose Response Model - mITT Population 
U 
Figure 14.2.1.2 - Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Missing Data Handling - mITT Population 
U 
Figure 14.2.1.3 - Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Co-Medication Subgroup - mITT Population 
R 
Figure 14.2.1.4 - Daily Pain NRS: MMRM LS Means (95% Confidence Interval) over 12-weeks by Treatment Group (Observed Cases) - 
mITT Population 
U 
Figure 14.3.6.1.1 - Vital Sign Profiles: Mean (±SD) Systolic Blood Pressure over time - Safety Population 
U 
Figure 14.3.6.1.2 - Vital Sign Profiles: Mean (±SD) Diastolic Blood Pressure over time - Safety Population 
R 
Figure 14.3.6.1.3 - Vital Sign Profiles: Mean (±SD) Heart Rate over time - Safety Population 
R 
Figure 14.3.6.1.4 - Vital Sign Profiles: Mean (±SD) Respiratory Rate over time - Safety Population 
R 
Figure 14.3.6.1.5 - Vital Sign Profiles: Mean (±SD) Temperature over time - Safety Population 
R 
Figure 14.4.1.1 - Pharmacokinetics: Line Plot of Geometric Mean (with and without gSD) Serum MEDI7352 over time - PK Population 
R 
Figure 14.4.1.2 - Pharmacokinetics: Individual Plot of Serum MEDI7352 Concentrations over time - PK Population 
U 
Figure 14.4.2.1 - Pharmacodynamics: Line Plot of Geometric Mean (with and without gSD) total NGF over time - Safety Population 
R 
Figure 14.4.2.2 - Pharmacodynamics: Individual Plot of Serum total NGF over time - Safety Population 
R 
 
 
 
 
 
 
 
 
 
 
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Figures Change Log 
Output 
Number 
Date of 
Change 
Change 
Made By 
(initials) 
Description/Rationale 
 
 
 
 
 
 
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Figure 14.2.1.1 
Daily Pain NRS: MCP-Mod Dose Response Model 
mITT Population 
 
CI = Confidence Interval; CFB = Change from Baseline; DPS = Daily Pain Score; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive. Envelope depicts 95% CI of mean dose-response. Added dots are actual doses ± 95% CI.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
I 
..-
0 
rn 
LL 
..-
0 
I 
(J) 
n:: 
N 
z 
I 
C 
(U 
Q_ 
(") 
I 
>-
(U 
0 
'i' 
lO 
I 
0 
Weekly Average to Week 12 Daily Pain NRS CFB, 
Emax dose-response model 
I 
I 
I 
I • 
100 
200 
300 
Dose (µg/kg) 
Hyperbolic Emax 
Eo = -0.21 
Emax = -5.54 
ED50 = 197.56 
400 
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Programming Notes: 
• 
Insert the following text as legend: “Weekly Average to Week 12 Daily Pain NRS CFB, xxxx dose-response model”, with ‘xxxx’ as the selected dose-
response model (e.g., Hyperbolic Emax). 
• 
Dose (µg/kg) in x axis and Daily Pain NRS CFB in y axis. 
• 
Add model parameter values as an inset plot. For e.g., Sigmoid Emax; E0 = xxx, Emax = xxx, ED50 = xxx, λ = xxx. 
• 
The MCP-MOD approach will only be performed if stage 4 is initiated, otherwise there would be insufficient dosing data to fit the non -linear models. 
 
 
 
 
 
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Figure 14.2.1.2 
Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Missing Data Handling 
mITT Population 
 
 
BOCF = Baseline Observation Carried Forward; CFB = Change from Baseline; DPS = Daily Pain Score; LOCF = Last Observation 
Carried Forward; NRS = Numeric Rating Scale; OBS = Observed Cases. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment wh ile receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
 
I 
m 
LL 
0 
0 
(f) -2 
n:: z 
C ·ro 
Q_ 
2-
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0 
-4 
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Weekly Average CFB to Week 12 Daily Pain NRS 
0 
5 
Dose (~tg/kg) 
150 
450 
Data 
OBS 
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LOCF 
BOCF 
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Programming Notes: 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS”. 
• 
Dose (µg/kg) and Observed/LOCF/BOCF in x axis and Daily Pain NRS CFB in y axis. 
• 
A level for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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Figure 14.2.1.3 
Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Co-Medication Subgroup 
mITT Population 
 
 
CFB = Change from Baseline; DPS = Daily Pain Score; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.2 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS”. 
• 
Dose (µg/kg) in x axis, Anticonvulsant/ Antidepressant/ Both/ None in right side Co-medication labels, and Daily Pain NRS CFB in y axis. 
• 
A level for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.2.1.4 
Daily Pain NRS: MMRM LS Means (95% Confidence Interval) over 12-weeks by Treatment Group (Observed Cases) 
mITT Population 
 
CFB = Change from Baseline; CI = Confidence Interval; DPS = Daily Pain Score; LS = Least Square; MMRM = Mixed Model for 
Repeated Measures; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment wh ile receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
I 
...- -
0 
-
m 
LL 
...-
u 
I 
-
(I) 
{Y z 
N 
-
C 
I 
·ro 
0.. 
>-
(") 
·ro 
I 
-
0 
'I" -
Ii) -
I 
2 
·-• ·- 0 
···•··· 5 
_..__ 150 
--
450 
4 
Weekly Average CFB to Week 12 
Daily Pain NRS ± 95% Cl 
6 
8 
Week 
10 
12 
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Programming Notes: 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS ± 95% CI”. 
• 
Week in x axis and Daily Pain NRS CFB in y axis. 
• 
Include a profile for each dose treatment group. 
• 
Include the following timepoints: Week 2, 4, 6, 8, 10, and 12. 
• 
Extract data for this figure from the MMRM of CFB Daily Pain NRS with Observed Cases. 
• 
A profile for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Figure 14.3.6.1.1 
Vital Sign Profiles: Mean (±SD) Systolic Blood Pressure over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; SBP = Systolic Blood Pressure; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = Week 
11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average SBP ± Standard Deviation”. 
• 
Study Visit in x axis and Systolic Blood Pressure (mmHg) in y axis. 
• 
Include a profile for Resting SBP and another for Standing SBP. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.3.6.1.2 
Vital Sign Profiles: Mean (±SD) Diastolic Blood Pressure over time 
Safety Population 
 
 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; DBP = Diastolic Blood Pressure; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = 
Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average DBP ± Standard Deviation”. 
• 
Study Visit in x axis and Diastolic Blood Pressure (mmHg) in y axis. 
• 
Include a profile for Resting DBP and another for Standing DBP. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated) 
 
 
 
 
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Figure 14.3.6.1.3 
Vital Sign Profiles: Mean (±SD) Heart Rate over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; HR = Heart Rate; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = Week 11; W12 = 
Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average HR ± Standard Deviation”. 
• 
Study Visit in x axis and Heart Rate (Beats/min) in y axis. 
• 
Include a profile for Resting HR and another for Standing HR. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.3.6.1.4 
Vital Sign Profiles: Mean (±SD) Respiratory Rate over time 
Safety Population 
 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 4H PD = 4 hours Post-Dose; 5M PD = 
5 minutes after Infusion Completion; BASE = Baseline; D1 = Day 1; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; 
W10 = Week 10; W11 = Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average Respiratory Rate ± Standard Deviation”. 
• 
Study Visit in x axis and Respiratory Rate (Breaths/min) in y axis. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-
Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-
Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 
minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Make one plot with 4 profiles (one for each treatment group). 
• 
A profile for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Figure 14.3.6.1.5 
Vital Sign Profiles: Mean (±SD) Temperature over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 2H PD = 2 Hours Post-Dose; 4H PD = 4 hours Post-Dose; 5M PD = 5 minutes after Infusion 
Completion; BASE = Baseline; D1 = Day 1; T° = Temperature; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = 
Week 10; W11 = Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average Body Tº ± Standard Deviation”. 
• 
Study Visit in x axis and Body Temperature (ºC) in y axis. 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 
5 minutes after Infusion Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after 
Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion 
Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Make one plot with 4 profiles (one for each treatment group). 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
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Figure 14.4.1.1 
Pharmacokinetics: Line Plot of Geometric Mean (with and without gSD) Serum MEDI7352 Concentrations over Time  
PK Population 
 
 
ADA = Antidrug Antibodies; gSD = Geometric Standard Deviation; LLOQ = Lower Limit of Quantification. 
I 
Geometric Mean serum MEDl7352 ± Geometric Standard Deviation 
Overall 
C 
0 
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75 
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50 
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N 
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,.._ 
0 
w 
::e 
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u 1 
(!) 
10 
Geometric Mean serum MEDl7352 
Overall 
50 
50 
Study Vise (days) 
Study Vise (days) 
100 
100 
Treatment 
-
150 
. .. . 450 
Treatment 
-
150 
.... 450 
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PK Population = includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
ADA positive represents participants with at least one positive ADA result. 
ADA negative represents participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.1 
 
 
 
Programming Notes: 
• 
Insert the following text as upper legend: “Geometric Mean serum MEDI7352 ± Geometric Standard Deviation (Linear Scale)” followed by “Geometric 
Mean serum MEDI7352” for the linear plot, and “Geometric Mean serum MEDI7352 ± Geometric Standard Deviation (Semi-Logarithmic Scale)” 
followed by “Geometric Mean serum MEDI7352” for the semi-log plot. Below legend, add legend for ADA status: “Overall”, “ADA Positive”, “ADA 
Negative”. 
• 
Insert legend with different point symbols and colors for each treatment group (
) for the Overall plot, and a legend with different point 
symbols and colors for each ADA status (ADA+, ADA-) for each treatment group plot by ADA status. 
• 
Time (Days) in x axis and Serum MEDI7352 concentration (ng/mL) in y axis (in linear and log10 scale, for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10: Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 10 + 14 days, Week 18.   
• 
Make one overall plot by treatment group, and a plot for each treatment group by ADA status for a total of 4 plots. 
• 
Include a marker for LLOQ, and an inset within the plot with “LLOQ (1.00 ng/mL)”. 
• 
A line for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
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Figure 14.4.1.2 
Pharmacokinetics: Individual Plot of Serum MEDI7352 Concentrations over time  
PK Population 
 
ADA = Antidrug Antibodies; LLOQ = Lower Limit of Quantification. 
PK Population = includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.1 
 
I 
::]' 20000 
i 
5 15000 
1 
C 3 10000 
N 
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M ..... 
i5 
5000 
(/) 
? 10000 
l 
1000 l 
100 
N 
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M ..... 
i5 
w 
10 
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E 
(/) 
MEDl7352 Concentration by Subject, Treatment Group, and ADA Status 
450 11g/kg 
50 
Study Vis~ (days) 
MEDl7352 Concentration by Subject, Treatment Group, and ADA Status 
450 11g/kg 
50 
Study Visit (days) 
100 
100 
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ADA_Status 
NegatiVe 
-
Positive 
ADA_Status 
Negative 
-
Positive 
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Programming Notes: 
• 
Insert the following text as upper legend: “MEDI7352 Concentration by Subject, Treatment group, and ADA status” followed by “(Linear Scale)” or 
“(Semi-Logarithmic Scale)” depending on the plot (linear or semi-log). Below legend, add legend for Treatment Group: 
 
. 
• 
Insert legend with different colors for each ADA status (Positive/ Negative). 
• 
Time (days) in x axis and Serum MEDI7352 concentration (ng/mL) in y axis (in linear and log10 scale, for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 10 + 14 days, Week 18.   
• 
Make one plot for each Treatment group (
), for a total of 3 plots. 
• 
Include a marker for LLOQ, and an inset within the plot with “LLOQ (1.00 ng/mL)”. 
• 
Plots for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Figure 14.4.2.1 
Pharmacodynamics Line Plot of Geometric Mean (with and without gSD) Serum total NGF over time  
Safety Population 
 
 
ADA = Antidrug Antibodies; gSD = Geometric Standard Deviation; LLOQ = Lower Limit of Quantification, NGF = Nerve-Growth 
Factor. 
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
ADA positive represents participants with at least one positive ADA result. 
ADA negative represents participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.3 
 
 
Programming Notes: 
• 
Same shell as Figure 14.4.1.1 
• 
Insert the following text as upper legend: “Geometric Mean Serum Concentration of tNGF ± Geometric Standard Deviation (Linear Scale)” followed by 
“Geometric Mean Serum Concentration of tNGF” for the linear plot, and “Geometric Mean Serum Concentration of tNGF (Semi-Logarithmic Scale)” 
followed by “Geometric Mean Serum Concentration of tNGF” for the semi-log plot. Below legend, add legend for ADA status: “Overall”, “ADA 
Positive”, “ADA Negative”. 
• 
Insert legend with different point symbols and colors for each treatment group (Placebo, 
) for the Overall plot, and a legend with 
different point symbols and colors for each ADA status (ADA+, ADA-) for each treatment group plot by ADA status. 
• 
Time (Days) in x axis and Serum tNGF Concentration (pg/mL) in y axis (in linear and log10 scale for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10: Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12, Week 18.   
• 
Make one overall plot by treatment group, and a plot for each treatment group by ADA status for a total of 5 plots . 
• 
Include a marker for LLOQ, and an inset within the plot with “LLOQ (10.00 pg/mL)”. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Figure 14.4.2.2 
Pharmacodynamics: Individual Plot of Serum total NGF over time  
Safety Population 
 
ADA = Antidrug Antibodies; LLOQ = Lower Limit of Quantification; NGF = Nerve-Growth Factor. 
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.3 
 
 
Programming Notes: 
• 
Same shell as Figure 14.4.1.2 
• 
Insert the following text as legend: “Total NGF by Subject, Treatment group, and ADA status” followed by “(Linear Scale)” or “(Semi-Logarithmic 
Scale)” depending on the plot (linear or semi-log). Below legend, add legend for Treatment Group: 
. 
• 
Insert legend with different colors for each ADA status (Positive/ Negative). 
• 
Time (days) in x axis and Serum tNGF concentration (pg/mL) in y axis (in linear and log10 scale for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18.   
• 
Make one plot for each Treatment group (
 Placebo), for a total of 4 plots. 
• 
Include a marker for LLOQ, and an inset within the plot with “LLOQ (10.00 pg/mL)”. 
• 
Plots for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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 Page 1 of 218 
Sponsor: 
AstraZeneca 
Protocol Title 
A Randomised, Double-Blind, Placebo-Controlled, Dose-
Response Study of the Efficacy and Safety of MEDI7352 in 
Subjects with Painful Diabetic Neuropathy 
Development Phase 
2 
Protocol Numbers: 
D5680C00002 
Premier Research PCNs: 
MEDU177093 
Document Version: 
Final Version 1.2 
Document Date: 
04-Oct-2023
Document History 
Version 
Date 
Author 
Description 
0.1 
24-Mar-2023
 
Draft Version 
0.2 
21-Apr-2023
 
Draft Version 
0.3 
24-May-2023
 
Draft Version 
1 
12-Jul-2023
 
Final Version 
1.1 
31-Aug_2023
 
Final Version 
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Tables, Listings, and Figures Conventions 
All listings, tables, and graphs will have a header showing the sponsor company name, protocol 
and version of delivery and a footer showing the version of SAS, the file name and path, and the 
source of the data (listing number). 
The following reporting conventions will be adopted for the presentation of study data. These 
conventions will enhance the review process and help to standardize the presentation with common 
notations. 
General Reporting Conventions 
• All tables and data listings will be developed in landscape orientation. 
• Specialized text styles, such as bolding, italics, borders, shading, and superscripted and 
subscripted text will not be used in tables, figures, and data listings unless they add 
significant value to the table, figure, or data listing.  
• Only standard keyboard characters should be used in tables and data listings. Special 
characters, such as nonprintable control characters, printer-specific characters, or font 
specific characters, will not be used on a table, figure, or data listing. 
• Adverse events with missing MedDRA coding will have their system organ class preferred 
term presented as “Not Coded” and the Preferred Term presented as verbatim in the tables. 
The “Not Coded” frequencies will be sorted to the end of the tables. This will only be 
applicable for any deliveries sent before database lock (e.g., for dry runs). 
• Programming notes may be inserted into the shells, these notes will not appear in the final 
output. 
 
Population Summary Conventions 
• Population sizes may be presented for each classification factor as totals in the column 
header as (N=xx), where appropriate.  
• All population summaries for categorical variables will include all categories that were 
planned and for which the participants may have had a response. 
• All population summaries for continuous variables will include: n, mean, SD, median, 
quartiles, minimum, and maximum. Other summaries (e.g., number missing, geometric 
mean, 95% CIs, and coefficient of variation [CV] or % CV) may be used as appropriate. 
The precision of the maximum and minimum will match the maximum precision in the 
observed data and 2 decimals for derived data unless specifically mentioned in the 
corresponding shell. The mean and median will have 1 additional decimal place. The SD 
will have 2 additional decimal places. For derived data, minimum and maximum will be 
reported to 2 degrees of precision. Measures of location (mean and median) will be reported 
to 3 degree of precision, and measures of spread will be reported to 4 degrees of precision. 
• 
All percentages are rounded and reported to a single decimal point (xx.x%). Exceptions 
are 0 and 100 that will be displayed as 0 and 100% respectively. 
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Planned Tables, Figures and Listings  
• The table and listing numbers are place holders only and will be determined when the 
outputs are produced. 
• In all listings a blank line will be placed between each participant. Within a data listing, if 
an item appears line after line (e.g., repetition of participant number), then only the first 
occurrence will be displayed. 
• In data listings, the information for 1 participant will be kept on 1 page, if possible, rather 
than splitting a Subjects’s information across pages. 
 
 
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Planned Table Descriptions and Shells 
Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.1.2 - - Screening Population 
U 
Table 14.1.3 - Summary of Reasons for Screening Failure - Screen Failure Population 
U 
Table 14.1.4.1 - Demographics and Baseline Characteristics - Screening Population 
U 
Table 14.1.4.2 - Demographics and Baseline Characteristics - Safety Population 
R 
Table 14.1.4.3 - Demographics and Baseline Characteristics - mITT Population 
R 
Table 14.1.4.4 - Demographics and Baseline Characteristics - PK Population 
R 
Table 14.1.5.1 - Osteoarthritis Characteristics - Screening Population 
U 
Table 14.1.5.2 - Osteoarthritis Characteristics - Safety Population 
R 
Table 14.1.5.3 - Osteoarthritis Characteristics - mITT Population 
R 
Table 14.1.5.4 - Osteoarthritis Characteristics - PK Population 
R 
Table 14.1.6 - Medical History by System Organ Class and Preferred Term - Safety Population 
U 
Table 14.1.7 - Prior Medications by ATC Level 2 and Preferred Name - Safety Population 
U 
Table 14.1.8 - Protocol Deviations - Safety Population 
U 
Table 14.1.9 - Overall Study Drug Exposure - Safety Population  
U 
Table 14.2.1.1.1 - Daily Pain NRS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.1.1.2 - Daily Pain NRS: Summary Statistics (LOCF)Error! Reference source not 
found.- mITT Population 
R 
Table 14.2.1.1.3 - Daily Pain NRS: Summary Statistics (BOCF) - mITT Population 
R 
Table 14.2.1.2.1 - Daily Pain NRS: Primary MCP-Mod Analysis (LOCF) - mITT Population 
U 
Table 14.2.1.2.2 - Statistical Analysis of CFB to Week 12 Daily Pain NRS: Primary ANCOVA 
Analysis (LOCF) - mITT Population 
U 
Table 14.2.1.3.1 - Statistical Analysis of CFB Daily Pain NRS: MMRM Analysis. (Observed 
Cases) - mITT Population 
U 
Table 14.2.1.3.2 - Daily Pain NRS: Sensitivity of Primary MCP-Mod Analysis (BOCF) - mITT 
Population 
R 
Table 14.2.2.1 - Galer NPS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.2.2 - Galer NPS: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.3.1 - DSIS: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.3.2 - DSIS: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.4.1 - SF-36: Summary Statistics (Observed Cases) - mITT Population 
U 
Table 14.2.4.2 - SF-36: MMRM Analysis (Observed Cases) - mITT Population 
U 
Table 14.2.5.1 - Rescue Medication Use: Summary Statistics - mITT Population 
U 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.2.6.1.1 - Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel Haenszel 
(Observed Cases) - mITT Population 
U 
Table 14.2.6.1.2 - Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel Haenszel 
(Observed Cases): All Visits - mITT Population 
 
Table 14.2.6.2 - Daily Pain NRS Responder Analysis (≥30%): GEE Analysis (Observed Cases) 
- mITT Population 
U 
Table 14.2.7.1.1 - Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel Haenszel 
(Observed Cases) - mITT Population 
R 
Table 14.2.7.1.2 - Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel Haenszel 
(Observed Cases): All Visits - mITT Population 
 
Table 14.2.7.2 - Daily Pain NRS Responder Analysis (≥50%): GEE Analysis (Observed Cases) 
- mITT Population 
R 
Table 14.2.8.1 - Patient Global Impression of Change: Summary Statistics - mITT Population 
U 
Table 14.2.8.2 - Patient Global Impression of Change: Cochran-Mantel Haenszel - mITT 
Population 
U 
 
U 
Table 14.3.1.1 - Summary of Overall Adverse Events - Safety Population 
U 
Table 14.3.1.2 - Treatment Emergent of Adverse Events by System Organ Class and Preferred 
Term - Safety Population 
U 
Table 14.3.1.3 - Treatment Emergent of Adverse Events by Severity, System Organ Class and 
Preferred Term - Safety Population 
U 
Table 14.3.1.4 - Treatment Emergent Adverse Events by Relationship to Study Medication, 
System Organ Class and Preferred Term - Safety Population 
U 
Table 14.3.1.5 - Treatment Emergent Adverse Events by ADA Status Category, System Organ 
Class and Preferred Term - Safety Population 
U 
Table 14.3.1.6 - Treatment Emergent Adverse Events Leading to Discontinuation of Study drug 
by System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.1.7 - Non-Serious Adverse Events Occurring in More than 5% of Subjects by 
System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.1.8 - Treatment Emergent Adverse Events Occurring in More than 5% of Subjects 
by Preferred Term - Safety Population 
R 
Table 14.3.1.9 - Treatment Emergent Adverse Events by Preferred Term - Safety Population 
R 
Table 14.3.2.1.1 - Serious Adverse Events by System Organ Class and Preferred Term - Safety 
Population 
R 
Table 14.3.2.1.2 - Life-Threatening Serious Adverse Events by System Organ Class and 
Preferred Term - Safety Population  
R 
Table 14.3.2.1.3 - Serious Adverse Events with Outcome Death by System Organ Class and 
Preferred Term - Safety Population 
R 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.3.2.1.4 - Serious Adverse Events by Relationship to Study Medication, System Organ 
Class and Preferred Term - Safety Population 
R 
Table 14.3.3.1 - Listing of Serious Adverse Events - Safety Population 
U 
Table 14.3.3.2 - Listing of Deaths - Safety Population 
U 
Table 14.3.2.2.1 - Treatment Emergent Adverse Events Associated with Abnormal Liver by 
System Organ Class and Preferred Term - Safety Population 
R 
Table 14.3.2.2.2 - Potential Joint Related Adverse Events of Special Interest by System Organ 
Class and Preferred Term - Safety Population 
R 
 Table 14.3.2.2.3 - Serious and/or severe Infections by System Organ Class and Preferred Term 
- Safety Population 
R 
Table 14.3.2.2.4 - Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions 
Leading to Discontinuation of IP by System Organ Class and Preferred Term - Safety 
Population 
R 
Table 14.3.4.1 - Descriptive Summary of Clinical Chemistry - Safety Population 
U 
Table 14.3.4.2 - Shift Table of Clinical Chemistry Results - Safety Population 
U 
Table 14.3.4.3 - Descriptive Summary of Hematology - Safety Population 
R 
Table 14.3.4.4 - Shift Table of Hematology Results - Safety Population 
R 
Table 14.3.4.5 - Descriptive Summary of Coagulation - Safety Population 
R 
Table 14.3.4.6 - Shift Table of Coagulation Results - Safety Population 
R 
Table 14.3.4.7 - Descriptive Summary of Urinalysis - Safety Population 
U 
Table 14.3.4.8 - Shift Table of Urinalysis Results - Safety Population 
R 
Table 14.3.4.9 - Maximum On-Treatment ALT and AST versus Maximum On-Treatment Total 
Bilirubin - Safety Population 
U 
Table 14.3.5.1 - Descriptive Summary of Vital Signs - Safety Population 
U 
Table 14.3.5.2 - Descriptive Summary of Digital ECG Data - Safety Population 
U 
Table 14.3.5.3 - Summary of Overall Evaluation of safety ECG Data - Safety Population 
U 
Table 14.3.5.4 - Covid-19 Screening - Safety Population 
U 
Table 14.3.5.5 - Summary of Sub-Scores for Total Neuropathy Score-Nurse - Safety Population 
U 
Table 14.3.5.6 - Descriptive Summary of Total Neuropathy Score-Nurse - Safety Population 
U 
Table 14.3.5.7.1 - Summary of Motor and Sensory Nerve Conduction Studies - Safety 
Population 
U 
Table 14.3.5.7.2 - Shift Table of Motor and Sensory Nerve Conduction Results - Safety 
Population 
 
Table 14.3.5.8 - Summary of Strength and Deep Tendon Reflexes - Safety Population 
U 
Table 14.3.5.9 - Summary of Local Injection Site Reactions - Safety Population 
U 
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Number     Title     Population 
Unique (U) or 
Repeated (R) 
Table 14.3.5.10 - Summary of Hypersensitivity/Anaphylactic Reactions - Safety Population 
U 
Table 14.3.5.11 - Summary of Liver Diagnostic Investigations - Safety Population 
U 
Table 14.3.5.12 - Summary of Liver Risk Factors and Lifestyle Events - Safety Population 
U 
Table 14.3.5.13 - Summary of Liver Signs and Symptoms - Safety Population 
U 
Table 14.3.5.14 - Summary of Infection Diagnostic Investigations - Safety Population 
U 
Table 14.3.5.15 - Summary of Infection Risk Factors and Lifestyle Events - Safety Population 
U 
Table 14.3.5.16 - Summary of Infection Signs and Symptoms - Safety Population 
U 
Table 14.3.5.17 - Summary of Concomitant Medications by ATC Level 2 and Preferred Name - 
Safety Population 
R 
Table 14.3.5.18 - Summary of Concomitant Procedures - Safety Population 
R 
Table 14.3.5.19 - Anti-Drug Antibody Results and Titre Summary by Timepoint - Safety 
Population 
U 
Table 14.3.5.20 - Descriptive Summary of Anti-Drug Antibody Results and Titre by ADA 
Categories - Safety Population 
U 
Table 14.4.1 - Summary of Serum MEDI7352 Concentrations - PK Population 
U 
Table 14.4.2 - Summary of Serum total NGF Concentrations - PD Population 
U 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table Change Log 
Output 
Number 
Date of 
Change 
Change Made 
By (initials) 
Description/Rationale 
 
 
 
 
 
 
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1. Demographic Data 
Table 14.1.2 
Subject Disposition  
Screening Population 
 
Placebo 
MEDI7352 
Total 
Status 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Screening Population [1] 
 
 
 
 
xx (100%) 
  Screen Failures 
 
 
 
 
xx (xx.x %) 
  Enrolled Subjects 
 
 
 
 
xx (xx.x %) 
  Re-screened Subjects 
 
 
 
 
xx (xx.x %) 
 
 
 
 
 
 
Randomized Subjects  
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
Randomized and Not Treated Subjects 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
    Reason for Discontinuation 
 
 
 
 
 
        Adverse Event 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
        Other 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
Safety Population [2] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
mITT Population [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evaluable Week 12 Efficacy  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evaluable LOCF Efficacy [4] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not Efficacy Evaluable 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
PK Population [5] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Completed Study Treatment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Discontinued Study Treatment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Reason for Discontinuation: 
 
 
 
 
 
   Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lack of Efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lost to Follow-up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Non-compliance with Study Drug 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Physician Decision 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pregnancy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Progressive Disease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Protocol Violation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
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   Study Terminated by Sponsor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Technical Problems 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Withdrawal by Subject 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sponsor Decision 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Completed Study  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Withdrawn from the Study 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Reason for Discontinuation: 
 
 
 
 
 
   Adverse Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lack of Efficacy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lost to Follow-up 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 = Coronavirus disease 2019; LOCF = Last Observation Carried Forward; mITT = modified intent-to-treat; N = number of subjects per treatment 
group; PK = pharmacokinetic. 
Note: Percentages are n/Number of subjects randomized*100 as displayed in column header N, except for the screened, enrolled  and re-screened where 
n/Number of Screening subjects*100, and for the randomized, where n/Number of Enrolled subjects*100. 
Re-screened subjects are a subset of the Screening population. 
[1] The Screening Population includes all subjects who provide informed consent and provide demographic and/or baseline screening assessments. 
[2] The Safety Population includes all subjects who receive at least 1 dose of double-blind study medication. 
[3] The mITT Population includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
[4] Subjects in the mITT Population with LOCF applied for missing efficacy data at week 12, 
[5] The PK Population includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
 
Reference Listings: 16.2.1.1, 16.2.1.2, 16.2.1.3, 
 
 
Programming Notes:  
• 
Display only reasons for early discontinuation with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
  
 
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Table 14.1.3 
Summary of Reasons for Screening Failure 
Screen Failure Population 
 
Total 
 
(N=xx) 
 
 
Number of Subjects Who Don’t Meet Inclusion/Exclusion Criteria  
xx (xx.x%) 
 
 
  IC 01: Xxxxxxxxxxxx 
xx (xx.x%) 
 
 
  IC 02: Xxxxxxxxxxxx 
xx (xx.x%)  
 
 
… 
 
 
 
  EC 01: Xxxxxxxxxxxx 
xx (xx.x%) 
 
 
  EC 02: Xxxxxxxxxxxx 
xx (xx.x%)  
 
 
  … 
 
 
 
Number of Subjects Who are Screen Failure for other Reason than Eligibility Criteria 
xx (xx.x%) 
 
 
EC = exclusion criteria; IC = inclusion criteria; N = number of subjects. 
Note:  subject can be counted in more than one criterion. 
Reference Listing 16.2.1.4 
 
 
 
 
 
 
 
 
 
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Table 14.1.4.1 
Demographics and Baseline Characteristics 
Screening Population 
 
Variable 
Placebo 
MEDI7352 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Age (years) [1] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Age Category 
 
 
 
 
 
   ≥18 - <65 years 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   ≥65 years 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Gender 
 
 
 
 
 
   Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Ethnicity 
 
 
 
 
 
   Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Race 
 
 
 
 
 
   American Indian or Alaska Native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Black or African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Native Hawaiian or Other Pacific Islander 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Not Specified 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Screening Height (cm) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
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Screening Weight (kg)  
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Screening BMI (kg/m²) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Female characteristics [2] 
 
 
 
 
 
   Surgically sterile 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Postmenopausal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Fully vaccinated for COVID-19 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
BMI = Body Mass Index; COVID-19 = Coronavirus disease 2019; n = number of subjects by treatment group with collected parameter; N = number of 
subjects per treatment group; SD = standard deviation. 
Note: The Screening Population includes all subjects who are enrolled and provide informed consent and demographic and/or baseline screening assessments. 
[1] Age was calculated as age at time of consent. 
[2] Percentages are n/Number of Female subjects from Analysis Population*100 
Reference Listing: 16.2.4.1 
 
Programming Notes: 
• 
If a variable is between 2 pages, start the variable in the second page. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.1.4.2 
Demographics and Baseline Characteristics 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.4.3 
Demographics and Baseline Characteristics 
mITT Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.4.4 
Demographics and Baseline Characteristics 
PK Population 
Programming Notes: 
• 
Same shell as Table 14.1.4.1. 
• 
Keep all possible values for each category even if no subject. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.1.5.1 
Osteoarthritis Characteristics 
Screening Population 
 
Placebo 
MEDI7352 
Total 
Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
Subjects diagnosed with Osteoarthritis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Joint(s)/Area(s) affected: 
 
 
 
 
 
   Shoulder 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Elbow 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hip 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Knee 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ankle 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Spine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hands 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Feet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Osteoarthritis clinically significant 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Radiologic investigations conducted [1] 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Plain radiography 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     MRI 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Joint(s)/Area(s) investigated: 
 
 
 
 
 
   Shoulder 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Elbow 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hip 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Knee 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ankle 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Spine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
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   Hands 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Feet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Osteoarthritis radiologically significant 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Kellgren-Lawrence score reported 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 0  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Grade 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No/Not applicable 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Radiologic Scoring System Used? 
 
 
 
 
 
   Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
MRI = magnetic resonance imaging; N = number of subjects per treatment group. 
[1] Subjects who reported more than one radiologic investigation within each category were only counted once. 
Reference Listing: 16.2.4.3 
 
Programming Notes: 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
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Table 14.1.5.2 
Osteoarthritis Characteristics 
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.5.3 
Osteoarthritis Characteristics 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
Table 14.1.5.4 
Osteoarthritis Characteristics 
PK Population 
 
Programming Notes: 
• 
Same shell as Table 14.1.5.1. 
• 
Display only Joint(s)/Areas(s) affected and investigated with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
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Table 14.1.6 
Medical History by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xxx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xxx) 
 
 
 
 
 
 
Any Medical History 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   … 
… 
… 
… 
… 
… 
 
 
 
 
 
 
System Organ Class n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Note: All medical history terms were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 26.0. At each level of summarization 
(system organ class or preferred term), subjects having more than one medical history term were counted only once. System organ class and preferred terms 
are sorted in descending order of frequency of Total column, and alphabetically if same frequency. 
 
Reference Listing: 16.2.4.2 
 
Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Sort SOC and PT (within SOC) in descending order of frequency in the Total column.  Sort alphabetically in case of ties. 
• 
Uncoded Medical History Events 
o When there are uncoded Medical History Events in the database, the events will be summarized with SOC and PT set to [Not Coded]. The [Not 
Coded] will be sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.1.7  
Prior Medications by ATC Class and Preferred Name 
Safety Population 
 
ATC Class [1] 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Subjects with at Least One Prior 
Medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC Level 2 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC Level 2 n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Preferred Name n 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
ATC = Anatomical Therapeutic Class; N = number of subjects per treatment group. 
[1] ATC Class is defined as ATC Level 2. 
Note: Prior medications are defined as medications that started before first dose of study, whether they were stopped before first dose of study medication or 
not. All prior medications are coded using WHO drug dictionary version vMar2023. At each level of summarization (ATC Level 2 or Preferred Name), 
subjects who reported more than one prior medication were only counted once. ATC Level 2 and Preferred Term are sorted in descending order of frequency 
of total, and alphabetically if same frequency.  
Reference Listing: 16.2.9.16 
 
Programming Notes: 
• 
If uncoded ATC Level or Preferred Name, please put them as [Not Coded] 
• 
ATC and Preferred Name texts should be in proper case in table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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Table 14.1.8  
Protocol Deviations 
Safety Population 
 
 
Placebo 
MEDI7352 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Subjects With Any Important Protocol 
Deviation/Violation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Protocol Deviation Type 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 5 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Protocol Deviation Type 6 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
………….. 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Notes: Percentages are n/Number of subjects by treatment group*100. 
Subjects with one or more deviations within a type of protocol deviation were counted only once. 
 
Reference Listing 16.2.2.1 
 
Programming Notes: 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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2. 
Exposure and Compliance 
Table 14.1.9 
Overall Study Drug Exposure 
Safety Population 
 
Placebo 
MEDI7352 
Total 
Category/ Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
Maximum Number of Doses Administered [1] 
 
 
 
 
 
1 Dose 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
3 Doses 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
4 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
5 Doses 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
6 Doses 
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
xx (xx.x%)  
 
 
 
 
 
 
Total Duration of Exposure (days) [2] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Total (cumulative) IP volume infused (mL) 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
n = number of subjects by treatment group with collected parameter; N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; 
Q3 = third quartile. 
[1] Subjects are counted once for each level of dose administered. 
[2] Duration of exposure (days) = min(date of last dose of treatment + 14 days or date of death) – date of first dose of treatment + 1. 
Reference Listing: 16.2.5.1 
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Programming Notes: 
• 
Add all categories even if count is 0. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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3. 
Primary Efficacy Analysis 
Table 14.2.1.1.1 
Daily Pain NRS: Summary Statistics (Observed Cases) 
mITT Population 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; DPS = Daily Pain Score; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per 
treatment group; NRS = Numeric Rating Scale; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are weekly averages of the average daily pain scores on an 11-point (0-10) NRS and CFB for the same variable. Total N for the mITT 
population = 106 at Week 2 as Subject 
 has < 4 days of diary pain data on that visit, completing the following visits till Week 12. 
[1] Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e., Day -7 to Day -1, inclusive.  
Reference Listing: 16.2.6.1 
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Programming Notes: 
• 
Include all observed data (Not the LOCF) on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, 12 and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.1.1.2 
Daily Pain NRS: Summary Statistics (LOCF) 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.2.1.1.1. 
• 
Include all observed and LOCF data on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and  12 
• 
Add abbreviation in footnote: LOCF = Last Observation Carried Forward. 
• 
Add the following note in footnote: “LOCF applied to Week 12 only”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
Table 14.2.1.1.3 
Daily Pain NRS: Summary Statistics (BOCF) 
mITT Population 
 
Programming Notes: 
• 
Same shell as Table 14.2.1.1.1. 
• 
Include all observed and BOCF data on weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and 12 
• 
Add abbreviation in footnote: BOCF = Baseline Observation Carried Forward. 
• 
Add the following note in footnote: “BOCF applied to Week 12 only”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
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Table 14.2.1.2.1 
Daily Pain NRS: Primary MCP-Mod Analysis (LOCF) 
mITT Population 
Primary ‘MCP’ step 
Model 
        Contrast [1] 
 
 
 
t value 
1-sided adjusted P-value [2] 
Hyperbolic Emax 
 
 
 
 
 
        ED50 = 7.5 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 15 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 30 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 60 
 
 
 
xx.xx 
0.xxxx 
        ED50 = 750 
 
 
 
xx.xx 
0.xxxx 
 
 
 
 
 
 
Primary Overall MCP test 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; LOCF = Last Observation Carried Forward; MCP = Multiple Comparisons; Procedure; NRS = Numeric rating scale. 
[1] ED50 = Effective Dose giving half of the asymptotic maximum effect. 
[2] Multiplicity Adjusted P-value. 
Reference Listing: 16.2.6.1 
 
 
 
 
 
 
 
 
 
 
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‘MOD’ step [3] 
Selected Model xxxxxxxxxx 
Parameter 
Estimate 
95% CI of Estimate [6] 
ED50 
xx.x 
[ x.xx to x.xx ] 
ED90 [4] 
xx.x 
[ x.xx to x.xx ] 
Asymptotic ED90 [5] 
xx.x 
[ x.xx to x.xx ] 
Dose to achieve target (-1.25) effect 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 
 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 
 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 
 
xx.x 
[ x.xx to x.xx ] 
Treatment effect at dose = 
 
xx.x 
[ x.xx to x.xx ] 
CI: Confidence Interval; LOCF = Last Observation Carried Forward; MCP = Multiple Comparisons; Procedure; MOD = Modelling; NRS = Numeric rating 
scale. 
[3] Results from the ‘MOD’ step will only be available in case any of the MCP tests is statistically significa nt. 
[4] ED90 = Effective Dose giving 90% of the effect of the maximum dose studied. 
[5] Asymptotic ED90 = Effective Dose giving 90% of the asymptotic maximum effect. 
[6] 2.5% and 97.5% quantiles taken from 100000 samples from the multivariate normal distribution for model fitted estimates and its covariance matrix. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
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Table 14.2.1.2.2 
Statistical Analysis of CFB to Week 12 Daily Pain NRS: Primary ANCOVA Analysis (LOCF)  
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
[ x.xx to x.xx ] 
 
 
Co-Medication Type 
 
 
3 
 
 
 
0.xxxx 
Baseline pain NRS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
ANCOVA = analysis of covariance; CFB = Change from Baseline; 
CL = Confidence limits; LOCF = Last Observation Carried Forward; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: ANCOVA by dose using NRS baseline value and co-medication as covariates, with CFB to Week 12 (LOCF) 
as dependent variable. 
 
Least Square Means 
Treatment 
Number of Subjects 
LS mean [3] 
95% CI of LS mean 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LOCF = Last Observation Carried Forward; LS = least square; NRS = Numeric rating scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average pain NRS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.1 
 
 
 
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Programming Notes: 
• 
Concomitant co-medication Type indicated for Painful Diabetic Neuropathy: either anticonvulsant class (pregabalin or gabapentin) or antidepressant 
class (duloxetine, venlafaxine, or amitriptyline). 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.1.3.1 
Statistical Analysis of CFB Daily Pain NRS: MMRM Analysis. (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
3 
 
 
 
0.xxxx 
Week 
 
 
6 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
18 
 
 
 
0.xxxx 
Baseline pain NRS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM = Mixed Model for Repeated Measures; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, NRS baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
Note: model was fitted using an unstructured covariance structure. Estimates for difference vs Placebo at Week 12. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: Week xxxxx 
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
- Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square; NRS = Numeric rating scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average pain NRS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
Include LSmeans and difference in LSmean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.1.3.2 
Daily Pain NRS: Sensitivity of Primary MCP-Mod Analysis (BOCF) 
mITT Population  
 
Programming Notes: 
• 
Same shell as Table 14.2.1.2.1, substituting “LOCF = Last Observation Carried Forward” by “BOCF = Baseline Observation Carried Forward”. 
• 
The MCP-MOD approach will only be performed if stage 4 is initiated, otherwise there would be insufficient dosing data to fit the non-linear models. 
 
 
 
 
 
 
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4. 
Secondary Efficacy Analysis 
Table 14.2.2.1 
Galer NPS: Summary Statistics (Observed Cases)  
mITT Population 
Parameter: xxxxx 
 
 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
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For Pain Duration Frequency  
 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   I feel a background pain all of the time and occasional flare-ups 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   I feel a single type of pain all the time 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   feel a single type of pain only sometimes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NPS = 
Neuropathic Pain Scale; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are Pain Intensity, Unpleasantness, and Descriptor scores on an 11-point (0-10) NRS, and Pain Duration/Frequency on a 3-point NRS (1-3), 
plus CFB for the same variables. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.6.2 
 
Programming Notes: 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Repeat for the Parameters: Pain intensity, Pain Unpleasantness, Pain Sharpness, Pain Hotness, Pain Dullness, Pain Coldness, Pain Sensitivity, Pain 
Itching, Deep Pain Intensity, Surface Pain Intensity (All in an 11-point NRS), Galer NPS Total Score (ranging from 0 to 100), and Pain 
Duration/Frequency (in a 3-point NRS). 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.2.2 
Galer NPS: MMRM Analysis (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-Medication type 
 
 
3 
 
 
 
0.xxxx 
Week 
 
 
3 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
9 
 
 
 
0.xxxx 
Baseline NPS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; NPS = Neuropathic Pain Scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, baseline total NPS score value, and Co-medication type as 
covariates, with total NPS score CFB as dependent variable. 
Note: model was fitted using an unstructured covariance structure. 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: Week: xxxx  
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square; NPS = Neuropathic Pain Scale. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline total NPS score evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.2 
 
Programming Notes: 
• 
Include LSmeans and difference in LSmean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Analysis is done for Galer NPS Total Score. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Table 14.2.3.1 
DSIS: Summary Statistics (Observed Cases) 
mITT Population  
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 4 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; DSIS = Daily Sleep Interference; n = number of subjects by treatment group at each visit for the parameter; N = number of 
subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are weekly averages of the average daily sleep interference scores on an 11-point (0-10) NRS and CFB for the same variable. 
[1] Baseline is defined as the average of the ‘non-missing’ DSIS within the seven-day period prior to randomization i.e., Day -7 to Day -1, inclusive. 
Reference Listing: 16.2.6.3 
 
 
 
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Programming Notes: 
• 
Include all observed data on weekly averages of the average daily Sleep Interference score for Baseline, Week 4, 8, 12, and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.3.2 
DSIS: MMRM Analysis (Observed Cases) 
mITT Population 
Model parameter estimates 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
3 
 
 
 
0.xxxx 
Week 
 
 
3 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
9 
 
 
 
0.xxxx 
Baseline DSIS 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; DSIS = Daily Sleep Interference. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Time, Treatment, Treatment*Time, DSIS baseline value, and Co-medication type as covariates, 
with CFB as dependent variable. 
Note: model was fitted using an unstructured covariance structure. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Least Square Means: Week xxxx 
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
- Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline 
weekly average DSIS parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.3 
 
Programming Notes: 
• 
Include LS means and difference in LS mean with Placebo in repeated tables for the Treatment*Week interaction. 
• 
Include all observed data on weekly average DSIS for Baseline, Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.4.1 
SF-36: Summary Statistics (Observed Cases) 
mITT Population  
Parameter: xxxxx 
 
 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 12 CFB 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
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When parameter is “Change in general Health” 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   Much better now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Somewhat better now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   About the same as one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Somewhat worse now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Much worse now than one year ago 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 12 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NRS = 
numeric rating scale; SD = standard deviation; SF-36 = 36-Item Short-Form Health Survey; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are derived SF-36 scores and Change in General Health on a 5-point NRS (1-5), plus CFB for the same variables. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.6.4 
 
Programming Notes: 
• 
Include all observed data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical functioning, Role limitations due to physical health, Role limitations due to emotional problems, Vitality 
(Energy/fatigue), Emotional well-being, Social functioning, Pain and General Health (from 0 to 100), Physical Health Summary, Mental Health 
Summary, and Change in general Health (in a 5-point NRS). 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.2.4.2 
SF-36: MMRM Analysis (Observed Cases) 
mITT Population 
 
Model parameter estimates: xxxxxxxx 
Parameter 
Estimate 
t value 
Degrees of freedom Standard Error 
2-sided 95% unadjusted 
CL 
Asymmetric CL 
[1] 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
 
Co-medication type 
 
 
3 
 
 
 
0.xxxx 
Week 
 
 
1 
 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
 
0.xxxx 
Treatment*Week 
 
 
3 
 
 
 
0.xxxx 
Baseline SF-36 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
[ x.xx to x.xx ] 
0.xxxx 
Model residual standard deviation 
xx.xx 
 
 
 
 
 
 
CFB = Change from Baseline; CL = Confidence limits; MMRM: Mixed Model for Repeated Measures; SF-36 = 36-Item Short-Form Health Survey. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: MMRM using Treatment, SF-36 baseline value, and Co-medication type as covariates, with CFB as dependent 
variable. 
Note: model was fitted using an unstructured covariance structure. 
 
 
 
 
 
 
 
 
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Least Square Means: xxxxxxxx  
Treatment 
Number of patients 
LS mean [3] 
95% CI of LS mean 
Placebo 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 
xx 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
MEDI7352 
 - Placebo 
 
x.xx 
[ x.xx to x.xx ] 
CI = Confidence interval; LS = least square. 
[3] The LS mean is a model estimate using fitted group parameter and the baseline SF-36 parameter evaluated at the grand mean over each group. 
Reference Listing: 16.2.6.4 
 
Programming Notes: 
• 
Include LSmeans and difference in LSmean with Placebo.. 
• 
Include all observed data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical Health Summary, and Mental Health Summary Add parameter name after ‘Model parameter estimates:’ and after 
‘Least Square Means:’ 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Table 14.2.5.1 
Rescue Medication Use: Summary Statistics 
mITT Population 
 
Variable   
Placebo 
MEDI7352 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
Number of subjects taking any 
rescue medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Number of subjects taking any 
permitted rescue medication  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Total number of days rescue 
medication was used [1] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Cumulative consumption of 
Paracetamol Rescue Medication 
(mg) [2] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Paracetamol Rescue Medication 
Average Daily Dose (mg) [3] 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
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Number of subjects taking any 
prohibited rescue medication 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Each day on which permitted rescue medication was used at least once is counted. 
[2] Calculated as the total dose of paracetamol rescue medication (mg). 
[3] Calculated as: cumulative consumption of paracetamol rescue medication (mg) /total number of days rescue medication was used. 
 
Reference Listing: 16.2.6.5 
 
 
Programming Notes: 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
• 
Refer to  
 
 
 
 
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Table 14.2.6.1.1 
Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel Haenszel (Observed Cases) 
mITT Population 
Cochran-Mantel-Haenszel Test 
Treatment/ 
    Category 
Number of  
Subjects (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Placebo (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
 
 
 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata of MEDI7352 dose - Placebo. 
[2] P-value < 0.05 indicates a significant association between number of subjects with >=30% decrease from Baseline and treatment across strata. 
Note: a separate CMH test is performed for each dose versus placebo at Week 12. 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 12. 
 
 
 
 
 
 
 
 
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Table 14.2.6.1.2 
Daily Pain NRS Responder Analysis (≥30%): Cochran-Mantel Haenszel (Observed Cases): All Visits   
mITT Population 
 
Cochran-Mantel-Haenszel Test: MEDI7352 xxx μg/kg vs Placebo 
Visit/ 
    Category 
Number of  
Patients (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Placebo, Week 4 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Placebo, Week 4 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 8 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Placebo, Week 12 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
 
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Placebo, Week 18 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   >=30% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata of MEDI7352 dose - Placebo. 
[2] P-value < 0.05 indicates a significant association between number of subjects with >=30% decrease from Baseline and treatment across strata. 
Note: a separate CMH test is performed for each dose versus placebo. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
Include all observed data for Week 4, 8, 12, and 18. 
 
 
 
 
 
 
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Table 14.2.6.2 
Daily Pain NRS Responder Analysis (≥30%): GEE Analysis (Observed Cases)  
mITT Population 
 
Model parameter estimates: Week X 
Parameter 
Estimate 
Z value 
Degrees of freedom 
Standard Error 
2-sided 95% CL 
2-sided  
P-value [2] 
Intercept 
xx.xx 
xx.xx 
 
xx.xxx 
 
 
Co-medication type 
 
 
3 
 
 
0.xxxx 
Week 
 
 
3 
 
 
0.xxxx 
Treatment 
 
 
3 
 
 
0.xxxx 
Treatment*Week 
 
 
9 
 
 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
MEDI7352 
 vs Placebo 
xx.xx 
xx.xx 
1 
xx.xxx 
[ x.xx to x.xx ] 
0.xxxx 
Dispersion 
xx.xx 
 
 
 
 
 
CL = Confidence limits; GEE: Generalized Estimation Equations; NRS = Numeric rating scale. 
[1] Lower limit of 1-sided 90% CL and upper limit of 1-sided 80% CL. 
[2] P-value is derived from the following model: GEE using Time, Treatment, Treatment*Time and Co-medication type as covariates, with dependent binary 
variable indicating whether weekly average pain NRS has >=30% decrease from Baseline. 
Note: model was fitted using a first-order autoregressive covariance structure. Estimates for MEDI7352 dose vs placebo and for 2-sided 95% CL displayed in 
odds ratio scale. 
 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
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Table 14.2.7.1.1 
Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel Haenszel (Observed Cases) 
mITT Population 
 
Cochran-Mantel-Haenszel Test 
Treatment/ 
    Category 
Number of  
Subjects (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Placebo (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
 
 
 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
MEDI7352 
 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata of MEDI7352 dose - Placebo. 
[2] P-value < 0.05 indicates a significant association between number of subjects with >=50% decrease from Baseline and treatment across strata. 
Note: a separate CMH test is performed for each dose versus placebo at Week 12. 
Reference Listing: 16.2.6.1 
 
Programming notes: 
• 
Include all observed data for Week 12. 
 
 
 
 
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Table 14.2.7.1.2 
Daily Pain NRS Responder Analysis (≥50%): Cochran-Mantel Haenszel (Observed Cases): All Visits   
mITT Population 
 
Cochran-Mantel-Haenszel Test: MEDI7352 xxx μg/kg vs Placebo 
Visit/ 
    Category 
Number of  
Patients (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Placebo, Week 4 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Placebo, Week 4 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 8 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Placebo, Week 12 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
 
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Placebo, Week 18 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   >=50% decrease from Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata of MEDI7352 dose - Placebo. 
[2] P-value < 0.05 indicates a significant association between number of subjects with >=50% decrease from Baseline and treatment across strata. 
Note: a separate CMH test is performed for each dose versus placebo. 
Reference Listing: 16.2.6.1 
 
Programming Notes: 
• 
Include all observed data for Week 4, 8, 12, and 18. 
 
  
 
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Table 14.2.7.2 
Daily Pain NRS Responder Analysis (≥50%): GEE Analysis (Observed Cases) 
mITT Population 
 
Programming notes: 
• 
Same shell as Table 14.2.6.2. Change footnote in [2] as: “p-value is derived from the following model: GEE using Time, Treatment, Treatment*Time 
and Co-medication type as covariates, with dependent binary variable indicating whether weekly average pain NRS has >=50% decrease from Baseline. 
Note: model was fitted using an unstructured covariance structure, with 'MEDI7352
' and 'MEDI7352 
 treatment groups, together with 
co-medication categories (both types at the same time and none) dropped from the analysis to make the generalized Hessian matrix positive definite. 
Estimates for MEDI7352 dose vs placebo and for 2-sided 95% CL displayed in odds ratio scale.”. 
• 
Include all observed data for Week 4, 8, 12, and 18. 
• 
Rows for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.2.8.1 
Patient Global Impression of Change: Summary Statistics 
mITT Population 
 
 
Placebo 
MEDI7352 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=XX) 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
   Number of PGIC Responders 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Very Much Improved   
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Much Improved 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Minimally Improved 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      No change 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Minimally Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Much Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Very Much Worse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
Week 8 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group; PGIC = Patient Global Impression of Change. 
Note: Percentages for Number of subjects in the different improvement categories relative to baseline are n/Number of Subject s by treatment group at each 
visit *100. 
 
Reference Listing: 16.2.6.6 
 
Programming notes: 
• 
Include all observed data on PGIC scores for Week 4, 8, 12 and 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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Table 14.2.8.2 
Patient Global Impression of Change: Cochran-Mantel Haenszel  
mITT Population 
 
Cochran-Mantel-Haenszel Test: MEDI7352 xxx μg/kg vs Placebo 
Visit/ 
    Category 
Number of  
Patients (%) 
Risk Difference [1] 
95% CI of Risk 
Difference 
2-sided  
P-value [2] 
Placebo, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Placebo, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 8 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
Placebo, Week 12 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
 
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Placebo, Week 18 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
 
 
 
MEDI7352 xxx μg/kg, Week 4 (n = xx) 
 
 
 
 
   Improved relative to Baseline 
xx (xx.x%) 
x.xx 
[ x.xx to x.xx ] 
0.xxxx 
 
 
 
 
 
CI = confidence interval; CMH = Cochran-Mantel-Haenszel; NRS = numeric rating scale. 
[1] Common effect for the strata (co-medication type*median Baseline Pain NRS) specific risk difference, representing common difference in probability across 
strata of MEDI7352 dose - Placebo. 
[2] P-value < 0.05 indicates a significant association between improvement relative to Baseline and treatment across strata. 
Note: median Baseline Pain NRS was calculated from subjects having valid NRS data on at least one of the above four post-baseline visits. Note: a separate 
CMH test is performed for each dose versus placebo. 
Reference Listing: 16.2.6.6 
 
Programming Notes: 
• 
Include all observed data on PGIC scores for Week 4, 8, 12 and 18. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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5. 
Exploratory Efficacy Analyses 
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6. 
Safety and Tolerability 
6.1. 
Displays of Adverse Events 
Table 14.3.1.1 
Summary of Overall Adverse Events  
Safety Population 
 
 
Placebo 
MEDI7352 
Total 
Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with any AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE possibly related 
to IP [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE leading to 
Discontinuation of IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any TEAE related to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Mild related to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Moderate related 
to IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   TEAE categorized as Severe related to 
IP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with any SAE leading to Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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AE = adverse event; IP = Investigational product, N = number of subjects per treatment group; SAE = serious adverse event; TEAE = treatment emergent 
adverse event. 
[1] Possibly related is defined as with reasonable possibility that the AE was caused by the IP, as assessed by investigator. 
Note: Subjects who reported more than one adverse event within each category were only counted once. A TEAE is defined as an adverse event with an onset 
at the time of or following the start of treatment with IP. For TEAEs categorized by severity, subjects were counted at the maximum severity. 
Reference Listing: 16.2.7.1, 16.2.7.2, 16.2.7.3, 16.2.7.4 
 
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• 
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Table 14.3.1.2 
Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
 
System Organ Class 
Placebo 
MEDI7352 
Total 
    Preferred Term 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
All MEDI7352 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each SOC/PT 
category; N = number of subjects per treatment group; IP = investigational product; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-
emergent adverse event. 
Note: Results are n (n/N * 100) m is number of events.  
A TEAE is defined as AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT.  
AEs are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency.  
Reference Listing: 16.2.7.1 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. 
• 
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) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.3 
Treatment Emergent Adverse Events by Severity, System Organ Class and Preferred Term 
Safety Population 
System Organ Class 
 
 
 
 
 
 
   Preferred Term 
Placebo 
MEDI7352 
Total 
      Severity 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Subjects with at Least One TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
   Preferred Term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each 
SOC/PT/Severity category; N = number of subjects per treatment group; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-emergent 
adverse event. 
Note: Results are n (n/N * 100).  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT at the maximum severity.  
AEs are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency. 
Reference Listing 16.2.7.1 
 
 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Present only severity categories with at least one subject. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.4 
Treatment Emergent Adverse Events by Relationship to Study Medication, System Organ Class and Preferred Term  
Safety Population 
System Organ Class 
 
 
 
 
 
 
   Preferred Term 
Placebo 
MEDI7352 
Total 
      Relatedness 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Subjects with at Least One TEAE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
   Preferred Term 1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Related [1] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each 
SOC/PT/Relatedness category; N = number of subjects per treatment group; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-emergent 
adverse event. 
[1] Related is defined as reasonable possibility that the AE was caused by investigational product, as assessed by the investigator. If investigator's assessment 
is missing the event is judged as related. 
Note: Results are n (n/N *100).  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT for the most related AE.  
AEs are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency. 
Reference Listing 16.2.7.1 
 
 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Present only severity categories with at least one subject. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.1.5 
Treatment Emergent Adverse Events by ADA Status Category, System Organ Class and Preferred Term 
Safety Population 
Treatment: xxxxxxx 
 
 
 
 
 
System Organ Class 
ADA 
Negative  
ADA Positive 
TE-ADA + 
Non-TE-
ADA + 
TE 
Persistently 
ADA + 
TE 
Transiently 
ADA + 
Post-Baseline 
and Baseline 
Positive 
Only Baseline 
Positive 
    Preferred Term 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
 
 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 2 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
System Organ Class 3 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx xx (xx.x%) xx 
xx (xx.x%) xx 
 
AE = adverse event; ADA = Anti-Drug Antibodies; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of 
subjects within each SOC/PT category; N = number of subjects per ADA status category; PT = Preferred Term; SOC = System Organ Class; TE-ADA + = 
Treatment emergent ADA positive; TEAE = treatment-emergent adverse event. 
ADA categories are defined in the Statistical Analysis Plan. 
Note: Results are n (n/N *100) m is number of events.  
A TEAE is defined as an AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT.  
Table is sorted by international order for SOC, and alphabetically for PT. 
Reference Listing: 16.2.7.1 
 
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Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Repeat for Placebo,
 and Overall. 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”, and sorted at the end of the table. SOC. 
• 
A table for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.1.6 
Treatment Emergent Adverse Events Leading to Discontinuation of Study Drug by System Organ Class and Preferred Term  
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One TEAE leading to IP discontinuation”. 
• 
Update Reference Listing to 16.2.7.2. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.1.7 
Non-Serious Adverse Events Occurring in More than 5% of Subjects by System Organ Class and Preferred Term  
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One Non-Serious TEAEAE”. 
• 
Update footnote adding: “The 5% threshold for an AE to be displayed is taken from the Total column.” 
• 
Update Reference Listing  to 16.2.7.1. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
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Table 14.3.1.8 
Treatment Emergent Adverse Events Occurring in More than 5% of Subjects by Preferred Term   
Safety Population 
 
Placebo 
MEDI7352 
Total 
    Preferred Term 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
All MEDI7352 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
 
 
 
 
 
 
 
Subjects with at Least 
One TEAE 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
… 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each PT category; 
N = number of subjects per treatment group; PT = Preferred Term; TEAE = treatment-emergent adverse event. 
Note: Results are n (n/Number of subjects in the Safety population within each PT*100) m is number of events.  
A TEAE is defined as AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each PT.  
AEs are displayed by descending frequency of PT based on ‘All MEDI7352’ column, and alphabetically for PT of same frequency.  
The 5% threshold for a TEAE to be displayed is taken from the Total column. 
Reference Listing: 16.2.7.1 
 
Programming Notes: 
• 
PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as “Not Coded [PT]” and sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.3.1.9 
Treatment Emergent Adverse Events by Preferred Term  
Safety Population 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.8. 
• 
Display all TEAEs, not only the most common. 
• 
PT texts should be in proper case in table. 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as Not Coded [PT]”, and sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.2. 
Summary of Deaths and Other Serious Adverse Events 
 
Table 14.3.2.1.1 
Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One Treatment Emergent SAE”, add “SAE = Serious Adverse 
Event” to abbreviations. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
Table 14.3.2.1.2 
Life-Threatening Serious Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One Life-Threatening SAE”, add “SAE = Serious Adverse 
Event” to abbreviations. 
• 
Add “Note: Life-threatening SAEs as judged by the investigator”. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated  
 
 
 
 
 
 
 
 
 
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Table 14.3.2.1.3 
Serious Adverse Events with Outcome Death by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Number of Subjects with at Least One SAE with Outcome Death”, add “SAE = Serious Adverse 
Event” to abbreviations. 
• 
Change footnote for “Reference Table 14.3.3.2”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated . 
 
 
 
 
Table 14.3.2.1.4 
Serious Adverse Events by Relationship to Study Medication, System Organ Class and Preferred Term  
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.4. Change first row to be “Number of subjects with at Least One Treatment Emergent SAE”, add “SAE = Serious Adverse 
Event” to abbreviations. 
• 
Change footnote for “Reference Table 14.3.3.1”. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.3.1 
Listing of Serious Adverse Events 
Safety Population 
Subject ID/ 
Treatment Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
AE Start Date/Time 
(Study Day)/ 
   End Date/Time (Study 
Day) 
Severity/ 
   Relationship [1] 
Outcome/ 
  Action Taken with IP/ 
    Therapy taken for this AE? 
 
SAE 
Leading 
to Study 
DC? 
TEAE? 
Serious? /
Serious 
Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:M
M (X)/ 
DDMMMYYYY/HH:M
M (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
     XXXXXXXXXX/ 
                         Yes 
No 
No  
XX 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXXXX 
 
DDMMMYYYY/HH:M
M (X)/ 
DDMONYYYY/HH:
MM (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
   XXXXXXXXXX/ 
                        No 
Yes 
XX 
XX / 
XXX 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMONYYYY/HH:M
M (X)/ 
   Ongoing 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXXXX/No 
No 
XX 
XX / 
XXX 
 
DC = discontinuation; ID = identification; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; SAE = serious adverse event; 
TEAE = treatment emergent adverse event. 
[1] Reasonable possibility AE caused by IP as assessed by the investigator. 
Note: Study Day = date of interest – date of first infusion. A TEAE is defined as an adverse event with an onset at the time of or following the start of treatment 
with IP. 
SAEs were coded using MedDRA version 26.0 
 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e, no AEs occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment ID/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g.. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.3.2 
Listing of Deaths 
Safety Population 
Subject ID/ 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date/Time 
(Study Day)/ 
   End Date/Time 
(Study Day) 
Severity/ 
   Relationship 
Outcome/ 
      Action Taken/ 
           Therapy? 
AE 
Leading 
to IP DC? TEAE?  
Serious? / 
 Serious 
 Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/H
H:MM (X)/ 
   
DDMMMYYYY/H
H:MM (X) 
XXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX/ 
  XXXXXXXXXX/ 
                     Yes 
No 
No  
XX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
  XXXXXXXXXXXXX 
 
DDMMMYYYY/H
H:MM (X)/ 
   
DDMMMYYYY/H
H:MM (X) 
XXXXXXXX/ 
XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXXX/No 
Yes 
XX 
XX / XXX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMMMYYYY/H
H:MM (X)/ 
   Ongoing 
XXXXXXXX/ 
XXXXXXXX 
XXXXXXXXXX/ 
XXXXXXXX/ 
                No 
No 
XX 
XX / XXX 
 
DC = discontinuation; ID = identification; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; TEAE = treatment emergent 
adverse event. 
Note: Study Day = date of interest – date of first infusion. A TEAE is defined as an adverse event with an onset at the time of or following the start of treatment 
with IP. 
AEs were coded using MedDRA version 26.0 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e, no Aes occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g., in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.3. 
Displays of Significant Adverse Events and Adverse Events of Special Interest 
 
 
Table 14.3.2.2.1 
Treatment Emergent Adverse Events Associated with Abnormal Liver by System Organ Class and Preferred Term  
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at least One TEAE Associated with Abnormal Liver”. 
• 
Update Reference Listing to 16.2.7.3. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
Table 14.3.2.2.2 
Potential joint Related Adverse Events of Special Interest by System Organ Class and Preferred Term  
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at least One Potential Joint Related AESI” 
• 
Add abbreviation for AESI = Adverse Event of Special Interest. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.4 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
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Table 14.3.2.2.3 
Serious and/or severe Infections by System Organ Class and Preferred Term 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One SAE or Severe AE Related to Infection”. Add “SAE = Serious Adverse 
Event” to abbreviations. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.5. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.2.2.4 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of IP by System Organ Class and Preferred Term 
Safety Population 
System Organ Class 
Placebo 
MEDI7352 
Total 
    Preferred Term 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
 
(N=xx) 
n (n/N * 100) m 
All MEDI7352 
(N=xx) 
n (n/N * 100) m 
(N=xx) 
n (n/N * 100) m 
 
 
 
 
 
 
 
Subjects with at Least 
One Anaphylactic 
Reaction, 
Hypersensitivity or 
Infusion-Related 
Reactions Leading to 
Discontinuation of IP 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
Subjects with at Least 
One Anaphylactic 
Reaction, 
Hypersensitivity or 
Infusion-Related 
Reactions Not Leading to 
Discontinuation of IP [1] 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 1 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 2 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
    Preferred Term 3 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
xx (xx.x%) xx 
 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; n = number of subjects within each SOC/PT 
category; N = number of subjects per treatment group; IP = investigational product; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-
emergent adverse event. 
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[1] Anaphylactic reactions, hypersensitivity or infusion-related reactions not leading to discontinuation of IP were included in table as they were categorized as 
AE of special interest under Protocol Amendment 4 (V5.0). Definition for AE of special interest changed from Amendment 6 (V6.0) onwards, including 
anaphylactic reactions, hypersensitivity or infusion-related reactions leading to permanent discontinuation of IP.. 
Note: Results are n (n/N * 100) m is number of events.  
A TEAE is defined as AE with an onset at the time of or following the start of treatment with IP.  
AEs were coded using MedDRA version 26.0. Subjects are counted once for each SOC and once for each PT.  
AEs are displayed by descending frequency of SOC, then descending frequency of PT within SOC, based on ‘All MEDI7352’ column. Table is sorted by 
international order for SOC of same frequency, and alphabetically for PT of same frequency.  
Reference Listing: 16.2.7.6 
 
Programming Notes: 
• 
Same shell as Table 14.3.1.2. Change first row to be “Subjects with at Least One Anaphylactic Reaction, Hypersensitivity or Infusion-Related Reactions 
Leading to Discontinuation of IP”. Remove references to TEAEs in footnote. 
• 
Update Reference Listing to 16.2.7.6. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.4. 
Laboratory Data 
 
Table 14.3.4.1 
Descriptive Summary of Clinical Chemistry 
Safety Population 
Parameter: xxxxx (unit) 
Visit/ 
    Statistic 
Placebo 
MEDI7352 
 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
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Day 1 CFB 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically Significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects 
per treatment group; NCS = not clinically significant; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages are n/Number of subjects with not missing data by treatment group at each visit*100.  
Reference Listing: 16.2.8.1 
 
Programming Notes: 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Albumin, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), 
Bicarbonate, Calcium, Chloride, Creatinine, High-Sensitivity C-Reactive Protein (hs-CRP), Estimated Glomerular Filtration Rate (eGFR by Cockcroft - 
Gault), Serum Glucose, Lactate Dehydrogenase (LDH), Potassium, Sodium, Total Bilirubin, Total Protein, Blood Urea Nitrogen (BUN), Uric Acid. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.2 
Shift Table of Clinical Chemistry Results 
Safety Population 
Parameter (Unit)/ 
    Visit  
        Post-Baseline 
        Grade    
Baseline Grade [1] 
Placebo 
 (N=xxx) 
MEDI7352, 
 
 (N=xxx) 
Low 
Normal 
High 
Missing 
Total 
Low 
Normal 
High 
Missing 
Total 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX (Unit) 
 
 
 
 
 
 
 
 
 
 
    Week x 
 
 
 
 
 
 
 
 
 
 
        Low 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        High 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Missing 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Total 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     Week x 
 
 
 
 
 
 
 
 
 
 
        Low 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        High 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Missing 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Total 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects within each category; N = number of subjects per treatment group. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Percentages are n/Number of subjects by treatment group at each visit for the parameter*100. 
Reference Listing 16.2.8.1 
Programming Notes: 
• 
Repeat above in new pages for MEDI7352, 
 MEDI7352, 
 and All MEDI7352. 
• 
Repeat the above for 
 dosing only if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.4.1. 
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Table 14.3.4.3 
Descriptive Summary of Hematology 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.1 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Absolute basophil count, absolute eosinophil count, absolute lymphocytes count, Absolute Monocyte Count, 
Absolute Neutrophil Count, Basophils %, Eosinophils %, Hematocrit (HCT), Hemoglobin (HGB), hemoglobin A1C (HgbA1C), Lymphocytes %, mean 
corpuscular hemoglobin (MHC), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), Monocytes %, Neutrophils 
%, Platelets, Red blood cell count (RBC), Red Cell Distribution Width, white blood cell Count (WBC). 
• 
Update Reference listing to 16.2.8.2. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.4.4 
Shift Table of Hematology Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.2 
• 
Repeat the shell for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.4.3. 
• 
Update Reference listing to 16.2.8.2 
 
 
 
 
 
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Table 14.3.4.5 
Descriptive Summary of Coagulation 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.1 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Activated Partial Thromboplastin Clotting Time (APTT), Fibrinogen, International normalized ratio (INR), 
Prothrombin Time (PT). 
• 
Update Reference listing to 16.2.8.3. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.4.6 
Shift Table of Coagulation Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.2 
• 
Repeat for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.4.5. 
• 
Update Reference listing to 16.2.8.3. 
 
 
 
 
 
 
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Table 14.3.4.7 
Descriptive Summary of Urinalysis 
Safety Population 
Parameter: xxxxx (unit) 
Visit/ 
    Statistic 
Placebo 
MEDI7352 
 
Total 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
Low NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Low CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 CFB 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
      Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
      Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
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… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for all visits for Parameters: Specific 
Gravity and pH 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
       n 
xx 
xx 
xx 
xx 
xx 
xx 
       Negative 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
       Positive 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
If Positive, Specify [2] 
 
 
 
 
 
 
   100 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   250 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   500 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   >= 1000 mg/dL 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
       n 
xx 
xx 
xx 
xx 
xx 
xx 
       Negative 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
       Positive 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High NCS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
High CS 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for all visits for Parameters: Blood, 
Glucose, Ketones and Protein 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects 
per treatment group; NCS = not clinically significant; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
[2] Percentages are n/Number of Subjects with a Positive Result*100. 
Note: Percentages are n/Number of subjects with not missing data by treatment group at each visit*100.  
Reference Listing: 16.2.8.4 
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Programming Notes: 
• 
Present only scheduled visits. 
• 
Sort Parameters in the following Order: Blood Urine, Glucose, Ketones, pH, Protein, Specific Gravity. 
• 
Categories for If Positive, Specify: 
o Blood, Urine: Trace, Small, Moderate. 
o Glucose: 100 mg/dL, 250 mg/dL, 500 mg/dL, >= 1000 mg/dL. 
o Ketones: Trace, 15 mg/dL, 40 mg/dL. 
o Protein: Trace, 30 mg/dL, 100 mg/dL, 300 mg/dL. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.8 
Shift Table of Urinalysis Results 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.3.4.2 
• 
Repeat for 
 dosing if Stage 4 is initiated. 
• 
Repeat for every scheduled visit.  
• 
Present parameters in the same order as in Table 14.3.4.7. 
• 
Update Reference listing to 16.2.8.4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.4.9 
Maximum On-Treatment ALT and AST versus Maximum On-Treatment Total Bilirubin 
Safety Population 
 
  
  
  
Total Bilirubin 
 
 
 
<2 x ULN 
>=2 x ULN 
Group 
Nobs 
 
n (%) 
n (%) 
Placebo 
 
  
  
  
N=xxx 
xxx 
ALT 
 
 
 
 
<3 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=3 - <5 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=5 - <10 x ULN 
0 
0 
 
 
>=10 x ULN 
0 
0 
 
 
 
 
 
xxx 
AST 
 
 
 
 
<3 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=3 - <5 x ULN 
x (xx.x%) 
x (xx.x%) 
 
 
>=5 - <10 x ULN 
0 
0 
 
 
>=10 x ULN 
0 
0 
… 
 
 
 
 
Repeat for: 
 All MEDI7352 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; IP = investigational product; n = number of subjects per category; N = number of 
subjects per treatment group; Nobs = number of subjects per treatment group with at least one post-baseline assessment on treatment; ULN = upper limit of 
normal.  
Note: On-treatment assessments include assessments on or after the date of first dose of IP. Baseline is defined as the last observation recorded prior to the 
first dose of treatment. 
Percentages are based on Nobs. 
Reference Listing: 16.2.8.1 
 
 
 
 
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Programming Notes: 
• 
Per Protocol, the elevations of ALT or AST and Total Bilirubin do not have to occur at the same time or within a specified time frame. That is the reason 
why the table is presented by Subject instead of by visit. So, if for example, one subject has ALT >=3 - <5 x ULN at Day 1, and TBL >=2 x ULN at 
Week 18, n in that cell will increase by one. 
• 
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 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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6.5. 
Other Safety Data  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.1 
Descriptive Summary of Vital Signs 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 15 Minutes Post-
Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 15 Minutes Post-
Dose CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
CFB = Change from Baseline; eCRF = Electronic Case Report Form; n = number of subjects by treatment group at each visit for the parameter; N = number 
of subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Note: ‘Day 1: 5 minutes after Infusion Completion’ time point was only applied to subjects enrolled in Stage 1, with data collected under eCRF versions 4.0 
(11DEC2018) or older.  
Reference Listing: 16.2.9.1 
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Programming Notes: 
• 
Repeat for Supine Heart Rate, Supine Systolic Blood Pressure, Supine Diastolic Blood Pressure, Respiratory Rate, Body Temperature, Standing Heart 
Rate, Standing Systolic Blood Pressure, Standing Diastolic Blood Pressure. 
• 
After Week 2 (inclusive), Supine measure are taken in sitting position. We will consider them as supine (in resting position) for calculating Change from 
Baseline (always at supine position). 
• 
Include the following timepoints: Baseline, Day 1: 5 Minutes Post-Dose, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 
Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion 
Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 
8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, 
Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Note that Body Tº, and standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.2 
Descriptive Summary of Digital ECG Data 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group ; SD = 
standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Data shown are averages of the 3 replicates taken for each parameter and timepoint, and CFB for the same variables.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.9.2 
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Programming Notes: 
• 
Repeat for PR, QRS, QT, RR, HR (Heart Rate) and QTcF taken from external data. 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, Week 12, 
and Week 18.  
• 
A column for 
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) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.3 
Summary of Overall Evaluation of Safety ECG Data 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Day 1: 1 hour Post-Dose 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Abnormal NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NCS = Not 
clinically significant. 
Note: Data are taken as the most conservative from the 3 replicates taken by tim epoint. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Reference Listing: 16.2.9.2 
 
 
Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, Week 12, 
and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.3.5.4 
Covid-19 Screening 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
Subjects Screened for COVID-19 Symptoms 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
COVID-19 Symptoms Screened: 
 
 
 
 
 
 
   Fever 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sore Throat 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Loss of Taste 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Loss of Smell 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Body Temperature Check 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Subjects with COVID-19 Swab Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Subjects with COVID-19 Antibody Testing 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Confirmed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Suspected 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
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Subjects with COVID-19 Antigen Testing 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Positive 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%)  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   COVID-19 Negative 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment 
group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
Note: Percentages for COVID-19 screened subjects are n/Number of subjects by treatment group*100. Percentages for symptoms/test results are n/Number of 
subjects by treatment group at each visit without missing result*100. 
Reference Listing: 16.2.8.8 
 
 
Programming Notes: 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.5 
Summary of Sub-Scores for Total Neuropathy Score-Nurse 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
Subjects performing TNSn 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Sensory Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Motor Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Autonomic Symptom Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Pin Sensibility Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
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   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vibration Sensibility Score 
 
 
 
 
 
 
   0 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 xx (xx.x%) 
 xx (xx.x%) 
xx (xx.x%) 
   1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 N = number of subjects per treatment group; TNSn = Total Neuropathy Score-Nurse.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages for subjects performing TNSn are n/Number of subjects by treatment group*100. Percentages for each Score are n/Number of subjects by 
treatment group at each visit without missing score*100. 
Reference Listing: 16.2.9.5 
 
Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12 and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.6 
Descriptive Summary of Total Neuropathy Score-Nurse 
Safety Population 
Score: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Day 1 CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
TNSn = Total Neuropathy Score-Nurse; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment 
group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile.  
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. Reference Listing: 16.2.9.5 
Programming Notes: 
- Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12 and Week 18.  
- Include the following scores: Sensory Symptom Score, Motor Symptom Score, Autonomic Symptom Score, Pin Sensibility Score, Vibration Sensibility Score, 
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and TNSn Total. 
- A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
Table 14.3.5.7.1 
Summary of Motor and Sensory Nerve Conduction Studies 
Safety Population 
Parameter: xxxxx 
 
 
 
 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Week 18 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Week 18 CFB 
 
 
 
 
 
 
   n  
xx 
xx 
xx 
xx 
xx 
xx 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Evaluation Result 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abnormal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Week 18 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abnormal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
CFB = Change from Baseline; n = number of subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group;  SD = 
standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages are number of subjects by treatment group at each visit for each category /Number of subjects with not missing data by treatment group for 
each visit*100. 
Reference Listing: 16.2.9.6 
 
Programming Notes: 
• 
Repeat for the following Parameters: Lower Limb - Right Side/Fibular Nerve/Motor Evaluation/Amplitude (mV), Lower Limb - Right Side/Tibial 
Nerve/Motor Evaluation/Amplitude (mV), Lower Limb - Right Side/Sural Nerve/Sensory Evaluation/Amplitude (uV), Lower Limb - Left Side/Fibular 
Nerve/Motor Evaluation/Amplitude (mV), Lower Limb - Left Side/Tibial Nerve/Motor Evaluation/Amplitude (mV), Lower Limb - Left Side/Sural 
Nerve/Sensory Evaluation/Amplitude (uV), Upper Limb - Right Side/Medial Nerve/Motor Evaluation/Amplitude (mV), Upper Limb - Right Side/Ulnar 
Nerve/Motor Evaluation/Amplitude (mV), Upper Limb - Right Side/Medial Nerve/Sensory Evaluation/Amplitude (mV), Upper Limb - Right Side/Ulnar 
Nerve/Sensory Evaluation/Amplitude (mV), Upper Limb - Left Side/Medial Nerve/Motor Evaluation/Amplitude (mV), Upper Limb - Left Side/Ulnar 
Nerve/Motor Evaluation/Amplitude (mV), Upper Limb - Left Side/Medial Nerve/Sensory Evaluation/Amplitude (mV), Upper Limb - Left Side/Ulnar 
Nerve/Sensory Evaluation/Amplitude (mV), Lower Limb - Right Side/Fibular Nerve/Motor Evaluation/Conduction Velocity (msec), Lower Limb - 
Right Side/Tibial Nerve/Motor Evaluation/Conduction Velocity (msec), Lower Limb - Right Side/Sural Nerve/Sensory Evaluation/Conduction Velocity 
(msec), Lower Limb - Left Side/Fibular Nerve/Motor Evaluation/Conduction Velocity (msec), Lower Limb - Left Side/Tibial Nerve/Motor 
Evaluation/Conduction Velocity (msec), Lower Limb - Left Side/Sural Nerve/Sensory Evaluation/Conduction Velocity (msec), Upper Limb - Right 
Side/Medial Nerve/Motor Evaluation/Conduction Velocity (msec), Upper Limb - Right Side/Ulnar Nerve/Motor Evaluation/Conduction Velocity 
(msec). Upper Limb - Right Side/Medial Nerve/Sensory Evaluation/Conduction Velocity (msec), Upper Limb - Right Side/Ulnar Nerve/Sensory 
Evaluation/Conduction Velocity (msec), Upper Limb - Left Side/Medial Nerve/Motor Evaluation/Conduction Velocity (msec), Upper Limb - Left 
Side/Ulnar Nerve/Motor Evaluation/Conduction Velocity (msec), Upper Limb - Left Side/Medial Nerve/Sensory Evaluation/Conduction Velocity 
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(msec), Upper Limb - Left Side/Ulnar Nerve/Sensory Evaluation/Conduction Velocity (msec), Lower Limb - Right Side/Fibular Nerve/Motor 
Evaluation/Duration of Action Potential (msec), Lower Limb - Right Side/Tibial Nerve/Motor Evaluation/Duration of Action Potential (msec), Lower 
Limb - Right Side/Sural Nerve/Sensory Evaluation/Duration of Action Potential (msec), Lower Limb - Left Side/Fibular Nerve/Motor 
Evaluation/Duration of Action Potential (msec), Lower Limb - Left Side/Tibial Nerve/Motor Evaluation/Duration of Action Potential (msec), Lower 
Limb - Left Side/Sural Nerve/Sensory Evaluation/Duration of Action Potential (msec), Upper Limb - Right Side/Medial Nerve/Motor 
Evaluation/Duration of Action Potential (msec), Upper Limb - Right Side/Ulnar Nerve/Motor Evaluation/Duration of Action Potential (msec), Upper 
Limb - Right Side/Medial Nerve/Sensory Evaluation/Duration of Action Potential (msec), Upper Limb - Right Side/Ulnar Nerve/Sensory 
Evaluation/Duration of Action Potential (msec), Upper Limb - Left Side/Medial Nerve/Motor Evaluation/Duration of Action Potential (msec), Upper 
Limb - Left Side/Ulnar Nerve/Motor Evaluation/Duration of Action Potential (msec), Upper Limb - Left Side/Medial Nerve/Sensory 
Evaluation/Duration of Action Potential (msec), Upper Limb - Left Side/Ulnar Nerve/Sensory Evaluation/Duration of Action Potential (msec), Lower 
Limb - Right Side/Fibular Nerve/Motor Evaluation/Peak Latency (msec), Lower Limb - Right Side/Tibial Nerve/Motor Evaluation/Peak Latency 
(msec), Lower Limb - Right Side/Sural Nerve/Sensory Evaluation/Peak Latency (msec), Lower Limb - Left Side/Fibular Nerve/Motor Evaluation/Peak 
Latency (msec), Lower Limb - Left Side/Tibial Nerve/Motor Evaluation/Peak Latency (msec), Lower Limb - Left Side/Sural Nerve/Sensory 
Evaluation/Peak Latency (msec), Upper Limb - Right Side/Medial Nerve/Motor Evaluation/Peak Latency (msec), Upper Limb - Right Side/Ulnar 
Nerve/Motor Evaluation/Peak Latency (msec), Upper Limb - Right Side/Medial Nerve/Sensory Evaluation/Peak Latency (msec), Upper Limb - Right 
Side/Ulnar Nerve/Sensory Evaluation/Peak Latency (msec), Upper Limb - Left Side/Medial Nerve/Motor Evaluation/Peak Latency (msec), Upper Limb 
- Left Side/Ulnar Nerve/Motor Evaluation/Peak Latency (msec), Upper Limb - Left Side/Medial Nerve/Sensory Evaluation/Peak Latency (msec), Upper 
Limb - Left Side/Ulnar Nerve/Sensory Evaluation/Peak Latency (msec). 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.7.2 
Shift Table of Motor and Sensory Nerve Conduction Results 
Safety Population 
Parameter (Unit)/ 
    Visit  
        Post-Baseline 
        Grade    
Baseline Grade [1] 
Placebo 
 (N=xxx) 
MEDI7352, 
 
 (N=xxx) 
Normal 
Abnormal 
Missing 
Total 
Normal 
Abnormal 
Missing 
Total 
 
 
 
 
 
 
 
 
 
XXXXXX (Unit) 
 
 
 
 
 
 
 
 
    Week 18 
 
 
 
 
 
 
 
 
        Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Abnormal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Missing 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Total 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
   
 
 
 
 
 
 
 
 
XXXXXX (Unit) 
 
 
 
 
 
 
 
 
     Week 18 
 
 
 
 
 
 
 
 
        Normal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Abnormal 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Missing 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
        Total 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects within each category; N = number of subjects per treatment group. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Percentages are n/Number of subjects by treatment group at each visit for the parameter*100. 
Reference Listing 16.2.9.6 
Programming Notes: 
• 
Repeat above in new pages for MEDI7352, 
 MEDI7352, 
 and All MEDI7352. 
• 
Repeat the above for 
 dosing only if Stage 4 is initiated. 
• 
Repeat for every scheduled visit. 
• 
Present parameters in the same order as in Table 14.3.5.7.1. 
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Table 14.3.5.8 
Summary of Strength and Deep Tendon Reflexes 
Safety Population 
Visit/ 
Placebo 
MEDI7352 
 
Total 
  Variable 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
(N=xx) 
   Statistic or Category 
 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
 
Subjects performing SDTR assessment 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Ankle Dorsiflexion Strength 
 
 
 
 
 
 
   0 - Normal Power 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 - Mild Weakness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 - Moderate Weakness   
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 - Severe Weakness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 - Paralysis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Deep Tendon Reflexes 
 
 
 
 
 
 
   0 - Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   1 - Ankle reflex reduced 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   2 - Ankle reflex absent 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   3 - Ankle reflex absent and knee reflex 
reduced 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   4 - All reflexes (both ankle and knee) 
absent 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects by treatment group at each visit for each category; N = number of subjects per treatment group; SDTR = strength and deep tendon 
reflexes. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: Percentages for subjects performing SDTR assessment are n/Number of subjects by treatment group*100. Percentages for each Score are n/Number of 
subjects by treatment group at each visit*100. 
Reference Listing: 16.2.9.7 
 
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Programming Notes: 
• 
Include the following timepoints: Baseline, Day 1, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12, and Week 18.  
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.9 
Summary of Local Injection Site Reactions 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
Visit/ 
       Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Day 1: 15 Minutes after 
Start of Infusion 
 
 
 
 
 
 
    Subjects with injection 
Site Assessed  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Pain 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Tenderness 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Erythema/ Redness 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
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Induration/ Swelling 
 
 
 
 
 
 
   None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
n = number of subjects by treatment group at each visit for each category; N = number of subjects per treatment group. 
Note: Percentages for subjects performing injection site assessment are n/Number of subjects by treatment group*100. Percenta ges for each Score are 
n/Number of subjects by treatment group at each visit*100. Subject 
 suffered an injection site reaction starting on 25MAR2019 and ending on 
23APR2019, spanning Study visits Week 8, 10 and 12. However, injection site assessment was not performed on this subject  till Week 18, existing high 
possibility for symptoms to have receded by then. 
Reference Listing: 16.2.9.8 
 
Programming Notes: 
• 
Include the following timepoints: Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour Post-Dose, 
Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2, Week 4, Week 6, Week, 8, Week 10, Week 12, and Week 18.  
• 
A column for 
 dosing 
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.10 
Summary of Hypersensitivity/Anaphylactic Reactions 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with any 
Hypersensitivity/   
Anaphylaxis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Highest Severity Grade 
 
 
 
 
 
 
      Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Type of Reaction 
 
 
 
 
 
 
   Urticaria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pruritus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Flushing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Swollen Lips, Tongue, 
Uvula and/or Vulva 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Wheeze-Bronchospasm 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Stridor 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hypoxia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hypotension 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Crampy Abdominal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Diarrhoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.9 
 
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Programming Notes: 
• 
Display only Type of reaction with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.11 
Summary of Liver Diagnostic Investigations 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Diagnostics 
Performed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Type of Diagnostic Investigation 
 
 
 
 
 
 
   Ultrasound 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   CT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   MRI/MRCP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Flushing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   ERCP 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   X-Ray 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening for 
Acetaminophen/Paracetamol 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening for Ethanol 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tox Screening, Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Specialist Consulted 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis A 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis B 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis C 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis D 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Hepatitis E 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Serology for Cytomegalovirus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serology for Epstein Barr Virus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Autoimmune Serology 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CT = Computerized tomography; ERCP = Endoscopic retrograde cholangiopancreatography; MRI = Magnetic resonance imaging; MRCP = Magnetic 
resonance cholangiopancreatography; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.10 
 
 
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Programming Notes: 
• 
Display only Diagnostic Investigations with non-missing value. 
• 
A column for 
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) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.12 
Summary of Liver Risk Factors and Lifestyle Events 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Risk Factors 
Assessed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Liver Risk Factor 
 
 
 
 
 
 
   Alcohol Abuse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Increased Alcohol Consumption    
within 1 Month of Reported Event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   IV Drug Abuse 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tattoo 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Acupuncture 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sexually Transmitted Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Toxic/Chemical Agent Exposure 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Travel (Areas at Risk in the Last Year) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pregnancy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Parenteral Nutrition 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Excessive Physical Exercise 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Changes Diet/Fasting Episodes/Weight 
Loss Diet 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Previous Drug Reaction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Blood Transfusion 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Patient Exposed to Anyone with 
Jaundice in the Last Month 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   History of Hypotension 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
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   Low Blood Pressure at Time of Event 
of Liver Injury and/or Abnormal Liver 
Laboratory Value 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   History of Liver Disease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV = intravenous; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.10 
 
 
 
Programming Notes: 
• 
Display only Liver Risk Factor with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.13 
Summary of Liver Signs and Symptoms 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Liver Signs/Symptoms 
Assessed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Liver Sign/Symptom 
 
 
 
 
 
 
   Anorexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Asthenia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pyrexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pruritus 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Jaundice  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Arthralgia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abdominal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Abdominal Tenderness 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Nausea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Mucosal Inflammation 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Purpura 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hepatomegaly 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Splenomegaly 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Lymphadenopathy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Ascites 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Confusional State 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Coma 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Upper Quadrant Tenderness 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
xx xx.x%) 
   Biliary Obstruction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Eosinophilia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dark Urine 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.12 
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Programming Notes: 
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Display only Liver Signs/Symptoms with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.14 
Summary of Infection Diagnostic Investigations 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Diagnostic 
Investigations 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Method 
 
 
 
 
 
 
   Microscopy, Culture and Sensitivity 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Serological Tests 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Nucleic Acid Based Tests 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   X-Ray 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.13 
 
 
 
Programming Notes: 
• 
Display only Methods with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.15 
Summary of Infection Risk Factors and Lifestyle Events 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Risk Factor Occurred 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Infection risk factor 
 
 
 
 
 
 
   Extensive Burns within the Last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tattoo, Piercing or Acupuncture within the 
last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Sexually Transmitted Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Travel to Areas at Risk of Tuberculosis or 
Tropical Diseases 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Infections Related to Travel 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Blood Transfusion (within the Last Year) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Exposure to Nosocomial Pathogens within the 
Last Year 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Contact History with Infection Source 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Previous BCG Immunization 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Evidence of BCG Scar 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Tuberculin Skin or Quantiferon Test Confirms 
     Previous Exposure or Immunity to 
Tuberculosis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
BCG = Bacillus Calmette-Guerin; N = number of subjects per treatment group. 
Reference Listing: 16.2.9.14 
Programming Notes: 
• 
Display only infection risk factors with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Table 14.3.5.16 
Summary of Infection Signs and Symptoms 
Safety Population 
 
Placebo 
MEDI7352 
 
Total 
   Statistic or Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
 
 
Subjects with Infection Sign/Symptom 
Occurred 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Infection Sign/Symptoms 
 
 
 
 
 
 
   Pyrexia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Headache 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Confusional State 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Convulsion 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Rhinitis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Oropharyngeal Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Productive Cough 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Haemoptysis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Wheezing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dyspnoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Pleuritic Pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Vomiting 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Diarrhoea 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Genital Discharge 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Haematuria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Dysuria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Hepatosplenomegaly 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Jaundice 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Lymphadenopathy 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
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   Rash 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Petechial 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Vesicular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Macular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Papular 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Urticaria 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Erythema 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Blanching 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
      Splinter Haemorrhages 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Night sweats 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Chills 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Myalgia 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Weight Decrease 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
N = number of subjects per treatment group. 
Reference Listing: 16.2.9.15 
 
 
Programming Notes: 
• 
Display only infection Signs/Symptoms with non-missing value. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.17 
Summary of Concomitant Medications by ATC Level 2 and Preferred Name 
Safety Population 
Programming Notes: 
• 
Same shell as Table 14.1.7. 
• 
Change footnote Note by: “Note: Concomitant medications are defined as medications continuing or starting on or after first dose of study medication. 
All concomitant medications are coded using WHO drug dictionary version vMar2023. At each level of summarization (ATC Level 2 or Preferred 
Name), subjects who reported more than one concomitant medication were only counted once. ATC Level 2 and Preferred Name are sorted in in 
descending order of frequency of total, and alphabetically if same frequency”. 
• 
If uncoded ATC Level or Preferred Name, please put them as [Not Coded] 
• 
ATC and Preferred Name texts should be in proper case in table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.3.5.18 
Summary of Concomitant Procedures 
Safety Population 
System Organ Class 
Placebo 
MEDI7352 
Total 
   Preferred Term 
(N=xxx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
(N=xxx) 
 
 
 
 
 
 
Any Concomitant Procedure 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
System Organ Class 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   … 
… 
… 
… 
… 
… 
 
 
 
 
 
 
System Organ Class n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term 1 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
   Preferred Term n 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
xx (xx.x %) 
 
 
 
 
 
 
N = number of subjects per treatment group; PT = Preferred Term; SOC = System Organ Class. 
Note: All Procedure terms were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 2 6.0. At each level of summarization 
(system organ class or preferred term), subjects having more than one Procedure term were counted only once. System organ class and preferred terms are 
sorted in descending order of frequency of Total column, and alphabetically if same frequency. 
When there are uncoded Procedure Events in the database, the events will be summarized with SOC and PT set to [Not Coded]. The [Not Coded] are sorted at 
the end of the table. 
 
Reference Listing: 16.2.9.18 
 
Programming Notes: 
• 
SOC and PT texts should be in proper case in table. 
• 
Sort SOC and PT (within SOC) in descending order of frequency in the Total column.  Sort alphabetically in case of ties. 
• 
Uncoded Procedure events 
o When there are uncoded Procedure Events in the database, the events will be summarized with SOC and PT set to [Not Coded]. The [Not 
Coded] will be sorted at the end of the table. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
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Table 14.3.5.19 
Anti-Drug Antibody Results and Titre Summary by Timepoint 
Safety Population 
 
Placebo 
MEDI7352 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
 
 
 
 
 
Baseline [1] 
 
 
 
 
 
   n [2] 
xx 
xx 
xx 
xx 
xx 
ADA Positive: n (%) [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
   n [2] 
xx 
xx 
xx 
xx 
xx 
ADA Positive: n (%) [3] 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
… 
 
 
 
 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; N = number of subjects per treatment group; SD = standard deviation; Q1 = first quartile; Q3 = third quartile. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
[2] Number of subjects with at least one ADA assessment at the specific visit. 
[3] Number of subjects with a positive result at the specific visit. The denominator for all percentages is the number of subjects with an ADA result for each 
visit. 
Reference Listing: 16.2.9.19 
Programming Notes: 
• 
Keep in mind that in this table ‘Total’ column does not include placebo. 
• 
Repeat for all scheduled post-baseline visits. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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Table 14.3.5.20 
Descriptive Summary of Anti-Drug Antibody Results and Titre by ADA Categories  
Safety Population 
 
Placebo 
MEDI7352 
ADA Category 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
All MEDI7352 
(N=xx) 
 
 
 
 
 
 
ADA positive at baseline and/or post-baseline (ADA 
prevalence) 
 
 
 
 
 
   n/Nobs (%) [1] [2] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
TE-ADA positive (ADA incidence) [5] 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Treatment Induced ADA Positive 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
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Treatment-Boosted ADA Positive 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Non-TE-ADA Positive [6] 
 
 
 
 
 
   n/Nobs (%) [1] [3] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Both baseline and post-baseline positive 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
Only baseline positive 
 
 
 
 
 
   n/Nobs (%) [1] [4] 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
TE-persistently ADA positive [7] 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
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TE-transiently ADA positive [8] 
 
 
 
 
 
   n/Nobs (%) [1] [3]  
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
xx/xxx (xx.x%) 
Maximum ADA Titre 
 
 
 
 
 
   Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max  
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; N = number of subjects per treatment group; TE-ADA = Treatment Emergent ADA; SD = standard deviation; Q1 = first 
quartile; Q3 = third quartile. 
[1] n represents the number of subjects satisfying the conditions of the specified ADA category  
[2] Nobs represents the number of subjects with any ADA result at baseline and/or post-baseline. 
[3] Nobs represents the number of subjects with an ADA result at baseline and at least one post-baseline ADA assessment. 
[4] Nobs represents the number of subjects with an ADA result at baseline. 
[5] TE-ADA positive is defined as either ADA negative at baseline and post-baseline ADA positive (Treatment Induced ADA Positive), or as ADA positive at 
baseline with pre-existing titre boosted by 4-fold or greater during the study period (Treatment-boosted ADA Positive). ADA incidence is the proportion of 
TE-ADA+ subjects in a population. 
[6] ADA post-baseline positive but not fulfilling the conditions for TE-ADA+ 
[7] ADA negative at baseline and having at least 2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between first and last positive, or an 
ADA positive result at the last available post-baseline assessment. 
[8] ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. 
Reference Listing: 16.2.9.19 
 
 
Programming Notes: 
• 
If a participant has more than 1 non-missing titre during the study, the maximum titre for each participant is summarized. 
• 
Only present summary statistics if titre is available. 
• 
If no positive results for a particular block of the table, then the summary statistics for the titres for that particular block would not appear. 
• 
It is assumed that participants with a missing baseline ADA result are ADA negative at baseline. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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7. 
Pharmacokinetic/Pharmacodynamic Data  
Table 14.4.1 
Summary of Serum MEDI7352 Concentrations 
PK Population 
ADA Status: xxxxxxxxxx 
 
 
MEDI7352 
Visit/ 
    Statistic 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
Baseline [1] 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
   gCV% 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Week 2 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
   gCV% 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
Week 4 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
   gCV% 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
… 
 
 
 
gCV% = Geometric Coefficient of Variation (%); gMean = Geometric Mean; gSD = Geometric SD; LLOQ = Lower Limit of Quantification; n = number of 
subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; NC =not calculable; NQ = not quantifiable. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Note: serum MEDI7352 concentration units = ng/mL 
Reference Listing: 16.2.10.1 
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Programming Notes: 
• 
Include the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 
10: 8 Hours after Infusion, Week 10 + 24 hours/ Pre-Dose, Week 11/ Pre-Dose, Week 10 + 14 Days/Pre-Dose; Week 18. 
• 
Repeat the table for ‘ADA Positive’, ‘ADA Negative’ and ‘Overall'. 
• 
Any values reported as NRR (not reportable) or NS (missing) will be excluded from the summary tables. 
• 
At a time point where less than or equal to 50% of the concentration values are NQ (below LLOQ), all NQ values will be set to the LLOQ, and all 
descriptive statistics will be calculated accordingly. 
• 
At a time point where more than 50% (but not all) of the values are NQ, the gmean, gmean ± gSD and gCV% will be set to NC. Th e maximum value 
will be reported from the individual data, and the minimum and median will be set to NQ. 
• 
If all concentrations are NQ at a time point, no descriptive statistics will be calculated for that time point. The gmean, minimum, median and maximum 
will be reported as NQ and the gCV% and gmean ± gSD as NC. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 14.4.2 
Summary of Serum total NGF Concentrations 
Safety Population 
ADA Status: xxxxxxxxxx 
 
 
 
Placebo 
MEDI7352 
Visit/ 
    Statistic 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
(N=xx) 
 
 
 
 
 
Baseline [1] 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Week 2 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Week 4 
 
 
 
 
   n (n < LLOQ) 
xx (xx) 
xx (xx) 
xx (xx) 
xx (xx) 
   Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
xx.x (xx.xx) 
  gMean [gMean ± gSD] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 x.xx [x.xx to x.xx] 
 
   gCV% 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
… 
 
 
 
 
 
 
 
 
 
gCV% = Geometric Coefficient of Variation (%); gMean = Geometric Mean; gSD = Geometric SD; LLOQ = Lower Limit of Quantification;  n = number of 
subjects by treatment group at each visit for the parameter; N = number of subjects per treatment group; ; NC =not calculable; NGF = Nerve-Growth Factor; 
NQ = not quantifiable. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment. 
Note: serum total NGF concentration units = pg/mL 
Reference Listing: 16.2.10.2 
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Programming Notes: 
• 
Repeat for ADA Status: “ADA Positive”, “ADA Negative” and “Overall”.  
• 
Include the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 
10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18. 
• 
A column for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
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Planned Listing Descriptions and Shells 
Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
Listing 16.2.1.1 - Subject Disposition - Screening Population 
U 
Listing 16.2.1.2 - Assignment to Analysis Populations - Screening Population 
U 
Listing 16.2.1.3 - Reason for IP Discontinuation and Withdrawal from the Study - Safety Population 
U 
Listing 16.2.1.4 - List of Reasons for Screening Failure - Screen Failure Population 
U 
Listing 16.2.1.5 - Subject Visits and COVID-19 Impact - Screening Population 
U 
Listing 16.2.2.1 - Subjects Not Meeting All Inclusion Criteria or Meeting any Exclusion Criteria  - Screening Population 
U 
Listing 16.2.2.2 - Protocol Deviations - Safety Population Error! Reference source not found.Error! Reference source not found.Error! 
Reference source not found.Error! Reference source not found.Error! Reference source not found. 
U 
Listing 16.2.3 - Randomization and Treatment Group - Safety Population Error! Reference source not found.Error! Reference source 
not found.Error! Reference source not found.Error! Reference source not found.Error! Reference source not found. 
U 
Listing 16.2.4.1 - Demographic and Baseline Characteristics - Screening Population 
U 
Listing 16.2.4.2 - Medical History - Safety Population 
U 
Listing 16.2.4.3 - Osteoarthritis Characteristics - Screening Population 
U 
Listing 16.2.5.1 - Study Drug Administration: Individual Doses - Safety Population 
U 
Listing 16.2.6.1 - Daily Pain NRS - mITT Population 
U 
Listing 16.2.6.2 - Error! Reference source not found. Galer NPS - mITT Population 
U 
Listing 16.2.6.3 - DSIS - mITT Population 
U 
Listing 16.2.6.4 - SF-36 - mITT Population 
U 
Listing 16.2.6.5 - Rescue Medication Usage - mITT Population 
R 
Listing 16.2.6.6 - Patient Global Impression of Change - mITT Population 
U 
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Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
 
U 
Listing 16.2.7.1 - Adverse Events - Safety Population 
U 
Listing 16.2.7.2 - Treatment Emergent Adverse Events Leading to Study Drug DiscontinuationError! Reference source not found. - Safety 
Population 
R 
Listing 16.2.7.3 - Treatment Emergent Adverse Events Associated with Abnormal Liver - Safety Population 
R 
Listing 16.2.7.4 - Joint Related Adverse Events of Special Interest - Safety Population 
R 
Listing 16.2.7.5 - Serious and/or Severe Infections - Safety Population 
R 
Listing 16.2.7.6 - Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of Study Drug - Safety Population 
R 
Listing 16.2.8.1 - Clinical Chemistry Laboratory Evaluations - Safety Population 
U 
Listing 16.2.8.2 - Hematology Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.3 - Coagulation Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.4 - Urinalysis Laboratory Evaluations - Safety Population 
R 
Listing 16.2.8.5 - Serology Laboratory Evaluations - Safety Population 
U 
Listing 16.2.8.6 - Pregnancy Test Results - Safety Population 
U 
Listing 16.2.8.7 - Drug Test Results - Safety Population 
U 
Listing 16.2.8.8 - COVID-19 Screening and Vaccination - Safety Population 
U 
Listing 16.2.9.1 - Vital Signs Measurements - Safety Population 
U 
Listing 16.2.9.2.1 - 12-Lead Digital ECG Results - Safety Population  
U 
Listing 16.2.9.2.2 - 12-Lead Safety ECG Results - Safety Population 
U 
Listing 16.2.9.3 - Physical Examination Results - Safety Population 
U 
Listing 16.2.9.4 - Neurological Examination Results - Safety Population 
U 
Listing 16.2.9.5 - Total Neuropathy Score-Nurse - Safety Population 
U 
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Number        Title       Population 
Unique (U) 
or Repeated 
(R) 
Listing 16.2.9.6 - Motor and Sensory Nerve Conduction Studies - Safety Population 
U 
Listing 16.2.9.7 - Strength and Deep Tendon Reflexes - Safety Population 
U 
Listing 16.2.9.8 - Injection Site Reactions - Safety Population 
U 
Listing 16.2.9.9 - Hypersensitivity/Anaphylactic Reactions - Safety Population 
U 
Listing 16.2.9.10 - Liver Diagnostic Investigations - Safety Population 
U 
Listing 16.2.9.11 - Liver Risk Factors and Lifestyle Events - Safety Population 
U 
Listing 16.2.9.12 - Liver Signs and Symptoms - Safety Population 
U 
Listing 16.2.9.13 - Infection Diagnostic Investigations - Safety Population 
U 
Listing 16.2.9.14 - Infection Risk Factors and Lifestyle Events - Safety Population 
U 
Listing 16.2.9.15 - Infection Signs and Symptoms - Safety Population 
U 
Listing 16.2.9.16 - Prior and Concomitant Medications - Safety Population 
U 
Listing 16.2.9.17 - Prohibited Concomitant Medications - Safety Population 
R 
Listing 16.2.9.18 - Concomitant Procedures - Safety Population 
R 
Listing 16.2.9.19 - Anti-drug Antibody Test Results - Safety Population 
U 
Listing 16.2.10.1 - Serum MEDI7352 Concentrations - PK Population 
U 
Listing 16.2.10.2 - Serum total NGF Concentrations - PD Population 
U 
 
 
 
 
 
 
 
 
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Listing Change Log: 
Output 
Number 
Date of 
Change 
Change 
Made By 
(initials) 
Description/Rationale 
 
 
 
 
 
 
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Listing 16.2.1.1 
Subject Disposition  
Screening Population  
 
Subject 
ID 
Re-screened?/ 
Previous 
Subject ID 
Treatment 
Arm 
Re-consent/ 
Date/Time of Initial IC/ 
Initial Protocol Version 
Date/Time of 
Informed Consent 
Protocol 
Version at 
consent/ 
Re-consent 
Consent for 
 
sample? /Date of 
Consent 
Consent for 
COVID-19 Safety 
Measures /Date of 
Consent 
Current 
Protocol 
version 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
Yes/ XXXX 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
Yes/ 
DDMMMYYYY 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
Yes / 
DDMMMYYYY/hh:mm 
/ XXXX 
DDMMMYYYY/
hh:mm 
XXXX 
Yes/ 
DDMMMYYYY 
No 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
No 
XXXX 
No 
DDMMMYYYY/
hh:mm 
XXXX 
No 
No 
XXXXX 
 
 
 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; IC = Informed Consent; 
 
. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
 
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Listing 16.2.1.2 
Assignment to Analysis Populations 
Screening Population  
Subject ID 
Treatment 
Arm 
Screened [1] 
Randomized 
SAF [2] 
mITT [3] 
PK [4] 
Reason to Exclude from 
Safety [5] 
Reason to Exclude from 
mITT [6] 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
No 
No 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
No 
No 
No 
XXX 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
Yes 
Yes 
No 
No 
XXX/ XXX 
XXX/ XXX 
 
 
 
 
 
 
 
 
 
mITT = Modified Intent-To-Treat Population Set; NRS = numeric rating scale; PK = pharmacokinetics; SAF = Safety Population Set. 
[1] The Screening Population includes all subjects who provide informed consent and provide demographic and/or baseline screening assessments. 
[2] The Safety Population includes all subjects who receive at least 1 dose of double-blind study medication. 
[3] The mITT Population includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
[4] The PK Population includes all subjects for who a pharmacokinetic sample was obtained and analysed. 
[5] Major deviation reason/s to exclude from Safety Population for randomized subject. 
[6] Major deviation reason/s to exclude from mITT Population for randomized subject. 
 
 
Programming Notes: 
• 
If there is more than one major deviation, please concatenate with “/” 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
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Listing 16.2.1.3 
Reason for IP Discontinuation and Withdrawal from the Study 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
IP 
Discontinuation 
[1]/ Study 
Withdrawal 
Completion/ 
Discontinuation 
Date (Study Day) 
Date of Last Dose 
Number of 
doses 
Primary 
Reason for 
DC/ 
Withdrawal 
Blind Broken? / 
Date/Time / 
Reason 
Reason for 
breaking 
the Blind 
Study 
Duratio
n 
 
 
 
 
 
 
 
 
 
XXXXXX/
XXXX 
IP 
Discontinuation  
DDMMMYYYY(XX) 
DDMMMYYYY 
XX 
XXXXXX
X 
Yes /  
DDMMMYYYY/
hh:mm 
XXXXXX 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX/
XXXX 
IP 
Discontinuation  
DDMMMYYYY (XX) 
DDMMMYYYY 
XX 
XXXXXX
X 
No 
 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX/
XXXX 
Study 
Withdrawal 
DDMMMYYYY (XX) 
DDMMMYYYY 
XX 
Other: 
XXXXXX
X 
No 
 
XX 
 
 
 
 
 
 
 
 
 
DC = Discontinuation; IP = Investigational product.  
[1] Any withdrawal from the study before last IP dose (Week 10) is considered an IP discontinuation. 
Note: Study Day is calculated relative to the date of first dose. Study Duration = Reference end date – date of first dose of treatment + 1. 
 
Programming Notes: 
• 
If reason for non-completion is Other, concatenate the specify text as follows: “Other: XXXXXXXXX”.  
• 
If reason for non-completion is adverse event, concatenate with AE line number as follows: “Adverse event number X”.  
• 
For Physician decision, screen-fail and withdrawal by subject, please provide explanation if presented on the logic “Physician decision: XXX”.  
• 
Do not include subjects who completed the study. 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
 
 
 
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Listing 16.2.1.4  
List of Reasons for Screening Failure 
Screen Failure Population 
 
Subject ID 
Treatment Arm 
Screen failure Date 
Primary Reason for Screen Failure 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
Other: XXXXXXXXX 
 
 
 
 
XXXXXX 
Screen Failure 
DDMMMYYYY 
 
 
 
 
 
 
 
Programming Notes: 
• 
If reason for non-completion is Other, concatenate the “Primary Reason for Screen Failure” text as follows: “Other: XXXXXXXXX”.  
• 
Sort by Subject ID. 
 
 
 
 
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Listing 16.2.1.5 
Visits List and COVID-19 Impact 
Screening Population 
 
Subject ID/ 
Treatment 
Arm 
Visit 
Name 
Visit Date 
(Study 
Day) 
Is COVID-
19 
Pandemic 
Ongoing? 
Impacted 
by 
COVID-19 
Was visit 
performed? / 
Visit Type 
Visit 
Performe
d Via 
VS Data 
provided? / 
Assessments 
Missed? 
IP dosing 
missed due to 
COVID-19 / 
Details 
End of 
Treatment 
linked to 
COVID-19 
Subject 
discontinued 
due to 
COVID-19? / 
Details 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
Yes 
 
Yes 
Yes/ 
Delayed 
On site 
Y/  
Efficacy 
Y/ XXXX 
Other: XXXX 
Y/ XXXX 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
Yes 
 
No 
Yes 
 
N/ Safety 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
No 
 
Yes 
Yes 
Video 
N/  
Efficacy, 
Safety 
Y/ Other: 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxx/ 
xxxx 
Visit 
X 
DDMMM
YYYY 
(XX) 
No 
 
No 
No / Missed 
 
 
 
 
 
 
COVID-19 = coronavirus disease 2019; IP = Investigational Product; VS = Vital Signs. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
• 
Visit Type: Missed, Abbreviated, Delayed. 
• 
Visit Performed Via: Video, Phone, On Site Other: xxxxxx. 
• 
Details on IP dosing missed: Treatment on hold due to Sponsor Decision, Subject infected with COVID-19, Subject decision, Other: xxxxxx. 
• 
End of treatment, reason if due to COVID: Subject infected with COVID-19, Subject decision, Travel restrictions, Site closed, Study delayed/cancelled, 
Other: xxxxxx. 
• 
Details on Subjects discontinuing due to COVID-19: Subject infected with COVID-19, Subject decision, End of Treatment due to Sponsor, Other: xxxxxx. 
• 
Sort by Treatment Arm/ Subject ID/ Visit Date. 
 
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Listing 16.2.2.1 
Subjects Not Meeting All Inclusion Criteria or Meeting any Exclusion Criteria 
Screening Population 
Subject ID 
Treatment Arm 
Enrolled 
Randomized 
Inclusion or 
Exclusion 
Criteria 
Number 
Criteria Label 
 
 
 
 
 
 
 
XXXXXX 
Screen Failure 
Yes 
No 
Inclusion 
XX 
XXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
Yes 
No 
Exclusion 
XX 
XXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
Programming Notes: 
 
• 
Sort by Subject ID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.2.2 
Protocol Deviations 
Safety Population 
 
Subject ID Treatment Arm Analysis Population Event Date (Study Day) Event Type 
Description 
Category 
Covid-
19 
Related? 
 
 
 
 
 
XXXXXX 
XXXX 
Screened\RND\SAF\
mITT 
DDMMMYYYY (XX) 
XXXXXXXXXXX 
XXXXXXX 
Non-
important 
Y 
 
 
XXXXXXXXXXXXXX 
XXXXXXXXXXXXXXX Important 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (XX) 
XXXXXXXXXXXX 
XXXXXXXXXXXXXXX
XXX 
XXXXX 
 
 
XXXXXXXXXXXXXXXX XXXXXXXXXXX 
XXXXX 
 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY (XX) 
XXXXXXXXXXXX 
XXXXXXXXXXXXXXX
XXX 
XXXXX 
COVID-19 = Coronavirus disease 2019; mITT = Modified Intent-To-Treat Population; RND = Randomized Subjects; SAF = Safety Population. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
o The structure of this listing may change depending on the information in the protocol deviations file. In the analysis population column, include only the 
analysis population where subject is included in. 
o 
Sort by Treatment Arm/ Subject ID. If date is present in file, add a column for date of event and sort by date. If no date is present, sort by category with 
non-important first and then important. 
o 
Event Type: Inclusion Criteria, Exclusion Criteria, Study Drug, Assessment − Safety, Assessment − Efficacy, Lab/endpoint data, Visit Window, 
Informed Consent, Prohibited Co-Medication, Overdose/Misuse, Other. 
 
 
 
 
 
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Listing 16.2.3 
Randomization and Treatment group 
Safety Population 
 
Subject ID 
Treatment Arm 
Randomization Stage 
Randomization Treatment 
Randomization Date / Time 
(Study Day) 
Randomization 
Number 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 1 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 3 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 2 
Placebo 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 2 
Active 
 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
XXXXXX 
XXXX 
Stage 3 
Placebo 
DDMMMYYYY/hh:mm (-X) 
XXXX 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
 
• 
Sort by Treatment Arm/ Subject ID. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.4.1 
Demographic and Baseline Characteristics 
Screening Population 
Subject 
ID 
Treatment 
Arm 
Birth Date 
Age 
(years) 
[1] 
Sex 
Surgically sterile?/ 
Postmenopausal? [2] 
Ethnicity 
Race 
Weight 
(kg) 
Height 
(cm) 
BMI 
(kg/m²) 
Fully 
vaccinated 
for COVID-
19? 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
XXX 
DDMMMYYY 
XX 
XX 
 
XXXXX 
XXXX 
XX.X 
XX.X 
XX.X 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
XXX 
XXX 
--MMMYYY 
XX 
XX 
No/ Yes 
XXXXX 
XXXX 
XX.X 
XX.X 
XX.X 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COVID-19 = Coronavirus disease 2019. 
Note: Height and weight are the values at Screening.  
[1] Age was calculated as age at time of consent. 
[2] For Female Subject Only. 
 
 
 
 
Programming Notes: 
o 
Sort by Treatment Arm/ Subject ID 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.4.2 
Medical History 
Safety Population 
 
 
System Organ Class/ 
 
 
 
  Preferred Term/ 
Start Date (Study Day)/ 
 Subject ID 
Treatment Arm 
    Verbatim Term 
   End Date (Study Day)/ 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
     XXXXXXXXXXXXX 
MMMYYYY (X)/ 
   Ongoing 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
     XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   Ongoing 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXXXXX/ 
    XXXXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
 
 
 
 
 
 
 
 
MedDRA = Medical Dictionary for Regulatory Activities.  
Note: Study Day is calculated relative to the date of first dose. 
Medical History were coded using MedDRA version 26.0.  
Only subjects with medical history recorded are listed. 
 
Programming Notes: 
 
• 
SOC & PT text should be in proper case in listing. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date of medical event. 
 
 
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Listing 16.2.4.3 
Osteoarthritis Characteristics 
Screening Population 
 
Subject ID 
Treatment 
Arm 
Subject with 
OA? / Joint/ 
Area affected 
Is OA 
considered 
CS? 
Radiological 
Investigations 
Conducted? / Details 
Joint Area 
Investigated 
Is OA 
considered 
RS? 
K-L Score 
Reported 
Radiologic Scoring 
System / Details/  
Result 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Y / Shoulder 
Y 
Y/ Other: XXXXXX 
Shoulder 
Y 
Grade 3 
XXXXXX/ 
         XXXXXX/ 
   XX 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Y / Ankle 
N 
Y / MRI 
Ankle 
N 
N 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CS = Clinically Significant; K-L = Kellgren-Lawrence; OA = Osteoarthritis; RS = Radiologically Significant. 
. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.5.1 
Study Drug Administration: Individual Doses 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
Visit 
Name 
Start 
Date/ 
Time 
(Study 
Day) 
End 
Date/ 
Time 
(Study 
Day) 
Was 
Infusion 
Performed?/ 
Infusion 
Volume 
(mL)[1]/ 
Reason not 
Performed 
Actually 
Administered 
Volume (mL) 
[2] 
If 
Difference 
between 
[1] and [2] 
Volume, 
Reason 
Any 
Injection 
Site 
Reactions? 
Any 
Infusion 
Related 
Reactions  
Infusion 
Rate 
(mL/ 
hour) 
Rate Change 
Justification 
Reason 
for 
Infusion 
Rate 
Change 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
DDMM
MYYYY
/hh:mm 
(X) 
DDMM
MYYYY
/hh:mm 
(X) 
Y/  
XX 
XX 
 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
DDMM
MYYYY
/hh:mm 
(X) 
DDMM
MYYYY
/hh:mm 
(X) 
Y/  
XX 
XX 
XXXXX 
Y 
Y 
xx.x 
XXXXX 
XXXXX
XX 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
XXX 
 
 
N/  
XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date. 
• 
Rate Change Justification: Increased, Decreased, Interrupted. 
 
 
 
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Listing 16.2.6.1 
Daily Pain NRS 
mITT Population 
 
Subject ID 
Treatment Arm 
Study Visit [1] 
Subject Diary (ePRO) Date / Study Day Baseline Flag [2] 
DPS 
 
 
 
 
 
 
XXXXXX 
XXXX 
Baseline 
DDMMMYYYY/ (-7) 
Y 
X 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-6) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-2) 
Y 
XX 
 
 
 
 
 
 
 
 
Baseline 
DDMMMYYYY/ (-1) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY/ (13) 
 
XX 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY/ (14) 
 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
XXXXXX 
XXXX 
Baseline 
DDMMMYYYY/ (-7) 
Y 
XX 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
DPS = Daily Pain Score; ePRO = Electronic Patient-Reported Outcome; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘DPS’ are average daily pain scores on an 11-point (0-10) NRS. Study Day is calculated relative to the date of first dose. 
[1] Study Visit is defined as the 7-day period ending within the protocol window Day ± 3, where at least 4 days out of 7 have recorded diary pain scores. 
[2] Baseline is defined as the 7-day period prior to randomization i.e., Day -7 to Day -1, inclusive. A subject is considered to have an evaluable baseline pain 
score if there are at least 4 days of recorded diary pain scores in the 7-day period. 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Subject Diary Date. 
• 
Display all measurement per Subject, starting on the Study Day = -7. 
• 
Display Study Visit for days involved in weekly averages of the average daily pain scores for Baseline, Week 2, 4, 6, 8, 10, and 12 
• 
Flag Baseline records only when there is at least 5 days of recorded diary pain scores in the 7-day Baseline period 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.6.2 
Galer NPS 
mITT Population 
Subject ID 
Treatment Arm 
Parameter 
Study Visit 
Collection Date / Study 
Day 
Baseline Flag [1] 
NPS 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Pain intensity 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
Week 4 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
XX 
 
 
 
 
 
 
 
 
 
 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
XX 
 
 
 
 
 
 
 
 
 
XXXX 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Pain intensity 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
XXXX 
Week X 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
NPS = Neuropathic Pain Scale; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘NPS’ are Pain Intensity, Unpleasantness, and Descriptor scores on an 11-point (0-10) NRS, and Pain Duration/Frequency on a 3-
point NRS (1-3).  
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter /Collection Date. 
• 
Keep Parameter sorting from the last bullet point in this programming notes. 
• 
Include all observed data on Galer NPS scores for Baseline, Week 4, 8, 12, and 18. 
• 
Repeat for the Parameters: Pain intensity, Pain Unpleasantness, Pain Sharpness, Pain Hotness, Pain Dullness, Pain Coldness, Pain Sensitivity, Pain 
Itching, Deep Pain Intensity, Surface Pain Intensity (All in an 11-point NRS), and Pain Duration/Frequency (in a 3-point NRS). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.6.3 
DSIS 
mITT Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.6.1. 
• 
Update footnote as:  
DSIS = Daily Sleep Interference Scale; ePRO = Electronic Patient-Reported Outcome; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘DSIS’ are daily Sleep Interference scores on an 11-point (0-10) NRS. Study Day is calculated relative to the date of the 
day of first dose. 
[1] Study Visit is defined as the seven-day period ending within the protocol window Day ± 3. 
[2] Baseline is defined as the seven-day period prior to randomization i.e., Day -7 to Day -1,. 
• 
Sort by Treatment Arm/ Subject ID / Subject Diary Date. 
• 
Display all measurement per Subject, starting on the Study Day = -7. 
• 
Display Study Visit for days involved in weekly averages of the average Sleep interference scores for Baseline, Week 4, 8, 12 , and 18. 
 
 
 
 
 
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Listing 16.2.6.4 
SF-36 
mITT Population 
Subject ID 
Treatment 
Arm 
Parameter 
Item 
Number 
Item name 
Study Visit 
Collection Date / Study 
Day 
Baseline 
Flag [1] 
SF-36 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Physical 
functioning 
3 
Vigorous 
Activities 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
Moderate 
Activities 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
… 
… 
… 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
 
 
 
- 
Total 
Baseline 
DDMMMYYYY/ (X) 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Role 
limitations 
due to 
physical 
health 
13 
Cut Amount 
of Time 
Spent on 
Work/Act 
Baseline 
DDMMMYYYY/ (X) 
Y 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
… 
… 
.. 
… 
 
 
 
 
 
 
 
 
 
… 
 
… 
… 
 
… 
… 
… 
… 
 
 
 
 
 
 
 
 
 
SF-36 = 36-Item Short-Form Health Survey; NRS = Numeric Rating Scale. 
Note: Data shown in column ‘SF-36’ are derived SF-36 scores and Change in General Health on a 5-point NRS (1-5).  
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Item /Collection Date. 
• 
Keep Parameter sorting from the last bullet point in this programming notes. 
• 
Include all data on SF-36 scores for Baseline and Week 12. 
• 
Repeat for the Parameters: Physical functioning (items 3, 4, 5, 6, 7, 8, 9, 10, 11, 12), Role limitations due to physical health (items: 13, 14, 15, 16), Role 
limitations due to emotional problems (items: 17, 18, 19), Vitality (Energy/fatigue) (items: 23, 27, 29, 31), Emotional well-being (items: 24, 25, 26, 28, 
30), Social functioning (20, 32), Pain (items: 21, 22) and General Health (items: 1, 33, 34, 35, 36), all with values ranging from 0 to 100. Change in 
general Health (in a 5-point NRS, item: 2). 
 
 
 
 
 
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Listing 16.2.6.5 
Rescue Medication Usage 
mITT Population 
 Subject 
ID 
Treatment Arm 
ATC Class (Level 2)/ 
   Preferred Name/ 
      Verbatim Term 
Primary 
Indication 
Start Date (Study Day)/ 
   End Date (Study Day) 
Dose 
(unit) 
Route 
Frequency 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
--MMMYYYY (-XX)/ 
   DDMMMYYYY (-X) 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
  XXXXXXXXX/ 
   XXXXXXXXXXXXXXX/ 
      XXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
--MMMYYYY (-X)/ 
   Ongoing 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
XXXX 
XXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXXXXX 
Painful 
Diabetic 
Neuropathy 
DDMMMYYYY (X)/ 
   DDMMMYYYY 
(XX) 
XXXX 
unit 
XXXXXXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ATC = anatomical therapeutic chemical. 
Note: Study Day is calculated relative to the date of first dose. 
Medications were coded using WHO drug dictionary version vMar2023. 
 
 
Programming Notes: 
• 
ATC & Preferred Name text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications 
 
 
 
 
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Listing 16.2.6.6 
Patient Global Impression of Change 
mITT Population 
Subject ID 
Treatment Arm 
Study Visit 
Collection Date / Study Day 
PGIC 
 
 
 
 
 
XXXXXX 
XXXX 
Week 4 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
XXXXXX 
XXXX 
Week 4 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 8 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 12 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY/ (X) 
XXXXXXXX 
 
 
 
 
 
 
 
… 
… 
… 
 
 
 
 
 
PGIC =Patient Global Impression of Change. 
Note: Data shown in column ‘PGIC’ are Subjects ratings about overall improvement in health status. 
Study Day is calculated relative to the date of first dose. 
[1] Baseline is defined as the last observation recorded prior to the first dose of treatment.  
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include all observed data on PGIC scores for Week 4, 8, 12, and 18. 
 
 
 
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Listing 16.2.7.1 
Adverse Events 
Safety Population 
 
Subject ID/ 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
AE Start Date/Time 
(Study Day)/ 
   End Date/Time 
(Study Day) 
Severity/ 
Relationship 
[1] 
Outcome/ 
      Action Taken with IP/ 
           Therapy taken for this AE? 
AE Leading 
to Study DC? 
TEAE 
Serious? / 
Serious 
Criteria 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMMMYYYY/HH:
MM (X)/ 
DDMMMYYYY/HH:
MM (X) 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                       Yes 
No 
Yes 
  
No 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMMMYYYY/HH:
MM (X)/ 
DDMONYYYY/HH:
MM (X) 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                     No 
Yes 
No 
Yes / XXX 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
X 
XXXXXXXXXXX/  
XXXXXXX/ 
XXXXXXX 
DDMONYYYY/HH:
MM (X)/ 
   Ongoing 
XXXXXX/ 
XXXXXX 
XXXXXXXXX/  
XXXXXXX/ 
                   No 
No 
No  
Yes / XXX 
 
AE = adverse event; DC = discontinuation; IP = investigational product; MedDRA = Medical Dictionary for Regulatory Activities; SAE = serious adverse event; 
TEAE = treatment emergent adverse event. 
[1] Reasonable possibility AE caused by IP as assessed by the investigator . 
Note: Study Day is calculated relative to the date of first dose. A TEAE is defined as an AE with an onset at the time of or following the start of treatment with 
IP. 
AEs were coded using MedDRA version 26.0 
 
 
 
 
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Programming Notes: 
• 
If time missing, display “- -:- -”.  
• 
AE ID number represents Record position within Subject. 
• 
If no events meet the criteria for display (i.e, no AEs occur in the study), present “No events are reported.”. 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically by SOC /PT if same date for two events). 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT 
abbreviations should be added in this case in footnote. 
 
 
 
Listing 16.2.7.2 
Treatment Emergent Adverse Events Leading to Study Drug Discontinuation 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update listing deleting seventh and eight columns 
 
 
Listing 16.2.7.3 
Treatment Emergent Adverse Events Associated with Abnormal Liver 
Safety Population 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update listing deleting 8th column. 
 
 
 
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Listing 16.2.7.4 
Joint Related Adverse Events of Special Interest 
Safety Population 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
 
 
Listing 16.2.7.5 
Serious and/or Severe Infections 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
 
 
Listing 16.2.7.6 
Anaphylactic Reactions, Hypersensitivity or Infusion-Related Reactions Leading to Discontinuation of Study Drug  
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.7.1.  
• 
Update footnote: Anaphylactic reactions, hypersensitivity or infusion-related reactions not leading to discontinuation of IP were included in listing as 
they were categorized as AE of special interest under Protocol Amendment 4 (V5.0). Definition for AE of special interest changed from Amendment 6 
(V6.0) onwards, including anaphylactic reactions, hypersensitivity or infusion-related reactions leading to permanent discontinuation of IP. 
 
 
 
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Listing 16.2.8.1 
Clinical Chemistry Laboratory Evaluations 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Parameter 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Original 
Result 
(Unit) 
Standard 
Results 
(unit) 
Reference 
Range 
[1] 
 
 
 
 
Baseline 
Flag 
 
 
 
 
CFB 
Results 
Assessment 
/ Reason 
CS 
Lab ID 
Number 
Fasting 
Status 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Chemistry 
panel 
XXXXXX 
 
 
 
 
 
 
ND: xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Albumin 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
Y 
 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-NCS 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; CS = clinically significant; H = High; L = Low; NCS = not clinically significant; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
 [1] Reference range is used to identify potentially clinica lly significant laboratory values. 
 
Programming Notes: 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Chemistry panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Albumin, Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), 
Bicarbonate, Calcium, Chloride, Creatinine, High-Sensitivity C-Reactive Protein (hs-CRP), Estimated Glomerular Filtration Rate (eGFR by Cockcroft - 
Gault), Serum Glucose, Lactate Dehydrogenase (LDH), Potassium, Sodium, Total Bilirubin, Total Protein, Blood Urea Nitrogen (BUN), Uric Acid. 
 
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Listing 16.2.8.2 
Hematology Laboratory Evaluations 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.8.1. 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Hematology panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Absolute basophil count, absolute eosinophil count, absolute lymphocytes count, Absolute Monocyte Count, 
Absolute Neutrophil Count, Basophils %, Eosinophils %, Hematocrit (HCT), Hemoglobin (HGB), hemoglobin A1C (HgbA1C), Lymphocytes %, mean 
corpuscular hemoglobin (MHC), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), Monocytes %, Neutrophils 
%, Platelets, Red blood cell count (RBC), Red Cell Distribution Width, white blood cell Count (WBC). 
 
 
Listing 16.2.8.3 
Coagulation Laboratory Evaluations 
Safety Population 
 
Programming Notes: 
• 
Same shell as Listing 16.2.8.1. 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Coagulation panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Activated Partial Thromboplastin Clotting Time (APTT), Fibrinogen, International normalized ratio (INR), 
Prothrombin Time (PT). 
 
 
 
 
 
 
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Listing 16.2.8.4 
Urinalysis Laboratory Evaluations 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Parameter 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Original 
Result 
(Unit) 
Standard 
Results 
(unit) 
Reference 
Range 
[1] 
 
 
 
 
Baseline 
Flag 
 
 
 
 
CFB 
Results 
Assessment 
/ Reason 
CS 
Lab ID 
Number 
Fasting 
Status 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
Urinalysis 
panel 
XXXXXX 
 
 
 
 
 
 
ND: xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
pH/ 
Specific 
Gravity 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
Y 
 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
 
XXXXXXX 
Y 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX 
(XX) 
XX 
(XX) 
XX - YY 
 
XX.X 
H-NCS 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
Urine/ 
Glucose/ 
Ketones/ 
Protein 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Trace 
 
 
Y 
 
H-NCS 
XXXXXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
100 
(mg/dL) 
100 
(mg/dL) 
 
 
 
H-CS / 
XXX 
XXXXXXX 
Y 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Negative 
 
 
 
 
 
XXXXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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CFB = change from baseline; CS = clinically significant; H = High; L = Low; NCS = not clinically significant; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
 [1] Reference range is used to identify potentially clinically significant laboratory values. 
 
 
Programming Notes: 
• 
Keep parameter sorting from the last bullet point below. 
• 
For results assessment, do not populate column if result is normal. 
• 
Sort by Treatment Arm/ Subject ID / Parameter / Date time of collection. 
• 
If the whole panel is not done at a visit, present the information on first row of the subject under ‘Urinalysis panel’ parameter and don’t present the ‘not 
done’ information for each parameter. Display “ND: reason why” in the result assessment column. 
• 
Sort Parameters in the following Order: Blood Urine, Glucose, Ketones, pH, Protein, Specific Gravity. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.5 
Serology Laboratory Evaluations 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Was 
Serology 
Test 
Collected? 
Date/Time of 
Collection 
(Study Day) 
Test (Unit) [1] 
Result 
Lab ID 
Number 
Fasting 
Status 
Reason not 
collected 
Comments 
 
 
 
 
 
 
 
 
 
 
XXXX 
XXXX 
Yes 
DDMMMYYY
Y/HH:MM (X) 
Hepatitis B Ag 
Negative 
XXXX 
Y 
 
XXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis C Ab 
Positive 
XXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1/ -2 Ag 
Not Done 
XXXX 
Y 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Quantiferon 
Gold Plus NIL 
X.XX (IU/mL) 
XXXX 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
Ab = antibody; Ag = antigen; HIV = human immunodeficiency virus; TB = tuberculosis. 
Note: Study Day is calculated relative to the date of first dose. 
[1] if Applicable 
 
Programming Notes: 
 
• 
Sort by Treatment Arm/ Subject ID / Date of collection / Test. 
• 
Keep parameter sorting from the last bullet point below 
• 
Sort Parameters in the following Order: Hepatitis B Antigen, Hepatitis C Virus Antigen, Hepatitis C Virus Antibody, HIV-1/ -2 Antigen, Quantiferon 
Gold Plus NIL, Quantiferon Gold Plus TB, Quantiferon Gold Plus Mitogen minus NIL, Quantiferon Gold Plus TB1 m inus NIL, Quantiferon Gold Plus 
TB2 minus NIL 
 
 
 
 
 
 
 
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Listing 16.2.8.6 
Pregnancy Test Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Was a Urine pregnancy test 
performed? 
Date/Time Performed (Study Day) 
If not, Reason 
Result 
xxxxx 
xxxx 
xxxxx 
Xxxx 
Ddmmmyyyy/ hh:mm (XX) 
xxxx 
xxxx 
 
 
xxxxx 
Xxxx 
Ddmmmyyyy/ hh:mm (XX) 
Other: xxxx 
xxxx 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.7 
Drug Test Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Was Drug Test 
Performed? 
Date/ Time Assessment 
(Study Day) 
Result 
Findings 
Reason Test 
not Performed 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
DDMMMYYYY/ HH:MM 
(XX) 
Negative 
Negative 
 
 
 
 
 
 
 
 
XXXXXX 
XXXX 
Yes 
DDMMMYYYY/ HH:MM 
(XX) 
Positive 
Cocaine /  
Opiates 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Concatenate all findings by “/” 
• 
Sort by Treatment Arm/ Subject ID / Date of assessment. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.8.8 
COVID-19 Screening 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
COVID-19 Sx 
Screening?/Date
/ Time (Study 
Day) 
Sx 
Body Tº 
Check?/ Date/ 
Time (Study 
Day) 
Body Tº 
(Unit) 
COVID-19 
swab?/ Date/ 
Time (Study 
Day) 
Swab 
result 
COVID-19 Ab 
testing?/ Date/ 
Time (Study 
Day) 
 
Ab 
testing 
results 
COVID-19 
Ag testing?/ 
Date/ Time 
(Study Day) 
Ag 
testing 
results 
xxxxx/ 
xxxx 
xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XXX/ 
XXX 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XX (XX) 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy
/ hh:mm (XX) 
Xxxx 
 
xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XXX 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
XX (XX) 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy/ 
hh:mm (XX) 
Xxxx 
Yes/ 
Ddmmmyyyy
/ hh:mm (XX) 
Xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
Ab = Antibody; Ag = Antigen; COVID-19 = Coronavirus disease 2019; Sx = Symptoms; Tº = Temperature. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Concatenate all Symptoms by “/” 
• 
Sort by Treatment Arm/ Subject ID / Date of assessment 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.1 
Vital Signs Measurements 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Parameter 
Study 
Visit 
Position [1] / 
 Tº Method 
Date/Time of 
Collection 
(Study Day) 
Original Result 
(Unit) 
 
Baseline Flag 
CFB 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Body 
Temperature 
XXXXXX 
XXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX (XX) 
Y 
 
 
 
 
XXXXXX 
XXXX 
DDMMMYYYY/ 
HH:MM (X) 
XX (XX) 
 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
Resting 
Heat Rate 
Screening 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
 
 
 
 
Day 1: 
Pre-Dose 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
Y 
XX 
 
 
 
XXXXXX 
Supine 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
XX 
 
 
 
XXXXXX 
Sitting 
 
ND 
 
 
 
 
 
XXXXXX 
Sitting 
DDMMMYYYY/ 
HH:MM (X) 
XX 
 
XX 
 
 
 
 
 
 
 
 
 
CFB = change from baseline; eCRF = Electronic Case Report Form; ND = not done. 
Note: Study Day is calculated relative to the date of first dose. 
Baseline is defined as the last observation recorded prior to the first dose of treatment. 
‘Day 1: 5 minutes after Infusion Completion’ time point was only applied to subjects enrolled in Stage 1, with data collected under eCRF versions 4.0 
(11DEC2018) or older. 
[1] Resting position measurements encompass Sitting and Supine position measurements.  
 
 
 
 
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Parameter (Order in the second bullet point)/ Date time of collection. 
• 
Repeat for Resting Heart Rate, Resting Systolic Blood Pressure, Resting Diastolic Blood Pressure, Respiratory Rate, Body Temperature, Standing Heart 
Rate, Standing Systolic Blood Pressure, Standing Diastolic Blood Pressure. 
• 
After Week 2 (inclusive), Supine measure are taken in sitting position. We will consider them as supine (in resting position) for calculating Change from 
Baseline (always at supine position). 
• 
Include the following timepoints: Screening, Baseline (Day 1: Pre-Dose), Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 
Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion 
Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 
8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, 
Week 11, Week 12, Week 18.   
• 
Note that Body Tº, and standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.2.1 
12-Lead Digital ECG Results 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Visit 
 
ECG Date / Time 
(Study Day) 
Tracin
g 
PR Interval 
(msec) 
QRS 
duration  
(msec) 
QT 
Interval  
(msec) 
RR 
interval 
(bpm) 
Heart Rate 
(beats/min) 
QTcF 
Interval  
(msec) 
Findings 
Reason 
Not 
Done 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
Day 1: 
Pre-Dose 
DDMMMYYYY 
/ HH:MM (XX) 
1 
xx 
xx 
xx 
xx 
xx 
xx 
xx: 
xxxxx 
 
 
 
 
2 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
3 
xx 
xx 
xx 
xx 
xx 
xx 
xx: 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
 
DDMMMYYYY/ 
HH:MM (XX)  
1 
xx 
xx 
xx 
xx 
xx 
xx 
xx: 
xxxxx 
 
 
 
 
2 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
3 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant; ECG = electrocardiogram; NCS = Not clinically significant 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Date time of collection / Tracing. 
• 
For Findings, concatenate test name with test result for category “FINDINGS”.  
• 
Include the following timepoints: Day 1: Pre-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, Week, 8, 
Week 12, and Week 18. 
 
 
 
 
 
 
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00Listing 16.2.9.2.2 
12-Lead Safety ECG Results 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
 
ECG Date / Time 
(Study Day) 
Tracing 
ECG Result/ 
Comment 
PR Interval 
(msec) 
QRS duration  
(msec) 
QTcF 
Interval  
(msec) 
Reason 
Not Done 
 
 
 
 
 
 
 
 
 
XXXXX 
Day 1: Pre-
Dose 
DDMMMYYYY / 
HH:MM (XX) 
1 
Abnormal CS/ xxxx 
xx 
xx 
xx 
 
 
 
 
2 
Abnormal CS/ xxxx 
xx 
xx 
xx 
 
 
 
 
3 
Abnormal NCS/ 
xxxx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
 
DDMMMYYYY/ 
HH:MM (XX) 
1 
Normal 
xx 
xx 
xx 
 
 
 
 
2 
Normal 
xx 
xx 
xx 
 
 
 
 
3 
Normal 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
CS = clinically significant; ECG = electrocardiogram; NCS = Not clinically significant 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Date time of collection / Tracing. 
• 
Include the following timepoints: Screening, Day 1: Pre-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 4, 
Week, 8, Week 12, and Week 18. 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.3 
Physical Examination Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Examination 
Type 
Exam Date/ Time 
(Study Day) 
Body System 
Result / Change 
from previous 
assessment [1] 
If Abnormal, 
findings / 
Specify 
Changes [2] 
Reason Not 
Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
Complete 
DDMMMYYYY 
/ HH:MM (XX) 
Head, Neck and 
Thyroid 
Normal 
 
 
 
 
 
 
 
Ears, Eyes, Nose 
and Throat 
Abnormal CS 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
Targeted 
DDMMMYYYY 
/ HH:MM (XX) 
Ears, Eyes, Nose 
and Throat 
XXXXXXXXXX 
XXXXXXXX 
 
 
 
 
 
 
  
 
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant 
Note: Study Day is calculated relative to the date of first dose. 
[1] For targeted examination type: Change from previous assessment. 
[2] For targeted examination type: Specify Changes. 
 
 
Programming Notes: 
• 
Keep sorting from eCRF: Head, Neck and Thyroid/ Ears, Eyes, Nose and Throat/ Chest (including breasts)/ Lungs / Heart / Lymph Nodes / Abdomen / 
Hepatic / Gastrointestinal / Anorectal / Genitourinary/ Skin / Musculoskeletal/Extremities / Neurological / Other. 
• 
Complete Physical examination only at Screening, Week 12, 18 (it can also be unscheduled). 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Body system 
 
 
 
 
 
 
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Listing 16.2.9.4 
Neurological Examination Results 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Exam Date/ Time 
(Study Day) 
Body System 
Result  
If Abnormal, 
findings 
Reason Not 
Done 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
DDMMMYYYY / 
HH:MM (XX) 
Mental Status 
Normal 
 
 
 
 
 
 
Cranial Nerves 
Abnormal CS 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY / 
HH:MM (XX) 
Cranial Nerves 
XXXXXXXXXX 
XXXXXXXX 
 
 
 
 
 
  
 
 
 
CS = Clinically Significant, NCS = Not Clinically Significant 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Keep sorting from eCRF: Mental status/ Cranial Nerves/ Motor Function/ Reflexes / Sensation and Propioception / Coordination / Other. 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Body system 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.5 
Total Neuropathy Score-Nurse 
Safety Population 
Subject 
ID/ 
Treatment 
Arm 
Visit 
Date/ Time of 
collection 
(Study Day) 
Sensory 
Symptom 
Score 
(0−4) 
Motor 
Symptom 
Score 
(0−4) 
Autonomic 
Symptom 
Score (0−4) 
Pin 
Sensibility 
Score 
(0−4) 
Vibration 
Sensibility 
Score 
(0−4) 
TNSn Total 
(0−20) 
Reason Not Done 
 
 
 
 
 
 
 
 
 
 
XXXXX/ 
XXXX 
Screening 
DDMMMYYYY 
/ HH:MM (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY 
/ HH:MM (XX) 
XX 
XX 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY 
/ HH:MM (XX) 
ND 
ND 
ND 
ND 
ND 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
ND = Not Done; TNSn = Total Neuropathy Score-Nurse. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.6 
Motor and Sensory Nerve Conduction Studies 
Safety Population 
Subject ID/ 
Treatment 
Arm 
Visit 
 
Date / Time of 
Collection 
(Study Day) 
Location / 
Evaluation 
Was 
Evaluation 
Preformed
? / Nerve 
Amplitude 
(Motor = 
mV; sensory 
= microV) / 
Range 
Peak 
Latency 
(msec) / 
Range 
Conduction 
velocity 
(msec) / 
Range 
Duration 
of action 
potential 
(msec) / 
Range 
Evaluation 
Result 
If 
Abnormal, 
Specify/ 
Reason 
Not Done 
Significant 
Changes 
from 
Baseline? / 
if Yes, 
Specify 
 
 
 
 
 
 
 
 
 
 
 
 
XXXX/ 
XXXX 
Screening 
DDMMMYY
YY / HH:MM 
(XX) 
Lower Limb 
- Right Side/  
         Motor 
Evaluation 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
NA 
 
 
 
XXXXXX/    
XXXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Normal 
 
NA 
 
 
 
XXXXXX/   
XXXXX 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 18 
 
DDMMMYY
YY/ HH:MM 
(XX) 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
N 
 
 
 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Normal 
 
N 
 
 
 
XXXXXX/   
XXXXX 
Y/  
XXXXXX 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
xx  
[ x.xx to 
x.xx ] 
Abnormal 
XXXXX 
Y/  
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
NA = Not Applicable 
Note: Study Day is calculated relative to the date of first dose. 
 
 
 
 
 
 
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Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment / Location - Evaluation 
• 
Keep sorting from eCRF: Lower Limb - right side/Motor evaluation, Lower Limb - right side/Sensory evaluation, Lower Limb - left side/ Motor evaluation, 
Lower Limb - left side/ Sensory evaluation, Upper Limb - right side /Motor evaluation, Upper Limb - right side/ Sensory evaluation, Upper Limb - left 
side/ Motor evaluation, Upper Limb - left side /Sensory evaluation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.7 
Strength and Deep Tendon Reflexes 
Safety Population 
Subject ID 
Treatment 
Arm 
Visit 
Date/ Time of 
collection 
(Study Day) 
Ankle Dorsiflexion 
Strength 
Deep Tendon Reflexes 
Reason Not Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Screening 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Week 2 
DDMMMYYYY / 
HH:MM (XX) 
ND 
 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
ND = Not Done. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.8 
Injection Site Reactions 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Visit 
Date/ Time of Assessment 
(Study Day) 
Pain 
Tenderness 
Erythema/redness 
Induration/
swelling 
Reason Not Done 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
Day 1: 15 
Minutes 
after Start of 
Infusion 
DDMMMYYYY / 
HH:MM (XX) 
XXXX 
XXXX 
XXXX 
XXXX 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1: 30 
Minutes 
after Start of 
Infusion 
DDMMMYYYY / 
HH:MM (XX) 
XX 
XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Week 18 
DDMMMYYYY / 
HH:MM (XX) 
ND 
ND 
ND 
ND 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
ND = Not Done. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Visit / Date of assessment  
• 
Include the following timepoints: Day 1: 15 Minutes after Start of Infusion, Day 1: 30 Minutes after Start of Infusion, Day 1: 45 Minutes after Start of 
Infusion, Day 1: 60 Minutes after Start of Infusion, Day 1: 2 hours after Start of Infusion, Day 1: 4 hours after Start of Infusion, Week 2, Week 4, Week 
6, Week, 8, Week 10, Week 12, and Week 18.  
 
 
 
 
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Listing 16.2.9.9 
Hypersensitivity/Anaphylactic Reactions 
Safety Population 
Subject 
ID 
Treatment 
Arm 
AE ID 
Number 
Onset Date/Time (Study Day)/ 
   Resolution Date/Time (Study 
Day) 
Type of 
Reaction 
Severity grade for 
the Symptom 
with Highest 
Severity 
Onset Time 
for Highest 
Severity 
Leading to IP 
Discontinuation? 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMMMYYYY/HH:MM (X) 
XXXX 
XXXX 
/HH:MM 
Yes 
 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMONYYYY/HH:MM (X) 
XXXXX 
 
 
No 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
   DDMONYYYY/HH:MM (X) 
XXXXX 
XXXX 
/HH:MM 
No 
 
 
 
 
 
 
 
 
AE = Adverse Event. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Onset Date/Time / Resolution Date/Time / Reaction Type. 
• 
Keep sorting from eCRF: Urticaria, Pruritus, Rash, Flushing, Swollen lips, tongue, uvula and/or vulva, Dyspnoea, Wheeze-bronchospasm, Stridor, 
Hypoxia, Hypotension, Crampy abdominal pain, Vomiting, Diarrhoea, Other. 
 
 
 
 
 
 
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Listing 16.2.9.10 
Liver Diagnostic Investigations 
Safety Population 
Subject ID 
Treatment 
Arm 
Potential Hy's 
Law Case 
Number 
Liver Diagnostic Investigation 
Date (Study Day) 
Liver Diagnostic 
Investigation 
Liver Diagnostic 
Investigation 
Results 
Comments 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X) 
 
XXXX 
XXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY (X) 
 
XXXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X) 
 
XXXXX 
XXXXX 
 
 
 
CT = Computerized tomography; ERCP = Endoscopic retrograde cholangiopancreatography; MRI = Magnetic resonance imaging; MRCP = Magnetic 
resonance cholangiopancreatography. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Diagnostic Date / Liver Diagnostic Investigation. 
• 
Keep sorting from eCRF: Ultrasound, CT, MRI/MRCP, ERCP, Liver Biopsy, X-Ray, Tox Screening for Acetaminophen/Paracetamol, Tox Screening for 
Ethanol, Tox Screening, Other, Specialist (e.g. Hepatologist) Consulted, Serology for Hepatitis A, Serology for Hepatitis B, Serology for Hepatitis C, 
Serology for Hepatitis D, Serology for Hepatitis E, for Cytomegalovirus (CMV), Serology for Epstein Barr Virus (EBV), Autoimmune Serology, Other. 
 
 
 
 
 
 
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Listing 16.2.9.11 
Liver Risk Factors and Lifestyle Events 
Safety Population 
Subject ID 
Treatment 
Arm 
Potential 
Hy's Law 
Case 
Number 
Assessment Date 
(Study Day) 
 
Liver Risk Factor Start Date 
(Study Day)/ 
Liver Risk Factor Stop Date 
(Study Day) 
Liver Risk 
Factor / 
Reference 
Period 
Liver Risk 
Factor Details 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/  
       DDMMMYYYY (X) 
XXXX/ 
   XXX 
XXXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/  
         DDMMMYYYY (X) 
XXXXX/  
   XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY 
(X) 
DDMMMYYYY (X)/ 
      Ongoing  
XXXXX/ 
   XXX 
XXXXX 
 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Assessment Date / Liver Risk Factor Start Date / Stop Date / Liver Risk Factor. 
• 
Keep sorting from eCRF: Alcohol Abuse, Increased Alcohol Consumption within 1 Month of Reported Event, IV Drug Abuse, Tattoo, Acupuncture, 
Sexually Transmitted Diseases, Toxic/Chemical Agent Exposure, Travel (Areas at Risk in the Last Year), Pregnancy, Parenteral Nutrition, Excessive 
Physical Exercise, Changes Diet/Fasting Episodes/Weight Loss Diet, Previous Drug Reaction (Associated with an Elevation of Liver Tests), Blood 
Transfusion, Subject Exposed to Anyone with Jaundice in the Last Month, History of Hypotension, Low Blood Pressure at Time of Event of Liver Injury 
and/or Abnormal Liver Laboratory Value, History of Liver Disease, Other. 
• 
Concatenate comments with “/”. 
 
 
 
 
 
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Listing 16.2.9.12 
Liver Signs and Symptoms 
Safety Population 
Subject ID 
Treatment Arm 
Potential Hy's 
Law Case Number 
Start Date (Study Day)/ 
Stop Date (Study Day) 
Liver Sign/ 
Symptom 
Intermittent 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X)/  
       DDMMMYYYY (X) 
XXXX 
 
N 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY (X)/  
         DDMMMYYYY (X) 
XXXXX 
  
N 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY (X)/ 
      Ongoing  
XXXXX 
 
Y 
 
 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Liver Sign/Symptom. 
• 
Keep sorting from eCRF: Anorexia, Asthenia, Pyrexia, Pruritus, Jaundice, Arthralgia, Abdominal Pain, Abdominal Tenderness, Nausea, Vomiting, Rash, 
Mucosal Inflammation, Purpura, Hepatomegaly, Splenomegaly, Lymphadenopathy, Ascites, Confusional State, Coma, Upper Quadrant Tenderness, 
Biliary Obstruction, Eosinophilia, Dark Urine, Other. 
• 
If Rash, Lymphadenopathy or Other, Concatenate Symptom with Comment as: “Rash: xxxxxx”. “Lymphadenopathy: xxxxxx”, “Other: xxxxxxxx” 
 
 
 
 
 
 
 
 
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Listing 16.2.9.13 
Infection Diagnostic Investigations 
Safety Population 
Subject ID 
Treatment Arm 
AE ID 
Number 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Method 
Examination 
performed 
Test Result 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
XXXXX 
 
 
AE = adverse event. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Method. 
• 
Keep sorting from eCRF: Microscopy, Culture and Sensitivity, Serological Tests, Nucleic Acid Based Tests, X-Ray, Other. 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.14 
Infection Risk Factors and Lifestyle Events 
Safety Population 
Subject ID 
Treatment 
Arm 
AE ID 
Number 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Infection Risk 
Factor 
Infection Risk 
Occurrence 
Comments 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
X 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM (X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
Ongoing 
 
 
AE = adverse event; BCG = Bacillus Calmette–Guérin. 
Note: Study Day is calculated relative to the date of first dose. 
 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Infection Risk Factor. 
• 
Keep sorting from eCRF: Extensive Burns within the Last Year (Thermal Burn), Tattoo, Piercing or Acupuncture within the Last Year, Sexually 
Transmitted Diseases, Travel to Areas at Risk of Tuberculosis or Tropical Diseases, Infections Related to Travel (e.g. Tuberculosis and Tropical Diseases), 
Blood Transfusion (within the Last Year), Exposure to Nosocomial Pathogens within the Last Year, Contact History with Infection Source, Previous BCG 
Immunization, Evidence of BCG Scar, Tuberculin Skin or Quantiferon Test Confirms Previous Exposure or Immunity to Tuberculosis. 
• 
Fill Comment column if Infection risk factor test = Unknown Previous BCG Immunization, not done, known Sexually Transmitted Disease reference 
Period, or Infection risk factor specifications. 
 
 
 
 
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Listing 16.2.9.15 
Infection Signs and Symptoms 
Safety Population 
Subject ID 
Treatment 
Arm 
AE ID 
Number 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date/ Time (Study Day)/ 
Stop Date/ Time (Study Day) 
Clinical 
Event 
Infection 
Sign/Symptom 
Occurrence 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM 
(X) 
XXXXX 
Y 
 
XXXXX 
 
 
 
 
 
 
 
 
 
 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/  
       DDMMMYYYY/HH:MM 
(X)) 
XXXXX 
Y 
  
XXXXX 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
X 
XXXXXXXXXXX/ 
   
XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY/HH:MM (X)/ 
      Ongoing  
XXXXX 
N 
 
Ongoing 
 
 
AE = adverse event. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Start Date / Stop Date / Clinical Event. 
• 
Keep sorting from eCRF: Pyrexia, Headache, Confusional State, Convulsion, Rhinitis, Oropharyngeal Pain, Cough, Productive Cough, Haemoptysis, 
Wheezing, Dyspnoea, Pleuritic Pain, Vomiting, Diarrhoea, Genital Discharge, Haematuria, Dysuria, Hepatosplenomegaly, Jaundice, Lymphadenopathy, 
Rash, Night sweats, Chills, Myalgia, Weight Decrease. 
• 
Fill Comment column if Maximum Tº (Unit) available for Pyrexia, or if site for Rash or Lymphadenopathy is known.  
 
 
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Listing 16.2.9.16 
Prior and Concomitant Medications 
Safety Population 
 Subject 
ID/ 
Treatment 
Arm 
Prior/ 
Concomitant 
[1] 
ATC Class (Level 2)/ 
   Preferred Name/ 
      Verbatim Term 
 
 
 
 
Given 
for/as 
Primary 
Indication 
Start Date (Study 
Day)/ 
   End Date (Study 
Day) 
Dose (unit) 
Route 
Frequency 
 
 
 
 
 
 
 
 
 
XXXXXX
/ XXXX 
Prior 
XXXXXXXXXXXXXXXXX/ 
   XXXXXXXXXXXXXX/ 
      XXXXXXXXXXXXX 
Medical 
History 
XXXXXXX 
--MMMYYYY     
(-XX)/ 
  DDMMMYYYY 
(-X) 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
Both 
  XXXXXXXXX/ 
   XXXXXXXXXXXXXXX/ 
      XXXXXXXXXXX 
Prophylaxis XXXXXXX 
--MMMYYYY     
(-X)/ 
   Ongoing 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
Concomitant XXXXXXXXX/ 
   XXXXXXXXXXXXXX/    
XXXXXXXXXXXXXXXXX 
Adverse 
event 
XXXXXXX 
DDMMMYYYY 
(X)/ 
  DDMMMYYYY 
(XX) 
XXXX unit 
XXXXXX
XXX 
XXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ATC = anatomical therapeutic chemical; WHO-DDE = World Health Organization-Drug Dictionary Enhanced. 
Note: Study Day is calculated relative to the date of first dose. 
Medications were coded using WHO-DDE version vMar2023. 
[1] Prior medications are defined as medications that started before first dose of study, whether they were stopped before first dose of study medication or not. 
Concomitant medications are defined as medications starting on or after first dose of study medication Both indicates medication that was started before the 
day of first dose and continued after. 
 
 
 
 
 
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Programming Notes: 
• 
ATC & Preferred Name text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by Treatment ID/ Subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.17 
Prohibited Concomitant Medications 
Safety Population 
 
Programming Notes: 
• 
Same Shell as Listing 16.2.9.16.  
• 
Display prohibited prior and concomitant medications provided by the Medical Coder: 
• 
Prohibited concomitant medications:  
o NSAIDs analgesic therapies (with acetylsalicylic acid with doses >= 325 mg/day). 
o COX-2 analgesic therapies. 
o Immunotherapeutics. 
o Live viral or attenuated bacterial vaccines. 
o Oral, IV, intramuscular, or any other parenteral (other than oral) steroids (inhaled or topical steroids are permitted). 
o Biologic therapeutic agents. 
• 
Prohibited prior and/or concomitant medications: 
o Anti-NGF therapies. 
o Anti-TNF therapies. 
• 
ATC & PN text should be in proper case in table. 
• 
Ensure proper WHO-DDE version is printed in footnote. 
• 
Sort by subject, start date/time, end date/time, ATC level 2 & Preferred Name . 
• 
If Dose unit, Route or Frequency is Other, display other specify text only (ie, do not display “Other: XXXXXX” but just “XXXXXX “). 
• 
Adjust footnotes for frequency and routes as needed. 
• 
Sort by subject ID / Start Date / End Date (alphabetically for ATC Class Level 2 if same date for two medications) 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.9.18 
Concomitant Procedures 
Safety Population 
Subject 
ID 
Treatment 
Arm 
System Organ Class/ 
   Preferred Term/ 
      Verbatim Term 
Start Date (Study Day)/ 
   End Date (Study Day) 
Reason for Procedure 
Reason (derived verbatim 
term) 
If Reason is Other, 
Specify 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
  XXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
XXXXXXXXX/ 
   XXXXXXXX 
XXXXXXXXXX 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
XXXXXXXXXXXXX 
DDMMMYYYY (X)/ 
   DDMMMYYYY (X) 
XXXXXXXXX/ 
 XXXXXXXX 
XXXXXXXXXX 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXXXXXXXXXX/ 
  XXXXXXXXXXXXXX 
      XXXXXXXXXX 
DDMMMYYYY (X)/ 
   Ongoing 
OTHER 
OTHER 
 
XXXXXXXXXXX 
 
 
MedDRA = Medical Dictionary for Regulatory Activities. 
Note: Study Day is calculated relative to the date of first dose. All Procedure terms were coded using the MedDRA version 26.0. Concomitant Procedures are 
defined as medications continuing or starting on or after first dose of study medication.  
 
Programming Notes: 
• 
SOC & PT text should be in proper case in table. 
• 
Sort by Treatment Arm/ Subject ID / Start Date / End Date (alphabetically for SOC if same date for two events). 
• 
In case a term is not coded (e.g. in a dry run) it will be labelled as “Not Coded [SOC]” and “Not Coded [PT]”. SOC and PT abbreviations should be added 
in this case in footnote. 
 
 
 
 
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Listing 16.2.9.19 
Anti-drug Antibody Test Results 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Study 
Visit 
Date/Time of 
Collection 
(Study Day) 
Screening  
Status Result 
Confirmatory 
Status result 
ADA Titer 
Lab ID 
Number 
Comments 
 
 
 
 
 
 
 
 
 
XXXXX XXXX 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Positive 
Positive 
xx 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Positive 
Positive 
xx 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Negative 
Negative 
xx 
XXXXXXX 
 
 
 
XXXXXX 
DDMMMYYYY/ 
HH:MM (X) 
Missing 
Not 
Reportable 
Result 
NRR 
XXXXXXX 
XXXX 
 
 
 
 
 
 
 
 
 
ADA = Anti-Drug Antibodies; NA = Not Applicable; NRR = Not Reportable Result; QNS = Quantity Not Sufficient. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
ADA titre reported as <30 (below the minimum required dilution) is a negative result for the presence of ADA. 
• 
Include Following timepoints: Screening, Weeks 2, 4, 8, 10, 12, 18. 
 
 
 
 
 
 
 
 
 
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Listing 16.2.10.1 
Serum MEDI7352 Concentrations 
PK Population 
Subject 
ID 
Treatment 
Arm 
Study 
Visit 
PK Blood 
Sample 
Collected? / 
Reason Not 
Collected 
Date/Time of 
Collection 
(Study Day) 
MEDI7352 
Concentration 
(ng/mL) 
Lab ID Number 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXX 
Yes 
 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
XXXXXX 
Yes 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
XXXXXX 
Yes 
DDMMMYYYY/ 
HH:MM (X) 
NRR 
XXXXXXX 
XXXX 
 
 
XXXXXX 
No / 
XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
NA = Not Applicable; NRR = Not Reportable Result. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 10: 8 Hours 
after Infusion, Week 10 + 24 hours: after Week 10/ Pre-Dose, Week 11: after Week 10/ Pre-Dose, Week 10 + 14 Days: after Week 10/ Pre-Dose, Week 
18. 
 
 
 
 
 
 
 
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Listing 16.2.10.2 
Serum total NGF Concentrations 
Safety Population 
Subject 
ID 
Treatment 
Arm 
Study 
Visit 
PD Blood Sample 
Collected? / 
Reason Not 
Collected 
Date/Time of 
Collection 
(Study Day) 
Total NGF 
Concentration 
(pg/mL)  
Lab ID Number 
Comments 
 
 
 
 
 
 
 
 
XXXXX 
XXXX 
XXXXXX 
Yes 
 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
XXXXXX 
Yes 
DDMMMYYYY/ 
HH:MM (X) 
XX 
XXXXXXX 
 
 
 
XXXXXX 
Yes 
DDMMMYYYY/ 
HH:MM (X) 
NS 
XXXXXXX 
XXXX 
 
 
XXXXXX 
No / 
XXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
BLLOQ = Below the Lowest Limit of Quantitation; NA = Not Applicable; ND = Not Detected; NS = No Value due to Insufficient Volume or No Sample 
Received; PD: Pharmacodynamic; SAT = Greater than the Top of the Standard Curve; tNGF = total Nerve-Growth Factor. 
Note: Study Day is calculated relative to the date of first dose. 
 
Programming Notes: 
• 
Sort by Treatment Arm/ Subject ID / Collection Date. 
• 
Include the following timepoints: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of Infusion, Week 10: 8 Hours 
after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18. 
 
 
 
 
 
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Planned Figure Descriptions and Shells 
Number        Title       Population 
Unique (U) or 
Repeated (R) 
Figure 14.2.1.1 - Daily Pain NRS: MCP-Mod Dose Response Model - mITT Population 
U 
Figure 14.2.1.2 - Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Missing Data Handling - mITT Population 
U 
Figure 14.2.1.3.1 - Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Co-Medication Subgroup - mITT Population 
R 
Figure 14.2.1.3.2 - Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Co-Medication Subgroup, Including Opioids - 
mITT Population 
 
Figure 14.2.1.4 - Daily Pain NRS: MMRM LS Means (95% Confidence Interval) over 12-weeks by Treatment Group (Observed Cases) - 
mITT Population 
U 
Figure 14.3.6.1.1 - Vital Sign Profiles: Mean (±SD) Systolic Blood Pressure over time - Safety Population 
U 
Figure 14.3.6.1.2 - Vital Sign Profiles: Mean (±SD) Diastolic Blood Pressure over time - Safety Population 
R 
Figure 14.3.6.1.3 - Vital Sign Profiles: Mean (±SD) Heart Rate over time - Safety Population 
R 
Figure 14.3.6.1.4 - Vital Sign Profiles: Mean (±SD) Respiratory Rate over time - Safety Population 
R 
Figure 14.3.6.1.5 - Vital Sign Profiles: Mean (±SD) Temperature over time - Safety Population 
R 
Figure 14.4.1.1 - Pharmacokinetics: Line Plot of Geometric Mean (with and without gSD) Serum MEDI7352 over time - PK Population 
R 
Figure 14.4.1.2 - Pharmacokinetics: Individual Plot of Serum MEDI7352 Concentrations over time - PK Population 
U 
Figure 14.4.2.1 - Pharmacodynamics: Line Plot of Geometric Mean (with and without gSD) total NGF over time - Safety Population 
R 
Figure 14.4.2.2 - Pharmacodynamics: Individual Plot of Serum total NGF over time - Safety Population 
R 
 
 
 
 
 
 
 
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Figures Change Log 
Output 
Number 
Date of 
Change 
Change 
Made By 
(initials) 
Description/Rationale 
 
 
 
 
 
 
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Figure 14.2.1.1 
Daily Pain NRS: MCP-Mod Dose Response Model 
mITT Population 
 
CI = Confidence Interval; CFB = Change from Baseline; DPS = Daily Pain Score; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive. Envelope depicts 95% CI of mean dose-response. Added dots are actual doses ± 95% CI.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
I 
0 
m 
I.L 
,;-
0 
I 
if) 
(I'.'. 
N 
z 
I 
C ·ro 
0... 
(") 
I 
>, 
ro 
0 
"i" 
Ii) 
I 
0 
Weekly Average to Week 12 Daily Pain NRS CFB, 
Emax dose-response model 
I 
I 
I 
I • 
100 
200 
300 
Dose (~tg/kg) 
Hyperbolic I;,_ 
Eo = -0-21 
Emaoc: = -5.54 
ED50 = 197.56 
400 
I 
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Programming Notes: 
• 
Insert the following text as legend: “Weekly Average to Week 12 Daily Pain NRS CFB, xxxx dose-response model”, with ‘xxxx’ as the selected dose-
response model (e.g., Hyperbolic Emax). 
• 
Dose (µg/kg) in x axis and Daily Pain NRS CFB in y axis. 
• 
Add model parameter values as an inset plot. For e.g., Sigmoid Emax; E0 = xxx, Emax = xxx, ED50 = xxx, λ = xxx. 
• 
The MCP-MOD approach will only be performed if stage 4 is initiated, otherwise there would be insufficient dosing data to fit the non -linear models. 
 
 
 
 
 
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Figure 14.2.1.2 
Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Missing Data Handling 
mITT Population 
 
 
BOCF = Baseline Observation Carried Forward; CFB = Change from Baseline; DPS = Daily Pain Score; LOCF = Last Observation 
Carried Forward; NRS = Numeric Rating Scale; OBS = Observed Cases. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment wh ile receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
 
I 
m 
I.L 
0 
0 
(/) -2 
IY z 
C 
(U 
0... 
2-
(U 
0 
-4 
-6 
Weekly Average CFB to Week 12 Daily Pain NRS 
0 
5 
Dose (itg/kg) 
150 
450 
Data 
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Programming Notes: 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS”. 
• 
Dose (µg/kg) and Observed/LOCF/BOCF in x axis and Daily Pain NRS CFB in y axis. 
• 
A level for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
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Figure 14.2.1.3.1 
Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Co-Medication Subgroup 
mITT Population 
 
 
CFB = Change from Baseline; DPS = Daily Pain Score; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.2 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS”. 
• 
Dose (µg/kg) in x axis, Anticonvulsant/ Antidepressant/ Both/ None in right side Co-medication labels, and Daily Pain NRS CFB in y axis. 
• 
A level for 
 dosing 
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.2.1.3.2 
Daily Pain NRS CFB: Boxplots at Week 12 by Treatment Group and Co-Medication Subgroup, Including Opioids 
mITT Population 
 
 
BOTH = Anticonvulsant and Antidepressant; CFB = Change from Baseline; DPS = Daily Pain Score; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment while receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.2 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS”. 
• 
Dose (µg/kg) in x axis, Anticonvulsant/ Antidepressant/ Both/ Opioid/ None in right side Co-medication labels, and Daily Pain NRS CFB in y axis. 
• 
A level for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Figure 14.2.1.4 
Daily Pain NRS: MMRM LS Means (95% Confidence Interval) over 12-weeks by Treatment Group (Observed Cases) 
mITT Population 
 
CFB = Change from Baseline; CI = Confidence Interval; DPS = Daily Pain Score; LS = Least Square; MMRM = Mixed Model for 
Repeated Measures; NRS = Numeric Rating Scale. 
Baseline is defined as the average of the ‘non-missing’ DPS within the seven-day period prior to randomization i.e.,  
Day -7 to Day -1, inclusive.  
I 
rn 
ILL 
0 
-
0 
"";" -
(f) 
rr:: z 
r.:: 
(';'I -
2 
·-• ·- 0 
···•··· 5 
_.._ _ 150 
---+- 4 5 0 
4 
Weekly Average CFB to Week 12 
Daily Pain NRS ± 95% Cl 
6 
8 
Week 
10 
12 
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mITT Population = includes all subjects in the Safety Population who have at least 1 daily NRS assessment wh ile receiving double-blind treatment. 
Reference Listing:  16.2.6.1 
 
 
Programming Notes: 
• 
Insert the following text as legend: “Weekly Average CFB to Week 12 Daily Pain NRS ± 95% CI”. 
• 
Week in x axis and Daily Pain NRS CFB in y axis. 
• 
Include a profile for each dose treatment group. 
• 
Include the following timepoints: Week 2, 4, 6, 8, 10, and 12. 
• 
Extract data for this figure from the MMRM of CFB Daily Pain NRS with Observed Cases. 
• 
A profile for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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Figure 14.3.6.1.1 
Vital Sign Profiles: Mean (±SD) Systolic Blood Pressure over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; SBP = Systolic Blood Pressure; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = Week 
11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average SBP ± Standard Deviation”. 
• 
Study Visit in x axis and Systolic Blood Pressure (mmHg) in y axis. 
• 
Include a profile for Resting SBP and another for Standing SBP. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.3.6.1.2 
Vital Sign Profiles: Mean (±SD) Diastolic Blood Pressure over time 
Safety Population 
 
 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; DBP = Diastolic Blood Pressure; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = 
Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average DBP ± Standard Deviation”. 
• 
Study Visit in x axis and Diastolic Blood Pressure (mmHg) in y axis. 
• 
Include a profile for Resting DBP and another for Standing DBP. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated) 
 
 
 
 
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Figure 14.3.6.1.3 
Vital Sign Profiles: Mean (±SD) Heart Rate over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 30M PD = 30 Minutes Post-Dose; 4H 
PD = 4 hours Post-Dose; 45M PD = 45 Minutes Post-Dose; 5M PD = 5 minutes after Infusion Completion; BASE = Baseline; D1 = 
Day 1; HR = Heart Rate; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = Week 10; W11 = Week 11; W12 = 
Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average HR ± Standard Deviation”. 
• 
Study Visit in x axis and Heart Rate (Beats/min) in y axis. 
• 
Include a profile for Resting HR and another for Standing HR. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 30 Minutes Post-Dose, Day 1: 45 Minutes Post-Dose, Day 1: 1 hour 
Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, 
Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes 
after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do 
not include Screening records).   
• 
Note that standing measures are not taken on Day 1, at 15, 30 and 45 minutes post-dose. 
• 
Make one plot for each dose treatment group, for a total of 4 plots with two profiles each. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
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Figure 14.3.6.1.4 
Vital Sign Profiles: Mean (±SD) Respiratory Rate over time 
Safety Population 
 
 
1H PD = 1 Hour Post-Dose; 15M PD = 15 Minutes Post-Dose; 2H PD = 2 Hours Post-Dose; 4H PD = 4 hours Post-Dose; 5M PD = 
5 minutes after Infusion Completion; BASE = Baseline; D1 = Day 1; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; 
W10 = Week 10; W11 = Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average Respiratory Rate ± Standard Deviation”. 
• 
Study Visit in x axis and Respiratory Rate (Breaths/min) in y axis. 
• 
Include the following timepoints: Baseline, Day 1: 15 Minutes Post-Dose, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-
Dose, Week 2: Pre-Dose, Week 2: 5 minutes after Infusion Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-
Dose, Week 6: 5 minutes after Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 
minutes after Infusion Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Make one plot with 4 profiles (one for each treatment group). 
• 
A profile for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
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research} 
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Figure 14.3.6.1.5 
Vital Sign Profiles: Mean (±SD) Temperature over time 
Safety Population 
 
1H PD = 1 Hour Post-Dose; 2H PD = 2 Hours Post-Dose; 4H PD = 4 hours Post-Dose; 5M PD = 5 minutes after Infusion 
Completion; BASE = Baseline; D1 = Day 1; T° = Temperature; W2 = Week 2; W4 = Week 4; W6 = Week 6; W8 = Week 8; W10 = 
Week 10; W11 = Week 11; W12 = Week 12; W18 = Week 18. 
Baseline is defined as the last observation recorded prior to the first dose of treatment.  
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
Reference Listing:  16.2.9.1 
 
 
Programming Notes: 
• 
Same shell as Figure 14.2.1.4 
• 
Insert the following text as legend: “Average Body Tº ± Standard Deviation”. 
• 
Study Visit in x axis and Body Temperature (ºC) in y axis. 
• 
Include the following timepoints: Baseline, Day 1: 1 hour Post-Dose, Day 1: 2 hours Post-Dose, Day 1: 4 hours Post-Dose, Week 2: Pre-Dose, Week 2: 
5 minutes after Infusion Completion, Week 4: Pre-Dose, Week 4: 5 minutes after Infusion Completion, Week 6: Pre-Dose, Week 6: 5 minutes after 
Infusion Completion, Week 8: Pre-Dose, Week 8: 5 minutes after Infusion Completion, Week 10: Pre-Dose, Week 10: 5 minutes after Infusion 
Completion, Week10 + 24 hours, Week 11, Week 12, Week 18. (Do not include Screening records).   
• 
Make one plot with 4 profiles (one for each treatment group). 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
I 
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research} 
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Figure 14.4.1.1 
Pharmacokinetics: Line Plot of Geometric Mean (with and without gSD) Serum MEDI7352 Concentrations over Time  
PK Population 
 
 
ADA = Antidrug Antibodies; gSD = Geometric Standard Deviation; LLOQ = Lower Limit of Quantification. 
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PK Population = includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.1 
 
 
 
Programming Notes: 
• 
Insert the following text as upper legend: “Geometric Mean serum MEDI7352 ± Geometric Standard Deviation (Linear Scale)” for the linear plot, and 
“Geometric Mean serum MEDI7352 (Semi-Logarithmic Scale)” for the semi-log plot. Below legend, add legend for ADA status: “Overall”, “ADA 
Positive”, “ADA Negative”. 
• 
Insert legend with different point symbols and colors for each treatment group (
) for the Overall plot, and a legend with different point 
symbols and colors for each ADA status (ADA+, ADA-) for each treatment group plot by ADA status. 
• 
Study Day in x axis and Serum MEDI7352 concentration (ng/mL) in y axis (in linear and log10 scale, for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10: Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 10 + 14 days, Week 18.   
• 
Make one overall plot by treatment group, and a plot for each treatment group by ADA status for a total of 4 plots. 
• 
Include a marker for LLOQ, and an inset within the plot with “LLOQ (1.00 ng/mL)”. 
• 
A line for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
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Figure 14.4.1.2 
Pharmacokinetics: Individual Plot of Serum MEDI7352 Concentrations over time  
PK Population 
 
ADA = Antidrug Antibodies; LLOQ = Lower Limit of Quantification. 
PK Population = includes all subjects for who a pharmacokinetic sample was obtained and analyzed. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.1 
 
 
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Programming Notes: 
• 
Insert the following text as upper legend: “MEDI7352 Concentration by Subject, Treatment group, and ADA status” followed by “(Linear Scale)” or 
“(Semi-Logarithmic Scale)” depending on the plot (linear or semi-log). Below legend, add legend for Treatment Group: 
 
. 
• 
Insert legend with different colors for each ADA status (Positive/ Negative). 
• 
Time (days) in x axis and Serum MEDI7352 concentration (ng/mL) in y axis (in linear and log10 scale, for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 10 + 14 days, Week 18.   
• 
Make one plot for each Treatment group (
), for a total of 3 plots. 
• 
Include a marker for LLOQ, and an inset within the plot with “LLOQ (1.00 ng/mL)”. 
• 
Plots for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Figure 14.4.2.1 
Pharmacodynamics Line Plot of Geometric Mean (with and without gSD) Serum total NGF over time  
Safety Population 
 
 
ADA = Antidrug Antibodies; gSD = Geometric Standard Deviation; LLOQ = Lower Limit of Quantification, NGF = Nerve-Growth 
Factor. 
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.3 
 
 
Programming Notes: 
• 
Same shell as Figure 14.4.1.1 
• 
Insert the following text as upper legend: “Geometric Mean Serum Concentration of tNGF ± Geometric Standard Deviation (Linear Scale)” for the 
linear plot, and “Geometric Mean Serum Concentration of tNGF (Semi-Logarithmic Scale)” for the semi-log plot. Below legend, add legend for ADA 
status: “Overall”, “ADA Positive”, “ADA Negative”. 
• 
Insert legend with different point symbols and colors for each treatment group (Placebo, 
) for the Overall plot, and a legend with 
different point symbols and colors for each ADA status (ADA+, ADA-) for each treatment group plot by ADA status. 
• 
Study Day in x axis and Serum tNGF Concentration (pg/mL) in y axis (in linear and log10 scale for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10: Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12, Week 18.   
• 
Make one overall plot by treatment group, and a plot for each treatment group by ADA status for a total of 5 plots . 
• 
Include a marker for LLOQ, and an inset within the plot with “LLOQ (10.00 pg/mL)”. 
• 
A plot for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
 
 
 
 
 
 
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Figure 14.4.2.2 
Pharmacodynamics: Individual Plot of Serum total NGF over time  
Safety Population 
 
ADA = Antidrug Antibodies; LLOQ = Lower Limit of Quantification; NGF = Nerve-Growth Factor. 
Safety Population = includes all subjects who receive at least 1 dose of double-blind study medication. 
ADA positive represents number of participants with at least one positive ADA result. 
ADA negative represents number of participants with only negative ADA results (no positive). 
Reference Listing:  16.2.10.3 
 
 
Programming Notes: 
• 
Same shell as Figure 14.4.1.2 
• 
Insert the following text as legend: “Total NGF by Subject, Treatment group, and ADA status” followed by “(Linear Scale)” or “(Semi-Logarithmic 
Scale)” depending on the plot (linear or semi-log). Below legend, add legend for Treatment Group: 
. 
• 
Insert legend with different colors for each ADA status (Positive/ Negative). 
• 
Time (days) in x axis and Serum tNGF concentration (pg/mL) in y axis (in linear and log10 scale for each plot). 
• 
Include data from the following timepoints: Baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10: Pre-Dose, Week 10; Before End of 
Infusion, Week 10: 8 Hours after Infusion, Week 10 + 24 hours, Week 11, Week 12; Week 18.   
• 
Make one plot for each Treatment group (
 Placebo), for a total of 4 plots. 
• 
Include a marker for LLOQ, and an inset within the plot with “LLOQ (10.00 pg/mL)”. 
• 
Plots for 
 dosing (
) will only be added if Stage 4 is initiated. 
 
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