Clinical trial NCT02504645
Conditions: Lupus Erythematosus, Systemic
Sponsor: ImmuPharma
Start date: 2015-03-01; Completion date: 2018-01-01
Enrollment: 202 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This current Phase 3 study will evaluate the efficacy and safety of administration of subcutaneous (sc) IPP-201101 in patients with active SLE.

Detailed description:

Arms: arm 1: Patients randomly assigned to IPP-201101 will be administered a dosage of 200 mcg subcutaneously (sc) every 4 weeks for 48 weeks (a total of 13 doses will be administered). arm 2: Patients randomly assigned to placebo will be administered placebo subcutaneously (sc) every 4 weeks for 48 weeks (a total of 13 doses will be administered).
Interventions: intervention 1: IPP-201101 intervention 2: Placebo intervention 3: Standard of Care
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents:
Prot_000.pdf: 


ImmuPharma 
IPP-201101 
 Study IPP-201101/005 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
2 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
 
 
 
INVESTIGATOR AGREEMENT 
 
 
 
Clinical Study Protocol 
A 52-Week, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to 
Evaluate the Efficacy and Safety of a 200-mcg Dose of IPP-201101 Plus Standard of Care 
in Patients With Systemic Lupus Erythematosus 
 
 
Investigator (Country):  
  
 
Title:  
 
 
 
Address of Study Center:    
 
 
 
 
 
 
 
________________________ 
 
 
 
 
  
 
 
 
 
 
 
 
________________________ 
 
 
 
 
 
 
 
 
 
Tel:   
 
 
 
 
Fax:   
 
 
 
 
Cell:   
 
 
 
 
 
I have read the protocol and agree that it contains all necessary details for carrying out this study. 
I will conduct the study as outlined therein. 
 
I will provide copies of the protocol and all information on the drug relating to the nonclinical 
and prior clinical experience, which were furnished to me by the sponsor, to all physicians and 
other study personnel responsible to me who participate in this study, and will discuss this 
material with them to ensure that they are fully informed regarding the drug and the conduct of 
the study. 
 
I agree to keep records on all patient information (ie, case report forms and informed consent 
statements), study drug shipment and return forms, and all other information collected during the 
study, in accordance with local and national regulations. 
 
 
 
 
 
 
Investigator’s Signature 
 
 
Date 


ImmuPharma 
IPP-201101 
 Study IPP-201101/005 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
3 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
 
SPONSOR’S MEDICAL EXPERT 
Robert Zimmer 
ImmuPharma SA 
5 Rue du Rhône 
Mulhouse F-68100 France 
Robert.Zimmer@immupharma.com  
Tel: +33 (0)6 18 22 16 50 
 
SPONSOR’S SAFETY OFFICER 
David Nightingale 
ORION Clinical Services 
7 Bath Road, Slough  
Berkshire SL1 3UA 
pharmacovigilance@orioncro.com   
Tel: +44 1753 578 080 
 
CLINICAL LABORATORY AND OTHER DEPARTMENTS AND 
INSTITUTIONS 
Simbec Research Ltd 
Merthyr Tydfil 
CF48 4DR 
United Kingdom 
 
CLINICAL STUDY PERSONNEL CONTACT INFORMATION 
Nathalie-Ernault Roseau 
ORION Santé SARL 
Centre d’Affaires La Boursidière 
Bâtiment le Jura BP 141 
92357 Le Plessis-Robinson Cedex 
France 
 
 


ImmuPharma 
IPP-201101 
 Study IPP-201101/005 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
4 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
CLINICAL STUDY PROTOCOL SYNOPSIS 
 
Sponsor: ImmuPharma SA 
Investigational Product: IPP-201101 
Title of Study: A 52-Week, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the 
Efficacy and Safety of a 200-mcg Dose of IPP-201101 Plus Standard of Care in Patients With Systemic Lupus 
Erythematosus 
Number of Centers Planned: Approximately 50 centers globally 
Planned Study Period: 3rd quarter 2015 to 4th quarter 2017 
Phase of Development: 3 
Primary Objective: The primary objective of this study is to evaluate the efficacy of a 200-mcg dose every 4 weeks 
for 48 weeks of IPP-201101 compared with placebo in patients with active systemic lupus erythematosus (SLE) as 
assessed by the SLE responder index (SRI) at week 52. An SRI response is defined as a reduction from baseline in 
the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of at least 4 points, no 
worsening in Physician’s Global Assessment (PhGA) (with worsening defined as an increase in PhGA of more than 
0.30 point from baseline), no new British Isles Lupus Assessment Group A (BILAG A) body system score, and no 
more than 1 new BILAG B body system score from baseline. 
Secondary Objectives: The secondary efficacy objectives of the study are to evaluate the following: 
• 
the SRI response at each visit during the study 
• 
the reduction in the SLEDAI-2K total score by at least 4 points at each visit during the treatment period 
• 
the effect of IPP-201101 on disease activity, as assessed by the BILAG-2004 disease activity index, at each 
visit during the treatment period 
• 
the effect of IPP-201101 on the status of disease (PhGA scale) at each visit during the treatment period 
• 
the reduction of the SLEDAI-2K total score by at least 5 points at each visit during the treatment period 
• 
the reduction of the SLEDAI-2K total score by at least 6 points at each visit during the treatment period 
• 
the SRI-5 response at each visit during the treatment period 
• 
the SRI-6 response at each visit during the treatment period 
• 
the effect of IPP-201101 on arthritis, as assessed by the 28-joint count examination for pain and tenderness at 
each visit during the treatment period 
• 
the effect of IPP-201101 on the incidence of disease flares (ie, Safety of Estrogens in Lupus Erythematosus: 
National Assessment [SELENA] Flare Index [SFI] and SLEDAI-2K score of greater than 15) at each visit 
during the treatment period 
• 
the effect of IPP-201101 on the occurrence of SLE–induced organ damage (eg, Systemic Lupus International 
Collaborative Clinics/American College of Rheumatology [SLICC/ACR] Damage Index (SDI) and adverse 
event inquiry) at visits at weeks 24 and 52 (or final assessment) 
• 
the effect of IPP-201101 on health-related quality of life, as assessed by completion of the Medical Outcome 
Survey Short Form 36 (SF-36) at visits at weeks 12, 24, 36, and 52 (or final assessment) 
• 
the effect of IPP-201101 on steroid dose over time throughout the study The exploratory efficacy objectives of 
the study are to determine the following: 
• 
the effect of IPP-201101 on the following biologic markers of disease activity at each visit during the 
treatment period: 
anti–double-stranded deoxyribonucleic acid antibody (anti-dsDNA Ab) complement components (C3 and C4) 
• 
the effect of IPP-201101 on the following biologic markers of disease activity at visits at weeks 4, 12, 24, 36, 
and 52 (or final assessment): 
— 
antinuclear antibody (ANA) 
— 
anti-uridine rich 70 kilodalton small nuclear ribonucleoprotein particle Ab (anti–U1-70K snRNP Ab) 
— 
anti-Smith antibody (anti-Sm Ab) 
— 
C-reactive protein (CRP) 
— 
immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin E (IgE), immunoglobulin A 
(Ig A) 
• 
the effect of IPP-201101 on fatigue using the Functional Assessment of Chronic Illness Therapy–Fatigue 
(FACIT-Fatigue) scale at visits at weeks 12, 24, 36, and 52 (or final assessment) 


ImmuPharma 
IPP-201101 
 Study IPP-201101/005 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
5 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
• 
in vitro intracellular and secreted cytokine response 
The safety and tolerability of IPP-201101 will be evaluated by the following: 
• 
occurrence of adverse events throughout the study 
• 
clinical laboratory (serum chemistry, hematology, and urinalysis) test results at each visit during the treatment 
period 
• 
vital signs (systolic and diastolic blood pressures, pulse, temperature, and body weight) measurements at each 
visit during the treatment period 
• 
12-lead electrocardiogram (ECG) findings at week 52 (or final assessment) 
• 
physical examination findings, including physical examination symptom directed findings, at specified time 
points at each visit during the treatment period 
• 
evaluation for suicidality at each visit during the treatment period using the Columbia-Suicide Severity Rating 
Scale (C-SSRS) 
• 
concomitant medication usage throughout the study 
The immunogenicity of IPP-201101 will be assessed by the following: 
• 
any presence of anti–IPP-201101 antibodies (anti–IPP-201101 Ab) at visits at weeks 2, 4, 12, 20, 28, 36, 44, 
and 52 (or final assessment) 
Number of Patients Planned: It is anticipated that approximately 270 patients may be screened for participation in 
the study prior to completion of enrollment. Approximately 200 patients are planned to be enrolled in the study, to 
provide 100 evaluable patients per treatment group. To be evaluable for efficacy, a patient must be treated with at 
least 1 dose of study drug and must have all components of the SRI (baseline SLEDAI-2K total score, BILAG-2004 
body system scores, and PhGA score) available. 
Diagnosis and Criteria for Inclusion: Patients are included in the study if all of the following criteria are met: 
(a) The patient is a man or woman between 18 and 70 years of age with an established diagnosis of SLE as 
defined by ACR Classification Revised Criteria. The diagnosis is fulfilled provided that at least 4 criteria are 
met. 
(b) The patient has a positive test result for ANA at screening (titer must be at least 1:80 [by human epithelial cell 
tumor line (HEp-2) ANA assay]) and/or a positive test result for anti-dsDNA Ab at screening (value must be 
30 IU/mL or more by enzyme-linked immunosorbent assay [ELISA]). 
(c) Written informed consent is obtained. 
(d) Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing potential, using a medically 
accepted method of contraception, and must agree to continued use of this method for the duration of the study 
and for 30 days after discontinuation of study drug treatment. Acceptable methods of contraception include 
barrier method with spermicide, abstinence (when this is in line with the preferred and usual lifestyle of the 
subject), intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in 
conjunction with a barrier method. 
(e) The patient has a SLEDAI-2K clinical score of at least 6 points during screening. A SLEDAI-2K clinical 
score is the calculated score without inclusion of the points that may be contributed by having a positive titer 
for anti-dsDNA Ab or decreased serum complement levels. 
(f) 
The patient does not have an “A” score on the BILAG-2004 scale. 
(g) If the patient is using oral corticosteroids, the weekly cumulative dose must not exceed 80 mg of prednisone 
equivalent; the weekly dose must be stable over the 4 weeks preceding the 1st dose of study drug. 
(h) If the patient is using antimalarials, methotrexate, leflunomide, mycophenolate mofetil (MMF), or 
azathioprine, the start date must be at least 3 months prior to the 1st dose of study drug, and the daily dose must 
be stable over the 4 weeks preceding the 1st dose of study drug. 
(i) 
If the patient is not currently using corticosteroids, antimalarials, methotrexate, MMF, or azathioprine, the last 
dose (in case of previous use) must be at least 4 weeks prior to the 1st dose of study drug. For leflunomide, the 
stop date must be at least 8 weeks before the 1st dose of study drug unless an adequate cholestryamine washout 
has been performed. If cholestyramine washout is performed, the last use of leflunomide must be at least 4 
weeks before the 1st dose of study drug. 
(j) 
The patient must be willing and able to comply with study restrictions, to remain at the study center for the 
required duration during each study visit, and to return to the study center for the final assessment as specified 
in this protocol. 


ImmuPharma 
IPP-201101 
 Study IPP-201101/005 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
6 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
 
Criteria for Exclusion: Patients are excluded from participating in this study if 1 or more of the following criteria 
are met: 
(a) The patient has been treated with intramuscular or intravenous (iv) pulse steroids (ie, 250 to 1000 mg iv total 
daily dose of methylprednisolone) within 4 weeks of the 1st dose of study drug. The use of intra-articular 
steroids may be allowed after consultation with the medical expert. 
(b) The patient has received tacrolimus, cyclosporin A, or iv immunoglobulins (IVIG) within 3 months of the 1st 
dose of study drug. 
(c) The patient has received cyclophosphamide within 6 months prior to the 1st dose of study drug. 
(d) The patient has been treated for SLE with agents such as fusion proteins, therapeutic proteins, or monoclonal 
antibodies or antibody fragments, within 6 months of the 1st dose of study drug. 
(e) The patient has received B-cell depleting agents such as rituximab,  belimumab or epratuzumab within one year 
of the 1st dose and has not yet normalized the B-cell count (ie, CD20+ B-cell count is less than normal range and 
the absolute lymphocyte count [ALC] is less than normal range). 
(f) 
The patient has New York Heart Association (NYHA) Class III or IV congestive heart failure. 
(g) The patient has an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2 (via 
Modification of Diet in Renal Disease [MDRD] equation). 
(h) The patient has an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value greater 
than 2 times the upper limit of the normal range (ULN) or a total bilirubin level greater than 1.5 times ULN. 
(i) 
The patient has a planned immunization with a live or live attenuated vaccine within 3 months prior to 
administration of the 1st dose of study drug and for 3 months after administration of the last dose of study drug. 
(j) 
The patient has any clinically significant abnormalities on ECG that are not related to SLE, as determined by 
the investigator. Patients with stable ECG changes without evidence of active cardiovascular disease may 
participate at the discretion of the investigator and medical monitor. 
(k) The patient has an ongoing active systemic infection requiring treatment or a history of severe infection, such 
as hepatitis or pneumonia, in the 3 months prior to administration of the 1st dose of study drug. Less severe 
infections in the 3 months prior to administration of the 1st dose of study drug are permitted at the discretion of 
the investigator and medical monitor. 
(l) 
The patient has any concomitant medical condition unrelated to SLE that may interfere with his or her safety or 
with evaluation of the study drug, as determined by the investigator. 
(m) The patient has a history of a medical condition other than SLE that has required treatment with oral 
corticosteroids in excess of 80 mg of prednisone equivalent/week within 3 months of the 1st dose of study drug. 
(n) The patient has a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody 
(HCV Ab). 
(o) The patient has a known positive history of antibodies to human immunodeficiency virus (HIV) or HIV disease 
or other immunosuppressive state (eg, agammaglobulinemia, etc). 
(p) The patient has a history of alcohol or substance dependence or abuse (with the exception of 
nicotine),according to the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric 
Association, Fourth Edition, Text Revision (DSM-IV-TR), within 3 months of the screening visit or has 
current substance abuse. 
(q) The patient has a history of severe allergic reactions to or hypersensitivity to any component of the study drug 
or placebo. 
(r) 
The patient has undergone or is undergoing treatment with another investigational drug for the treatment of 
lupus within 6 months prior to the 1st dose of study drug or has received any other investigational drug for any 
other condition within 4 weeks prior to the 1st dose of study drug. 
(s) 
The patient has previously participated in a ImmuPharma- or ImmuPharma-sponsored clinical study with IPP-
201101. 
(t) 
The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be 
withdrawn from the study.) 
(u) The patient is unlikely to comply with the study protocol or is unsuitable for any other reason, as judged by the 
investigator or medical monitor. 
Study Drug Dose, Mode of Administration, and Administration Rate: 
Investigational Product: IPP-201101 is a white to off-white, amorphous powder and is supplied in single-dose 


ImmuPharma 
IPP-201101 
 Study IPP-201101/005 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
7 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
glass vials as lyophilized product for reconstitution. Before reconstitution, vials of study drug must be stored under 
refrigerated conditions (2° to 8° C [36° to 46° F]) in a secure place and protected from light. Each vial contains a 
sterile formulation of 220 mcg of IPP-201101, mannitol (and acetic acid used for pH adjustment, if necessary). This 
product does not contain preservatives. The study center will receive box(es) with up to 13 vials per box. Each vial 
will be labeled with a 4-digit treatment number and each box will contain IPP-201101. Prior to administration, IPP-
201101 should be reconstituted with 1.1 mL sterile water for injection (volume of injection of 1.0 mL). After 
reconstitution, the vial can be stored at controlled room temperature (20° to 25° C [68° to 77° F]) for up to 2 hours 
prior to administration and does not need to be protected from light. Patients randomly assigned to IPP-201101 will 
be administered a dosage of 200 mcg subcutaneously (sc) every 4 weeks for 48 weeks (a total of 13 doses will be 
administered). 
Placebo: Placebo vials matching the single-dose vials of IPP-201101 will be supplied by ImmuPharma. Each vial 
contains a white to off-white, amorphous powder as a lyophilized sterile formulation of mannitol (and acetic acid 
used for pH adjustment, if necessary). Before reconstitution, vials of placebo must be stored under refrigerated 
conditions (2° to 8° C [36° to 46° F]) in a secure place and protected from light. The study center will receive 
box(es) with up to 13 vials per box. Each vial will be labeled with a 4-digit treatment number and each box will 
contain placebo vials. Prior to administration, placebo should be reconstituted with 1.1 mL sterile water for 
injection (volume of injection of 1.1 mL). After reconstitution, the vial can be stored at controlled room temperature 
(20° to 25° C [68° to 77° F]) for up to 2 hours prior to administration and does not need to be protected from light. 
Patients randomly assigned to placebo will be administered placebo sc every 4 weeks for 48 weeks (a total of 13 
doses will be administered). 
Method of Blinding: Patients will be randomly assigned to treatment through a qualified randomization service 
provider (eg, interactive response technology [IRT]). Patients and investigators will remain blinded to treatment 
assignment during the study. Study drug may not be administered by the same individual performing the SLEDAI-
2K, BILAG-2004, or PhGA. Study drug should be administered at each study visit after all study visit procedures 
and assessments have been completed. 
Duration of Participation: This study will consist of a screening period up to 2 weeks and a 48-week treatment 
period. Patients will return to the study center approximately 4 weeks after administration of the last dose of study 
drug (at 48 weeks) for the final assessment (week 52). Patients are expected to participate in the study for up to 
approximately 54 weeks. 
General Design and Methodology: This is a randomized, double-blind, placebo-controlled study to evaluate the 
efficacy and safety of a 200-mcg dose of IPP-201101 plus standard of care (SOC) compared with placebo plus SOC 
in patients with active SLE. The study consists of a 2-week screening period (visit 1), a 48-week treatment period 
beginning with a baseline visit in which randomization will be completed and study drug treatment will start (visit 2 
and visits 4 through 14), and a final assessment 4 weeks after the last dose of study drug (visit 16 [week 52]). 
NOTE: If needed during the screening period, up to 14 additional days are permitted to confirm eligibility (eg, 
BILAG-2004, SLEDAI-2K, and PhGA central system assessment, laboratory results ….). In addition to the typical 
assessments obtained at the screening visit, such as obtaining medical, psychiatric, and medication history 
(medication history to be obtained from start of screening) and performing a physical examination and tests to 
determine the patients’ health status and eligibility for participation in the study, procedures will include assessment 
of disease activity using the SLEDAI-2K and BILAG-2004 disease activity indices and the SFI, and disease marker 
testing (ie, at screening, anti-dsDNA Ab, C3, C4, and ANA only]). Eligibility will be confirmed by using a central 
system to validate the BILAG-2004, SLEDAI-2K, and PhGA assessments. Eligible patients will return to the study 
center at baseline and will be randomly assigned (stratified by region, SLEDAI-2K screening total score [6 to 9 or 
≥10], and racial-ethnic group classification [black/Hispanic or others]) at baseline with an equal probability and in a 
blinded fashion to receive either IPP-201101 or placebo sc every 4 weeks for 48 weeks. Pretreatment assessments 
will be performed and the 1st dose of 200 mcg sc of IPP-201101 or placebo (sc) will be administered after all 
assessments have been completed. Patients will be monitored for systemic symptoms for at least 1 hour after the 
first 2 doses of study drug have been administered. For subsequent doses, patients will be monitored, at the 
discretion of the investigator, in the study center after study drug treatment. Patients will return to the study center 2 
weeks after administration of the 1st dose of study drug for immunogenicity testing, and every 4 weeks for 48 
weeks (weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48) to receive study drug. Patients may continue on their 
usual treatment for SLE (ie, SOC) as long as the inclusion and exclusion criteria regarding these treatments are met 
and the total weekly steroid dose does not exceed 80 mg of prednisone equivalent/week; the dosages for 


ImmuPharma 
IPP-201101 
 Study IPP-201101/005 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
8 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
immunosuppressive medications may change, if needed, only as directed in the protocol. Efficacy assessments 
include SLEDAI-2K, BILAG-2004, PhGA scale, SF-36 questionnaire, biologic markers of disease, SFI, SDI, 
FACIT-Fatigue scale, and change in steroid dose over time. Adverse events will be recorded throughout the study. 
Safety will also be assessed by evaluating clinical laboratory test results, vital signs measurements, 12-lead ECG 
findings, physical examination findings, assessment of suicidality using the C-SSRS, assessment for anaphylaxis 
using the Clinical Criteria for Diagnosing Anaphylaxis, and concomitant medication usage throughout the study. 
Immunogenicity will also be assessed at weeks 4, 12, 20, 28, 36, 44, and 52 by detection of any presence of anti–
IPP-201101 Ab . In vitro intracellular and secreted cytokine response will be assessed at weeks 0, 4, 24 and 48 
weeks to assess intracellular modification linked to the treatment.  In addition to standard safety monitoring, an 
independent, external Data and Safety Monitoring Board (DSMB) will oversee the safety of the patients and 
monitor the occurrence of flare throughout the study. The DSMB will meet as specified in its charter. Blood 
samples for measurement of IPP-201101 plasma concentrations will be collected prior to and after study drug 
administration at weeks 0, 16, and 32 from patients at selected North American and Western European study 
centers. A blood sample for measurement of the concentration of IPP-201101 will also be obtained from all patients 
who have a serious adverse event and/or have an adverse event leading to withdrawal from the study. Patients who 
complete the 48-week treatment period will return to the study center at week 52 for final procedures and 
assessments. Patients who withdraw from the study before completion of the 48-week treatment period will have 
their final procedures and assessments performed at their last visit. Any patient with a positive test result for anti–
IPP-201101 Ab at the final study visit will be followed with additional immunogenicity testing at 8-week intervals 
until the level returns to baseline value or the levels are judged by the investigator to be chronic, or the patient is lost 
to follow-up.  
Primary Efficacy Variable and Endpoint: The primary efficacy variable for this study is the proportion of 
patients achieving a combined clinical response using the SRI at week 52. An SRI response is defined as a 
reduction from baseline in the SLEDAI-2K score of at least 4 points, no worsening in PhGA (with worsening 
defined as an increase in PhGA of more than 0.30 point from baseline), no new BILAG A body system score and no 
more than 1 new BILAG B body system score from baseline. 
Secondary Efficacy Variables and Endpoints: 
The secondary efficacy variables and endpoints for this study are as follows: 
• 
proportion of patients achieving an SRI response at each visit during the treatment period 
• 
proportion of patients achieving a reduction of at least 4 points in the SLEDAI-2K total score at each visit 
during the treatment period 
• 
proportion of patients achieving a clinical SLEDAI-2K response at each visit during the treatment period, 
where the clinical response is defined as a reduction of at least 4 points in the SLEDAI-2K clinical score 
• 
proportion of patients achieving a BILAG-2004 response at each visit during the treatment period (no new 
BILAG A body system score and no more than 1 new BILAG B body system score from baseline) 
• 
proportion of patients achieving a BILAG-2004 clinical response at each visit during the treatment period (an 
improvement in at least 1 category from a B score to a C or D score, with no worsening in any other category) 
• 
proportion of patients showing no worsening on a PhGA scale at each visit during the treatment period 
• 
proportion of patients achieving a reduction of 5 points in the SLEDAI-2K total score at each visit during the 
treatment period 
• 
proportion of patients achieving a reduction of 6 points in the SLEDAI-2K total score at each visit during the 
treatment period 
• 
proportion of patients achieving an SRI-5 response at each visit during the treatment period 
• 
proportion of patients achieving an SRI-6 response at each visit during the treatment period 
• 
proportion of patients showing an improvement in tender and swollen joint counts using the 28-joint count 
examination for pain and tenderness at each visit during the treatment period 
• 
SFI at each visit during the treatment period 
— time to first mild to moderate flare 
— incidence of mild to moderate flare 
— time to severe flare (NOTE: A severe flare leads to early withdrawal) 
• 
changes in the SDI over time (assessed at screening and weeks 24 and 52 [or final assessment]) 
• 
absolute and relative changes in the SF-36 at weeks 12, 24, 36, and 52 (or final assessment) 
• 
proportion of patients with changes in steroid dose over time throughout the study The exploratory efficacy 


ImmuPharma 
IPP-201101 
 Study IPP-201101/005 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
9 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
variables and endpoints for this study are as follows: 
• 
changes in the biomarkers anti-dsDNA Ab, C3, and C4 at each visit during the treatment period 
• 
changes in the following biomarkers at weeks 4, 12, 24, 36, and 52 (or final assessment): 
— ANA 
— anti–U1-70K snRNP Ab 
— anti-Sm Ab 
— CRP 
— IgG, (Ig A), IgM, and IgE 
• 
absolute and relative changes in the FACIT-Fatigue at weeks 12, 24, 36, and 52 (or final assessment) 
• 
in vitro intracellular and secreted cytokine response 
Safety Variables and Endpoints: Safety measures and endpoints will include the following: 
• 
occurrence of adverse events throughout the study 
• 
clinical laboratory (serum chemistry, hematology, and urinalysis) test results at each visit during the treatment 
period 
• 
vital signs (systolic and diastolic blood pressures, pulse, temperature, and body weight) measurements at each 
visit during the treatment period 
• 
12-lead electrocardiogram (ECG) findings at week 52 (or final assessment) 
• 
physical examination findings, including physical examination symptom directed findings, at specified time 
points at each visit during the treatment period 
• 
evaluation for suicidality at each visit during the treatment period using the C-SSRS 
• 
concomitant medication usage throughout the study 
Immunogenicity: The immunogenicity variable/endpoint for this study is as follows: any presence of anti–IPP-
201101 Ab at visits at weeks 2, 4, 12, 20, 28, 36, 44, and 52 (or final assessment). Any patient with a positive test 
result for anti–IPP-201101 Ab at the final study visit will be followed with additional immunogenicity testing at 8-
week intervals until the level returns to baseline value or the levels are judged by the investigator to be chronic, or 
the patient is lost to follow-up. 
Pharmacokinetics/Pharmacodynamics: Blood samples (5 mL) for pharmacokinetics will be collected from 
patients at selected North American and Western European study centers via venipuncture or indwelling catheter 
prior to and 5 minutes and 1, 2, and 24 hours after study drug administration at weeks 0, 16, and 32 (visits 2, 7, and 
11, respectively). A blood sample for measurement of the concentration of IPP-201101 will also be obtained from 
all patients who have a serious adverse event and/or have an adverse event leading to withdrawal from the study. 
In vitro intracellular and secreted cytokine response: Blood samples (5 mL) will be collected from patients at 
selected study centers via venipuncture or indwelling catheter prior study drug administration at weeks 0, 4 24 and 
48 (visits 2,4,9 and 15, respectively). 
Statistical Considerations: The primary efficacy variable is the proportion of patients achieving a combined 
clinical response using the SRI at week 52. With 100 evaluable patients per group (200 total), this study will have a 
90% or greater power to detect a 25% or greater difference or a 20% difference with a 80% power in the proportion 
of SRI responders between the IPP-201101 group and the placebo group. This projection using the Pearson Chi-
square test (2-sided, alpha=0.05) is based on an anticipated placebo effect at week 52 of 40% to 45%. This range 
covers the placebo effect reported in the literature and in a Phase 2b, multicenter, randomized, double-blind, 
placebo-controlled dose-ranging study of IPP-201101 (study IP-004). The response rate under active is based on 
the Phase IIb study performed with the mannitol formulation outside the US. This study showed an absolute 25% 
response of active over placebo increasing to 40% in the interim analysis. Using a 80% or a 90%power leads to a 
sample size of 100 evaluable patients per group.  The efficacy evaluation will be based on the full analysis set that 
includes all patients who received at least 1 dose of the study drug.. The statistical method to be used for the SRI is 
the logistic regression model with treatment and stratification factors as main factors. The SRI is linked to the model 
factors through the logit function. The likelihood-ratio–based Chi-square statistics will be used for testing the 
treatment difference between IPP-201101 and placebo in SRI at week 52 at the significance level 0.05. The odds 
ratio (active/placebo) and associated 95% confidence interval will be determined from the logistic regression model. 
As sensitivity analyses, the primary analysis will be repeated using another 3 imputation methods to estimate 
missing SRI at week 52 according to the reason for withdrawal. In the 1st method, patients who withdraw because 
of lack of efficacy will be classified as treatment failures assessed by SRI at week 52. For patients who withdraw 


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because of other reasons, their missing SRI at week 52 will be estimated using the multiple imputation method. The 
imputation values will be drawn from the categories formed by treatment group and randomization stratum to which 
the patient belongs. In the 2nd method, the missing SRI at week 52 will be imputed using the last observation carried 
forward (LOCF) method. In the 3rd method, patients who withdraw and those completers who used prohibited 
medication within 8 weeks from week 52 will be classified as nonresponders. Secondary efficacy variables will be 
summarized using the descriptive statistics by treatment group and time point. Safety evaluations will include all 
patients who took at least 1 dose of study drug. Descriptive statistics will be used to summary the safety variables. 


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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL SYNOPSIS ....................................................................................................... 4 
TABLE OF CONTENTS ........................................................................................................................................ 11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................................................................ 16 
1 
BACKGROUND INFORMATION ......................................................................................................... 19 
1.1 
Introduction ............................................................................................................................................... 19 
1.2 
Name and Description of Investigational Product .................................................................................. 20 
1.3 
Findings From Nonclinical and Clinical Studies ..................................................................................... 20 
1.3.1 
Nonclinical Studies .................................................................................................................................... 20 
1.3.1.1 
Pharmacology Studies .......................................................................................................................... 20 
1.3.1.2 
Toxicology Studies ................................................................................................................................ 21 
Table 1: 
Comparative Doses in the Animal Toxicity Studies and the Proposed ............................................. 22 
1.3.2 
Clinical Studies .......................................................................................................................................... 22 
1.3.2.1 
Safety and Tolerability Results From a Completed Phase 1 Study in Healthy Men ........................ 22 
1.3.2.2 
Efficacy and Safety Results From a Completed Phase 2a Study in Patients With Systemic Lupus 
Erythematosus ......................................................................................................................................................... 23 
1.3.2.3 
Efficacy and Safety Results From a Completed Phase 2b Study in Patients With Active Systemic 
Lupus Erythematosus ............................................................................................................................................. 24 
1.3.2.4 
Efficacy and Safety Results from a Completed Phase 2b Study with trehalose formulation in 
patients with Active Systemic Lupus Erythematosus ........................................................................................... 26 
1.4 
Known and Potential Risks and Benefits to Human Subjects ................................................................ 27 
1.5 
Selection of Drugs and Dosages ................................................................................................................ 27 
1.6 
Compliance Statement .............................................................................................................................. 27 
1.7 
Population To Be Studied ......................................................................................................................... 28 
1.8 
Relevant Literature and Data ................................................................................................................... 28 
2 
PURPOSE OF THE STUDY AND STUDY OBJECTIVES .................................................................. 28 
2.1 
Purpose of the Study ................................................................................................................................. 28 
2.2 
Study Objectives ........................................................................................................................................ 28 
3 
STUDY DESIGN ....................................................................................................................................... 30 
3.1 
General Design and Study Schema .......................................................................................................... 30 
Figure 1:   Overall Study Schema ........................................................................................................................... 33 
3.2 
Primary and Secondary Measures/Variables and Endpoints................................................................. 33 
3.2.1 
Primary Efficacy Measure/Variable and Endpoint ................................................................................ 33 
3.2.2 
Secondary Efficacy Measures/Variables and Endpoints ........................................................................ 34 
3.2.3 
Safety Measures and Endpoints ............................................................................................................... 35 
3.2.4 
Pharmacokinetic Measure/Variable and Endpoint ................................................................................. 35 
3.2.5 
Immunogenicity Measure/Variable and Endpoint .................................................................................. 35 
3.3 
Randomization and Blinding .................................................................................................................... 35 
3.4 
Study Drugs and Dosage ........................................................................................................................... 36 
3.4.1 
Investigational Product and Dosage ......................................................................................................... 36 
3.4.2 
Other Study Drugs and Dosage ................................................................................................................ 36 


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3.5 
Duration of Patient Participation ............................................................................................................. 37 
3.6 
Stopping Rules and Discontinuation Criteria .......................................................................................... 37 
3.7 
Study Drug Supply and Accountability ................................................................................................... 39 
3.7.1 
Study Drug Storage and Security ............................................................................................................. 39 
3.7.2 
Study Drug Accountability ....................................................................................................................... 39 
3.8 
Maintenance of Randomization and Blinding ......................................................................................... 39 
3.9 
Source Data Recorded on the Case Report Form ................................................................................... 40 
3.10 
Time Schedule ............................................................................................................................................ 40 
3.11 
Study Procedures ....................................................................................................................................... 40 
Table 2: 
Study Procedures and Assessments ..................................................................................................... 41 
3.11.1 
Procedures for Screening and Enrollment (Visit 1) ................................................................................ 43 
3.11.2 
Procedures Before Study Drug Treatment (Baseline/Start Study Drug Treatment [Visit 2/Week 0]) 44 
3.11.3 
Procedures During Study Drug Treatment ............................................................................................. 45 
3.11.3.1 
Visit 3 (Week 2) ..................................................................................................................................... 45 
3.11.3.2 
Visit 4 (Week 4) ..................................................................................................................................... 45 
3.11.3.3 
Visit 5 (Week 8) ..................................................................................................................................... 46 
3.11.3.4 
Visit 6 (Week 12) ................................................................................................................................... 46 
3.11.3.5 
Visits 7 and 8 (Weeks 16 and 20) ......................................................................................................... 47 
3.11.3.6 
Visit 9 (Week 24) ................................................................................................................................... 48 
3.11.3.7 
Visits 10 and 11 (Weeks 28 and 32) ..................................................................................................... 49 
3.11.3.8 
Visit 12 (Week 36) ................................................................................................................................. 49 
3.11.3.9 
Visits 13, 14, and 15 (Weeks 40, 44, and 48)........................................................................................ 50 
3.11.4 
Procedures After Study Drug Treatment (Visit 16/Week 52) ................................................................ 51 
4 
SELECTION AND WITHDRAWAL OF PATIENTS ........................................................................... 52 
4.1 
Patient Inclusion Criteria.......................................................................................................................... 52 
4.2 
Patient Exclusion Criteria ......................................................................................................................... 53 
4.3 
Withdrawal Criteria and Procedures ...................................................................................................... 54 
5 
TREATMENT OF PATIENTS ................................................................................................................ 55 
5.1 
Study Drugs Administered ....................................................................................................................... 55 
5.1.1 
Investigational Product and Dosage ......................................................................................................... 55 
5.1.2 
Other Study Drugs and Dosage ................................................................................................................ 55 
5.2 
Prior and Concomitant Therapy or Medication ..................................................................................... 55 
5.3 
Procedures for Monitoring Patient Compliance ..................................................................................... 57 
6 
ASSESSMENT OF EFFICACY ............................................................................................................... 57 
6.1 
Primary Efficacy Variable ........................................................................................................................ 58 
6.2 
Secondary Efficacy Variables ................................................................................................................... 58 
6.2.1 
Medical Outcome Survey Short Form 36 ................................................................................................ 60 
6.2.2 
28-Joint Count Examination for Pain and Tenderness ........................................................................... 60 
6.2.3 
Biomarkers ................................................................................................................................................ 60 
6.2.4 
Functional Assessment of Chronic Illness Therapy–Fatigue .................................................................. 60 


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6.2.5 
Safety of Estrogens in Lupus Erythematosus: National Assessment Flare Index ................................. 60 
6.2.6 
Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage 
Index 
60 
6.2.7 
Steroid Dose ............................................................................................................................................... 61 
6.3 
Methods and Timing of Assessing, Recording, and Analyzing Efficacy Data ....................................... 61 
7 
ASSESSMENT OF SAFETY .................................................................................................................... 61 
7.1 
Adverse Events .......................................................................................................................................... 61 
7.1.1 
Definition of an Adverse Event ................................................................................................................. 61 
7.1.2 
Recording and Reporting Adverse Events ............................................................................................... 62 
7.1.3 
Severity of an Adverse Event .................................................................................................................... 62 
7.1.4 
Relationship of an Adverse Event to the Study Drug ............................................................................. 63 
7.1.5 
Serious Adverse Events ............................................................................................................................. 63 
7.1.5.1 
Definition of a Serious Adverse Event ................................................................................................. 63 
7.1.5.2 
Reporting a Serious Adverse Event ..................................................................................................... 64 
7.1.6 
Withdrawal Due to an Adverse Event...................................................................................................... 66 
7.1.7 
Withdrawal From the Study Due to Severe Flares ................................................................................. 66 
7.1.8 
Medical Emergencies ................................................................................................................................. 66 
7.1.9 
Protocol Deviations Because of an Adverse Event .................................................................................. 66 
7.2 
Clinical Laboratory Tests ......................................................................................................................... 67 
7.2.1 
Serum Chemistry ....................................................................................................................................... 67 
7.2.2 
Hematology ................................................................................................................................................ 68 
7.2.3 
Urinalysis ................................................................................................................................................... 68 
7.2.4 
Other Clinical Laboratory Tests .............................................................................................................. 69 
(b) 
Hemolysis Testing ...................................................................................................................................... 69 
(c) 
Other Tests ................................................................................................................................................. 69 
7.3 
Vital Signs .................................................................................................................................................. 69 
7.4 
Electrocardiography ................................................................................................................................. 70 
7.5 
Physical Examinations .............................................................................................................................. 70 
7.6 
Other Safety Measures and Variables ..................................................................................................... 70 
7.6.1 
Concomitant Therapy or Medication ....................................................................................................... 70 
7.6.2 
Columbia-Suicide Severity Rating Scale .................................................................................................. 70 
7.6.3 
Anaphylaxis Evaluation ............................................................................................................................ 70 
7.7 
Methods and Timing of Assessing, Recording, and Analyzing Safety Data .......................................... 71 
8 
ASSESSMENT OF PHARMACOKINETICS AND IMMUNOGENICITY ........................................ 71 
8.1 
Pharmacokinetic Assessment .................................................................................................................... 71 
8.1.1 
Pharmacokinetic Blood Sampling ............................................................................................................ 71 
8.1.2 
Processing, Handling, and Shipping of Samples for Pharmacokinetic Analysis ................................... 71 
8.2 
Immunogenicity ......................................................................................................................................... 71 
8.3 
Methods and Timing of Pharmacokinetic Blood Sampling and Immunogenicity ................................ 72 
9 
ASSESSMENT OF IN VITRO INTRACELLULAR AND SECRETED CYTOKINE RESPONSE 72 


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9.1 
Blood Sampling for in vitro intracellular and secreted cytokine response ........................................... 72 
9.2 
Processing, Handling, and Shipping of Samples for in vitro intracellular and secreted cytokine 
response .................................................................................................................................................................... 72 
9.3 
Methods and Timing of in vitro proliferation and secreted cytokine response .................................... 72 
10 
STATISTICS ............................................................................................................................................. 72 
10.1 
Study Design and Randomization ............................................................................................................ 72 
10.2 
Sample Size and Power Considerations ................................................................................................... 73 
10.3 
Analysis Sets .............................................................................................................................................. 73 
10.4 
Data Handling Conventions ...................................................................................................................... 73 
10.5 
Study Population ....................................................................................................................................... 73 
10.5.1 
Patient Disposition ..................................................................................................................................... 74 
10.5.2 
Demographic and Baseline Characteristics ............................................................................................. 74 
10.6 
Efficacy Analysis ........................................................................................................................................ 74 
10.6.1 
Primary Variable ....................................................................................................................................... 74 
10.6.2 
Secondary Variables .................................................................................................................................. 74 
10.6.3 
Planned Method of Analysis ..................................................................................................................... 75 
10.6.3.1 
Primary Efficacy Analysis .................................................................................................................... 75 
10.6.3.2 
Secondary Efficacy Analysis ................................................................................................................ 76 
10.7 
Safety Variables and Analysis .................................................................................................................. 76 
10.7.1 
Study Drug Exposure ................................................................................................................................ 76 
10.7.2 
Safety Variables ......................................................................................................................................... 76 
10.7.3 
Safety Analysis ........................................................................................................................................... 77 
10.8 
Pharmacokinetic and Immunogenicity Analysis ..................................................................................... 77 
10.9 
In vitro intracellular and secreted cytokine response ............................................................................ 78 
10.10 
Planned Interim Analysis .......................................................................................................................... 78 
10.11 
Reporting Deviations From the Statistical Plan ...................................................................................... 78 
11 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ...................................................................... 78 
12 
QUALITY CONTROL AND QUALITY ASSURANCE........................................................................ 78 
12.1 
Protocol Amendments and Protocol Deviations and Violations ............................................................. 78 
12.1.1 
Protocol Amendments ............................................................................................................................... 78 
12.1.2 
Protocol Deviations, Violations, and Exceptions ..................................................................................... 79 
12.2 
Information to Study Personnel ............................................................................................................... 79 
12.3 
Study Monitoring ...................................................................................................................................... 79 
12.4 
Audit and Inspection ................................................................................................................................. 80 
12.5 
Data Quality Assurance ............................................................................................................................ 80 
13 
ETHICS ..................................................................................................................................................... 81 
13.1 
Informed Consent ...................................................................................................................................... 81 
13.2 
Health Authorities and Independent Ethics Committees/Institutional Review Boards ....................... 81 
13.3 
Confidentiality Regarding Study Patients ............................................................................................... 82 
14 
DATA HANDLING AND RECORD KEEPING .................................................................................... 82 


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14.1 
Completing and Signing Case Report Forms .......................................................................................... 82 
14.2 
Archiving of Case Report Forms and Source Documents ...................................................................... 82 
14.2.1 
Investigator Responsibilities ..................................................................................................................... 82 
14.2.2 
Sponsor Responsibilities............................................................................................................................ 83 
14.3 
Data Collected by Contractors ................................................................................................................. 83 
15 
FINANCING AND INSURANCE ............................................................................................................ 83 
16 
REPORTING AND PUBLICATION OF RESULTS ............................................................................. 84 
17 
REFERENCES .......................................................................................................................................... 84 
APPENDIX A ........................................................................................................................................................... 85 
Modified World Health Organization Toxicity Criteria ....................................................................................... 86 
WHO TOXOCITY GRADING CRITERIA .......................................................................................................... 87 
WHO TOXICITY GRADING CRITERIA ........................................................................................................... 88 
WHO TOXICITY GRADING CRITERIA ........................................................................................................... 89 
WHO TOXICITY GRADING CRITERIA ........................................................................................................... 90 
WHO TOXICITY GRADING CRITERIA ........................................................................................................... 91 
APPENDIX B ........................................................................................................................................................... 92 
Prednisone Equivalent Conversion Sheet .............................................................................................................. 95 
APPENDIX C ........................................................................................................................................................... 96 
APPENDIX D ........................................................................................................................................................... 99 
British Isles Lupus Assessment Group 2004 ........................................................................................................ 100 
APPENDIX E ......................................................................................................................................................... 101 
Medical Outcome Survey Short Form 36 ............................................................................................................. 102 
APPENDIX F ......................................................................................................................................................... 108 
28-Joint Count Examination for Pain and Tenderness ....................................................................................... 109 
APPENDIX G ........................................................................................................................................................ 110 
Functional Assessment of Chronic Illness Therapy–Fatigue FACIT-Fatigue Scale (Version 4) ..................... 111 
APPENDIX H ........................................................................................................................................................ 112 
Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index ..... 113 
APPENDIX I .......................................................................................................................................................... 114 
Clinical Criteria for Diagnosing Anaphylaxis ..................................................................................................... 115 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Ab 
antibody(ies) 
ACR 
American College of Rheumatology 
ALC 
absolute lymphocyte count 
ALT 
alanine aminotransferase (SGPT) 
ANA 
antinuclear antibodies 
ANC 
absolute neutrophil count 
anti-dsDNA Ab 
anti–double-stranded deoxyribonucleic acid antibody anti-Sm Ab anti-Smith antibody 
anti–U1-70K 
snRNP Ab 
anti–uridine rich 70 kilodalton small nuclear ribonucleoprotein particle antibody 
AST 
aspartate aminotransferase (SGOT) 
BILAG-2004 
British Isles Lupus Assessment Group 2004  
BUN 
blood urea nitrogen 
C3 
complement component 3 
C4 
complement component 4 
CFR 
Code of Federal Regulations 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index  
CNRS 
Centre National de la Recherche Scientifique 
CRF 
case report form 
CRP 
C-reactive protein 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DAI 
disease activity index 
DNA 
deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
DSM–IV-TR 
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision  
ECG 
electrocardiography, electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
ELISA 
enzyme-linked immunosorbent assay 
EU 
European Union 
FACIT-Fatigue 
Functional Assessment of Chronic Illness Therapy–Fatigue  
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl transpeptidase 
HBsAg 
hepatitis B surface antigen 
HCV Ab 
hepatitis C virus antibody 
HEp-2 
human epithelial cell tumor line 
HIV 
human immunodeficiency virus 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IgE 
immunoglobulin E 
IgG 
immunoglobulin G 


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IgM 
immunoglobulin M 
Ig A 
immunoglobulin A 
IL 
interleukin 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ISRB 
Interim Safety Review Board 
IU 
International Unit 
IUD 
intrauterine device 
iv 
intravenous, intravenously 
IVIG 
intravenous immunoglobulins 
LDH 
lactate dehydrogenase 
LOCF 
last observation carried forward 
Lupus QoL Questionnaire 
Lupus Quality of Life Questionnaire 
MDE 
missing data estimation 
MDRD 
Modification of Diet in Renal Disease  
MedDRA 
Medical Dictionary for Regulatory Activities  
MMF 
mycophenolate mofetil 
NYHA 
New York Heart Association 
OTC 
over-the-counter 
P140 
peptide 131-151 that has been phosphorylated at position 140 
P131-151 
peptide 131-151 
PBL 
peripheral blood leukocyte 
PBMC 
peripheral blood mononuclear cell 
PhGA 
Physician Global Assessment 
PtGA 
Patient Global Assessment 
RBC 
red blood cell 
sc 
subcutaneous, subcutaneously 
SD 
standard deviation 
SDI 
Systemic Lupus International Collaborative Clinics/American College of Rheumatology 
Damage Index 
SDV 
source document verification 
SE 
standard error 
SELENA 
Safety of Estrogens in Lupus Erythematosus: National Assessment  
SF-36 
Medical Outcome Survey Short Form 36 
SFI 
Safety of Estrogens in Lupus Erythematosus: National Assessment Flare Index  
SGOT 
serum glutamic oxaloacetic transaminase (AST) 
SGPT 
serum glutamic pyruvic transaminase (ALT) 
SLE 
systemic lupus erythematosus 
SLEDAI 
Systemic Lupus Erythematosus Disease Activity Index  
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLICC/ACR 
Systemic Lupus International Collaborative Clinics/American College of Rheumatology 


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SOC 
standard of care 
SOP 
standard operating procedure 
SRI 
systemic lupus erythematosus responder index 
SUSAR 
suspected unexpected serious adverse reactions 
TACI/BlyS 
transmembrane activator and calcium modulator and cyclophilin ligand interacter/B 
lymphocyte stimulator 
ULN 
upper limit of the normal range 
US(A) 
United States (of America) 
VAS 
visual analog scale 
WBC 
white blood cell 
WHO 
World Health Organization 
WHO Drug 
World Health Organization (WHO) drug dictionary 


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1 
BACKGROUND INFORMATION 
 
1.1 
Introduction 
 
Systemic lupus erythematosus (SLE) is a polygenic autoimmune disease characterized by B-cell 
hyperactivity leading to the occurrence of an array of autoantibodies, formation of immune 
complexes, and inflammation in different organs and tissues. In addition to the intrinsic 
hyperactivity of B cells, abnormalities also affect T-cell responses, the production of T-cell 
cytokines, and the B-T–cell dialogue. Current treatments for patients with SLE are based 
primarily on immunosuppressive drugs, such as corticosteroids and cyclophosphamide, which 
are often administered at high doses during acute exacerbation phases. Although these 
treatments can reduce mortality and significantly lengthen patients’ life expectancies, numerous 
adverse effects may result because these treatments are aggressive. For example, they cause 
nonspecific immune suppression, and the adverse effects are sometimes worse than the disease 
itself (Cunningham 2007, Kang and Park 2003, Vasoo and Hughes 2005, Vial and Descotes 
1995). More targeted immune suppression with monoclonal antibodies or other specific 
therapies is being developed to improve the benefit-risk balance ofSLE treatments. To avoid the 
long-term effects of immunosuppressive therapy, alternative strategies have been proposed on 
the basis of targeted molecular therapy, including antibodies against the B-cell–specific antigens 
CD20 or CD22 (rituximab and epratuzumab, respectively) or against the BlyS (transmembrane 
activator and calcium modulator and cyclophilin ligand interacter/B lymphocyte stimulator) 
pathway (atacicept and belimumab, respectively). These approaches require the identification of 
peptide sequences that can interfere with the final autoantibody production. 
 
IPP-201101 for injection, also known as peptide 140, P140, CEP 3357 LUPUZOR™, rigerimod, 
and forigerimod (herein referred to as IPP-201101), was initially developed by ImmuPharma 
France SA for SLE. ImmuPharma has a collaboration agreement with a group at Centre National 
de la Recherche Scientifique (CNRS; Strasbourg, France), France’s national scientific research 
institution, who identified the peptide 131–151 (P131–151) of the U1-70K snRNP self-protein as 
a potential candidate peptide antigen. After additional nonclinical development (see section 
1.3.1), IPP-201101, a form of P131–151 where the Serine in position 140 has been 
phosphorylated (hence the name), was selected for further development as a potential targeted 
agent for SLE, and a clinical program was initiated in January 2006 (see section 1.3.2). In 2009, 
Cephalon  acquired the worldwide rights to develop and market IPP-201101 which was reverted 
to ImmuPharma in 2011 (IND ownership transfer in March 2013) 
 
This current Phase 3 study will evaluate the efficacy and safety of administration of 
subcutaneous (sc) IPP-201101 in patients with active SLE. 
 
 
 
 
 
LUPUZOR is a licensed trademark of ImmuPharma plc or its affiliates. 


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1.2 
Name and Description of Investigational Product 
 
The investigational Product is supplied in 2-mL vials containing 220 mcg of IPP-201101 as a 
sterile lyophilizate formulated with mannitol (and acetic acid used for pH adjustment, if 
necessary). Prior to administration (by sc injection), IPP-201101 is reconstituted with 1.1 mL of 
sterile water for injection (volume for injection of 1.0 mL). 
 
Additional information on IPP-201101 is provided in section 3.4. 
 
1.3 
Findings From Nonclinical and Clinical Studies 
 
1.3.1 
Nonclinical Studies 
 
1.3.1.1 Pharmacology Studies 
 
Peptides that target specific autoreactive B and/or T cells are being actively pursued as 
alternatives to current treatment options for SLE. 
 
A peptide corresponding to the sequence  131–151 of the spliceosomal U1-snRNP protein has  
been identified as containing an epitope recognized by T cells in SLE (Monneaux et al 2000). On 
exposure ex vivo to this peptide called  P131–151, autoreactive CD4+ T cells from lupus-prone 
mice undergo proliferation and secrete interleukin-2 (IL-2). Studies with P131–151 in mouse 
models of lupus have led to the identification of IPP-201101 (also referred to in the literature as 
P140), a form of P131–151 (in which the serine at position 140 is phosphorylated). The 
phosphorylated peptide exhibits a number of unique properties, which suggests that it may 
function as an immunomodulator. 
 
In the MRL/lpr mouse model, lupus-like disease correlates with proteinuria (an indicator  of 
renal failure) and high anti–double-stranded deoxyribonucleic acid antibody (anti-dsDNA Ab) 
serum levels, both of which can be attenuated by IPP-201101. Preautoimmune MRL/lpr mice 
were treated with either saline, or P131–151, or IPP-201101 (4 doses of 100 mcg intravenously 
[iv] at 4, 6, 8, and 12 weeks of age). By week 15, the control (saline) and P131–151 groups 
developed severe proteinuria and animals began to die. The first deaths in the IPP-201101–
treated group were not observed until 22 weeks. At 38 weeks, 5 of 9 mice treated with IPP-
201101 survived (p=0.02: IPP-201101 vs control), with 2 of 8 mice and 0 of 8 mice surviving in 
the P131–151 and control groups, respectively. Serum anti-dsDNA Ab titers and proteinuria 
were significantly lower in IPP-201101–treated animals (Monneaux et al 2003), demonstrating 
the ability of the phosphorylated form of P131–151 to reduce disease progression, severity, and 
mortality in a severe lupus-prone mouse model. 
 
When incubated ex vivo with peripheral blood mononuclear cells (PBMCs) from patients with 
SLE, IPP-201101 did not stimulate T-cell proliferation but increased interleukin-10 (IL-10) 
secretion in approximately 50% of ambulatory lupus patients. . IPP-201101 had no effect on IL-
10 secretion in PBMCs from healthy subjects, suggesting the ability of the phosphorylated 
peptide to potentially modify SLE progression (Monneaux et al 2005). On the basis of these 
findings (see section 1.1), IPP-201101 was selected for development as a potential treatment for 


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SLE. Determination of the mechanism of action of IPP-201101 in SLE has been an area of 
active investigation for several years, using the MRL/lpr mouse as a model system. 
Administration of IPP-201101 to 6-week-old MRL/lpr mice by the treatment regimen utilized for 
efficacy studies resulted in reduction of elevated peripheral blood leukocyte (PBL) levels in 
MRL/lpr mice compared with those of control CBA/J mice at 14 weeks of age (Page et al 2009; 
Schall et al, 2012). This effect resulted from induction of apoptosis of B cells, activated T cells 
and CD3+CD4-CD8-B220+ (double negative) T cells, which was demonstrated to be dependent 
on the presence of γδ T cells. Apoptosis of CD4+ and CD8+ T cells was also observed following 
ex vivo treatment of MRL/lpr PBLs with IPP-201101 in a process that was shown to be 
granzyme B- and caspase-dependent (Page et al, 2009). Experiments designed to identify the 
cellular receptor for IPP-201101 demonstrated binding of the peptide to the constitutively 
expressed chaperone protein HSPA8/HSC70 on the surface of cells (Page et al, 2009). 
 
The consequences of the interaction of IPP-201101 with HSPA8 have recently been studied in 
greater detail (Page et al 2011). The expression of both HSPA8 and major histocompatibility 
(MHC) Class II molecules was shown to be elevated in splenic B cells from MRL/lpr mice 
compared with those isolated from CBA/J control mice. The levels of these proteins were 
decreased on treatment of the mice with IPP-201101. Since HSPA8 plays a role in autophagy 
and loading of endogenous peptides onto MHC class II molecules, the effect of IPP-201101 on 
autophagy was examined. Autophagy markers accumulated in MRL/lpr B cells treated with IPP-
201101, suggesting that the peptide decreased macroautophagic flux. Later on it was 
demonstrated that the primary target of IPP-201101 is chaperone-mediated autophagy (CMA) 
with implication on macroautophagy processes (Macri et al 2015). CMA was found to be 
hyperactivated in MRL/lpr lupus mice and significantly attenuated after IPP-201101 in vivo 
treatment. As a working hypothesis, these results and notably the down regulation of excessive 
CMA process are interpreted to indicate that the mechanism of action of IPP-201101 involves a 
decrease in autoantigen processing in MRL/lpr antigen-presenting B cells, resulting in a decrease 
in MHCII expression followed by a reduction of autoreactive T-cell priming and signaling. Past 
studies have effectively shown that compared to T cells from untreated mice, CD4+ T cells 
from P140-treated MRL/lpr mice reacted poorly with peptides containing self-T cell epitopes 
(Monneaux et al., 2007). As a matter of consequence, this effect on T helper cells leads to much 
weaker activation of B cells that will no longer maturate into plasma cells that secrete 
deleterious antibodies (Macri et al. 2015; Schall et al, article submitted).  A remarkable 
observation is that P140-treatment had no effect on T- or B-cell reactivity to non-self (for 
example viral) peptides (Monneaux et al. 2007, Schall et al. article submitted). B a s e d  o n  
t h e s e  d a t a ,  IPP-201101 is therefore proposed to have immunomdulatory effects on antigen 
presenting cells, B and T cells, resulting in the observed therapeutic effect. 
            
1.3.1.2 Toxicology Studies 
 
The local tolerance of repeated sc administration of IPP-201101 was evaluated in 2 studies 
performed in rats (study 19397/05) and dogs (study 19509/05). Both studies did not reveal any 
significant local intolerance reactions. Histopathologic results at the injection site did not reveal 
any abnormal findings deemed to be related to treatment with IPP-201101. 
 
The subchronic toxicity of IPP-201101 was evaluated in 3 repeated-dose studies performed in 


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rats (study 19397/05), dogs (study 19509/05), and monkeys (study CRNS UPR 9021). In these 3 
studies, the administration of IPP-201101 subcutaneously (sc) for a 2-week duration did not 
result in overt signs of toxicity. 
 
The chronic toxicity of IPP-201101 evaluated in rats (155 days) and dogs (239 days) when 
administered every 15 days for a total of 12 injections in rats and 18 injections in dogs did not 
result in any overt signs of toxicity. 
 
The effects of IPP-201101 on the reproduction and embryofetal development were evaluated in 
3 reproductive toxicology studies performed in mice (study CRNS UPR 9021), rats (study 
20060523TR), and rabbits (study 20060524TL). In these studies, there was no evidence of 
teratogenicity or arbortifacient effects of IPP-201101. There were no increases in prenatal 
mortality and no evidence of adverse effects on the embryofetal development associated with 
IPP-201101 treatment. 
 
In rats and rabbits tested with cumulative doses/kg body weight of IPP-201101, there were no 
signs of toxicity. These cumulative doses were, respectively, 133 and 12 times higher than the 
highest cumulative dose/kg that is anticipated to be used in a 1-year study in humans (Table 1). 
 
Table 1: 
Comparative Doses in the Animal Toxicity Studies and the Proposed 
Human Clinical Study 
 
Cumulative 
   Toxicity study 
Cumulative dose 
Body weight 
dose/kg 
Factor   
Rat toxicity (group 4) 
0.2 mg x 12 inj=2.4 mg 
0.24 kg (mean) 
10.000 mg/kg 
133 
Rabbit toxicity (group 3) 
0.2 mg x 14 inj=2.8 mg 
3.19 kg (mean) 
0.875 mg/kg 
12 
Human (Phase 3) (group 1), 1 year 
of treatment 
0.2 mg x 26 inj=5.2 mg 
70 kg (estimated) 
0.075 mg/kg 
1 
inj=injections. 
 
No single-dose toxicity studies have been conducted. 
 
1.3.2 
Clinical Studies 
 
The safety and efficacy of IPP-201101 administered sc have been evaluated in 3 completed 
clinical studies. Treatment with IPP-201101 at doses ranging from 200 to 2000 mcg was 
generally safe and well tolerated when administered to 18 healthy subjects and 121 patients with 
SLE in these Phase 1, 2a, and 2b clinical studies. Injection site adverse events were mild in 
severity and dose related. To date, the reported serious adverse events are due in part to the 
patients’ underlying disease. Data are insufficient to determine the long-term effect of peptide-
based therapy on immune competence. More details of the design and results of the completed 
studies are provided below. 
 
1.3.2.1 Safety and Tolerability Results From a Completed Phase 1 Study in Healthy Men 
 
The Phase 1 study (study IPP-LU.01-05) was a double-blind, placebo-controlled, single-
ascending-dose study to investigate the safety, tolerability, and pharmacokinetic profiles of 
IPP-201101 in 24 healthy men in France. Subjects were treated with an sc injection of either 


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IPP-201101 or placebo in 3 successive treatment groups (group 1: 500 mcg, group 2: 1000 
mcg, and group 3: 2000 mcg), starting with the lowest dose. Each treatment group consisted of 
8 subjects and, in each group, 6 subjects received IPP-201101 and 2 subjects received placebo. 
Subjects were administered the next highest dose only if the preceding dose was safe and well 
tolerated. During the study, 3 subjects reported a total of 3 adverse events. One adverse event 
(transient swelling at the injection site appearing 1 hour after injection of the 2000-mcg dose) 
was considered by the investigator to be possibly related to study drug treatment. 
This adverse event was of mild intensity. The other adverse events (ie, headache and bilateral 
paresthesias of the abdominal wall) were reported after administration of 500 mcg of IPP-
201101 and placebo, respectively, and were of moderate intensity. Overall, local tolerability at 
the injection site was good. No trends or clinically relevant changes from baseline were 
observed in clinical laboratory test results, vital signs measurements, and 12-lead 
electrocardiogram (ECG) or physical examination findings. 
 
Although plasma samples were collected for pharmacokinetic analysis, pharmacokinetic 
parameters could not be calculated because the plasma concentrations were below the lower 
limit of quantitation of the available assay. 
 
1.3.2.2 Efficacy and Safety Results From a Completed Phase 2a Study in Patients With 
Systemic Lupus Erythematosus 
 
The Phase 2a study (study IP-002) was an open-label, multiple-dose, 12-week study conducted 
in Bulgaria to evaluate the efficacy and safety of treatment with IPP-201101 in 20 patients with 
SLE who had elevated anti-dsDNA Ab titers (more than 70 IU/mL by enzyme-linked 
immunosorbent assay [ELISA]) at study entry. Two dose levels of IPP-201101 (200 and 1000 
mcg) were evaluated in 2 cohorts of 10 patients each. Patients were administered 3 sc injections 
of IPP-201101 (either 200 or 1000 mcg) on study days 1, 15, and 29, with follow-up visits on 
study days 8, 43, and 57. For the 200-mcg treatment group, long-term follow-up visits were also 
conducted at months 4, 5, and 6. Study treatment with 1000 mcg was initiated after the planned 
interim review of the safety data, up to and including day 15, by the Interim Safety Review 
Board (ISRB) from all patients receiving 200 mcg. 
 
In this study, there was a clinically meaningful response for patients who received 2 sc injections 
of 200 mcg of IPP-201101 on study days 1, 15, and 29, as assessed by decrease in anti-dsDNA 
Ab levels (7 patients had reductions in anti-dsDNA Ab titer of least 20% at study day 43, and 5 
patients had a reduction of at least 20% at study day 57; response was sustained in 3 patients at 
month 6) and reduction from baseline of at least  4 points in the Systemic Lupus Erythematosus 
Disease Activity Index (SLEDAI) score  (6 patients). In the 1000-mcg treatment group, 1 
patient had a reduction of at least 20% in anti-dsDNA Ab titer at study day 43 or study day 57. 
The average value for anti-dsDNA Ab titer was unchanged over the 6-week follow-up period 
after completion of study treatment in the 1000-mcg treatment group. 
 
In addition to the 6 patients in the 200-mcg treatment group who were responders by SLEDAI 
(defined as a reduction from baseline of at least 4 points in the SLEDAI score), 4 patients in the 
1000-mcg treatment group were responders by SLEDAI. Five of the 6 responding patients in the 
200-mcg treatment group also had at least a 20% reduction in anti-dsDNA Ab titer, whereas 1 of 


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4 patients in the 1000-mcg treatment group had both a reduction in SLEDAI score and a 
reduction in anti-dsDNA Ab titer at study day 57. 
 
There were no serious adverse events or withdrawals because of adverse events in the study. 
Nine (45%) patients experienced a total of 12 adverse events during the course of the study. 
Adverse events attributed to IPP-201101 treatment were mild dose-related injection site 
reactions. Injection site reactions were reported more frequently in the high-dose group. In the 
200-mcg dose group, 1 patient (10%) experienced mild erythema at the injection site, and 6 
patients (60%) in the 1000-mcg dose group experienced injection site reactions. In both 
treatment groups, reactions at the injection site were mild and resolved within 1 hour. Excluding 
local injection site reactions, the incidence of adverse events was low, with 2 (10%) patients 
experiencing an adverse event, including 1 case of muscular pain and 1 case of nausea. Both 
events occurred in the 1000-mcg dose group. No clinically significant changes in clinical 
laboratory (hematology, chemistry, or urinalysis) or vital signs results were reported during the 
study. 
 
 
1.3.2.3 Efficacy and Safety Results From a Completed Phase 2b Study in Patients With 
Active Systemic Lupus Erythematosus 
 
The Phase 2b study (study IP-004) was a multicenter, randomized, double-blind, placebo-
controlled, dose-ranging study conducted in Bulgaria, Romania, Spain, and Argentina to evaluate 
the efficacy and safety of treatment with IPP-201101 in patients 
with active SLE. Patients were randomly assigned to 1 of 3 treatment groups, as follows: 
 
(1) 200 mcg of IPP-201101 sc every 4 weeks (3 sc injections at baseline and weeks 4 and 8; 
total dose of 600 mcg) and 3 sc injections of matching placebo at weeks 2, 6, and 10, plus 
standard of care (SOC) 
(2) 200 mcg of IPP-201101 sc every 2 weeks (6 sc injections at baseline and weeks 2, 4, 
6, 8, and 10; total dose of 1200 mcg) plus SOC 
(3) placebo sc every 2 weeks (6 sc injections at baseline and weeks 2, 4, 6, 8, and 10) plus SOC 
 
A total of 204 patients were planned to be enrolled in this study. The primary efficacy variable 
for the study was the SLE responder index (SRI) at week 12. The SRI was defined as a 
reduction from baseline in the SLEDAI 2000 (SLEDAI-2K) total score of at least 4 points, no 
worsening in Physician’s Global Assessment (PhGA) (with worsening defined as an increase in 
PhGA of more than 0.30 point from baseline), no new British Isles Lupus Assessment Group A 
(BILAG A) body system score, and no more than 1 new BILAG B body system score from 
baseline. Statistical significance was assessed at alpha=0.025.Two interim analyses were 
conducted. The 1st interim analysis was conducted and data reviewed in December 2008 when 
125 patients enrolled in the study completed 12 weeks of study drug treatment and had at least 1 
efficacy measurement. After data from the 1st interim analysis were reviewed, a decision about 
the future clinical development of IPP-201101 was made, and enrollment of additional patients 
into the study was stopped. At this time, 150 patients had been enrolled in the study. The 2nd 
interim analysis was performed in June 2009 when the 125 patients from the 1st interim analysis 
completed the study (through week 24). At week 12, there was a statistically significant 


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difference (p=0.012) in favor of IPP-201101 for the SRI response in patients who received 200 
mcg of IPP-201101 every 4 weeks compared with those who received placebo every 2 weeks. At 
the final analysis, data were analyzed for 150 patients who completed 12 weeks of randomized 
study treatment and the 24-week follow-up visit or who withdrew from the study. A total of 150 
patients (49 patients 200 mcg of IPP-201101 every 4 weeks, 52 patients 200 mcg of IPP-201101 
every 2 weeks; and 49 patients placebo every 2 weeks) received study drug. A total of 96.0% of 
the patients were women; the mean age of the patients was 37.6 years. At week 12, a greater 
proportion of patients who were receiving 200 mcg of IPP-201101 every 4 weeks (53.1%) 
achieved an SRI response (p=0.048) compared with those receiving placebo (36.2%). Similarly, 
53.1% of patients receiving 200 mcg of IPP-201101 every 4 weeks achieved a clinical response 
as assessed by SLEDAI-2K at week 12 compared with 38.3% of those who were receiving 
placebo (p=0.073). Patients receiving 200 mcg of IPP-201101 every 2 weeks showed a response 
rate of 45.1% each for the SRI response and the clinical response as assessed by SLEDAI-2K, 
but the differences were not statistically significant when compared with those who were 
receiving placebo (36.2% for SRI response [p=0.185] and 38.3% for clinical response as 
assessed by SLEDAI-2K [p=0.248]). In a subgroup analysis of patients with a SLEDAI-2K 
clinical score of at least 6 at baseline, at week 12, a greater proportion of patients receiving 200 
mcg of IPP-201101 every 4 weeks (61.9%) achieved a statistically significant (p=0.016) SRI 
response compared with those receiving placebo (38.6%). At week 12, the proportion of patients 
receiving 200 mcg of IPP-201101 every 2 weeks (47.9%) and achieving an SRI response was 
also higher than that for those receiving placebo (38.6%); however, the difference was not 
statistically significant (p=0.185). For the subgroup analysis, at week 24, the differences 
between these groups were not statistically significant (p≥0.113; 69.0% for patients receiving 
200 mcg of IPP-201101 every 4 weeks, 56.5% for those receiving placebo, and 62.5% for those 
receiving 200 mcg of IPP-201101 every 2 weeks). 
 
At the final analysis, 65 patients (43.3%) reported a total of 202 adverse events. The majority of 
adverse events were mild or moderate in severity and considered by the investigator to be not 
related to study drug treatment. The most frequently reported adverse events overall (those 
occurring in more than 2% of patients) were urinary tract infection, nasopharyngitis, pharyngitis, 
influenza, bronchitis, nausea, diarrhea, injection site erythema, and headache. The most 
frequently reported adverse events in the IPP-201101 treatment groups (those occurring in more 
than 2% of patients) were urinary tract infection, nasopharyngitis, bronchitis, nausea, injection 
site erythema, and headache. The most frequently reported adverse events in the placebo group 
(those occurring in more than 2% of patients) were urinary tract infection, pharyngitis, 
pneumonia, herpes zoster, diarrhea, and conjunctivitis. 
 
Four serious adverse events were reported in 4 patients who have received IPP-201101, 
including 3 patients who received 200 mcg of IPP-201101 every 4 weeks (gastritis [1 patient], 
soft tissue infection [1 patient], and pneumonia [1 patient; event led to death of patient]) and 1 
patient who received 200 mcg of IPP-201101 every 2 weeks (herpes viral pneumonia). Three 
serious adverse events were reported in 3 patients who have received placebo (pneumonia in 2 
patients and diverticulitis in 1 patient). In the patients who received IPP-201101, of these events, 
soft tissue infection and herpes viral pneumonia were considered by the investigator to be related 
to study drug treatment with IPP-201101. Among the placebo patients, both events of 
pneumonia were considered by the investigator to be related to study drug treatment. 


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The patient who died because of a serious adverse event of pneumonia was receiving 200 mcg of 
IPP-201101 every 4 weeks; this event was considered by the investigator to be not related to 
study drug treatment. The pneumonia occurred 3 days after the patient had received the 4th dose 
of study drug, which was 19 days after the last dose of IPP-201101. The patient, who was being 
treated with azathioprine and prednisone at study entry, had pain around the back base of the 
right lung and hemoptysis. The patient was hospitalized and treated for pneumococcal 
pneumonia. Treatment in the intensive care unit was required and included mechanical 
ventilation, antibiotics, steroids, and pressor support. Treatment was complicated by the 
development of acinetobacter line sepsis. In the investigator’s opinion, the pneumonia was not 
related 
to 
treatment 
with 
IPP-201101, 
although 
the 
concomitantly 
administered 
immunosuppressive medication was considered a contributing factor to the development of 
pneumonia. 
 
Injection site reactions were more frequently reported in the IPP-201101 treatment groups than 
in the placebo group. Overall, 17 injection site reactions were reported for 11 patients. Four 
events were reported in 3 patients who received 200 mcg every 4 weeks, 12 events were reported 
in 7 patients who received 200 mcg every 2 weeks, and 1 event was reported in 1 patient who 
received placebo. All events were mild in severity. However, infections such as those listed 
above did not appear to be more frequently reported in the IPP-201101 treatment groups 
compared with the placebo group. No clinically significant changes in hematology, chemistry, 
urinalysis, vital signs results, or ECG findings were reported during the course of the study. 
 
There were 2 additional events of interest reported during the study in 2 patients who each 
received 200 mcg of IPP-201101 every 4 weeks (1 pregnancy and 1 intraductal breast 
papilloma). One patient became pregnant and was withdrawn from the study because of this 
event. The patient delivered a healthy baby at 37 weeks. During the course of the pregnancy, 
the patient experienced a urinary tract infection, high blood pressure, and proteinuria; the high 
blood pressure and proteinuria required hospitalization. 
 
Another patient had a nonserious adverse event of an intraductal breast papilloma (a benign 
tumor of the breast). The event was mild in intensity and considered by the investigator to be 
unlikely related to study drug treatment. The outcome of this event was resolved. (Zimmer et al. 
ACR 2012) 
 
1.3.2.4 Efficacy and Safety Results from a Completed Phase 2b Study with trehalose 
formulation in patients with Active Systemic Lupus Erythematosus 
 
One clinical study have been completed in the CEP 33457 clinical program developed by TEVA 
former Cephalon.  
 
TEVA, former Cephalon has sponsored an US Phase 2b (Study C33457/2047), randomized, double-
blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of a 200 mcg dose of 
IPP-201101 given every 4 weeks compared with placebo in patients with active SLE. The study 
consists of a 2-week screening period (visit 1), a 44-week treatment period beginning with a baseline 
visit in which randomization is completed and study drug treatment starts (visits 2 through 13), and a 
final assessment 4 weeks after the last dose of study drug (visit 14 [week 48]). 


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A trehalose formulation of IPP-201101 (P140, foregiremod) has been used. The clinical outcome was 
negative. IPP-201101 was ineffective with even a trend to be less effective than placebo (D = - 6 %).  
 
1.4 
Known and Potential Risks and Benefits to Human Subjects 
 
Treatment with IPP-201101 was generally safe and well tolerated when administered to both 
healthy subjects and patients with SLE. Injection site reactions were more frequently reported in 
the IPP-201101 treatment groups than in the placebo group. These injection site adverse events 
were mild in severity and dose related. The most frequently reported adverse events overall 
(those occurring in more than 2% of patients) in a Phase 2b study, in addition to injection site 
reaction, included urinary tract infection, nasopharyngitis, pharyngitis, influenza, bronchitis, 
nausea, diarrhea, and headache. However, infections such as those listed above did not appear to 
be more frequently reported in the IPP-201101 treatment groups compared with the placebo 
group. 
 
To date, the reported serious adverse events are due in part to the patients’ underlying disease. 
No clinically significant changes in hematology, chemistry, urinalysis, vital signs results, or 
ECG findings have been reported in the clinical program to date.  
No serious related unexpected adverse event reports (suspected unexpected serious adverse 
reactions [SUSAR] or Investigational New Drug [IND] safety reports) had been reported.  
 
Data are insufficient to determine the long-term effect of peptide-based therapy on immune 
competence. 
 
Additional information regarding risks and benefits to human patients may be found in the 
current Investigator’s Brochure. 
 
1.5 
Selection of Drugs and Dosages 
 
The dosage of IPP-201101 to be evaluated in this double-blind study (ie, 200 mcg sc every 4 
weeks for 48 weeks) was selected on the basis of results from a Phase 2b study (study IP-004); 
clinical response was observed with the 200-mcg dose after 12 weeks of study treatment. 
Review of available adverse event data from the Phase 2b study 2047 performed by TEVA former 
Cephalon with the trehalose formulation with a 44-week treatment period indicate that the 200-
mcg dose is safe and well tolerated. The adverse events reported are similar to those previously 
reported.  
 
A more detailed description of study drug administration is presented in section 5.1. 
 
1.6 
Compliance Statement 
 
This study will be conducted in full accordance with the Good Clinical Practice: Consolidated 
Guideline approved by the International Conference on Harmonisation (ICH) and any applicable 
national and local laws and regulations (eg, Title 21 Code of Federal Regulations [21CFR] Parts 
50, 54, 56, 312, and 314). Any episode of noncompliance will be documented. 
 
The investigators are responsible for performing the study in accordance with this protocol and 


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the ICH and Good Clinical Practice (GCP) guidelines and for collecting, recording, and 
reporting the data accurately and properly. Agreement of each investigator to conduct and 
administer this study in accordance with the protocol will be documented in separate study 
agreements with the sponsor and other forms as required by national authorities. 
 
Each investigator is responsible for ensuring the privacy, health, and welfare of the patients 
during and after the study and must ensure that trained personnel are immediately available in 
case of a medical emergency. Each investigator must be familiar with the background to, and 
requirements of, the study and with the properties of the study drug(s) as described in the 
Investigator’s Brochure or package insert. 
 
The principal investigator at each center has the overall responsibility for the conduct and 
administration of the study at that center and for contacts with study management, with the 
Independent Ethics Committee/Institutional Review Board (IEC/IRB) and with local authorities. 
1.7 
Population To Be Studied 
 
It is planned that this study will enroll approximately 200 men and women between 18 and 70 
years of age who have serologically active SLE with moderate disease activity on the basis of a 
standard assessment of disease activity, validated for use as a measure in clinical studies. To be 
considered for inclusion in this study, patients must have a positive test for antinuclear 
antibodies (ANA) and/or a positive test for anti-dsDNA Ab and a clinical SLEDAI-2K score of 
at least 6 points and may not have an “A” score on  the BILAG-2004 scale. In addition, patients 
who are using or were previously using oral corticosteroids or antimalarials, methotrexate, 
leflunomide, mycophenolate mofetil (MMF), or azathioprine must meet certain dosage 
requirements regarding these drugs  (see section 4.1). 
 
1.8 
Relevant Literature and Data 
 
Relevant literature is cited above. Further literature and data may be found in the current 
Investigator’s Brochure.  
2 
PURPOSE OF THE STUDY AND STUDY OBJECTIVES 
 
2.1 
Purpose of the Study 
 
The purpose of this study is to further evaluate the efficacy and safety of IPP-201101 given 
every 4 weeks for up to 48 weeks, for a maximum of 13 doses. The study will evaluate the 
clinical response to treatment with IPP-201101 and will also include further assessment of 
biomarkers and change in steroid use from baseline. Safety assessments will include monitoring 
of adverse events, clinical laboratory test results, vital signs measurements, 12-lead ECG 
findings, suicidality assessments, anaphylaxis evaluations, and concomitant medication use. 
 
2.2 
Study Objectives 
 
The primary objective of this study is to evaluate the efficacy of a 200-mcg dose every 4 weeks 
for 48 weeks of IPP-201101 compared with placebo in patients with active systemic lupus 
erythematosus (SLE) as assessed by the SLE responder index (SRI) at week 52. An SRI 
response is defined as a reduction from baseline in the Systemic Lupus Erythematosus Disease 


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Activity Index 2000 (SLEDAI-2K) score of at least 4 points, no worsening in Physician’s Global 
Assessment (PhGA) (with worsening defined as an increase in PhGA of more than 0.30 point 
from baseline), no new British Isles Lupus Assessment Group A (BILAG A) body system score, 
and no more than 1 new 
BILAG B body system score from baseline. 
 
The secondary efficacy objectives of the study are to evaluate the following: 
 
• 
the SRI response at each visit during the study 
• 
the reduction of the SLEDAI-2K total score by at least 4 points at each visit during the 
treatment period 
• 
the effect of IPP-201101 on disease activity, as assessed by the BILAG-2004 disease 
activity index, at each visit during the treatment period 
• 
the effect of IPP-201101 on the status of disease (PhGA scale) at each visit during the 
treatment period 
• 
the reduction of the SLEDAI-2K total score by at least 5 points at each visit during the 
treatment period 
• 
the reduction of the SLEDAI-2K total score by at least 6 points at each visit during the 
treatment period 
• 
the SRI-5 response at each visit during the treatment period 
• 
the SRI-6 response at each visit during the treatment period 
• 
the effect of IPP-201101 on arthritis, as assessed by the 28-joint count examination for pain 
and tenderness at each visit during the treatment period 
• 
the effect of IPP-201101 on the incidence of disease flares (ie, Safety of Estrogens in Lupus 
Erythematosus: National Assessment [SELENA] Flare Index [SFI] and SLEDAI-2K score 
of greater than 15) at each visit during the treatment period  
• 
the effect of IPP-201101 on the occurrence of SLE–induced organ damage (eg, Systemic 
Lupus 
International 
Collaborative 
Clinics/American 
College 
of 
Rheumatology 
[SLICC/ACR] Damage Index [SDI] and adverse event inquiry) at visits at weeks 24 and 52 
(or final assessment) 
• 
the effect of IPP-201101 on health-related quality of life, as assessed by completion of the 
Medical Outcome Survey Short Form 36 (SF-36) at visits at weeks 12, 24, 36, and 52 (or 
final assessment) 
• 
the effect of IPP-201101 on steroid dose over time throughout the study The exploratory 
efficacy objectives of the study are to determine the following: 
• 
the effect of IPP-201101 on the following biologic markers of disease activity at each visit 
during the treatment period: 
— anti–double-stranded deoxyribonucleic acid antibody (anti-dsDNA Ab) 
— complement components (C3 and C4) 
• 
the effect of IPP-201101 on the following biologic markers of disease activity at visits at 
weeks 4, 12, 24, 36, and 52 (or final assessment): 
— antinuclear antibody (ANA) 


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— anti-uridine rich 70 kilodalton small nuclear ribonucleoprotein particle Ab (anti–U1-70K 
snRNP Ab) 
— anti-Smith antibody (anti-Sm Ab) 
— C-reactive protein (CRP) 
— immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobuline A (IgA) and 
immunoglobulin E (IgE) 
• 
the effect of IPP-201101 on fatigue using the Functional Assessment of Chronic Illness 
Therapy–Fatigue (FACIT-Fatigue) scale at visits at weeks 12, 24, 36, and 52 (or final 
assessment) 
• 
in vitro intracellular and secreted cytokine response 
 
The safety and tolerability of IPP-201101 will be evaluated by the following: 
 
• 
occurrence of adverse events throughout the study 
• 
clinical laboratory (serum chemistry, hematology, and urinalysis) test results at each visit 
during the treatment period 
• 
vital signs (systolic and diastolic blood pressures, pulse, temperature, and body weight) 
measurements at each visit during the treatment period 
• 
12-lead electrocardiogram (ECG) findings at week 52 (or final assessment) 
• 
physical examination findings, including physical examination symptom directed findings, 
at specified time points at each visit during the treatment period 
• 
evaluation for suicidality at each visit during the treatment period using the Columbia-
Suicide Severity Rating Scale (C-SSRS) 
• 
concomitant medication usage throughout the study 
• 
The immunogenicity of IPP-201101 will be assessed by the following: any presence of anti–
IPP-201101 antibodies (anti–IPP-201101 Ab) at visits at weeks 2, 4, 12, 20, 28, 36, 44, and 
52 (or final assessment  
 
3 
STUDY DESIGN 
 
3.1 
General Design and Study Schema 
 
This is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety 
of a 200-mcg dose of IPP-201101 plus SOC compared with placebo plus SOC in patients with 
active SLE. The study consists of a 2-week screening period (visit 1), a 48 week treatment 
period beginning with a baseline visit in which randomization will be completed and study drug 
treatment will start (visit 2 and visits 4 through 14), and a final assessment 4 weeks after the last 
dose of study drug (visit 16 [week 52]). NOTE: If needed during the screening period, up to 14 
additional days are permitted to confirm eligibility (eg, BILAG-2004, SLEDAI-2K, and PhGA  
central system assessments, laboratory results ….). 
 
In addition to the typical assessments obtained at the screening visit, such as obtaining medical, 
psychiatric, and medication history (medication history to be obtained from start of screening) 
and performing a physical examination and tests to determine the patients’ health status and 


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eligibility for participation in the study, procedures will include assessment of disease activity 
using the SLEDAI-2K and BILAG-2004 disease activity indices and the SFI, and disease marker 
testing (ie, at screening, anti-dsDNA Ab, C3, C4, and ANA only]). Eligibility will be confirmed 
by using a central system  to validate the BILAG-2004, SLEDAI-2K, and PhGA  assessments . 
Eligible patients will return to the study center at baseline and will be randomly assigned 
(stratified by region, SLEDAI-2K screening total score [6 to 9 or ≥10], and racial-ethnic group 
classification [black/Hispanic or others]) at baseline with an equal probability and in a blinded 
fashion to receive either IPP-201101 or placebo sc every 4 weeks for 48 weeks. Pretreatment 
assessments will be performed and the 1st dose of 200 mcg sc of IPP-201101 or placebo (sc) will 
be administered after all assessments have been completed. Patients will be monitored for 
systemic symptoms for at least 1 hour after the first 2 doses of study drug have been 
administered. For subsequent doses, patients will be monitored, at the discretion of the 
investigator, in the study center after study drug treatment. 
 
Patients will return to the study center 2 weeks after administration of the 1st dose of study drug 
for immunogenicity testing, and every 4 weeks for 48 weeks (weeks 4, 8, 12,16, 20, 24, 28, 32, 
36, 40, 44, and 48) to receive study drug. Patients may continue on their usual treatment for 
SLE (ie, SOC) as long as the inclusion and exclusion criteria regarding these treatments are met 
and the total weekly steroid dose does not exceed   80 mg of prednisone equivalent/week; the 
dosages for immunosuppressive medications may change, if needed, only as directed in the 
protocol. Efficacy assessments include SLEDAI-2K, BILAG-2004, PhGA scale, SF-36 
questionnaire, biologic markers of disease, SFI, SDI, FACIT-Fatigue scale, and change in steroid 
dose over time. Adverse events will be recorded throughout the study. Safety will also be 
assessed by evaluating clinical laboratory test results, vital signs measurements, 12-lead ECG 
findings, physical examination findings, assessment of suicidality using the C-SSRS, assessment 
for anaphylaxis using the Clinical Criteria for Diagnosing Anaphylaxis, and concomitant 
medication usage throughout the study. Immunogenicity will also be assessed at weeks 4, 12, 
20, 28, 36, 44, and 52 by detection of any presence of anti–IPP-201101 Ab. In addition to 
standard safety monitoring, an independent, external Data and Safety Monitoring Board 
(DSMB) will oversee the safety of the patients and monitor the occurrence of flare throughout 
the study. The DSMB will meet as specified in its charter. 
 
Blood samples for measurement of IPP-201101 plasma concentrations will be collected prior to 
and after study drug administration at weeks 0, 16, and 32 from patients at selected North 
American and Western European study centers. A blood sample for measurement of the 
concentration of IPP-201101 will also be obtained from all patients who have a serious adverse 
event and/or have an adverse event leading to withdrawal from the study. 
 
Blood samples for measurement of in vitro intracellular and secreted cytokine response will be 
collected prior to study drug administration at weeks 0, 4, 12, 24 and 48 from patients at selected 
study centers.  
 
Patients who complete the 48-week treatment period will return to the study center at week 52 
for final procedures and assessments. Patients who withdraw from the study before completion 
of the 48-week treatment period will have their final procedures and assessments performed at 
their last visit. Any patient with a positive test result for anti–IPP-201101 Ab at the final study 


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visit will be followed with additional immunogenicity testing at 8-week intervals until the level 
returns to baseline value or the levels are judged by the investigator to be chronic, or the patient 
is lost to follow-up. Study procedures and assessments with their timing are summarized in Table 
2. Patients who complete all study visits will be eligible for participation in an open-label 
extension study to assess the continued effectiveness and safety of IPP-201101 treatment. . 
 
The study schema is presented in Figure 1.  


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Figure 1:   Overall Study Schema 
 
 
Screening (visit 1/ days –14 to –1) 
(assessment) 
 
 
Baseline/Start of Study Drug  
Treatment (visit 2/week 0) 
(assessment, randomization,  
and 1st dose of study drug) 
 
 
 
 
Blood sample for immunogenicity 
testing (visit 3/week 2) 
 
 
 
 
Continuation of double-blind treatment  
period (visits 4 through 15/weeks 4, 8,12,  
16, 20, 24, 28, 32, 36, 40, 44, and48)a 
(administration of study drug once at each visit) 
 
 
 
 
 
 
Final visit (visit 16/week 52)a  
(or early termination) (assessment) 
 
 
 
a If patient is withdrawn from the study before completion of 48 weeks of treatment (13 doses of study drug), final procedures 
and assessments will be performed at early termination visit. 
 
 
3.2 
Primary and Secondary Measures/Variables and Endpoints 
 
3.2.1 
Primary Efficacy Measure/Variable and Endpoint 
 
The primary efficacy variable for this study is the proportion of patients achieving a combined 
clinical response using the SRI at week 52. An SRI response is defined as a reduction from 
baseline in the SLEDAI-2K score of at least 4 points, no worsening in PhGA (with worsening 
defined as an increase in PhGA of more than 0.30 point from baseline), no new BILAG A body 
system score, and no more than 1 new BILAG B body system score from baseline. 
 
 


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3.2.2 
Secondary Efficacy Measures/Variables and Endpoints 
 
The secondary efficacy variables and endpoints for this study are as follows: 
 
• 
proportion of patients achieving an SRI response at each visit during the treatment period 
• 
proportion of patients achieving a reduction of at least 4 points in the SLEDAI-2K total 
score at each visit during the treatment period 
• 
proportion of patients achieving a clinical SLEDAI-2K response at each visit during the 
treatment period, where the clinical response is defined as a reduction of at least 4 points in 
the SLEDAI-2K clinical score 
• 
proportion of patients achieving a BILAG-2004 response at each visit during the treatment 
period (no new BILAG A body system score and no more than 1 new BILAG B body 
system score from baseline) 
• proportion of patients achieving a BILAG-2004 clinical response at each visit during the 
treatment period (an improvement in at least 1 category from a B score to a C or D score, 
with no worsening in any other category) 
• 
proportion of patients showing no worsening on a PhGA scale at each visit during the 
treatment period 
• 
proportion of patients achieving a reduction of 5 points in the SLEDAI-2K total score at 
each visit during the treatment period 
• 
proportion of patients achieving a reduction of 6 points in the SLEDAI-2K total score at 
each visit during the treatment period 
• 
proportion of patients achieving an SRI-5 response at each visit during the treatment period 
• 
proportion of patients achieving an SRI-6 response at each visit during the treatment period 
• 
proportion of patients showing an improvement in tender and swollen joint counts using the 
28-joint count examination for pain and tenderness at each visit during the treatment period 
• 
SFI at each visit during the treatment period 
— time to first mild to moderate flare 
— incidence of mild to moderate flare 
— time to severe flare (NOTE: A severe flare leads to early withdrawal) 
• 
changes in the SDI over time (assessed at screening and weeks 24 and 52 [or final 
assessment]) 
• 
absolute and relative changes in the SF-36 at weeks 12, 24, 36, and 52 (or final assessment) 
proportion of patients with changes in steroid dose over time throughout the study 
 
The exploratory efficacy variables and endpoints for this study are as follows: 
 
• 
changes in the biomarkers anti-dsDNA Ab, C3, and C4 at each visit during the treatment 
period 
• 
changes in the following biomarkers at weeks 4, 12, 24, 36, and 52 (or final assessment): 
— ANA 
— anti–U1-70K snRNP Ab 


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— anti-Sm Ab 
— CRP 
— IgG, IgM, IgA and IgE 
 
• 
absolute and relative changes in the FACIT-Fatigue at weeks 12, 24, 36, and 52 (or final 
assessment) 
• 
in vitro intracellular and secreted cytokine response 
 
3.2.3 
Safety Measures and Endpoints 
 
The safety and tolerability of IPP-201101 will be assessed throughout the study by evaluating 
adverse events; clinical laboratory results; vital signs measurements; 12-lead ECG findings; 
physical examination findings, including physical examination symptom directed findings; and 
concomitant medication usage. Suicidality will be assessed using the C-SSRS. Adverse events 
that are suggestive of anaphylaxis or a drug hypersensitivity reaction will be evaluated as per the 
Clinical Criteria for Diagnosing Anaphylaxis (Appendix I). 
 
3.2.4 
Pharmacokinetic Measure/Variable and Endpoint 
 
A blood sample for measurement of IPP-201101 concentrations will be obtained prior to and 5 
minutes and 1, 2, and 24 hours after study drug administration at weeks 0,16, and 32 (visits 2, 7, 
and 11, respectively) from patients at selected North American and Western European study 
centers. 
 
A blood sample for measurement of the concentration of IPP-201101 will be obtained from all 
patients who have a serious adverse event and/or have an adverse event leading to withdrawal 
from the study. 
 
3.2.5 
Immunogenicity Measure/Variable and Endpoint 
 
The immunogenicity variable/endpoint for this study is as follows: 
 
• 
any presence of anti–IPP-201101 Ab at visits at weeks 2, 4, 12, 20, 28, 36, 44, and 52 (or 
final assessment) 
 
Any patient with a positive test result for anti–IPP-201101 Ab at the final study visit will be 
followed with additional immunogenicity testing at 8-week intervals until the level returns to 
baseline value or the levels are judged by the investigator to be chronic, or the patient is lost to 
follow-up. 
 
3.3 
Randomization and Blinding 
 
This is a randomized, double-blind, placebo-controlled study. To balance the distribution of the 
standard of care at baseline among the patients, the randomization will be stratified for 3 baseline 
characteristics, as follows: by region, SLEDAI-2K screening total score (6 to 9 or ≥10), and 
racial-ethnic group classification (black/Hispanic or others). Within each stratum, eligible 
patients will be randomly assigned with a 1:1 ratio to receive either 200 mcg of IPP-201101 or 
placebo sc every 4 weeks for 48 weeks. 
 


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The randomization code will be generated by ImmuPharma or its designee following 
specifications from the Biometrics Department. A statistician not assigned to the study will be 
responsible for review and approval of the randomization code, and the final randomization code 
will be maintained by ImmuPharma or its designee t. ImmuPharma clinical personnel involved 
in the study will also be blinded to the study drug identity until the database is locked for 
analysis and the treatment assignment revealed. 
 
Patients will be randomly assigned to treatment through a qualified randomization service 
provider (eg, interactive response technology [IRT]). Upon receiving the required patient 
identification, region, SLEDAI-2K screening total score, and racial-ethnic group classification, 
the IRT will assign the new patient to the next available randomization code within the 
randomization stratum for the appropriate region, SLEDAI-2K screening total score, and racial-
ethnic group classification categories according to the sequence  that is specified by 
ImmuPharma. 
 
Patients and investigators will remain blinded to treatment assignment during the study. 
 
3.4 
Study Drugs and Dosage 
 
3.4.1 
Investigational Product and Dosage 
 
IPP-201101 is a white to off-white, amorphous powder and is supplied in single-dose glass vials 
as lyophilized product for reconstitution. Before reconstitution, vials of study drug must be 
stored under refrigerated conditions (2° to 8° C [36° to 46° F]) in a secure place and protected 
from light. Each vial contains a sterile formulation of 220 mcg of IPP-201101, 59 mg of mannitol 
(and acetic acid used for pH adjustment, if necessary). This product does not contain 
preservatives. The study center will receive box(es) with up to 13 vials per box. Each vial will 
be labeled with a 4-digit treatment number and each box will contain IPP-201101. Prior to 
administration, IPP-201101 should be reconstituted with 1.1 mL sterile water for injection 
(volume of injection of 1.0 mL). After reconstitution, the vial can be stored at controlled room 
temperature (20° to 25° C [68° to 77° F]) for up to 2 hours prior to administration and does not 
need to be protected from light. Patients randomly assigned to IPP-201101 will be administered 
a dosage of 200 mcg sc every 4 weeks for 48 weeks (a total of 13 doses will be 
administered).The pharmacy manual provided by ImmuPharma or its designee includes details 
on storage, administration, reconstitution, syringe information, and preparation of the 
Investigational Product. A more detailed description of the administration procedures is given in 
section 5.1. 
 
3.4.2 
Other Study Drugs and Dosage 
 
Placebo vials matching the single-dose vials of IPP-201101 will be supplied by ImmuPharma or 
its designee. Each vial contains a white to off-white, amorphous powder as a lyophilized sterile 
formulation of mannitol dehydrate (and acetic acid used for pH adjustment, if necessary). 
Before reconstitution, vials of placebo must be stored under refrigerated conditions (2° to 8° C 
[36° to 46° F]) in a secure place and protected from light. The study center will receive box(es) 
with up to 13 vials per box. Each vial will be labeled with a 4-digit treatment number and each 
box will contain placebo vials. Prior to administration, placebo should be reconstituted with 1.1 


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mL sterile water for injection (volume of injection of 1.0 mL). After reconstitution, the vial can 
be stored at controlled room temperature (20° to 25° C [68° to 77° F]) for up to 2 hours prior to 
administration and does not need to be protected from light. Patients randomly assigned to 
placebo will be administered placebo sc every 4 weeks for 48 weeks (a total of 13 doses will be 
administered). 
 
The pharmacy manual provided by ImmuPharma includes details on storage, administration, 
reconstitution, syringe information, and preparation of placebo. A more detailed description of 
the administration procedures is given in section 5.1. 
 
3.5 
Duration of Patient Participation 
 
This study will consist of a screening period up to 2 weeks and a 48-week treatment period. 
Patients will return to the study center approximately 4 weeks after administration of the last 
dose of study drug (at 48 weeks) for the final assessment (week 52). Patients are expected to 
participate in the study for up to approximately 54 weeks. 
 
3.6 
Stopping Rules and Discontinuation Criteria 
 
A patient may discontinue participation in the study at any time for any reason (eg, lack of 
efficacy, consent withdrawn, or adverse event). The investigator and/or sponsor can withdraw a 
patient from the study at any time for any reason (eg, protocol violation or deviation as defined 
in section 11.1.2, noncompliance, or adverse event). 
 
An independent, external DSMB will oversee the safety of the patients enrolled in the study and 
monitor the occurrence of flare throughout the study. The DSMB will meet as specified in its 
charter. The DSMB may recommend stopping the study for safety concerns. Toxicity will be 
monitored using the Modified World Health Organization (WHO) Toxicity Criteria, which 
includes graded adverse events on a scale from 0 to 4 (see Appendix A).Individual patients will 
be withdrawn from the study if any of the following occur: 
 
Event 
Rule for withdrawing patient 
Grade 2 event 
The patient will be treated according to the 
investigator’s usual standard of care  (SOC). 
If the event does not improve to grade 1 or 
less within 4 weeks from the onset of grade 2 
severity, the medical monitor should be 
contacted to determine if the patient should 
be withdrawn from the study. 


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Grade 3 event (one grade 3 event not related 
to treatment) 
The patient will be treated according to the
investigator’s usual SOC. If the event does
not improve to grade 1 or less within 
4 weeks from the onset of grade 3 severity, 
the medical monitor should be contacted to 
determine if the patient should be withdrawn 
from the study. 
Grade 3 event (one grade 3 event related to
treatment or two grade 3 events not related
to treatment) 
The patient will be withdrawn from the 
study. 
Grade 4 event (any grade 4 event, related or 
not related to treatment) 
The patient will be withdrawn from the 
study. 
Pregnancy 
The patient will be withdrawn from the 
study. 
Serious intercurrent illness or significant 
worsening of intercurrent illness 
(eg, diagnosis of any cancer, lymphoma or 
leukemia, anaphylaxis, severe infections) 
The patient will be withdrawn from the 
study. 
Severe flare 
The patient will be withdrawn from the 
study. 
 
This study may be prematurely terminated if, in the opinion of the DSMB or the sponsor, there 
is sufficient and reasonable cause. Written notification documenting the reason for study 
termination will be provided by the terminating party to all involved. 
 
In order to ensure patient safety, patients who are determined to be treatment failures will be 
withdrawn from the study. Patients may be treated for treatment failure at the discretion of the 
investigator. Treatment failure is defined as any of the following: 
 
• 
occurrence of a severe flare according to the SFI (also results in withdrawal from the study) 
• 
increase in use of background oral corticosteroids beyond 80 mg of prednisone 
equivalent/week. (NOTE: Treatment of mild/moderate flare is permitted as detailed in 
section 5.2. The use of steroids for the treatment of a mild or moderate flare or for the 
treatment of conditions other than SLE will not be permitted beginning at week 44 [visit 14] 
through week 52 [visit 16].) 
• 
initiation of pulse iv steroid therapy (ie, 250 to 1000 mg iv total daily dose of 
methylprednisolone) 
• 
increase in the dose of immunosuppressive agents (methotrexate, azathioprine, MMF, 
leflunomide) above the baseline level 
• 
initiation of new immunosuppressive therapy (cyclophosphamide, methotrexate, 
azathioprine, cyclosporin, tacrolimus, leflunomide, MMF) 


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• 
initiation of therapy with biologics for the treatment of SLEte, azathioprine, cyclosporin, 
tacrolimus, leflunomide, MMF) 
 
 
3.7 
Study Drug Supply and Accountability 
 
3.7.1 
Study Drug Storage and Security 
 
Before reconstitution, vials of the study drug must be stored under refrigerated conditions (2° to 
8°C [36° to 46° F]) in a secure place and protected from light. 
 
3.7.2 
Study Drug Accountability 
 
Each study drug shipment will include a packing slip, explaining the contents of the shipment, 
and drug return instructions and forms. 
 
The investigator is responsible for ensuring that deliveries of study drug and other study 
materials from the sponsor are correctly received and recorded, handled and stored safely and 
properly in accordance with the CFR or local regulations, and used in accordance with this 
protocol. 
 
A record of study drug accountability (ie, study drug and other materials received, used, 
returned, or destroyed) must be prepared and signed by the principal investigator or designee, 
with an account given for any discrepancies. Empty, partially used, and unused vials of study 
drug will be destroyed at the study center or returned to ImmuPharma or its designee. 
 
3.8 
Maintenance of Randomization and Blinding 
 
The final randomization code will be maintained by the Development Manufacturing group. At 
the time of analyses, when treatment codes are to be revealed, ImmuPharma or its designee  will 
provide the randomization code to the statistician assigned to this study. 
 
Individuals responsible for sample bioanalysis will know which patients received IPP-201101 
and which received placebo during the study for all patients for whom sample bioanalysis and 
pharmacokinetic data analysis is conducted. Bioanalytical staff will not have access to any 
clinical data and will provide concentration data to other staff  members during the study in a 
manner that will not identify individual patients (ie, a dummy patient identifier will be linked 
with an individual patient’s concentration data). 
 
In the case of an emergency, if it is necessary to know what treatment a specific patient has 
received, the investigator may determine the patient’s treatment using IRT after consultation 
with ImmuPharma or its designee. In an extreme emergency, if the investigator is unable to 
contact ImmuPharma or its designee, the investigator may determine the patient’s treatment 
using IRT without prior authorization. When this occurs, the investigator must contact the 
individual identified in the clinical study personnel contact information section of this protocol 
immediately; the patient will be withdrawn from the study, and the event will be recorded on the 
study completion record of the case report form (CRF). Proper documentation must be 
maintained when a treatment code is revealed. For a serious and unexpected adverse event 


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considered related to the study drug or study procedure, ImmuPharma or its designee may 
independently request that the treatment code be revealed (on a case-by-case basis). If this 
occurs, Biometrics Department personnel involved in analysis of the data will remain blinded to 
treatment. 
 
3.9 
Source Data Recorded on the Case Report Form 
 
All patient data must have supportive source documentation in the medical records, or 
equivalent, before they are transcribed onto the CRF. Data may not be recorded directly onto the 
CRF and considered as source data unless the study center obtains written documentation from 
ImmuPharma or its designee or its designee, prior to the beginning of the study, indicating which 
data are permitted to be recorded directly on to the CRF. Source documents, including test 
results and/or assessments (eg, clinical laboratory test results, ECG data and assessments, 
efficacy measurements) collected or performed by institutions outside of the study center, are 
retained by the study center (see section 13.2.1). The CRFs are filed in the ImmuPharma central 
file. 
 
3.10 
Time Schedule 
 
The study started in the 1st  quarter of 2016 and expected be completed in the 1st quarter of 2018, 
with a study duration of approximately 36 months. It is anticipated that approximately 270 
patients may be screened for participation in the study prior to completion of enrollment. 
Approximately 200 patients from approximately 50 centers globally are planned to be enrolled in 
the study. Patient enrollment accrual is expected to occur at an average rate of 0.60 
patient/month/center. Patient enrollment will end when the planned number of enrolled patients 
is reached, unless the study is terminated early. 
 
These accrual rates are based on available retrospective data from similar studies in this patient 
population. Each investigator should make every effort to ensure that the planned accrual rate is 
maintained, that CRFs are completed promptly and completely, and that data quality is 
maintained at all times. Each investigator should discuss with the study monitor any anticipated 
problems with recruitment or delays in study completion. 
 
3.11 
Study Procedures 
 
Study procedures and assessments with their timing are summarized in Table 2. 


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Table 2: 
Study Procedures and Assessments 
 
Procedures and assessments 
Pretreatment 
Treatment 
FV/ET 
V1 
V2 
V3 
V4 
V5 
V6 
V7/V8 
V9 
V10/V11 
V12 
V13/V14/V15 
V16 
Screening D 
–14 to –1 
BL/Start study treatment 
W0 
W2 
W4 
W8 
W12 
W16/W20 
W24 
W28/W32 
W36 
W40/W44/W48a 
W52a 
Informed consent 
X 
I/E criteria reviewb 
X 
X 
Medical/psychiatric history 
X 
PE 
Xc 
Xd 
PE symptom directedd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical laboratory tests (serum 
chemistry,e hematology,f urinalysisg) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HBsAg, HCV Ab 
X 
ANA 
X 
X 
X 
X 
X 
X 
X 
Anti-dsDNA Ab, C3, C4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti–U1-70K snRNP Ab, 
anti-Sm Ab, CRP, IgG, IgM, IgE, IgA 
X 
X 
X 
X 
X 
X 
Hemolysis testsh 
X 
Pharmacokinetic samplesi 
X 
Xi 
Xi 
Immunogenicity samplesj 
X 
X 
X 
 
X 
Xj
 
Xj
X 
Xj 
X 
In vitro intracellular and secreted 
cytokine response  
X 
 
X 
 
 
X 
 
 
X 
 
Vital signsk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
Concomitant medication review 
Xm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xm 
Xm 
Adverse event inquiryn 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SLEDAI-2Ko 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BILAG-2004o 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
28-joint count exam for pain and 
tenderness 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SFIv (,Safety of Estrogens in Lupus Erythematosus: 
National Assessment [SELENA] Flare Index) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SDIo(Systemic Lupus International Collaborative 
Clinics/American College of Rheumatology 
[SLICC/ACR] Damage Index)
 
X 
X 
X 
SF-36 
X 
X 
X 
X 
X 
PhGAv 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatigue 
X 
X 
X 
X 
X 
C-SSRSp 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Access IRT 
Xq 
Xr 
(X)r 
(X)r 
(X)r 
(X)r 
(X)r 
(X)r 
(X)r 
(X)r 
Xs 
Study drug administrationt,u 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Footnotes and abbreviations appear on the next page.(continued) 


ImmuPharma 
IPP-201101 
Study C33457/3095 
42 
CONFIDENTIAL 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
42 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
 
 
Footnotes to Table 2 
a If a patient is withdrawn from the study before completion of 48 weeks of treatment, final procedures and assessments will be performed at the last visit. 
b The clinical SLEDAI-2K score during screening must be at least 6 for the patient to be enrolled. 
c Physical examination will include measurement of height at screening only and measurement of body weight at week 52 (or final assessment). 
d Physical examination symptom directed will include measurement of body weight. 
e Serum chemistry laboratory parameters will include a comprehensive metabolic panel and creatine phosphokinase. 
f Hematology laboratory parameters will include complete blood count with differential. 
g Urinalysis parameters will include urine dipstick, microscopic urinalysis, and spot protein-creatinine ratio. 
h Coombs’ test will be obtained at screening. At subsequent visits, Coombs’ test, haptoglobin, and peripheral smear will be obtained if hemolysis is suspected or confirmed. 
i A blood sample (5 mL) for measurement of IPP-201101 concentrations will be obtained prior to and 5 minutes and 1, 2, and 24 hours after study drug administration at weeks 0, 16, and   32 
from patients at selected North American and Western European study centers.  A blood sample for measurement of the concentration of IPP-201101 will be obtained from all patients who 
have a serious adverse event and/or have an adverse event leading to withdrawal from the study. 
j Anti–IPP-201101 Ab testing will be performed at visit 2 (week 0; baseline/start of study drug treatment), visit 3 (week 2), visit 4 (week 4), visit 6 (week 12), visit 8 (week 20), visit 10   
(week 28), visit 12 (week 36), visit 14 (week 44), and the final assessment (or early termination) (visit 16 [week 52]). All samples will be collected prior to administration of study drug at 
that particular visit.  Any patient with a positive test result for anti–IPP-201101 Ab at the final study visit will be followed with additional immunogenicity testing at 8-week intervals until 
the level returns to baseline value or the levels are judged by the investigator to be chronic, or the patient is lost to follow-up. 
k Vital signs measurements will include systolic and diastolic blood pressures, pulse, and temperature.  The same position and arm should be used each time vital signs are measured for a 
given patient. 
l At screening, baseline, weeks 4 through 48, and week 52 (or final assessment), urine pregnancy tests will be performed on all women prior to study drug administration regardless of 
childbearing potential. 
m Concomitant medication usage will be obtained from the start of screening. Background therapies for SLE may not change from week 44 to week 52. 
n Adverse events that are suggestive of anaphylaxis or a drug hypersensitivity reaction will be evaluated as per the Clinical Criteria For Diagnosing Anaphylaxis. 
o Eligibility will be validated by a central system . 
p C-SSRS will be administered directly to the patient using IRT and assessed using C-SSRS Baseline version at baseline (visit 2) and C-SSRS Since Last Visit version at visits 4 through 16. 
q At screening, using IRT each patient will be assigned with a 6-digit personal identification screening number. 
r The  IRT will be accessed at baseline/start of study drug treatment for drug kit assignment.  The IRT will also assign a 5-digit treatment number.  In addition, the IRT will be accessed during 
the study for drug resupply. 
s The  IRT will be accessed at final visit for study disposition. 
t Patients will be randomly assigned to receive a 200-mcg dose of IPP-201101 or placebo.  IPP-201101 or placebo will be administered subcutaneously every 4 weeks from weeks 0 to 48. 
Patients who continue to meet the inclusion/exclusion criteria will be assigned a permanent 4-digit unique randomization number using the IRT. The IRT will assign a 5-digit treatment 
number.  The 1st dose of study drug will be administered at baseline (visit 2) after all assessments have been completed.  Patients should be monitored for at least 1 hour after study drug 
administration at visits 2 and 4 and then at the discretion of the investigator. 
u Study drug may not be administered by the same individual performing the SLEDAI-2K, BILAG-2004, PhGA, SFI, and SDI.  These disease activity indices must be completed before study 
drug is administered (at visits at which study drug is administered). 
v PhGA, SLEDAI 2K and SFI are captured on the same form and then assessed in BLIPS software. 
V=visit; D=day; W=week; BL=baseline; FV=final visit; ET=early termination; I/E=inclusion/exclusion; PE=physical examination; HBsAg=hepatitis B surface antigen; 
HCV Ab=hepatitis C virus antibody; ANA=antinuclear antibody; anti-dsDNA Ab=anti–double-stranded deoxyribonucleic acid antibody; C3=complement component 3; C4=complement 
component 4; anti–U1-70K snRNP Ab=anti-uridine rich 70 kilodalton small nuclear ribonucleoprotein particle antibody; anti-Sm Ab=anti–Smith antibody; CRP=C-reactive protein; 
IgG=immunoglobulin G; IgM=immunoglobulin M; IgE=immunoglobulin E, IgA=immunoglobulin A; Ab=antibody; ECG=electrocardiogram; IRT=Interactive Response Technology; 
SLEDAI-2K=Systemic Lupus Erythematosus Disease Activity Index 2000; BILAG-2004=British Isles Lupus Assessment Group 2004; exam=examination; SELENA=Safety of Estrogens in 
Lupus 
Erythematosus: National Assessment; SLICC/ACR=Systemic Lupus International Collaborative Clinics/American College of Rheumatology; SF-36=Medical Outcome Survey Short Form 
36; SFI=Safety of Estrogens in Lupus Erythematosus: National Assessment Flare Index; SDI=SLICC/ACR Damage Index; PhGA=Physician’s Global Assessment; 
FACIT-Fatigue=Functional Assessment of Chronic Illness Therapy–Fatigue Scale; C-SSRS=Columbia-Suicide Severity Rating Scale. 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
43 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
43 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
 
 
3.11.1 Procedures for Screening and Enrollment (Visit 1) 
 
A signed and dated informed consent form will be obtained before screening procedures. 
Evaluations obtained as part of routine medical care and performed during the screening period 
may be used in place of the study-specific evaluations. Patients will acknowledge and agree to 
the possible use of this information for the study by giving informed consent. 
 
After informed consent is obtained, patients who are screened will be assigned a 6-digit patient 
identification number via IRT such that all patients from each center are given consecutive 
identification numbers in successive order of inclusion. The two first digits of the screening 
number will be the designated investigator country, the two following digits will be designated the 
center number, and the last 2 digits will be assigned at the investigator center (eg, the 3rd patient 
screened at center 5 in USA would be given the number of 010503). 
 
The screening visit (visit 1) will take place not more than 2 weeks before the baseline visit. An 
additional 14 days will be allowed for the receipt of data needed to confirm eligibility (eg, 
BILAG-2004, SLEDAI-2K, and PhGA  central system assessment, laboratory results ….). The 
following procedures will be performed at visit 1: 
 
• 
obtain written informed consent 
• 
inclusion/exclusion criteria review; confirm that clinical SLEDAI-2K score is at least 6 
• 
medical and psychiatric history review 
• 
physical examination (including measurement of height at screening only) 
• 
clinical laboratory tests 
• 
hepatitis B surface antigen [HBsAg], hepatitis C virus antibody [HCV Ab], ANA 
• 
anti-dsDNA Ab, C3, and C4 
• 
hemolysis testing (Coombs’ test only) 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
12-lead ECG 
• 
concomitant medication review (at the start of screening) 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
SFI 
• 
SDI 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
44 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
44 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
 
3.11.2 Procedures Before Study Drug Treatment (Baseline/Start Study Drug Treatment 
[Visit 2/Week 0]) 
 
Patients who meet the inclusion/exclusion criteria at visit 1 will continue to visit 2 (week 0); if 
they 
continue 
to 
meet 
all 
criteria, 
baseline 
evaluations 
will 
be 
conducted, 
randomization/stratification will occur via IRT, and study drug will be administered. NOTE: 
Week 0 refers to the start of the 1st week of study drug treatment, which will begin with the 
baseline visit. 
 
In addition, a blood sample (5 mL) will be obtained for measurement of IPP-201101 plasma 
concentrations prior to and 5 minutes and 1, 2, and 24 hours after study drug administration from 
patients at selected North American and Western European study centers. The actual dates and 
times of study drug administration and the date and time of sampling will be recorded on the 
CRF. 
 
The following procedures will be performed at visit 2: 
 
• 
inclusion/exclusion criteria review 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
ANA 
• 
anti-dsDNA Ab, C3, and C4 
• 
anti–U1-70K snRNP Ab, anti-Sm Ab, CRP, IgG, IgM, , IgA 
• 
anti–IPP-201101 Ab 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
SF-36 
• 
PhGA 
• 
FACIT-Fatigue 
• 
C-SSRS Baseline version  
• 
In vitro intracellular and secreted cytokine response  
• 
access eCRF for randomization number and study drug administration. Randomization number 
and treatment number will be allocated automatically by the system.   
 
A patient who is not enrolled in the study at the end of the baseline visit, eg, because entry 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
45 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
45 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
criteria were not met or enrollment did not occur within the specified time, may be considered 
for screening again if, eg, there was a change in the patient’s medical background or a 
modification of study entry criteria. (NOTE: Details of rescreening criteria and procedures are 
included in the Monitoring Plan for this study.) 
 
Patients who continue to meet the inclusion/exclusion criteria and are approved for randomization 
will be assigned a permanent 4-digit unique randomization number preceded by ‘R’ using the IRT 
(integrated with the eCRF). The IRT will also assign a 5-digit treatment number at each visit at 
which study drug is administered (ie, baseline [visit 2] and visits 4 through 15). The 5-digit 
treatment number will correspond to the number on the individual vial of study drug that is to be 
administered. The 1st dose of study drug will be administered at this visit after all assessments 
have been completed. Patients should be monitored for at least 1 hour after study drug 
administration at visits 2 and 4 and then at the discretion of the investigator. 
 
Throughout the study, a blood sample for measurement of the concentration of IPP-201101 will 
be obtained from all patients who have a serious adverse event and/or have an adverse event 
leading to withdrawal from the study. 
 
3.11.3 Procedures During Study Drug Treatment 
 
3.11.3.1 Visit 3 (Week 2) 
 
The following procedures/assessments will be performed at visit 3 (week 2): 
 
• 
anti–IPP-201101 Ab 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
concomitant medication review 
• 
adverse event inquiry 
 
3.11.3.2 Visit 4 (Week 4) 
 
The following procedures/assessments will be performed at visit 4 (week 4): 
 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
ANA 
• 
anti-dsDNA Ab, C3, and C4 
• 
anti–U1-70K snRNP Abanti-Sm Ab, CRP, IgG, IgM, IgE, IgA 
• 
anti–IPP-201101 Ab 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review 
• 
adverse event inquiry 
• 
SLEDAI-2K 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
46 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
46 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
PhGA 
• 
C-SSRS Since Last Visit version 
• 
In vitro intracellular and secreted cytokine response 
• 
Access eCRF page for treatment allocation.. 
• 
study drug administration after all assessments have been completed. (Patients should be 
monitored for at least 1 hour after study drug administration.) 
 
3.11.3.3 Visit 5 (Week 8) 
 
The following procedures/assessments will be performed at visit 5 (week 8): 
 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
anti-dsDNA Ab, C3, and C4 only 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
PhGA 
• 
C-SSRS Since Last Visit version 
• 
access eCRF page for treatment allocation.  
• 
study drug administration after all assessments have been completed. (Patients should be 
monitored, at the discretion of the investigator, for at least 1 hour after study drug 
administration.) 
 
3.11.3.4 Visit 6 (Week 12) 
 
The following procedures/assessments will be performed at visit 6 (week 12): 
 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
ANA 
• 
anti-dsDNA Ab, C3, and C4 
• 
anti–U1-70K snRNP Ab, anti-Sm Ab, CRP, IgG, IgM, IgE, IgA 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
47 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
47 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
• 
anti–IPP-201101 Ab 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
SF-36 
• 
PhGA 
• 
FACIT-Fatigue 
• 
C-SSRS Since Last Visit version 
• 
access eCRF page for treatment allocation.  
• 
study drug administration after all assessments have been completed. (Patients should be 
monitored, at the discretion of the investigator, for at least 1 hour after study drug 
administration.) 
 
3.11.3.5 Visits 7 and 8 (Weeks 16 and 20) 
 
The following procedures/assessments will be performed at visits 7 and 8 (weeks 16 and 20, 
respectively): 
 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
anti-dsDNA Ab, C3, and C4 only 
• 
anti–IPP-201101 Ab (visit 8, week 20) 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
PhGA 
• 
C-SSRS Since Last Visit version  
• 
access eCRF page for treatment allocation.  


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
48 
CONFIDENTIAL 
 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
48 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
• 
study drug administration after all assessments have been completed. (Patients should be 
monitored, at the discretion of the investigator, for at least 1 hour after study drug 
administration.) 
 
In addition, a blood sample (5 mL) will be obtained for measurement of 
IPP-201101 plasma concentration prior to and 5 minutes and 1, 2, and 24 hours after study drug 
administration at visit 7 (week 16) from patients at selected North American and Western 
European study centers. The actual dates and times of study drug administration and the date 
and time of sampling will be recorded on the CRF. 
 
3.11.3.6 Visit 9 (Week 24) 
 
The following procedures/assessments will be performed at visit 9 (week 24): 
 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
ANA 
• 
anti-dsDNA Ab, C3, and C4 
• 
anti–U1-70K snRNP Ab, anti-Sm Ab, CRP, IgG, IgM, IgE, IgA 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
SDI 
• 
SF-36 
• 
PhGA 
• 
FACIT-Fatigue 
• 
C-SSRS Since Last Visit version  
• 
In vitro intracellular and secreted cytokine response 
• 
Access eCRF page for treatment allocation.  
• 
study drug administration after all assessments have been completed. (Patients should be 
monitored, at the discretion of the investigator, for at least 1 hour after study drug 
administration.) 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
CONFIDENTIAL 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
49 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
 
3.11.3.7 Visits 10 and 11 (Weeks 28 and 32) 
 
The following procedures/assessments will be performed at visits 10 and 11 (weeks 28 and 32, 
respectively): 
 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
anti-dsDNA Ab, C3, and C4 only 
• 
anti–IPP-201101 Ab (visit 10 [week 28]) 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
PhGA 
• 
C-SSRS Since Last Visit version 
• 
access eCRF page for treatment allocation.  
• 
study drug administration after all assessments have been completed. (Patients should be 
monitored, at the discretion of the investigator, for at least 1 hour after study drug 
administration.) 
 
In addition, a blood sample (5 mL) will be obtained for measurement of IPP-201101 plasma 
concentration prior to and 5 minutes and 1, 2, and 24 hours after study drug administration at 
visit 11 (week 32) from patients at selected North American and Western European study 
centers. The actual dates and times of study drug administration and the date and time of 
sampling will be recorded on the CRF. 
 
3.11.3.8 Visit 12 (Week 36) 
 
The following procedures/assessments will be performed at visit 12 (week 36): 
 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
ANA 
• 
anti-dsDNA Ab, C3, and C4 
• 
anti–U1-70K snRNP Ab, anti-Sm Ab, CRP, IgG, IgM, IgE, IgA 
• 
anti–IPP-201101 Ab 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
CONFIDENTIAL 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
50 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
SF-36 
• 
PhGA 
• 
FACIT-Fatigue 
• 
C-SSRS Since Last Visit version 
• 
Access eCRF page for treatment allocation.  
• 
study drug administration after all assessments have been completed. (Patients should be 
monitored, at the discretion of the investigator, for at least 1 hour after study drug 
administration.) 
 
3.11.3.9 Visits 13, 14, and 15 (Weeks 40, 44, and 48) 
 
The following procedures/assessments will be performed at visits 13, 14, and 15 (weeks 40, 44, 
and 48 respectively): 
 
• 
physical examination symptom directed 
• 
clinical laboratory tests 
• 
anti-dsDNA Ab, C3, and C4 only 
• 
anti–IPP-201101 Ab (visit 14 [week 44]) 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
concomitant medication review (NOTE: Background therapies for SLE may not change from 
week 44 to week 52.) 
• 
adverse event inquiry 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
PhGA 
• 
C-SSRS Since Last Visit version 
• 
In vitro intracellular and secreted cytokine at Visit 48 
 
access eCRF page for treatment allocation.  
 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
CONFIDENTIAL 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
51 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
Study drug administration after all assessments have been completed. (Patients should be 
monitored, at the discretion of the investigator, for at least 1 hour after study drug administration.) 
 
3.11.4 Procedures After Study Drug Treatment (Visit 16/Week 52) 
 
Patients who participate in the study in compliance with the protocol for at least 48 weeks of 
treatment will be considered to have completed the study. Patients who complete all study visits 
will be eligible for participation in a open-label study to assess the continued effectiveness and 
safety of IPP-201101 treatment. 
 
If a patient is withdrawn from the study before completion of 48 weeks of study drug treatment, 
final evaluations will be performed at the last visit. To be evaluable for efficacy, a patient must 
be treated with at least 1 dose of study drug and must have all components of the SRI (baseline 
SLEDAI-2K total score, BILAG-2004 body system scores, and PhGA score) available. Patients 
with ongoing adverse events or clinically significant abnormal laboratory test results (as 
interpreted by the investigator) will be monitored as described in section 7.1.2 and section 7.2, 
respectively. 
 
If a patient withdraws from the study during the treatment period, the reason must be determined 
and recorded on the patient’s CRF (see section 4.3). For patients who withdraw consent, every 
attempt will be made to determine the reason. A blood sample for measurement of the 
concentration of IPP-201101 will be obtained from all patients who have an adverse event 
leading to withdrawal from the study and/or all patients who have a serious adverse event. 
 
For patients who complete the study, final evaluations will be performed at visit 16 (week 52). 
For patients who withdraw prematurely from the study before completion of 48 weeks of study 
drug treatment, final evaluations will be performed at the last visit. The following procedures 
will be performed at visit 16 (week 52) or at early termination (before completion of the 48 
weeks of study drug treatment), if applicable: 
 
• 
physical examination 
• 
clinical laboratory tests 
• 
ANA 
• 
anti-dsDNA Ab, C3, and C4 
• 
anti–U1-70K snRNP Ab, anti-Sm Ab, CRP, IgG, IgM, IgE, IgA 
• 
anti–IPP-201101 Ab (NOTE: Any patient with a positive test result for anti–IPP-201101 Ab 
at the final study visit will be followed with additional 
immunogenicity testing at 8-week intervals until the level returns to baseline value or the 
levels are judged by the investigator to be chronic, or the patient is lost to follow-up) 
• 
vital signs measurements (includes systolic and diastolic blood pressures, pulse, and 
temperature) 
• 
urine pregnancy test on all women regardless of childbearing potential 
• 
12-lead ECG 
• 
concomitant medication review 
• 
adverse event inquiry 


ImmuPharma 
IPP-201101 
Study IPP-201101/005 
CONFIDENTIAL 
Placebo-Controlled Study–Systemic Lupus Erythematosus 
Clinical Study Protocol 
 
52 
Protocol IPP-201101/005 – version 2.5 – June  1st 2016 
• 
SLEDAI-2K 
• 
BILAG-2004 
• 
28-joint count examination for pain and tenderness 
• 
SFI 
• 
SDI 
• 
SF-36 
• 
PhGA 
• 
FACIT-Fatigue 
• 
C-SSRS Since Last Visit version 
• 
access IRT to record final patient disposition 
 
4 
SELECTION AND WITHDRAWAL OF PATIENTS 
 
4.1 
Patient Inclusion Criteria 
 
Patients are included in the study if all of the following criteria are met: 
 
(a) The patient is a man or woman between 18 and 70 years of age with an established 
diagnosis of SLE as defined by ACR Classification Revised Criteria. The diagnosis is 
fulfilled provided that at least 4 criteria are met. 
(b) The patient has a positive test result for ANA at screening (titer must be at least 1:80 [by 
human epithelial cell tumor line (HEp-2) ANA assay]) and/or a positive test result for anti-
dsDNA Ab at screening (value must be 30 IU/mL or more by enzyme-linked 
immunosorbent assay [ELISA]). 
(c) Written informed consent is obtained. 
(d) Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing potential, 
using a medically accepted method of contraception, and must agree to continued use of this 
method for the duration of the study and for 30 days after discontinuation of study drug 
treatment. Acceptable methods of contraception include barrier method with spermicide, 
abstinence (when this is in line with the preferred and usual lifestyle of the subject), 
intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and 
injected) in conjunction with a barrier method. 
(e) The patient has a SLEDAI-2K clinical score of at least 6 points during screening. A 
SLEDAI-2K clinical score is the calculated score without inclusion of the points that may be 
contributed by having a positive titer for anti-dsDNA Ab or decreased serum complement 
levels. 
(f) The patient does not have an “A” score on the BILAG-2004 scale. 
(g) If the patient is using oral corticosteroids, the weekly cumulative dose must not exceed 80 
mg of prednisone equivalent; the weekly dose must be stable over the 4 weeks preceding the 
1st dose of study drug. 
(h) If the patient is using antimalarials, methotrexate, leflunomide, MMF, or azathioprine, the 
start date must be at least 3 months prior to the 1st dose of study drug, and the daily dose 


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must be stable over the 4 weeks preceding the 1st dose of study drug. 
(i) If the patient is not currently using corticosteroids, antimalarials, methotrexate, MMF, or 
azathioprine, the last dose (in case of previous use) must be at least 4 weeks prior to the 1st 
dose of study drug. For leflunomide, the stop date must be at least 8 weeks before the 1st 
dose of study drug, unless an adequate cholestryamine washout has been performed. If 
cholestyramine washout is performed, the last use of leflunomide must be at least 4 weeks 
before the 1st dose of study drug. 
 
The patient must be willing and able to comply with study restrictions, to remain at the study 
center for the required duration during each study visit, and to return to the study center for the 
final assessment as specified in this protocol.  
4.2 
Patient Exclusion Criteria 
 
Patients are excluded from participating in this study if 1 or more of the following criteria are 
met: 
 
(a) The patient has been treated with intramuscular or intravenous (iv) pulse steroids (ie, 250 to 
1000 mg iv total daily dose of methylprednisolone) within 4 weeks of the 1st dose of study 
drug. The use of intra-articular steroids may be allowed after consultation with the medical 
expert. 
(b) The patient has received tacrolimus, cyclosporin A, or iv immunoglobulins (IVIG) within 3 
months of the 1st dose of study drug. 
(c) The patient has received cyclophosphamide within 6 months prior to the 1st dose of study 
drug. 
(d) The patient has been treated for SLE with agents such as fusion proteins, therapeutic 
proteins, or monoclonal antibodies or antibody fragments, within 6 months of the 
1st dose of study drug. 
(e) The patient has received B-cell depleting agents such as rituximab, belimumab or 
epratuzumab within one year of the 1st dose of study drug and has not yet normalized the B-
cell count (ie, CD20+ B-cell count is less than normal range  and the absolute lymphocyte 
count [ALC] is less than normal range). 
(f) The patient has New York Heart Association (NYHA) Class III or IV congestive heart 
failure. 
(g) 
The patient has an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 
m2 (via Modification of Diet in Renal Disease [MDRD] equation). 
(h) The patient has an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
value greater than 2 times the upper limit of the normal range (ULN) or a total bilirubin 
level greater than 1.5 times ULN. 
(i) The patient has a planned immunization with a live or live attenuated vaccine within 3 
months prior to administration of the 1st dose of study drug and for 3 months after 
administration of the last dose of study drug. 
(j) The patient has any clinically significant abnormalities on ECG that are not related to SLE, 
as determined by the investigator. Patients with stable ECG changes without evidence of 
active cardiovascular disease may participate at the discretion of the investigator and 


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medical monitor. 
(k) The patient has an ongoing active systemic infection requiring treatment or a history of 
severe infection, such as hepatitis or pneumonia, in the 3 months prior to administration of 
the 1st dose of study drug. Less severe infections in the 3 months prior to administration of 
the 1st dose of study drug are permitted at the discretion of the investigator and medical 
monitor. 
(l) The patient has any concomitant medical condition unrelated to SLE that may interfere with 
his or her safety or with evaluation of the study drug, as determined by the investigator. 
(m) The patient has a history of a medical condition other than SLE that has required treatment 
with oral corticosteroids in excess of 80 mg of prednisone equivalent/week within 3 months 
of the 1st dose of study drug. 
(n) The patient has a positive test result for HBsAg or HCV Ab. 
(o) The patient has a known positive history of antibodies to human immunodeficiency virus 
(HIV) or HIV disease or other immunosuppressive state (eg, agammaglobulinemia, etc). 
(p) The patient has a history of alcohol or substance dependence or abuse (with the exception of 
nicotine), according to the Diagnostic and Statistical Manual of Mental Disorders of the 
American Psychiatric Association, Fourth Edition, Text Revision (DSM-IV-TR), within 3 
months of the screening visit or has current substance abuse. 
(q) The patient has a history of severe allergic reactions to or hypersensitivity to any component 
of the study drug or placebo. 
(r) The patient has undergone or is undergoing treatment with another investigational drug for 
the treatment of lupus within 6 months prior to the 1st dose of study drug or has received any 
other investigational drug for any other condition within 4 weeks prior to the 1st dose of 
study drug. 
(s) The patient has previously participated in a clinical study with IPP-201101. 
(t) The patient is a pregnant or lactating woman. (Any women becoming pregnant during the 
study will be withdrawn from the study.) 
(u) The patient is unlikely to comply with the study protocol or is unsuitable for any other 
reason, as judged by the investigator or medical monitor. 
 
4.3 
Withdrawal Criteria and Procedures 
 
In accordance with the Declaration of Helsinki (in accordance with the applicable country’s 
acceptance), each patient is free to withdraw from the study at any time. Each investigator also 
has the right to withdraw a patient from the study in the event of intercurrent illness, adverse 
events, pregnancy (see section 7.2.4), or other reasons concerning the health or well-being of the 
patient, or in the case of lack of cooperation. In addition, a patient may be withdrawn from the 
study as described in sections 3.6, 3.8, 5.2, 5.3, and 7.1.6. 
 
Should a patient decide to withdraw after administration of study drug, or should the investigator 
decide to withdraw the patient, all efforts will be made to complete and report the observations 
up to the time of withdrawal as thoroughly as possible. A complete final evaluation at the time 
of the patient’s withdrawal should be made and an explanation given of why the patient is 
withdrawing or being withdrawn from the study. 


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The reason for and date of withdrawal from study drug treatment and the reason for and date of 
withdrawal from the study must be recorded on the CRF. If a patient withdraws consent, every 
attempt will be made to determine the reason. If the reason for withdrawal is an adverse event or 
a clinically significant abnormal laboratory test result, monitoring will continue until the event 
has resolved or stabilized, until the patient is referred to the care of a local health care 
professional, or until a determination of a cause unrelated to the study drug or study procedure is 
made. The specific event or test results must be recorded on the CRF. In addition, a blood 
sample will be obtained for measurement of the concentration of IPP-201101 from all patients 
who have a serious adverse event and/or have an adverse event leading to withdrawal from the 
study. All evaluations should be performed, according to the protocol, on the last day the patient 
receives study drug, or as soon as possible thereafter. 
 
5 
TREATMENT OF PATIENTS 
 
5.1 
Study Drugs Administered 
 
After successfully meeting entry criteria, during the screening and baseline visits, eligible 
patients will be randomly assigned to the IPP-201101 treatment group or to the placebo 
treatment group (see section 3.3). Study drug will be packaged in single-dose vials; the study 
center with receive box(es) with up to 13 vials per box. Each vial will be labeled with a 4-digit 
treatment number and each box will contain a mix of IPP-201101 or  placebo vials (see section 
3.4). Study drug exposure will be measured, and study drug will be administered sc by qualified 
study personnel at visit 2 and visits 4 through 15. Study drug may not be administered by the 
same individual performing the SLEDAI-2K, BILAG-2004, or PhGA. Study drug should be 
administered at each study visit after all study visit procedures and assessments have been 
completed. 
 
The pharmacy manual provided by ImmuPharma includes details on storage, administration, 
reconstitution, syringe information, and preparation of the study drug. 
 
5.1.1 
Investigational Product and Dosage 
 
Prior to administration, IPP-201101 should be reconstituted with 1.1 mL sterile water for 
injection (volume of injection of 1.0 mL). Patients randomly assigned to IPP-201101 will be 
administered a dosage of 200 mcg sc every 4 weeks for 48 weeks. 
 
A more detailed description of the product is provided in section 3.4. 
 
5.1.2 
Other Study Drugs and Dosage 
 
Patients randomly assigned to placebo will be administered placebo sc every 4 weeks for 48 
weeks. Prior to administration, placebo should be reconstituted with 1.1 mL sterile water for 
injection (volume of injection of 1.0 mL). 
 
A more detailed description of the product is provided in section 3.4. 
 
5.2 
Prior and Concomitant Therapy or Medication 


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Any prior or concomitant therapy or medication given to a patient from the start of screening or 
during study drug administration will be indicated on the CRF. Other medications used for SLE 
or other disorders will also be captured on the CRF, as detailed below. Dosage and generic name 
or trade name will be indicated. The sponsor will encode all therapy and medication according 
to the WHO drug dictionary (WHO Drug). 
 
As described in section 4.1, if the patient is using oral corticosteroids, the weekly cumulative 
dose must not exceed 80 mg of prednisone equivalent; the weekly dose must be stable over the 4 
weeks preceding the 1st dose of study drug. If a patient is taking oral corticosteroids at study 
entry, the dose may be decreased during the study at the investigator’s discretion. The dose of 
background corticosteroid medication may be increased to treat the patient for minor fluctuations 
in lupus disease activity (ie, a mild or moderate flare). However, the dose of oral corticosteroid 
may not exceed 30 mg of prednisone or equivalent per day for more than 2 weeks. If a patient 
not previously treated with corticosteroids requires initiation of treatment with corticosteroids 
during the study to treat minor fluctuations in lupus disease activity (ie, a mild or moderate 
flare), the dose of oral corticosteroid may not exceed 30 mg of prednisone or equivalent per day 
for more than 2 weeks. If a patient requires a temporary increase in corticosteroid dose or a short 
course of corticosteroid treatment (ie, 2 weeks) and the medication is unable to be tapered to the 
baseline dose or be withdrawn, respectively, the patient is to be withdrawn from the study. If a 
patient requires treatment with corticosteroids for a condition other than SLE, these same 
restrictions on corticosteroid use, and those detailed in section 4.2, will apply. The use of intra-
articular steroids may be allowed after consultation with the medical expert. 
 
Also, if the patient is using antimalarials, methotrexate, leflunomide, MMF, or azathioprine, the 
start date must be at least 3 months prior to the 1st dose of study drug, and the daily dose must be 
stable over the 4 weeks preceding the 1st dose of study drug. Dosages of these medications 
should remain stable during the study. In addition, if the patient is not currently using 
corticosteroids, antimalarials, methotrexate, MMF, or azathioprine, the last dose (in case of 
previous use) must be at least 4 weeks prior to the  1st dose of study drug. For leflunomide, the 
stop date must be at least 8 weeks before the 1st dose of study drug, unless an adequate 
cholestyramine washout has been completed. (NOTE: If cholestyramine washout is performed, 
the last use of leflunomide must be at least 4 weeks before the 1st dose of study drug.) If used, 
these medications should also be indicated on the CRF. If a patient requires treatment with any 
of these medications for a condition other than SLE, these same restrictions, and those detailed in 
section 4.2, will apply. 
 
Changes in background therapies, including use of corticosteroids as a background therapy or for 
treatment of a mild or moderate flare or of a condition other than SLE, should not occur 
beginning with week 44 (visit 14). Any tapering of medication (ie, for clinically meaningful 
improvement in disease activity, dose reduction, or medication discontinuation because of 
toxicity) should be discussed with the medical monitor. Medication holidays (eg, less than or 
equal to 2 weeks) for short periods because of intercurrent illness or surgical procedures may be 
permitted and should be discussed with the medical monitor. However, background therapies 
must be stable for at least 4 weeks prior to the 1st dose of study drug. 
Patients will be withdrawn from the study if any of the following occur: 
 


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• 
an increase in use of background oral corticosteroids beyond 80 mg of prednisone 
equivalent/week (NOTE: Treatment of mild/moderate flare is permitted as detailed in section 
5.2. The use of corticosteroids for the treatment of a mild or moderate flare or for the 
treatment of conditions other than SLE will not be permitted beginning at week 44 [visit 14] 
through week 52 [visit 16]) 
• 
an inability to reduce corticosteroid dose to the baseline dose or to withdraw therapy if the 
patient required a temporary increase in corticosteroid dose or a short course of 
corticosteroid treatment (ie, 2 weeks) and the medication is unable to be tapered to the 
baseline dose or be withdrawn, respectively 
• 
therapy is initiated with pulse iv steroids 
• 
an increase in the baseline dose of immunosuppressive agents (methotrexate, azathioprine, 
MMF) 
• 
initiation of new immunosuppressive therapy (cyclophosphamide, methotrexate, 
azathioprine, cyclosporin, tacrolimus, leflunomide, MMF) 
• 
initiation of therapy with biologics for the treatment of SLE 
• 
any change in the doses of background therapies beginning with week 44 (visit 14) More 
information is provided in section 3.6 and Appendix B. 
Patients will be excluded from participation in the study for any of the following reasons: 
• 
they have been treated with iv pulse steroids within 4 weeks of the 1st dose of study drug 
• 
they have received tacrolimus, cyclosporin A, or IVIG within 3 months of the 1st dose of 
study drug 
• 
they have received cyclophosphamide or have been treated with biologic agents for SLE, 
such as fusion proteins, therapeutic proteins, or monoclonal antibodies or antibody 
fragments, within 6 months of the 1st dose of study drug 
• 
they have received B-cell depleting agents such as rituximab or belimumab within one year 
of 1st dose of study drug and have not yet normalized the B-cell count 
• 
they have a planned immunization with a live or live attenuated vaccine within 
3 months prior to administration of the 1st dose of study drug and for 3 months after the last 
dose of study drug is administered 
 
More information is provided in section 4.2 and Appendix B. 
 
At each study center visit after the screening visit, the investigator will ask the patient whether 
any medications (other than study drug), including over-the-counter (OTC) medications, were 
taken since the previous visit (see Appendix B). 
 
5.3 
Procedures for Monitoring Patient Compliance 
 
Each investigator will be responsible for monitoring patient compliance. Patients can be 
withdrawn from the study at any time if the investigator or the sponsor determines that the patient 
is not in compliance with the study protocol. 
 
6 
ASSESSMENT OF EFFICACY 


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6.1 
Primary Efficacy Variable 
 
The primary efficacy variable for this study is the proportion of patients achieving a combined 
clinical response using the SRI at week 52. An SRI response is defined as a reduction from 
baseline in the SLEDAI-2K score of at least 4 points, no worsening in PhGA (with worsening 
defined as an increase in PhGA of more than 0.30 point from baseline), no new BILAG A body 
system score, and no more than 1 new BILAG B body system score from baseline. The 
combined clinical response is intended to demonstrate an improvement in overall disease activity 
without worsening of disease in any organ system as determined by the investigator’s 
quantitative and qualitative assessments. 
 
The SLEDAI-2K is a validated objective measure that assesses disease activity within the last 28 
days before completion of the index. It is a global index and includes 24 weighted clinical and 
laboratory variables. The total score (sum of all 24 scores) ranges from 0 to 105. A SLEDAI-2K 
score of 6 to 10 is indicative of moderate disease activity, and improvement is defined as a 
reduction of greater than 3 points (Appendix C). The SLEDAI-2K was chosen because it is an 
accepted scale for assessing disease activity, has been shown to be reliable and sensitive to 
change, and is easy for clinicians to use. The SLEDAI-2K should be administered at each visit 
throughout the study by the same physician assessor trained and qualified to use this scale. 
 
The PhGA will be completed by the physician using a 3-inch visual analog scale (VAS) labeled 
from 0=none to 3=severe (Appendix C). This scale was chosen because it measures a domain of 
disease activity that may not be fully assessed in the other measures of disease activity. A 
change of greater than 0.3 point on the VAS indicates worsening. The PhGA should be 
administered at each visit throughout the study by the same physician assessor trained and 
qualified to use this scale. 
 
The BILAG-2004 is a validated objective and subjective global measure of the disease activity 
of SLE based upon the physician intention to treat and refers to disease activity within the last 
month prior to completion of the index. It includes 97 clinical and laboratory items to evaluate 
SLE disease activity in 9 organ systems; each organ system is assigned a score displayed as a 
grade from A to E, as follows: A=very active disease; B=patient needs increase in treatment for 
moderately active disease; C=stable or mild disease; D=previous organ involvement but no 
current disease activity; and E=no current disease activity and the organ system has never been 
involved (Appendix D). The BILAG-2004 was chosen because it is a reliable scale for 
evaluating SLE disease activity on the basis of the physician’s intent to treat. The individual 
body system scores are evaluations of disease activity in individual organ systems that may be 
improving, worsening, or stable, and they provide information that is comparable and  
complementary to the SLEDAI-2K score. The BILAG-2004 should be administered at each visit 
throughout the study by the same physician assessor trained and qualified to use this scale. 
 
6.2 
Secondary Efficacy Variables 
 
The secondary efficacy variables and endpoints for this study are as follows: 
 
• 
proportion of patients achieving an SRI response at each visit during the treatment period 
• 
proportion of patients achieving a reduction of at least 4 points in the SLEDAI-2K total 


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score at each visit during the treatment period 
• 
proportion of patients achieving a clinical SLEDAI-2K response at each visit during the 
treatment period, where the clinical response is defined as a reduction of at least 4 points in 
the SLEDAI-2K clinical score 
• 
proportion of patients achieving a BILAG-2004 response at each visit during the treatment 
period (no new BILAG A body system score and no more than 1 new BILAG B body 
system score from baseline) 
• 
proportion of patients achieving a BILAG-2004 clinical response at each visit during the 
treatment period (an improvement in at least 1 category from a B score to a 
C or D score, with no worsening in any other category) 
• 
proportion of patients showing no worsening on a PhGA scale at each visit during the 
treatment period 
• 
proportion of patients achieving a reduction of 5 points in the SLEDAI-2K at each visit 
during the treatment period 
• 
proportion of patients achieving a reduction of 6 points in the SLEDAI-2K at each visit 
during the treatment period 
• 
proportion of patients achieving an SRI-5 response at each visit during the treatment period 
• 
proportion of patients achieving an SRI-6 response at each visit during the treatment period 
• 
proportion of patients showing an improvement in tender and swollen joint counts using the 
28-joint count examination for pain and tenderness at each visit during the treatment period 
• 
SFI at each visit during the treatment period 
— time to first mild to moderate flare 
— incidence of mild to moderate flare 
— time to severe flare (NOTE: A severe flare leads to early withdrawal) 
• 
changes in the SDI over time (assessed at screening and weeks 24 and 52 (or final 
assessment) 
• 
absolute and relative changes in the SF-36 at weeks 12, 24, 36, and 52 (or final assessment) 
• 
proportion of patients with changes in steroid dose over time throughout the study 
 
The exploratory efficacy variables and endpoints for this study are as follows: 
• 
changes in the biomarkers anti-dsDNA Ab, C3, and C4 at each visit during the treatment 
period 
• 
changes in the following biomarkers at weeks 4, 12, 24, 36, and 52 (or final assessment): 
— ANA 
— anti–U1-70K snRNP Ab 
— anti-Sm Ab 
— CRP 
— IgG, IgM, IgA and IgE 
• 
absolute and relative changes in the FACIT-Fatigue at weeks 12, 24, 36, and 52 (or final 
assessment) 


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• 
in vitro intracellular and secreted cytokine response 
 
These secondary and exploratory measures are generally accepted by the clinical and regulatory 
communities to assess the physical, serologic, and psychosocial aspects of SLE. The SLEDAI-
2K, BILAG-2004 (including body system scores), and PhGA are described in section 6.1. More 
information on the remaining measures is provided below (sections 6.2.1 through 6.2.7). 
 
6.2.1 
Medical Outcome Survey Short Form 36 
 
The SF-36 is a survey of patient health and evaluates vitality, physical functioning, bodily pain, 
general health perceptions, physical role functioning, emotional role functioning, social role 
functioning, and mental health (Appendix G). This survey was chosen because it monitors and 
compares the psychosocial aspects of disease burden that are not fully assessed by the global 
scores of SLE disease activity. 
 
6.2.2 
28-Joint Count Examination for Pain and Tenderness 
 
The 28-joint count examination for pain and tenderness was developed for use in the assessment 
of rheumatoid arthritis and has become a standard for use in both clinical practice and clinical 
studies. It has been thoroughly validated and employed reliably in clinical studies and other 
analyses (Appendix F). The 28-joint count examination for pain and tenderness was chosen 
because tender and swollen joints are a significant cause of morbidity in patients with SLE, and 
lupus arthritis will be quantitated and formally evaluated using this instrument as an exploratory 
endpoint. 
 
6.2.3 
Biomarkers 
 
Biomarkers in SLE are often used for diagnosis but do not always correlate with changes in 
disease activity. The following biomarkers will be evaluated to determine if a change in level 
correlates with a change in disease activity: anti-dsDNA Ab, anti–U1-70K snRNP Ab, ANA, 
anti-Sm Ab, and C3, C4, CRP, IgG, IgM, IgA and IgE. 
 
6.2.4 
Functional Assessment of Chronic Illness Therapy–Fatigue 
 
The FACIT-Fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its 
impact upon daily activities and function. The FACIT-Fatigue scale was chosen because it 
measures the fatigue component of health-related quality of life and is self-administered 
(Appendix G). 
 
6.2.5 
Safety of Estrogens in Lupus Erythematosus: National Assessment Flare Index 
 
The SFI divides flares into 2 categories: mild/moderate and severe (Appendix C). This index 
was chosen because it is a measure of the difference in disease activity over time. 
 
6.2.6 
Systemic Lupus International Collaborative Clinics/American College of 
Rheumatology Damage Index 
 


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The SDI assesses specific comorbidities associated with SLE. It consists of 39 items and covers 
12 organ systems (Appendix H). This index was chosen because it has been shown to be valid 
and reliable and is a measure that is distinct from disease activity. 
6.2.7 
Steroid Dose 
 
Because chronic treatment with glucocorticoids is associated with significant morbidity, such as 
bone loss, cataract formation, weight gain, and susceptibility to infection, the change in oral 
corticosteroid dose over the course of the study will be evaluated. The change in steroid dose 
will be evaluated to determine the proportion of patients taking a dose less than 7.5 mg of 
prednisone equivalent/day, a dose of 7.5 mg prednisone equivalent/day or more, and none per 
day. 
 
6.3 
Methods and Timing of Assessing, Recording, and Analyzing Efficacy Data 
 
Methods and timing of assessing efficacy data are discussed in section 3.11. Procedures for 
recording efficacy data are discussed in section 14.1, and methods of analyses are discussed in 
section 10. 
7 
ASSESSMENT OF SAFETY 
 
In this study, safety will be assessed by evaluating the following: reported adverse events clinical 
laboratory test results, vital signs measurements, 12-lead ECG findings, physical examination 
results (including physical examination symptom directed findings), concomitant medication 
usage, suicidality, and anaphylaxis. 
 
During the conduct of the study, an independent, external DSMB will oversee the safety of the 
patients enrolled in the study and monitor the occurrence of flare throughout the study to ensure 
the continuing safety of the study patients and study conduct issues. 
 
7.1 
Adverse Events 
 
7.1.1 
Definition of an Adverse Event 
 
An adverse event is any untoward medical occurrence in a patient that develops or worsens in 
severity during the conduct of a clinical study of a pharmaceutical product and does not 
necessarily have a causal relationship to the study drug. An adverse event can, therefore, be any 
unfavorable and unintended physical sign, symptom, or laboratory parameter that develops or 
worsens in severity during the course of the study, or significant worsening of the disease under 
study (or any concurrent disease), whether or not considered related to the study drug. 
 
Accordingly, an adverse event could include any of the following: 
 
• 
intercurrent illnesses 
• 
physical injuries 
• 
events possibly related to concomitant medication 
• 
significant worsening (change in nature, severity, or frequency) of the disease under study or 
other pre-existing conditions. (NOTE: A condition, recorded as pre-existing, that is 
intermittently symptomatic [eg, headache] and which occurs during the study should be 


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recorded as an adverse event.) 
• 
drug interactions 
• 
events occurring during diagnostic procedures or any washout phase of the study 
• 
laboratory or diagnostic test abnormalities occurring after the start of the study (ie, after 
screening and once confirmed by repeat testing) that results in the withdrawal of the patient 
from the study, requires medical treatment or further diagnostic work-up, or is considered by 
the study investigator to be clinically significant. 
NOTE: Abnormal laboratory test results at the screening visit that preclude a patient from 
entering the study or receiving study treatment are not considered adverse events, but will be 
recorded to monitor data from patients who do not meet screening criteria. 
 
7.1.2 
Recording and Reporting Adverse Events 
 
For the purpose of adverse event recording, the study period is defined as that time period from 
signature of the informed consent form through the end of the final assessment. All adverse 
events that occur during the study period must be recorded on the CRF, regardless of the severity 
of the event or judged relationship to the study drug. For serious adverse events, the Serious 
Adverse Event Transmittal Form must also be completed and the serious adverse event reported 
immediately (see section 7.1.5). Any reported serious adverse event that occurs after the study 
follow-up period (regardless of time after study participation) will be assessed for its relationship 
to the study drug or to the patient’s participation in the study. If a serious adverse event occurs 
after the study follow-up period and is considered related to the study drug or a study procedure 
by the investigator, it must be recorded on the Serious Adverse Event Transmittal Form and 
reported immediately. 
 
At each contact with the patient, the investigator must query the patient for adverse events by 
asking an open-ended question such as, “Have you had any unusual symptoms or medical 
problems since the last visit? If yes, please describe.” All reported or observed signs and 
symptoms will be recorded individually, except when considered manifestations of a medical 
condition or disease state. A precise diagnosis will be recorded whenever possible. When such a 
diagnosis is made, all related signs, symptoms, and any test findings will be recorded 
collectively as a single diagnosis on the Serious Adverse Event Transmittal Form and on the 
CRF. 
 
The clinical course of each adverse event will be monitored at suitable intervals until resolved or 
stabilized, until the patient is referred to the care of a local health care professional, or until a 
determination of a cause unrelated to the study drug or study procedure is made. 
 
The onset and end dates, duration, action taken regarding study drug, treatment administered, 
and outcome for each adverse event must be recorded on the CRF. The relationship of each 
adverse event to study drug treatment and study procedures, and the severity and seriousness of 
each adverse event, as judged by the investigator, must be recorded as described below. 
 
7.1.3 
Severity of an Adverse Event 
 
The severity of each adverse event will be graded according to the Modified WHO Toxicity 
Criteria, which is a toxicity scale with events from grades 0 to 4 (Appendix A). 


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Adverse events that are not included in the modified WHO Toxicity Scale will be graded 
according to a similar 4-point scale (grade 1=mild, 2=moderate, 3=severe, and 4=life-threatening) 
using the following definitions: 
 
Mild 
The patient is aware of the event or symptom, but the event or symptom is easily 
tolerated. 
Moderate 
The patient experiences sufficient discomfort to interfere with or reduce his or her 
usual level of activity. 
Severe 
Significant impairment of functioning: the patient is unable to carry out usual 
activities. 
Life-threatening 
The patient’s life is at risk from the event. 
 
7.1.4 
Relationship of an Adverse Event to the Study Drug 
 
For each adverse event, the relationship to the study drug must be recorded as either related 
(there is a reasonable possibility of a causal relationship between the event and the study drug) or 
not related (there is not a reasonable causal relationship between the event and the study drug). 
In general, a causal relationship will be assigned when facts, evidence, or arguments exist to 
support the causal relationship. 
 
When assessing a relationship between study drug and an adverse event, the following 
parameters are to be considered: 
 
• 
The causal relationship is reasonable on the basis of clinical judgment and given the 
currently available data. 
• 
A temporal relationship exists between treatment with the study drug or protocol-specified 
procedures and the adverse event. 
• 
A biologic plausibility of relationship is present. 
• 
Any underlying concurrent illness and/or therapies the patient has received are considered. 
• 
The event abates on discontinuation of treatment with the study drug (dechallenge), if 
applicable. 
• 
The event reappears on repeat exposure to treatment with the study drug (rechallenge), if 
applicable. 
 
7.1.5 
Serious Adverse Events 
 
7.1.5.1 Definition of a Serious Adverse Event 
A serious adverse event is an adverse event occurring at any dose that results in any of the 
following outcomes or actions: 
 
• 
death 
• 
a life-threatening adverse event (ie, the patient was at immediate risk of death from the event 
as it occurred); does not include an event that, had it occurred in a more severe form, might 
have caused death 
• 
inpatient hospitalization or prolongation of existing hospitalization  
• 
a persistent or significant disability/incapacity (refers to a substantial disruption of one’s 


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ability to conduct normal life functions) 
• 
a congenital anomaly/birth defect 
• 
an important medical event that may not result in death, be life-threatening, or require 
hospitalization, but may jeopardize the patient and may require medical intervention to 
prevent 1 of the outcomes listed in this definition 
NOTE: Any suspected transmission of an infectious agent via a medicinal product is 
considered an important medical event. 
Hospitalizations scheduled for an elective procedure or for treatment of a pre-existing condition 
that has not worsened during participation in the study will not be considered serious adverse 
events. 
 
An adverse event that does not meet any of the criteria for seriousness listed above will be 
regarded as a nonserious adverse event. 
 
7.1.5.2 Reporting a Serious Adverse Event 
All serious adverse events (as described in section 7.1.5.1) that occur either during the study 
period (including the protocol-defined follow-up period), regardless of judged relationship to the 
study drug, or after the study period, if considered related to study drug or to the patient’s 
participation in the study, must be immediately reported to ORION Pharmacovigilance . The 
report must be made within 24 hours of the investigator’s knowledge of the event. In addition, a 
blood sample will be obtained for measurement of the concentration of IPP-201101 from all 
patients who have a serious adverse event recorded as related to study drug (see also section 7.1.6). 
 
 
Within 24 hours of the investigator’s awareness of the serious adverse event, the investigator 
must provide ORION Pharmacovigilance, by facsimile, with a signed Serious Adverse Event 
Transmittal Form completed to the greatest extent possible and a copy of all relevant source 
documents, including the corresponding completed adverse event, medical history, and 
concomitant medications pages of the CRF as appropriate. (For adverse event reporting 
instructions see section 7.1.2.). 
 
If it is not possible to complete all sections of the SAE form within 24 hours, transmission of the 
form must not be delayed and the outstanding information should be sent on a follow-up SAE 
form. 
If the SAE is reported by telephone, all points on the SAE form should be covered in the initial 
telephone report and followed by a completed and signed SAE form to confirm the verbal 
information previously reported.  
Information on SAEs will be recorded on a specific Non Carbon Repeat (NCR) SAE form. Blank 
copies are included in the study Investigator’s File. 
The SAE form must be completed as fully as possible with information relevant to the SAE(s) 
being reported. All fields should be populated or marked accordingly if no information is 
available. 
In cases of death reported as an SAE, the report should detail the main and contributory causes of 
death. This information should also be accompanied by a death certificate or autopsy report, if 


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available. 
For all SAEs where important or relevant information is missing, active follow-up should be 
undertaken. Investigators or other site personnel should inform the ORION Clinical Services’ 
Pharmacovigilance Department of any follow-up information on a previously reported SAE. 
The follow-up information must be presented on an SAE form marked as follow-up. It is 
necessary only to provide the new information, with the SAE form signed by an Investigator. 
Investigators or other site personnel should send relevant or requested supporting 
documentation (e.g., ECG, laboratory results, autopsy report) to the Pharmacovigilance 
Department of ORION Clinical Services. 
The Investigator will ensure that all the necessary information is provided within the timelines 
stipulated by the ORION Clinical Services’ Pharmacovigilance Department when the request 
for information is made. 
Follow-up reports should be completed and faxed following the same procedure as for the 
initial report. 
 
 
In the US and European Union (EU), the facsimile to the sponsor is to be addressed as follows: 
 
Study Contact for Reporting Serious Adverse Events. 
ORION Clinical Services Ltd 
pharmacovigilance@orioncro.com 
EU SAE Fax: +44 (0)1753 695 101 
Back-up EU SAE Fax: +44 (0)1753 695 124 
US SAE Fax: +00 1 609 514 1000  
Back-up US SAE Fax: +00 1 609 452 7888  
 
 
In the US, the investigator must ensure that the IRB is also informed of the event in accordance 
with local regulations. 
 
In the EU, ImmuPharma or its designee must ensure that the IEC is also informed of the event in 
accordance with local regulations. 
 
Each report of a serious adverse event will be reviewed and evaluated to assess the nature of the 
event and the relationship of the event to the study drug, study procedures, and to underlying 
disease. This will be done by the investigator and ImmuPharma or its designee. On the basis of 
this assessment, a decision will be made concerning the need for further medical intervention. If 
a serious, unexpected adverse event is believed to be related to the study drug or study 
procedures, ImmuPharma or its designee will take appropriate steps to notify all investigators 
participating in clinical studies of IPP-201101 conducted under ImmuPharma IND applications 
and the appropriate regulatory authorities. 
 
In addition to notifying the investigators and regulatory authorities, other measures may be 
required, including the following: 
 
• 
alteration of existing research by modification of the protocol 


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• 
discontinuation or suspension of the study 
• 
alteration of the process of informed consent by modification of the existing consent form 
and informing current study participants of new findings  
• 
modification of listings of expected toxicities to include adverse events newly identified as 
related to IPP-201101 
 
7.1.6 
Withdrawal Due to an Adverse Event 
 
Any patient who experiences an adverse event may be withdrawn from the study at any time at 
the discretion of the investigator. If a patient is withdrawn wholly or in part because of an 
adverse event, both the adverse events page and termination page of the CRF will be completed 
at that time. In addition, a blood sample will be obtained for measurement of the concentration 
of IPP-201101 from all patients who have an adverse event assessed as related to study drug 
leading to withdrawal from the study (see also section 7.1.5.2). The patient will be monitored 
until the event has resolved or stabilized, until a determination of a cause unrelated to the study 
drug or study procedure is made, or until the patient is referred to the care of a local health care 
professional. The investigator must inform the medical monitor as soon as possible of all 
patients who are being considered for withdrawal due to adverse events. Additional reports must 
be provided when requested. 
 
If a patient is withdrawn from the study for multiple reasons that include adverse events, the 
termination page of the CRF should indicate that the withdrawal was related to an adverse event. 
 
Stopping rules and discontinuation criteria for any toxicity are described in section 3.6. 
 
7.1.7 
Withdrawal From the Study Due to Severe Flares 
 
A patient will be withdrawn from the study for a severe lupus flare as per the SFI as described in 
section 3.6. 
 
7.1.8 
Medical Emergencies 
 
Medical emergencies must be reported to the individual identified in the clinical study personnel 
contact information section of this protocol. 
 
Equipment, supplies, and properly skilled medical personnel must be accessible for an adverse 
event requiring immediate treatment. Any dose of study drug (whether the investigational 
product, reference therapy, or a placebo), whether taken intentionally or unintentionally, in 
excess of that prescribed must be immediately reported to ImmuPharma or its designee . When 
the identification of the study drug must be known, the investigator must follow the procedures 
outlined in section 3.8. 
 
7.1.9 
Protocol Deviations Because of an Adverse Event 
 
If a patient experiences an adverse event or medical emergency, departures from the protocol 
may be allowed on a case-by-case basis. After stabilization and/or treatment for the emergency 
to protect patient safety has been administered, the investigator or other physician in attendance 
in such an emergency must contact the individual identified in   the clinical study personnel 


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contact information section of this protocol, as soon as possible to discuss the circumstances of 
the emergency. The investigator, in consultation with ImmuPharma or its designee, will decide 
whether the patient should continue to participate in the study. Any protocol deviation related to 
adverse events must be noted on the CRF and in source documents along with the reason for 
such deviations. 
 
7.2 
Clinical Laboratory Tests 
 
All clinical laboratory test results outside of the reference range will be interpreted by the 
investigator using the following categories: 
 
• 
abnormal but not a clinically significant worsening 
• 
abnormal and a clinically significant worsening 
 
A laboratory test result that has significantly worsened (according to medical judgment) 
compared with the baseline result will be recorded on the CRF as an adverse event and 
monitored as described in section 7.1.2. An adverse event includes a laboratory or diagnostic 
test abnormality (once confirmed by repeat testing) that results in the withdrawal of the patient 
from the study, the temporary or permanent cessation of treatment with study drug, or requires 
medical treatment or further diagnostic work-up. 
 
Clinical laboratory tests (serum chemistry, hematology, and urinalysis) will be performed at 
screening (visit 1), baseline/start of study drug treatment (visit 2), visits 4 through 15, and at the 
final assessment (or early termination). Clinical laboratory tests will be performed using the 
central laboratory identified in the front matter of this protocol (and in the Laboratory Procedures 
Manual provided in the study file documents). Specific laboratory tests to be performed are 
listed below. 
 
7.2.1 
Serum Chemistry 
 
The following serum chemistry tests will be performed: 
 
• 
calcium 
• 
phosphate 
• 
sodium 
• 
potassium 
• 
chloride 
• 
bicarbonate or carbon dioxide 
• 
glucose 
• 
blood urea nitrogen (BUN) 
• 
creatinine 
• 
cholesterol 
• 
uric acid 
• 
ALT 
• 
AST 
• 
lactate dehydrogenase (LDH) 


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• 
gamma-glutamyl transpeptidase (GGT) 
• 
alkaline phosphatase  
• 
creatine phosphokinase 
• 
total protein 
• 
albumin 
• 
total bilirubin 
• 
direct bilirubin 
 
7.2.2 
Hematology 
 
The following hematology tests will be performed: 
 
• 
hemoglobin 
• 
hematocrit 
• 
platelet count 
• 
absolute neutrophil count (ANC) 
• 
white blood cell (WBC) count and differential count 
— polymorphonuclear leukocytes (neutrophils) 
— lymphocytes 
— eosinophils 
— monocytes 
— basophils 
— metamyelocytes 
 
7.2.3 
Urinalysis 
 
Urinalysis will include testing for the following: 
 
• 
protein 
• 
glucose 
• 
ketones 
• 
blood (hemoglobin) 
• 
pH 
• 
specific gravity 
• 
spot protein-creatinine ratio 
• 
creatinine Clearance 
• 
eGRF 
• 
microscopic 
— bacteria 
— red blood cells (RBCs) 
— WBCs 


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— Casts 
— crystals 
 
7.2.4 
Other Clinical Laboratory Tests 
 
(a) 
Serology Tests 
 
Serology tests to be performed at screening will consist of anti-dsDNA, ANA, C3, and C4. 
Serology tests to be performed at each subsequent visit (visit 2 [week 0; baseline/start of study 
drug treatment] through visit 16 [week 52], excluding visit 3  [week 2]) will consist of anti-
dsDNA Ab, C3, and C4. In addition, the following serology tests will be performed at visit 2 
(week 0; baseline/start of study drug treatment), visit 4 (week 4), visit 6 (week 12), visit 9 (week 
24), visit 12 (week 36), and the final assessment (or early termination) (visit 16 [week 52]): anti–
U1-70K snRNP Ab, ANA, anti-Sm Ab, and CRP, IgG, IgM, IgA and IgE. 
 
(b) 
Hemolysis Testing 
 
A Coombs’ test will be obtained at screening. At subsequent visits, if hemolysis is suspected or 
confirmed, Coombs’ test, haptoglobin, and a peripheral smear will be obtained. 
 
(c) 
Other Tests 
 
Other clinical laboratory tests will be performed to ensure the safety of the patients, but will not 
be an assessment of the safety of the study drug. 
At screening (visit 1), patients will have serology A tests for HBsAg and HCV Ab. A urine 
pregnancy test will be performed for all women, regardless of childbearing potential, at 
screening (visit 1), baseline (visit 2 [week 0]), visits 4 through 15 (weeks 4 through 48), and the 
final assessment (or early termination) (visit 16 [week 52]). Any patient becoming pregnant 
during the study will be withdrawn. All pregnancies that occur during the study, or within 14 
days of completion of the study, are to be reported immediately to the individual identified in the 
clinical study personnel contact information section of this protocol, and the investigator must 
provide ImmuPharma or its designee, by facsimile, with a signed pregnancy tracking form. The 
facsimile to the sponsor is to be addressed as follows: to be determined. All patients who become 
pregnant will be monitored to the completion or termination of the pregnancy. If the pregnancy 
continues to term, the outcome (health of the infant up to 8 weeks of age) will be reported to the 
sponsor. Any complication of pregnancy will be reported as an adverse event or serious adverse 
event, as appropriate. 
 
7.3 
Vital Signs 
 
Vital signs will be measured at all study visits. Vital signs include the following: 
 
• 
pulse 
• 
seated blood pressure (systolic and diastolic) 
• 
temperature 
 
Before pulse and blood pressure are measured, the patient must be in a seated position and 
resting for at least 5 minutes. (The same position and arm should be used each time vital signs 


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are measured for a given patient.) Any vital sign value that is judged by the investigator as a 
clinically significant change (worsening) compared to a baseline value will be considered an 
adverse event, recorded on the CRF, and monitored as described in section 7.1.2. 
 
7.4 
Electrocardiography 
 
A 12-lead ECG will be conducted at screening (visit 1) and at the final assessment (or early 
termination). A qualified physician will be responsible for providing interpretation of the ECG. 
Any ECG finding that is judged by the investigator as a clinically significant change (worsening) 
compared to a baseline value will be considered an adverse event, recorded on the CRF, and 
monitored as described in section 7.1.2. 
 
7.5 
Physical Examinations 
 
Physical examinations (including height to be obtained at the screening visit only) will be 
performed at screening (visit 1) and at the final assessment (or early termination). Symptom 
directed physical examination evaluations and the 28-joint count examination for pain and 
tenderness will be performed at baseline/start of study drug treatment (visit 2) and visits 4 
through 16. Body weight will be recorded during all physical examinations. Physical 
examination findings will be classified using standard categories as listed on the CRFs. Any 
physical examination finding that is judged by the investigator as a clinically significant change 
(worsening) compared to a baseline value will be considered an adverse event, recorded on the 
CRF, and monitored as described in section 7.1.2. 
 
7.6 
Other Safety Measures and Variables 
 
7.6.1 
Concomitant Therapy or Medication 
 
Concomitant therapy or medication usage will be monitored throughout the study. Details of 
prohibited medications may be found in section 5.2. 
 
7.6.2 
Columbia-Suicide Severity Rating Scale 
 
An evaluation for suicidality will be administered directly to the patient using IRT. (ERT), at 
baseline and at each visit during the treatment period using the Columbia-Suicide Severity 
Rating Scale (C-SSRS). The C-SSRS assesses suicidality from ideation to behaviors and 
monitors the potential emergence of suicidality in clinical studies. The C-SSRS Baseline version 
will be performed at baseline (visit 2) and the C-SSRS since Last Visit version will be performed 
at visits 4 through 16 (or final assessment visit). 
 
If the C-SSRS is positive at any visit during the treatment period, the patient will be evaluated by 
the investigator to determine if a formal evaluation by a trained mental health professional is 
indicated. If the patient is determined to be a risk to himself or herself or others, the sponsor will 
be notified and the patient will be withdrawn from the study. 
 
7.6.3 
Anaphylaxis Evaluation 
 


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Anaphylaxis is defined as a serious allergic reaction that is rapid in onset and may cause death 
(Sampson et al 2006). Any patient who experiences an adverse event that presents with signs 
and/or symptoms that are suggestive of an anaphylactic, anaphylactoid, or drug hypersensitivity 
reaction will be evaluated using the Clinical Criteria for Diagnosing Anaphylaxis. The clinical 
criteria to be applied for diagnosing anaphylaxis are in Appendix I. 
 
7.7 
Methods and Timing of Assessing, Recording, and Analyzing Safety Data 
 
Methods and timing of assessing safety data are discussed in section 3.11. Procedures for 
recording safety data are discussed in section 13.1, and methods of analyses are discussed in 
section 9.7. 
Furthermore, all adverse events will be reviewed on a periodic basis (eg, scheduled safety 
reviews for study drug) as interim/preliminary safety databases become available (see section 7). 
An independent, external DSMB will oversee the safety of the patients enrolled in the study and 
monitor the occurrence of flare throughout the study (see section 3.6). This study may be 
prematurely terminated if, in the opinion of the DSMB or the sponsor, there is sufficient and 
reasonable cause. Written notification documenting the reason for study termination will be 
provided by the terminating party to all involved. 
 
 
8 
ASSESSMENT OF PHARMACOKINETICS AND IMMUNOGENICITY 
 
8.1 
Pharmacokinetic Assessment 
 
8.1.1 
Pharmacokinetic Blood Sampling 
 
Blood samples (5 mL) for pharmacokinetics will be collected from patients at selected North 
American and Western European study centers via venipuncture or indwelling catheter prior to 
and 5 minutes and 1, 2, and 24 hours after study drug administration at weeks 0, 16, and 32 
(visits 2, 7, and 11, respectively). A blood sample for measurement of the concentration of IPP-
201101 will also be obtained from all patients who have a serious adverse event and/or have an 
adverse event leading to withdrawal from the study. The actual dates and times of study drug 
administration and the date and time of sampling will be recorded on the CRF. 
 
8.1.2 
Processing, Handling, and Shipping of Samples for Pharmacokinetic Analysis 
 
Instructions for processing, handling, and shipping blood samples for pharmacokinetic analysis 
will be provided to the study centers in the laboratory manual provided by ImmuPharma or its 
designee.. 
 
8.2 
Immunogenicity 
 
Anti–IPP-201101 Ab testing will be performed at visit 2 (week 0; baseline/start of study drug 
treatment), visit 3 (week 2), visit 4 (week 4), visit 6 (week 12), visit 8 (week 20), visit 10 (week 
28), visit 12 (week 36), visit 14 (week 44), and the final assessment (or early termination) (visit 
16 [week 52]). All samples will be collected prior to administration of study drug at that 
particular visit. 


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Any patient with a positive test result in the confirmatory assay at the final study visit will be 
followed with additional immunogenicity testing at 8-week intervals until the level returns to 
baseline value or the levels are judged by the investigator to be chronic, or the patient is lost to 
follow-up. 
 
8.3 
Methods and Timing of Pharmacokinetic Blood Sampling and Immunogenicity 
 
Methods and timing of blood sampling for plasma concentrations of IPP-201101 and presence of 
anti–IPP-201101 Ab are discussed in section 3.11. Procedures for recording blood sampling for 
plasma concentrations and detection of anti–IPP-201101 Ab are discussed in section 13.1. 
Methods for analyses of blood samples for concentrations of IPP-201101 and of anti–IPP-
201101 Ab (as noted above in section 8.2) are discussed in section 10.8. 
 
9 
ASSESSMENT OF 
IN 
VITRO 
INTRACELLULAR 
AND 
SECRETED 
CYTOKINE RESPONSE 
 
9.1 
Blood Sampling for in vitro intracellular and secreted cytokine response 
 
Blood samples (5 mL) for in vitro intracellular and secreted cytokine response will be collected 
from patients at selected study centers via venipuncture or indwelling catheter prior study drug 
administration at weeks 0, 4, 24, and 48 (visits 2, 4, 9 and 15, respectively). The actual dates and 
times of study drug administration and the date and time of sampling will be recorded on the 
CRF. 
 
9.2 
Processing, Handling, and Shipping of Samples for in vitro intracellular and 
secreted cytokine response 
 
Instructions for processing, handling, and shipping blood samples for in vitro intracellular 
analysis will be provided to the study centers in the laboratory manual provided by ImmuPharma 
or its designee. 
 
9.3 
Methods and Timing of in vitro proliferation and secreted cytokine response  
 
Methods and timing of blood sampling for in vitro intracellular and secreted cytokine response 
of IPP-201101 are discussed in section 3.11. Procedures for recording blood sampling are 
discussed in section 13.1. Methods for analyses of blood samples for in vitro proliferation and 
secreted cytokine response of IPP-201101 are discussed in section 10.9. 
 
10 
STATISTICS 
 
10.1 
Study Design and Randomization 
 
This is a Phase 3 randomized, double-blind, parallel-group, placebo-controlled study. Treatment 
assignment will be stratified for the following 3 baseline characteristics (as described in section 
3.3): by region, SLEDAI-2K screening total score (6 to 9 or ≥10), and racial-ethnic group 
classification (black/Hispanic or others). Within each stratum, eligible patients will be randomly 


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assigned with a 1:1 ratio to receive either 200 mcg of IPP-201101 or placebo sc every 4 weeks 
for 48 weeks. Study investigators, patients, and ImmuPharma study staff will be blinded to the 
treatment assignments during the study. 
 
10.2 
Sample Size and Power Considerations 
 
This study is designed to estimate and assess the significance of the difference between a 200-
mcg dose of IPP-201101 and placebo in the proportion of SRI responders at week 52. With 100 
evaluable patients per group (200 in total), this study will have 90% or greater power to detect a 
25% or greater difference in the proportion of SRI responders between the IPP-201101 group 
and the placebo group or to detect a 20% difference with an 80%power. This projection using 
the Pearson 
Chi-square test (2-sided, alpha=0.05) is based on an anticipated placebo effect at week 52 of 
40% to 45%. This range covers the placebo effect reported in the literature (Navarra et al 2009, 
van Vollenhoven et al 2010, Wallace et al 2009) and in a Phase 2b, multicenter, randomized, 
double-blind, placebo-controlled dose-ranging study of IPP-201101 (study IP-004). The 
difference between placebo and active which is used in the sample size calculation is 25% based 
on the results of the Phase IIb study (IP-004) with the same formulation (Zimmer et al. ACR 
2012) 
 
10.3 
Analysis Sets 
 
The set of randomized patients will include all patients randomly assigned to a treatment at 
enrollment, regardless of whether or not a patient took any study drug. 
 
The safety analysis set will include all patients who took at least 1 dose of study drug. The full 
analysis set will include all patients in the safety analysis set. 
 
10.4 
Data Handling Conventions 
 
All available data will be included for evaluation. For the purpose of efficacy analysis, missing 
or invalid values will be imputed using data from the previous visit for individual items and 
scores in the questionnaires and scales. For a derived score involving multiple items, the 
missing or invalid individual items will be imputed first before calculating the derived scores 
based on the complete individual item values. These rules apply only to the visits in which the 
patient is currently in the study and some data or an individual item is missing. If an assessment 
is not done at a visit, the missing data will not be imputed. The justification for using data from 
the previous visit is based on medical judgment. For the SF-36 questionnaire, the Half-Scale 
Missing Data Estimation (Half-Scale MDE) (Ware et al 2007) method will be used to estimate 
the missing values for calculating the 8 health domain scales. 
 
Missing or invalid laboratory test results will not be estimated for biomarker analysis or safety 
analysis. 
 
10.5 
Study Population 
 
The set of randomized patients (see section 10.3) will be used for all study population summaries 
unless otherwise noted. Summaries will be presented by treatment group and for all patients. 


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10.5.1 Patient Disposition 
 
Data from patients screened, patients screened but not randomized, patients randomized in the 
study, patients randomized but not treated, patients in the safety analysis set, patients in the full 
analysis set, patients who complete the study, and patients who withdraw from the study by 
reason for discontinuation will be summarized using descriptive statistics. 
 
10.5.2 Demographic and Baseline Characteristics 
 
Patient demographic and baseline characteristics, including medical history, prior medications, 
and physical examination and 12-lead ECG findings, will be summarized by treatment group and 
stratification factors and overall. For continuous variables, the descriptive summary statistics 
will include number (n), mean, standard deviation (SD), standard error (SE), median, minimum, 
and maximum. For categorical variables, patient counts and percentages will be provided. 
Categories for missing data will be presented if necessary. 
 
10.6 
Efficacy Analysis 
 
Efficacy evaluation will be based on the full analysis set (see section 10.3) that includes all 
patients who received at least 1 dose of the study drug. 
 
10.6.1 Primary Variable 
 
The primary efficacy variable is the proportion of patients achieving a combined clinical 
response using the SRI assessed at week 52. An SRI response is defined as a reduction from 
baseline in the SLEDAI-2K score of at least 4 points, no worsening in PhGA (with worsening 
defined as an increase in PhGA of more than 0.30 point from baseline), no new BILAG A body 
system score, and no more than 1 new BILAG B body system score from baseline. 
 
10.6.2 Secondary Variables 
 
Secondary efficacy variables and endpoints are as follows: 
 
• 
proportion of patients achieving an SRI response at each visit during the treatment period 
• 
proportion of patients achieving a reduction of at least 4 points in the SLEDAI-2K total 
score at each visit during the treatment period 
• 
proportion of patients achieving a clinical SLEDAI-2K response at each visit during the 
treatment period, where the clinical response is defined as a reduction of at least 4 points in 
the SLEDAI-2K clinical score 
• 
proportion of patients achieving a BILAG-2004 response at each visit during the treatment 
period (no new BILAG A body system score and no more than 1 new BILAG B body 
system score from baseline) 
• 
proportion of patients achieving a BILAG-2004 clinical response at each visit during the 
treatment period (an improvement in at least 1 category from a B score to a 


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C or D score, with no worsening in any other category) 
• 
proportion of patients showing no worsening on a PhGA scale at each visit during the 
treatment period 
• 
proportion of patients achieving a reduction of 5 points in the SLEDAI-2K total score at 
each visit during the treatment period 
• 
proportion of patients achieving a reduction of 6 points in the SLEDAI-2K total score at 
each visit during the treatment period 
• 
proportion of patients achieving an SRI-5 response at each visit during the treatment period 
• 
proportion of patients achieving an SRI-6 response at each visit during the treatment period 
• 
proportion of patients showing an improvement in tender and swollen joint counts using the 
28-joint count examination for pain and tenderness at each visit during the treatment period 
• 
SFI at each visit during the treatment period 
— time to first mild to moderate flare 
— incidence of mild to moderate flare 
— time to severe flare (NOTE: A severe flare leads to early withdrawal) 
• 
changes in the SDI over time (assessed at screening and weeks 24 and 52 [or final 
assessment]) 
• 
absolute and relative changes in the SF-36 at weeks 12, 24, 36, and 52 (or final assessment) 
proportion of patients with changes in steroid dose over time throughout the study.  
The exploratory efficacy variables and endpoints for this study are as follows: 
 
• 
changes in the biomarkers anti-dsDNA Ab, C3, and C4 at each visit during the treatment 
period 
• 
changes in the following biomarkers at weeks 4, 12, 24, 36, and 52 (or final assessment): 
— ANA 
— anti–U1-70K snRNP Ab 
— anti-Sm Ab 
— CRP 
— IgG, IgM, IgA and IgE 
 
• 
absolute and relative changes in the FACIT-Fatigue at weeks 12, 24, 36, and 52 (or final 
assessment) 
• 
in vitro intracellular and secreted cytokine response 
 
10.6.3 Planned Method of Analysis 
 
10.6.3.1 Primary Efficacy Analysis 
 
The efficacy evaluation will be based on the full analysis set, which will include all patients who 
receive at least 1 dose of study drug. The statistical method to be used for the SRI is the logistic 
regression model with treatment and stratification factors as main factors. Patients who 
withdraw from the study are classified as nonresponders as measured by SRI at week 52 in the 
primary analysis. The SRI is linked to the model factors through the logit function. The 


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likelihood-ratio–based Chi-square statistics will be used for testing the treatment difference 
between IPP-201101 and placebo in SRI at week 52 at the significance level 0.05. The odds 
ratio (active/placebo) and associated 95% confidence interval will be determined from the 
logistic regression model. 
 
As sensitivity analyses, the primary analysis will be repeated using another 3 imputation 
methods to estimate missing SRI at week 52 according to the reason for withdrawal. In the 1st 
method, patients who withdraw because of lack of efficacy will be classified as treatment 
failures assessed by SRI at week 52. For patients who withdraw because of other reasons, their 
missing SRI at week 52 will be estimated using the multiple imputation method (Little and 
Rubin, 2002). The imputation values will be drawn from the categories formed by treatment 
group and randomization stratum to which the patient belongs. In the 2nd method, the missing 
SRI at week 52 will be imputed using the last observation carried forward (LOCF) method. In 
the 3rd method, patients who withdraw and those completers who used prohibited medication 
within 8 weeks from week 52 will be classified as nonresponders. 
 
10.6.3.2 Secondary Efficacy Analysis 
 
Secondary efficacy variables will be summarized using the descriptive statistics by treatment 
group and time point. Safety evaluations will include all patients who received at least 1 dose of 
study drug. Descriptive statistics will be used to summarize the safety variables. 
 
10.7 
Safety Variables and Analysis 
 
The safety analysis set (see section 9.3) will be used for all safety analyses. 
 
10.7.1 Study Drug Exposure 
 
Study drug exposure will be summarized by treatment group and stratification factors at baseline 
for all patients who received at least 1 dose of the study drug (safety analysis set) during the 
study. The exposure will be characterized by treatment duration and number of injections 
received. Treatment duration is the number of days from the 1st to the last dose. 
 
10.7.2 Safety Variables 
 
The overall safety and tolerability of IPP-201101 treatment will be assessed throughout the study 
by evaluating adverse events and the following additional safety variables: 
 
• 
clinical laboratory (serum chemistry, hematology, and urinalysis) test results at each visit 
during the treatment period 
• 
vital signs (systolic and diastolic blood pressures, pulse, temperature, and body weight) 
measurements at each visit during the treatment period 
• 
12-lead ECG findings at week 24 and the final assessment (or early termination) (week 52) 
• 
suicidality using the C-SSRS at each visit during the treatment period 
• 
adverse events that suggest an anaphylactic reaction to study drug during the treatment 
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• 
physical examination findings, including physical examination symptom directed findings, 
at selected time points throughout the study 
• 
concomitant medication usage throughout the study 
10.7.3 Safety Analysis 
 
For continuous variables, descriptive statistics (n, mean, SD, median, minimum, and maximum) 
will be provided for actual values and changes from baseline to each time point, including 
endpoint. For categorical variables, patient counts and percentages will be provided. 
Descriptive summaries of serious adverse events, patient withdrawals because of adverse events, 
and clinically significant abnormal values (clinical laboratory or vital signs values) on the basis 
of predefined criteria will also be provided. Summaries will be presented by treatment group 
and for all patients. 
 
All adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). A patient will be counted only once in each preferred term or system organ class 
category for the analyses of safety. Summaries will be presented for all adverse events (overall 
and by severity), adverse events determined by the investigator to be treatment related (overall 
and by severity), serious adverse events, and adverse events causing withdrawal from the study. 
Summaries will be presented by treatment group and for all patients. Patient listings of deaths, 
other serious adverse events, and adverse events leading to withdrawal will be presented. 
 
Changes in laboratory and vital signs measurement data will be summarized descriptively. All 
values will be compared to prespecified boundaries in order to identify clinically significant 
changes or values, and such values will be listed. 
 
Newly occurring physical examination abnormalities will be identified and listed. 
 
The use of concomitant medications will be summarized by therapeutic class using descriptive 
statistics. Concomitant medications will include all medications taken while the patient is treated 
with study drug. Concomitant medication usage will be summarized as present at screening, 
ongoing at baseline/start of study drug treatment 
(visit 2 [week 0]), and started any time after visit 2 (week 0) through visit 16 (week 52). 
 
Cumulative positive C-SSRS outcomes during the study will be summarized by treatment group. 
 
10.8 
Pharmacokinetic and Immunogenicity Analysis 
 
IPP-201101 plasma concentration data will be summarized by time point. Plasma concentration 
data may also be included in population pharmacokinetic analyses. 
 
An attempt may be made to establish an exposure-response relationship and/or to correlate 
systemic exposure with relevant safety parameters. In order to perform the exposure-response 
analysis successfully, it is extremely important that the actual collection times for 
pharmacokinetic blood samples be recorded accurately. 
 
The immunogenicity of IPP-201101 will be evaluated by determining any presence of anti–IPP-
201101 Ab at weeks 2, 4, 12, 20, 28, 36, and 44 and the final assessment (week 52 or early 
termination). Testing results will be listed and findings may be summarized as necessary. 


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10.9 
In vitro intracellular and secreted cytokine response 
 
In vitro intracellular and secreted cytokine response data will be summarized by time point.  
 
 
In vitro intracellular and secreted cytokine response of IPP-201101 will be evaluated to assess 
secreted cytokine profile and intracellular modification linked to the treatment at weeks 0, 4, 24 
and 48.Testing results will be listed and findings may be summarized as necessary. 
 
 
10.10 
Planned Interim Analysis 
 
There is no planned interim analysis. 
 
10.11 
Reporting Deviations From the Statistical Plan 
 
Deviations from the statistical plan, along with the reasons for the deviations, will be described 
in protocol amendments, the complete statistical plan, the clinical study report, or any 
combination of these, as appropriate. 
 
11 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
 
The medical experts, study monitors, auditors, and health authority inspectors (or their agents) 
will be given direct access to source data and documentation (eg, medical charts/records, 
laboratory test results, printouts, videotapes) for source data verification, provided that patient 
confidentiality is maintained in accordance with local requirements. 
 
Each investigator must maintain, at all times, the primary records (ie, source documents) of each 
patient’s data. Examples of source documents are hospital records, office visit records, 
examining physician’s finding or notes, consultant’s written opinion or notes, laboratory reports, 
drug inventory, study drug label records, and CRFs that are used as the source (see section 3.9). 
 
Each investigator will maintain a confidential patient identification list that allows the 
unambiguous identification of each patient. All study-related documents must be kept until 
notification by ImmuPharma. 
 
12 
QUALITY CONTROL AND QUALITY ASSURANCE 
 
12.1 
Protocol Amendments and Protocol Deviations and Violations 
 
12.1.1 Protocol Amendments 
 
No changes from the final approved (signed) protocol will be initiated without the prior written 
approval or favorable opinion of a written amendment by the IEC/IRB, except when necessary to 
eliminate immediate safety concerns to the patients or when the change involves only logistics or 
administration. Each principal investigator and the sponsor will sign the protocol amendment. 
 


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12.1.2 Protocol Deviations, Violations, and Exceptions 
 
A protocol deviation is nonadherence to protocol-specific study procedures or schedules that 
does not involve inclusion/exclusion criteria, primary objective variable criteria, and/or GCP 
guidelines. Deviations are considered minor and do not impact the study.  For example, failure 
to perform scheduled study center visits within the protocol-defined window would be 
considered a deviation. 
 
A protocol violation is any significant divergence from the protocol, ie, nonadherence on the 
part of the patient, the investigator, or the sponsor to protocol-specific inclusion/exclusion 
criteria, primary objective variable criteria, and/or GCP guidelines. Protocol violations will be 
identified and recorded, by study center personnel, on the CRF. 
 
As a matter of policy, ImmuPharma or its designee will not grant exceptions to protocol-specific 
entry criteria to allow patients to enter a study. If under extraordinary circumstances such action 
is considered ethically, medically, and scientifically justified for a particular patient, prior 
approval from ImmuPharma or its designee and the responsible IRB/IEC, in accordance with the 
Standard Operating Procedure (SOP), is required before the patient will be allowed to enter the 
study. If investigative center personnel learn that a patient who did not meet protocol eligibility 
criteria was entered in a study (a protocol violation), they must immediately inform 
ImmuPharma or its designee. Such patients will be discontinued from the study, except in a rare 
instance following review and written approval by ImmuPharma or its designee and the 
responsible IRB/IEC, according to the applicable SOP. 
 
12.2 
Information to Study Personnel 
 
Each investigator is responsible for giving information about the study to all staff members 
involved in the study or in any element of patient management, both before starting the practical 
performance of the study and during the course of the study (eg, when new staff become 
involved). Each investigator must assure that all study staff members are qualified by education, 
experience, and training to perform their specific responsibilities. These study staff members 
must be listed on the study center authorization form, which includes a clear description of each 
staff member’s responsibilities. This list must be updated throughout the study, as 
necessary..The study monitor is responsible for explaining the protocol to all study staff, 
including each investigator, and for ensuring their compliance with the protocol. Additional 
information will be made available during the study when new staff become involved in the 
study and as otherwise agreed upon with either the investigator or the study monitor. 
 
12.3 
Study Monitoring 
 
To ensure compliance with GCP, the study monitor or representative is responsible for ensuring 
that the study is conducted according to applicable SOPs, the protocol, and other written 
instructions and regulatory guidelines. 
 
The study monitor is the primary association between the sponsor and each investigator. The 
main responsibilities of the study monitors are to visit each investigator before, during, and after 
the study to ensure adherence to the protocol, that all data are correctly and completely recorded 


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and reported, and that informed consent is obtained and recorded for all patients before their 
participation in the study. 
 
The study monitors will contact each investigator and visit the study center at regular intervals 
throughout the study. The study monitor will be permitted to check and verify the various 
records (CRFs and other pertinent source data records, to include specific electronic source 
documentation [see section 3.9]) relating to the study to verify adherence to the protocol and to 
ensure the completeness, consistency, and accuracy of the data being recorded. If electronic case 
report forms (eCRFs) are used for the study, the study monitor will indicate verification by 
electronically applying source document verification (SDV) flags to the eCRF and will ensure 
that all required electronic signatures are being implemented accordingly. 
 
As part of the supervision of study progress, other sponsor personnel may, on request, 
accompany the study monitor on visits to the study center. Each investigator and assisting staff 
must agree to cooperate with the study monitor to resolve any problems, errors, or possible 
misunderstandings concerning the findings detected in the course of these monitoring visits. 
 
12.4 
Audit and Inspection 
 
The sponsor may audit the study center to evaluate study conduct and compliance with 
protocols, SOPs, GCPs, and applicable regulatory requirements. The ImmuPharma or its 
designee quality assurance unit, independent of the Clinical Research Department, is responsible 
for determining the need for (and timing of) a study center audit. 
 
Each investigator must accept that regulatory authorities and sponsor representatives may 
conduct inspections to verify compliance of the study with GCPs. 
 
12.5 
Data Quality Assurance 
 
The handling of data, including data quality assurance, will comply with regulatory guidelines 
(eg, ICH and GCP) and the sponsor’s SOPs and working instructions. Data management and 
control processes specific to this study will be described in a data management plan. All steps 
and actions taken regarding data management and quality assurance will be documented in a data 
handling report. When data management is outsourced, the contract organization will be 
responsible for the development and implementation of the data management plan and 
preparation of the data handling report according to the sponsor’s standards. Incoming 
completed CRFs will be logged into the CRF tracking system and will be reviewed for 
completeness, the presence of mandatory values, dated signatures, and consistency. All 
medication and adverse event terms recorded on the CRF will be automatically encoded in the 
sponsor’s database. All entries rejected by the system will be re-evaluated and corrected as 
appropriate according to the data on the CRF. 
 
All data on the CRF will be entered into a validated database using double data entry.  Edit 
checks will be implemented in the data entry panel to ensure data quality and accuracy. 
Responses to requests for further clarification of data recorded on the CRF will be answered, 
dated, and signed by the investigator. Changes will be implemented in the sponsor’s database 
and the data review and validation procedures will be repeated as needed. All medication and 


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adverse event information and textual comments will be proofread for consistency between the 
database and the CRF; the database will be corrected appropriately. In the case when data 
management is outsourced, the contract organization will be responsible for database quality 
assurance including, but not limited to, all medication and adverse event terms as described 
above. 
 
If eCRFs are used, data management at ImmuPharma or its designee will implement edit checks 
on the eCRF to enforce data entry guidelines, data consistency, and compliance to the protocol 
and regulatory requirements. Each study center coordinator will be responsible for entering 
study data on the eCRFs. Data management will track eCRFs and review them for 
completeness, the presence of mandatory values, consistency, and dated electronic signatures. In 
addition to checking for SDV flags, data management will electronically attach data clarification 
queries directly onto the eCRFs during the review process to ensure data quality. Once study 
center personnel have provided acceptable responses to the queries and implemented the changes 
on the eCRFs, data management will close the queries with the appropriate resolution status. 
 
At the end of the study, the database will be locked and the data will be released for reporting 
and statistical analysis. 
 
13 
ETHICS 
 
13.1 
Informed Consent 
 
Written informed consent will be obtained from each patient before any study-specific 
procedures or assessments are done and after the aims, methods, anticipated benefits, and 
potential hazards are explained. The patient’s willingness to participate in the study will be 
documented in writing in a consent form, which will be signed by the patient with the date of 
that signature indicated. Each investigator will keep the original consent forms, and copies will 
be given to the patients. It will also be explained to the patients that they are free to refuse entry 
into the study and free to withdraw from the study at any time without prejudice to future 
treatment. 
 
Written and/or oral information about the study in a language understandable by the patient will 
be given to all patients. 
 
A separate informed consent will also be obtained from each patient for permission to obtain 
DNA for pharmacogenetic analysis. Entry into the study is not dependent on this separate 
consent. 
 
13.2 
Health Authorities and Independent Ethics Committees/Institutional Review 
Boards 
 
Before this study starts, the protocol will be submitted to the national/local health authorities and 
to each IEC/IRB for review. As required, the study will not start at a given center before the 
IEC/IRB and health authority (where applicable) for each center give written approval or a 
favorable opinion. 
 


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13.3 
Confidentiality Regarding Study Patients 
 
Each investigator must assure that the privacy of the patients, including their personal identity 
and all personal medical information, will be maintained at all times. In CRFs and other 
documents or image material submitted to the sponsor, patients will be identified not by their 
names, but by an identification code (eg, initials and identification number). 
 
Personal medical information may be reviewed for the purpose of verifying data recorded on the 
CRF. This review may be conducted by the study monitor, properly authorized persons on 
behalf of the sponsor, the quality assurance unit, or regulatory authorities. Personal medical 
information will always be treated as confidential. 
 
14 
DATA HANDLING AND RECORD KEEPING 
 
14.1 
Completing and Signing Case Report Forms 
 
Each investigator must keep a separate patient identification list showing code numbers, names, 
and dates of birth to allow unambiguous identification of each patient included in the study. A 
note will be made in the medical records that the patient is participating in a clinical study. 
 
All required data will be recorded on the CRF by study center personnel according to the data 
entry guidelines provided by ImmuPharma or its designee. All CRFs must be kept in good order 
and updated so they always reflect the latest observations on the patients participating in the 
study. 
 
When paper CRFs are used, they will be completed legibly in black ink, with reasons given for 
missing data. Any corrections to the data will be made in a manner that does not obscure the 
original entry and will be dated and initialed by the investigator or assigned designee. Each 
investigator will sign the statement on the last page of the CRF. 
 
When eCRFs are used, electronic signatures of the investigator (or designee) will be provided. 
Access to the eCRF for data entry and signature is controlled by user identification and 
password, which are provided ImmuPharma or its designee. Study center personnel will be 
trained, by ImmuPharma or a designated vendor, in the use of eCRFs and application of 
electronic signatures before the start of the study. 
 
Because it is extremely important to have proper data collection in a timely manner, the 
investigator shall complete the CRFs and provide them to the study monitor on an ongoing basis. 
When the study monitor requests additional data or clarification of data for the CRF, the request 
must be answered satisfactorily before the next monitoring visit. 
 
14.2 
Archiving of Case Report Forms and Source Documents 
 
14.2.1 Investigator Responsibilities 
 
All records related to the study (ie, source data, source documents, CRFs [see section 3.9], 
copies of protocols and protocol amendments, drug accountability forms, correspondence, 
patient identification lists, signed informed consent forms, and other essential documents) must 


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be retained until ImmuPharma notifies the institution, in writing, that records may be destroyed. 
 
If ImmuPharma has not provided written notification of records destruction after 10 years from 
study completion (or earlier in the case of an institution closing), and the institution determines 
the study record retention is unduly burdensome, the institution may submit a written request to 
ImmuPharma at least 60 days before the planned disposition of the study records. No study 
document or image (eg, scan, radiograph, ECG tracing) should be destroyed without prior 
written agreement between the sponsor and each investigator. Should an investigator wish to 
assign the study records to another party or move them to another location, advance written 
notice will be given to the sponsor. 
 
14.2.2 Sponsor Responsibilities 
 
The sponsor will be responsible for the processing and quality control of the data. Data 
management and filing will be carried out as described in the sponsor’s SOPs for clinical studies. 
 
If data management and filing for this study are delegated to a contract organization, these 
functions will be carried out as described in the SOPs for clinical studies at that organization. 
These SOPs will be reviewed by the sponsor prior to the start of data management and filing 
activities. 
 
The original CRFs will be archived by the sponsor for the lifetime of the product. If eCRFs are 
used in the study, electronic images will be archived by the sponsor for the lifetime of the 
product. Center-specific eCRF images will be sent to each study center for archiving. 
 
14.3 
Data Collected by Contractors 
 
The sponsor is responsible for the correct collection of all required data according to the protocol 
and for the archiving of data electronically in ImmuPharma Central File. 
 
Limathon, BLIPS system, is responsible for validation of selected lupus disease activity 
assessment . 
 
The sponsor is responsible to ensure that the collection and evaluation of data by vendors 
adheres to protocol specifications. Electronic data from vendors will be archived by the sponsor. 
 
15 
FINANCING AND INSURANCE 
 
A separate financial agreement will be made between each principal investigator and 
ImmuPharma ., before the study drug is delivered. 
 
The study is covered under a liability insurance policy. The certificate of insurance and essential 
information about the insurance coverage can be provided upon request. 
 
For covered clinical studies in the US (see 21CFR54), each investigator will provide 
ImmuPharma or its designee with financial information required to complete Form FDA 3454. 
Each investigator will notify ImmuPharma or its designee of any relevant changes during the 
conduct of the study and for 1 year after the study has been completed. 
 


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16 
REPORTING AND PUBLICATION OF RESULTS 
 
The sponsor is responsible for preparing a clinical study report, in cooperation with the 
coordinating investigator. The final report is signed by the sponsor and, if applicable, by the 
coordinating investigator. 
 
When ImmuPharma or its designee generates reports from the data collected in this study for 
presentation to regulatory authorities, drafts may be circulated to the coordinating investigator 
for comments and suggestions. An endorsement of the final report will be sought from the 
coordinating investigator when required by local regulatory agencies. 
 
All unpublished information given to each investigator by ImmuPharma or its designee shall not 
be published or disclosed to a third party without the prior written consent of ImmuPharma or its 
designee. The primary publication from this study will report the results of the study in 
accordance with the current “Uniform Requirements for Manuscripts Submitted to Biomedical 
Journals”  as established by the International Committee of Medical Journal Editors 
(www.ICMJE.org). Authorship will be restricted to parties who have editorial or conceptual 
input to protocol design, analysis, and manuscript preparation. The publications committee 
established by ImmuPharma or its designee will oversee this process. Additional publications 
may follow the first. Policies regarding the publication of the study results are defined in the 
financial agreement. 
 
No patent application(s) based on the results of the study may be made by any investigator nor 
may assistance be given to any third party to make such an application without the written 
authorization of ImmuPharma. 
 
17 
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1995;105(1):31–57. 
 
Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, et al. A phase II, randomized, 
double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active 
systemic lupus erythematosus. Arthritis & Rheumatism (Arthritis Care & Research) 
2009;61(9):1168–78. 
 
Ware Jr JE, Kosinski M, Bjorner JB, Turner-Bowker DM, Gandek B, Maruish ME. User’s 
Manual for the SF-36v2™ Health Survey. 2nd ed. Lincoln (RI): QualityMetric Incorporated, 
2007. 
 
Zimmer, R., Wallace, D.J. and  Muller, S. (2012)  Randomized, double-blind, placebo-
controlled studies of P140 peptide in mannitol (Lupuzor) and trehalose (Forigerimod) in 
patients with SLE. Arthritis Rheum 64 Suppl. 10: 2620. 
 
Schall, N., Page, N., Macri, M., Chaloin, O., Briand, J.-P. & Muller, S. (2012) Peptide-based 
approaches to treat lupus and other autoimmune diseases J. Autoimmunity 39:143-153 
 
Macri, C., Wang, F., Tasset, I.,Schall, N., Page, N., Briand, J.-P., Cuervo A. M.& Muller, S. 


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(2015) Modulation of deregulated chaperone-mediated autophagy by a phosphopeptide. 
Autophagy 11: 472-486. 


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APPENDIX A 
MODIFIED WORLD HEALTH ORGANIZATION TOXICITY CRITERIA 
 
(Sample provided in this appendix is for reference only.) 


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Modified World Health Organization Toxicity Criteria 
 
MODIFIED WHO RECOMMENDATIONS FOR GRADING OF ACUTE AND SUBACUTE 
TOXICITIES 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
HAEMATOLOGICAL 
WBC 
> 4.0 
3.0 - 3.9 
2.0 - 2.9 
1.0 - 1.9 
< 1 
PLT 
WNL 
75.0 - normal 
50.0 - 74.9 
25.0 - 49.9 
< 25.0 
Haemoglobin  (g/l) 
WNL 
100 - normal 
80 - 100 
65 - 79 
< 65 
mmol/l) 
WNL 
6.2 - normal 
4.95 - 6.2 
4.0 - 4.9 
< 4.0 
(g/100 ml) 
WNL 
10.0 - normal 
8.0 - 10.0 
6.5 - 7.9 
< 6.5 
Granulocytes/bands 
≥ 2.0 
1.5 - 1.9 
1.0 - 1.4 
0.5 - 0.9 
< 0.5 
Haematologic – other 
none 
mild 
moderate 
severe 
life- 
threatening 
HAEMORRHAGE 
none 
mild, no transfusion 
gross, 1 - 2 U per 
gross, 3 - 4 U per 
massive, 
(clinical) 
episode 
episode 
> 4 U per 
episode 
INFECTION 
none 
mild, no active 
moderate, PO 
severe, IV antibiotic, 
life- 
treatment 
antibiotic 
anti- fungal or 
threatening 
hospitalization 
GASTROINTESTINAL 
Nausea 
none 
able to eat 
intake significantly 
no significant intake 
- - 
reasonable intake 
decreased but can eat 
Vomiting 
none 
once in 24 hrs 
2-5 x in 24 hrs 
6 - 10 x in 24 hrs 
> 10 x in 
24 hrs or 
requiring IV 
support 
Diarrhoea 
none 
increase of 
increase of 
increase of 
increase of 
2 - 3 stools/day 
4 - 6 stools/ day, or 
7 - 9 stools/ day, or 
>10 stools/ 
over pre-Rx 
nocturnal stools, or 
incontinence, or 
day or grossly 
moderate cramping 
severe cramping 
bloody 
diarrhoea, or 
need for 
parenteral 
support 
Stomatitis 
none 
painless ulcers, 
painful erythema, 
painful erythema, 
requires 
erythema, or mild 
oedema, or ulcers but 
oedema, or ulcers and 
parenteral or 
soreness 
can eat 
cannot eat 
enteral 
support 
Oesophagitis/ 
none 
painless ulcers 
painful erythema, 
complete dysphagia, 
requires 
Obstruction 
erythema, mild 
soreness or 
oedema, or ulcers or 
moderate dysphagia 
cannot eat solids or 
requires narcotics to 
parenteral or 
enteral 
dysphagia 
but can eat without 
eat 
support or 
narcotics 
narcotics or 
perforation 
Anorexia 
none 
mild 
moderate 
severe 
life- 
threatening 
Gastritis/ulcer 
no 
antacid 
requires vigorous 
uncontrolled by 
perforation or 
medical management 
medical management; 
bleeding 
or nonsurgical 
requires surgery 
treatment 
Small bowel obstruction 
no 
- - 
intermittent, no 
requires intervention 
requires 
intervention 
operation 
Intestinal fistula 
no 
- - 
- - 
yes 
- - 
GI – other 
none 
mild 
moderate 
severe 
life- 
threatening 
OTHER MUCOSAL 
none 
erythema, or mild 
patchy and 
confluent fibrinous 
necrosis 
pain not requiring 
serosanguinous 
mucositis or 
treatment 
discharge or non- 
ulceration or narcotic 
narcotic for pain 
for pain 


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WHO TOXOCITY GRADING CRITERIA 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
LIVER 
Bilirubin 
WNL 
- - 
< 1.5 x N 
1.5 - 3.0 x N 
> 3.0 x N 
Transaminases 
WNL 
< 2.5 x N 
2.6 - 5.0 x N 
5.1 - 20.0 x N 
> 20.0 x N 
(SGOT/AST, 
SGPT/ALT) 
Alk phosphatase or 
WNL 
< 2.5 x N 
2.6 - 5.0 x N 
5.1 - 20.0 x N 
> 20.0 x N 
5'nucleotidase 
Liver – clinical 
no change 
- - 
- - 
precoma 
hepatic coma 
from 
baseline 
Liver – other 
- - 
mild 
moderate 
severe 
life- 
threatening 
RENAL & BLADDER 
Creatinine 
WNL 
<1.5 x N 
1.5 - 3.0 x N 
3.1 - 6.0 x N 
> 6.0 x N 
Proteinuria 
no change 
1+ or <0.3 g% or 
2 - 3 + or 0.3 - 1.0 
4 + or > 1.0 g% or > 
nephrotic 
<3 g/l 
g% or 3 - 10 g/l 
10 g/l 
syndrome 
Haematuria 
negative 
micro only 
gross, no clots 
gross + clots 
requires 
transfusion 
BUN 
(mg%) 
WNL, < 20 
21 - 30 
31 - 50 
> 50 
- - 
(mmol/l) 
WNL, < 7.5 
7.6 - 10.9 
11 - 18 
> 18 
- - 
Haemorrhagic cystitis 
none 
blood on 
frank blood, no 
bladder irrigation 
requires 
microscopic 
treatment required 
required 
cystectomy or 
examination 
transfusion 
Renal failure 
- - 
- - 
- - 
- - 
dialysis 
required 
Incontinence 
normal 
with coughing, 
spontaneous, some 
no control 
- - 
sneezing, etc 
control 
Dysuria 
none 
mild pain 
painful or burning 
not controlled by 
- - 
urination controlled 
pyridium 
by pyridium 
Urinary retention 
none 
residue > 100ml or 
self-catheter required 
surgery required(IUR 
- - 
occasional catheter 
for voiding 
or dilatation) 
or difficulty 
initiating stream 
Increased frequency/ 
no change 
increase in 
increase > 2 x normal 
with urgency and 
- - 
urgency 
frequency or 
but < hourly 
hourly or more or 
nocturia up to 2 x 
requires catheter 
normal 
Bladder cramps 
none 
- - 
yes 
- - 
- - 
Ureteral obstruction 
none 
unilateral, no 
bilateral, no surgery 
incomplete bilateral, 
complete 
surgery required 
required 
but 
bilateral 
stents,nephrostomy 
obstruction 
tubes or surgery 
needed 
GU fistula 
none 
- - 
- - 
yes 
- - 
Kidney/bladder - other 
- - 
mild 
moderate 
severe 
life- 
threatening 
ALOPECIA 
no loss 
mild hair loss 
pronounced or total 
- - 
- - 
hair loss 
PULMONARY 
Dyspnoea 
none or no 
asymptomatic, with 
dyspnoea on 
dyspnoea at normal 
dyspnoea at 
change 
abnormality in 
significant exertion 
level of activity 
rest 
PFTs 
pO2 / pCO2 
no change or 
pO2 71-85 
pO2 61-70 
pO2 51-60 
pO2 ≤ 50 or 
pO2 > 85 
and pCO2 < 
pCO2 41-50 
pCO2 51-60 
pCO2 61-70 
pCO2 > 71 
40 


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WHO TOXICITY GRADING CRITERIA 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
DLCO 
> 90% of 
pretreatment 
76 - 90% of 
pretreatment 
51 - 75% of 
pretreatment 
26 - 50% of 
pretreatment 
≤ 25% of 
pretreatment 
Pulmonary fibrosis 
none 
radiographic 
- - 
changes with 
- - 
changes, 
symptoms 
asymptomatic 
Pulmonary oedema 
none 
- - 
- - 
radiographic changes 
requires 
and diuretic needed 
intubation 
Pneumonia (non- 
none 
radiographic 
steroids required 
oxygen required 
assisted 
infectious) 
changes, no 
ventilation 
steroids needed 
required 
Pleural effusion 
none 
present 
- - 
- - 
- - 
ARDS 
none 
mild 
moderate 
severe 
life-threatening 
Cough 
no change 
mild, relieved by 
requires narcotic 
uncontrolled cough 
- - 
OTC medications 
antitussive 
Pulmonary - other 
- - 
mild 
moderate 
severe 
life-threatening 
ALLERGY 
none 
transient rash drug 
urticaria, drug fever 
serum sickness, 
anaphylaxis 
fever < 38°C 
≥ 38°C, mild 
bronchospasm 
bronchospasm, 
parenteral medication 
CARDIAC 
Cardiac 
none 
asymptomatic, 
recurrent or 
requires treatment 
requires 
dysrhythmias 
transient, no 
persistent, no therapy 
monitoring; or 
therapy required 
required 
hypotension or 
ventricular 
tachycardia or 
fibrillation 
Cardiac function 
none 
asymptomatic, 
asymptomatic decline 
mild CHF, responsive 
severe or 
decline of resting 
of resting LVEF 
CHF to therapy 
refractory 
LVEF < 20% of 
> 20% of baseline 
baseline 
Cardiac ischaemia 
none 
non-specific T 
asymptomatic ST and 
angina without 
acute myocardial 
wave flattening 
T wave changes for 
evidence for 
infarction 
ischaemia 
infarction 
Cardiac-pericardial 
none 
asymptomatic 
pericarditis (rub, 
symptomatic 
tamponade; 
effusion, no 
chest pain, 
effusion; drainage 
drainage urgently 
intervention 
ECG changes) 
required 
Cardiac - other 
none 
mild 
moderate 
severe 
life-threatening 
Hypertension 
none or no 
asymptomatic, 
recurrent or persistent 
requires therapy 
hypertensive 
change 
transient increase 
increase by > 20 mm 
crisis 
by > 20mm Hg (D) 
Hg (D) or to 
or to > 150/100 if 
>150/100 if 
previously WNL. 
previously WNL. 
No treatment 
No treatment 
Hypotension 
none or no 
changes not 
requires fluid 
requires therapy and 
requires therapy 
change 
requiring therapy 
replacement or other 
hospitalisation; 
and 
(including transient 
therapy but not 
resolves within 48 hrs 
hospitalisation for 
orthostatic 
hypotension) 
hospitalisation 
of stopping the agent 
> 48hrs the agent 
Phlebitis/thrombosis 
- - 
- - 
superficial 
deep vein thrombosis 
major event 
embolism 
phlebitis(not local) 
(cerebral/hepatic/ 
pulmonary/other 
infarction) or 
pulmonary 
embolism 
Oedema 
none 
1+ or dependent in 
2+ or dependent 
3+ 
4+, generalized 
evening only 
throughout day 
anasarca 


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WHO TOXICITY GRADING CRITERIA 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
NEUROLOGIC 
Neurosensory 
none or no 
change 
mild paraesthesias 
loss of deep tendon 
reflexes 
mild or moderate 
objective loss; 
moderate 
paraesthesias 
severe objective 
sensory loss or 
paraesthesias that 
interfere with 
function 
- - 
Neuromotor 
none or no 
change 
subjective 
weakness; no 
objective findings 
mild objective 
weakness but no 
significant 
objective weakness 
with impairment of 
function 
paralysis 
impairment of 
function 
Neurocortica 
none 
mild somnolence or 
agitation 
moderate somnolence 
or agitation 
severe somnolence, 
agitation, confusion, 
disorientation, 
hallucinations 
coma, seizures, 
toxic psychosis 
Neurocerebellar 
none 
slight incoordination 
dysdiadochokinesis 
intention tremour, 
dysmetria slurred 
speech, nystagmus 
locomotor ataxia 
cerebellar 
necrosis 
Neuromood 
no change 
mild anxiety or 
depression 
moderate anxiety or 
depression 
severe anxiety or 
depression 
suicidal 
ideation 
Neuroheadache 
none 
mild 
moderate or severe 
but transient 
unrelenting and 
severe 
- - 
Neuroconstipation 
none or no 
change 
mild 
moderate 
severe 
ileus 
> 96 hours 
Neurohearing 
none or no 
change 
asymptomatic, 
hearing loss on 
audiometry only 
tinnitus 
hearing loss interfering 
with function, 
correctable with 
hearing aid 
deafness not 
correctable 
Neurovision 
none or no 
change 
- - 
- - 
symptomatic subtotal 
loss of vision 
blindness 
Pain 
none 
mild 
moderate 
severe 
intolerable 
Behavioural change 
none 
change, not 
disruptive to 
subjects or family 
disruptive to subjects 
or family 
harmful to others or 
self 
psychotic 
behavior 
Dizziness/vertigo 
none 
non-disabling 
- - 
disabling 
- - 
Taste 
normal 
slightly altered 
taste, metallic taste 
markedly altered taste 
- - 
- - 
Insomnia 
normal 
occasional difficulty 
sleeping, may need 
pills 
- - 
difficulty sleeping 
despite medication 
- - 
Neurologic - other 
- - 
mild 
moderate 
severe 
life- 
threatening 
DERMATOLOGIC 
Skin 
none or no 
change 
scattered macular or 
papular eruption or 
erythema that is 
asymptomatic 
scattered macular or 
macular or papular 
eruption or erythema 
with pruritus or other 
associated symptoms 
generalized 
symptomatic macular, 
papular, or vesicular 
eruption 
exfoliative 
dermatitis or 
ulcerating 
dermatitis 
Local 
none 
pain 
pain and swelling 
ulceration 
plastic 
with inflammation or 
phlebitis 
surgery 
indicated 


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WHO TOXICITY GRADING CRITERIA 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
FLU-LIKE 
SYMPTOMS 
Fever in absence of 
none 
37.1 - 38.0°C 
38.1 - 40.0°C 
> 40.0°C (104.0°F) 
> 40.0°C 
infection 
98.7 - 100.4°F 
100.5 - 104.0°F 
for < 24 hrs 
(104.0°F) 
for> 24 hrs or 
with 
hypotension 
Chills 
none 
mild or brief 
pronounced or 
- - 
- - 
prolonged 
Myalgia/arthralgia 
normal 
mild 
decrease in ability to 
disabled 
- - 
move 
Sweats 
normal 
mild and occasional 
frequent or drenching 
- - 
- - 
Malaise 
none 
mild, able to 
impaired normal 
in bed or chair > 50% 
bed ridden or 
continue normal 
daily activity or 
of waking hours 
unable to care 
activities 
bedrest <50% of 
for self 
waking hours 
Flu-like symptoms 
- - 
mild 
moderate 
severe 
life- 
threatening 
WEIGHT GAIN 
< 5% 
5.0 - 9.9% 
10.0 - 19.9% 
≥ 20% 
- - 
WEIGHT LOSS 
< 5% 
5.0 - 9.9% 
10.0 - 19.9% 
≥ 20% 
- - 
METABOLIC 
Hyperglycaemia 
< 116 mg/dl 
116 – 160 
161 – 250 
251 – 500 
> 500 or 
< 6.2 mmol/l 
6.2 - 8.9 
9.0 - 13.9 
14.0 - 27.8 
ketoacidosis 
> 27.8 or 
ketoacidosis 
Hypoglycaemia 
> 64 mg/dl 
55 – 64 
40 – 54 
30 – 39 
< 30 
> 3.6 mmol/l 
3.1 - 3.6 
2.2 - 3.0 
1.7 - 2.1 
< 1.7 
Amylase 
WNL 
< 1.5 x N 
1.5 - 2.0 x N 
2.1 - 5.0 x N 
> 5.1 x N 
Hypercalcaemia 
< 10.6 mg/dl 
10.6 - 11.5 
11.6 - 12.5 
12.6 - 13.5 
≥ 13.5 
< 2.65 
mmol/l 
2.65 - 2.87 
2.88 - 3.12 
3.13 - 3.37 
≥ 3.37 
Hypocalcaemia 
> 8.4 mg/dl 
8.4 - 7.8 
7.7 - 7.0 
6.9 - 6.1 
≤ 6.0 
> 2.1 mmol/l 
2.1 - 1.95 
1.94 - 1.75 
1.74 - 1.51 
≤ 1.50 
Hypomagnaesia 
> 1.4 mmol/l 
1.4 - 1.2 
1.1 - 0.9 
0.8 - 0.6 
≤ 0.5 
Hyponatraemia 
WNL or 
131 - 135 
126 - 130 
121 - 125 
≤ 120 
> 135 
Hypokalaemia 
WNL or 
3.1 - 3.5 
2.6 - 3.0 
2.1 - 2.5 
≤ 2.0 
> 3.5 
Metabolic - other 
- - 
mild 
moderate 
severe 
life- 
threatening 
COAGULATION 
Fibrinogen 
WNL 
0.99 - 0.75 x N 
0.74 - 0.50 x N 
0.49 - 0.25 x N 
≤ 0.24 
Prothrombin time 
WNL 
1.01 - 1.25 x N 
1.26 - 1.50 x N 
1.51 - 2.00 x N 
> 2.00 x N 
Partial thromboplastin 
WNL 
1.01 - 1.66 x N 
1.67 - 2.33 x N 
2.34 - 3.00 x N 
> 3.00 x N 
time 
Coagulation - other 
- - 
mild 
moderate 
severe 
life- 
threatening 


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WHO TOXICITY GRADING CRITERIA 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ENDOCRINE 
Impotence/libido 
normal 
decrease in normal 
- - 
absence of function 
- - 
function 
Sterility 
- - 
- - 
yes 
- - 
- - 
Amenorrhoea 
no 
yes 
- - 
- - 
- - 
Gynaecomastia 
normal 
mild 
pronounced or 
- - 
- - 
painful 
Hot flushes 
none 
mild or < 1/day 
moderate and ≥ 1/day 
frequent and 
interferes with normal 
- - 
function 
Cushingoid 
normal 
mild 
pronounced 
- - 
- - 
Endocrine - other 
- - 
mild 
moderate 
severe 
life- 
threatening 
EYE 
Conjunctivitis/keratitis 
none 
erythema or 
steroids or antibiotics 
corneal ulceration or 
- - 
chemosis, no 
required 
visible opacification 
steroids or 
antibiotics 
Dry eye 
normal 
- - 
requires artificial 
- - 
requires 
tears 
enucleation 
no change 
- - 
- - 
yes 
- - 
Glaucoma 
- - 
mild 
moderate 
severe 
life- 
threatening 
Eye - other 


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APPENDIX B 
CONCOMITANT SYSTEMIC LUPUS ERYTHEMATOSUS 
MEDICATIONS 
 
(Sample provided in this appendix is for reference only.) 


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Concomitant Systemic Lupus Erythematosus Medicationsa Medication 
Start date
 
Stop date 
Stable date 
DMARDS/immunosuppressantsb 
 
Antimalarials 
Hydroxychloroquine sulfate 
Chloroquine 
 
 
3 months prior to 1st dose 
4 weeks prior to 1st dose 
4 weeks prior to 1st dose 
Methotrexate 
3 months prior to 1st dose 
4 weeks prior to 1st dose 
4 weeks prior to 1st dose 
 
Leflunomide 
3 months prior to 1st dose 
8 weeks prior to 1st dose unless an 
adequate cholestyramine washout has 
been completed.c  If cholestyramine 
washout is performed, the last use of 
leflunomide must be at least 4 weeks 
before the 1st dose of study drug. 
 
4 weeks prior to 1st dose 
Mycophenolate mofetil 
3 months prior to 1st dose 
4 weeks prior to 1st dose 
4 weeks prior to 1st dose 
Azathioprine 
3 months prior to 1st dose 
4 weeks prior to 1st dose 
4 weeks prior to 1st dose 
Steroids 
 
Prednisone or prednisolone (most 
likely to be used) 
 
 
NA 
NA 
4 weeks prior to 1st dose 
a Changes in background therapies, including use of steroids, should not occur after week 44. 
b Dosages of these medications should remain stable during the study. Patients will be withdrawn from the study if 
there is an increase in the dose of immunosuppressive agents (methotrexate, azathioprine, 
mycophenolate mofetil [MMF], leflunomide) above the baseline level or if any new immunosuppressive agents are 
introduced. 
c Cholestyramine washout (per ARAVA package insert) is 8 grams administered 3 times daily for 11 days 
(days do not need to be consecutive). Compliance for this washout is low. DMARDS=disease-modifying 
antirheumatic drugs; NA=not applicable. 


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Excluded medicationsa 
Must stop by: 
iv pulse steroids (methylprednisolone) 
>4 weeks prior to 1st dose 
 
Tacrolimus 
>3 months prior to 1st dose 
Cyclosporin A 
>3 months prior to 1st dose IVIG (intravenous immunoglobulin 
therapy) 
>3 months prior to 1st dose 
 
 
 
Cyclophosphamide 
>6 months prior to 1st dose 
Biologic agents 
Fusion proteins (eg, atacicept, abatacept, 
etanercept) 
Therapeutic proteins 
Monoclonal antibodiesb (eg, ocrelizumab, 
alemtuzumab, rituximab, epratuzumab, 
belimumab) 
B-cell depleting agentsb (eg, rituximab, 
epratuzumab, belimumab) 
Live or live-attenuated vaccines (eg, nasal flu 
vaccine; measles, mumps and rubella vaccine; oral 
polio vaccine, etc.) 
>6 months prior to 1st dose 
 
 
 
 
 
 
 
B-cell count  and ALC  ≥ normal ranges  
>3 months prior to 1st dosea 
Investigational drug for the treatment of lupus 
>6 months prior to 1st dose 
Investigational drug for the treatment of a 
condition other than lupus 
>4 weeks prior to 1st dose 
a Patients will be withdrawn from the study if there is an initiation of new immunosuppressive therapy (eg, 
cyclophosphamide, cyclosporin, tacrolimus) or if there is an initiation of therapy with biologics for the treatment of 
systemic lupus erythematosus (SLE). 
b For B-cell depleting agents that are also monoclonal antibodies, the most conservative restriction applies. 
iv=intravenous; IVIG=intravenous immuneglobulin; ALC=absolute lymphocyte count. 


 
95 
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Study IPP-201101/005 
Clinical Study Protocol 
 
 
Prednisone Equivalent Conversion Sheet 
 
Steroid type in milligrams (mg) 
Betametasone 
Cortisol 
(Hydrocortisone) 
Cortisone 
Deflazacort 
Dexamethasone 
Methylprednisolone 
Prednisolone 
Triamcinolone 
To convert to prednisone equivalent 
dose, divide steroid 
0.12 
4 
5 
1.2 
0.15 
0.8 
1 
0.8 
dose by factor in this row 
Dose of prednisone (mg) 
80 
9.6 
320 
400 
96 
12 
64 
80 
64 


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APPENDIX C 
SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE ACTIVITY INDEX 2000 
 
 
Centre:_____  Patient:______ Visit No:_____  Scheduled:____ Date:__________ Investigator:_____ 
 
 
 
 
 
 
 
 
 
        dd-mmm-yy 
 
 
 
 
  
Descriptor 
YES 
No 
Not Known 
1. Seizure 
 
 
 
2. Psychosis 
 
 
 
3. Organic brain syndrome 
 
 
 
4. Visual disturbance 
 
 
 
5. Cranial nerve disorder 
 
 
 
6. Lupus headache 
 
 
 
7. CVA 
 
 
 
8. Vasculitis 
 
 
 
9. Arthritis 
 
 
 
10. Myositis 
 
 
 
11. Urinary casts 
 
 
 
12. Hematuria 
 
 
 
13. Proteinuria 
 
 
 
14. Pyuria 
 
 
 
15. Rash 
 
 
 
16. Alopecia 
 
 
 
17. Mucosal ulcers 
 
 
 
18. Pleurisy 
 
 
 
19. Pericarditis 
 
 
 
20. Low complement 
 
 
 
21. Increased DNA binding 
 
 
 
22. Fever 
 
 
 
23. Thrombocytopenia 
 
 
 
24. Leukopenia 
 
 
 
SLEDAI FLARE INDEX 
YES 
NO 
Not Known 
25. Increase in Prednisone (mg/kg/day) 
Not 
done 
No 
Increase 
To  
< 0.5g 
To  
> 0.5 
26. Added NSAID or Plaquenil 
 
 
 
27. New Cytoxan, Azathioprine, Methotrexate, Hospitalization (SLE) 
 
 
 
28. Discoid Rash, new/worse 
 
 
 
29. Photosensitive Rash, new/worse 
 
 
 
30. Lupus Profundus, new/worse 
 
 
 
31. Cutaneous vasculitis, new/worse 
 
 
 
 Only record manifestations/items due to SLE Disease Activity  
 Score manifestations occurring in the last 4 weeks  
 TO BE USED IN CONJUCTION WITH THE SLEDAI 2000 GLOSSARY  


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32. Bullous lupus, , new/worse 
 
 
 
33. Nasopharyngeal ulcers, new/worse 
 
 
 
34. Pleuritis, new/worse 
 
 
 
35. Pericarditis, new/worse 
 
 
 
36. Arthritis , new/worse 
 
 
 
37. Fever (SLE), new/worse 
 
 
 
38. CNS-SLE, new/worse, requiring double prednisone or hospitalization 
 
 
 
39. Vasculitus, new/worse, requiring double prednisone or hospitalization 
 
 
 
40. Nephritis, new/worse, requiring double prednisone or hospitalization 
 
 
 
41. Myositis, new/worse, requiring double prednisone or hospitalization 
 
 
 
42. Platelets < 60.000, new/worse, req.  double prednisone or hospitalization 
 
 
 
43. Heme-anaemia: Hb <7% req.  double prednisone or hospitalization 
 
 
 
44. Decrease in Hb >3% requiring double prednisone or hospitalization 
 
 
 
 
 
 
 
 
SLEDAI 2000 GLOSSARY 
Seizure 
Recent onset (last 28 days). Exclude metabolic, infectious or drug cause, or seizure due to 
past irreversible CNS damage. 
Psychosis 
Altered ability to function in normal activity due to severe disturbance in the perception of 
reality. Include hallucinations, incoherence, marked loose associations, impoverished thought 
content, marked illogical thinking, bizarre, disorganized, or catatonic behaviour. Exclude 
uraemia and drug causes. 
Organic brain 
syndrome 
Altered mental function with impaired orientation, memory or other intellectual function, with 
rapid onset and fluctuating clinical features. Include clouding of consciousness with reduced 
capacity to focus, and inability to sustain attention to environment, plus at least two of the 
following: perceptual disturbance, incoherent speech, insomnia or daytime drowsiness, or 
increased or decreased psychomotor activity. Exclude metabolic, infectious or drug causes. 
Visual disturbance 
Retinal and eye changes of SLE. Include cytoid bodies, retinal haemorrhages, serous 
exudate or haemorrhages in the choroid, optic neuritis, Exclude hypertension, infection or 
drug causes. 
Cranial nerve 
disorder 
New onset of sensory or motor neuropathy involving cranial nerves. Include vertigo due to 
lupus. 
Lupus headache 
Severe persistent headache: may be migrainous, but must be non-responsive to narcotic 
analgesia. 
CVA 
New onset of cerebrovascular accident (s). Exclude arteriosclerosis or hypertensive causes. 
Vasculitis 
Ulceration, gangrene, tender finger nodules, periungual infarction, splinter haemorrhages, or 
biopsy, or angiogram proof of vasculitis. 
Arthritis 
More than two joints with pain and signs of inflammation, i.e., tenderness, swelling, or 
effusion. 
Myositis 
Proximal muscle aching/weakness, associated with elevated creatine phosphokinase (CK) / 
aldolase, or electromyogram changes or a biopsy showing myositis. 
Urinary casts 
Haeme-granular or red blood cell casts. 
Haematuria 
>5 red blood cells/high power field. Exclude stone, infection or other cause. 
Proteinuria 
> 0.5 g/24 hours. 
Pyuria 
>5 white blood cells/high power field. Exclude infection. 


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Rash 
Ongoing inflammatory lupus rash. 
Alopecia 
Ongoing abnormal, patchy or diffuse loss of hair due to active lupus. 
Mucosal ulcers 
Ongoing oral or nasal ulcerations due to active lupus. 
Pleurisy 
Classic and severe pleuritic chest pain or pleural rub or effusion or new pleural thickening 
due to lupus. 
Pericarditis 
Classic and severe pericardial pain or rub or effusion, or electrocardiogram, or echo 
confirmation. 
Low complement 
Decrease in CH50, C3 or C4 below the lower limit of normal for testing laboratory. 
Increased DNA 
binding 
>25% binding by Farr assay or above normal range for testing laboratory. 
Fever 
>38°C. Exclude infectious cause. 
Thrombocytopenia 
100,000 platelets/mm3 (or < 100 x 109 platelets/L) 
Leukopenia 
<3,000 white blood cells/mm3. Exclude drug causes.(or < 3 x 109 WBC/L) 
 
 


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APPENDIX D 
BRITISH ISLES LUPUS ASSESSMENT GROUP 2004 
 
(Sample provided in this appendix is for reference only.) 


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British Isles Lupus Assessment Group 2004 
 
 


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APPENDIX E 
MEDICAL OUTCOME SURVEY SHORT FORM 36 
 
(Sample provided in this appendix is for reference only.) 


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Medical Outcome Survey Short Form 36 
 
 


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APPENDIX F 
28-JOINT COUNT EXAMINATION FOR PAIN AND TENDERNESS 
 
 
(Sample provided in this appendix is for reference only.) 


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28-Joint Count Examination for Pain and Tenderness 
 
 


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APPENDIX G 
FUNCTIONAL ASSESSMENT OF CHRONIC ILLNESS THERAPY–FATIGUE 
 
(Sample provided in this appendix is for reference only.) 


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Functional Assessment of Chronic Illness Therapy–Fatigue FACIT-Fatigue 
Scale (Version 4) 
Below is a list of statements that other people with your illness have said are important. Please 
circle or mark one number per line to indicate your response as it applies to the past 7 
days. 
 
Not 
A
at 
little
all 
bit
Some- 
what 
Quite 
a bit 
Very 
much 
HI7 
I feel fatigued 
0 
1 
2 
3 
4 
HI12 
I feel weak all over 
0 
1 
2 
3 
4 
An1 
I feel listless (“washed out”) 
0 
1 
2 
3 
4 
An2 
I feel tired 
0 
1 
2 
3 
4 
An3 
I have trouble starting things because I am tired 
0 
1 
2 
3 
4 
An4 
I have trouble finishing things because I am tired 
0 
1 
2 
3 
4 
An5 
I have energy 
0 
1 
2 
3 
4 
An7 
I am able to do my usual activities 
0 
1 
2 
3 
4 
An8 
I need to sleep during the day 
0 
1 
2 
3 
4 
An12 
I am too tired to eat 
0 
1 
2 
3 
4 
An14 
I need help doing my usual activities 
0 
1 
2 
3 
4 
An15 
I am frustrated by being too tired to do the things I want 
do 
to 
0 
1 
2 
3 
4 
An16 
I have to limit my social activity because I am tired 
0 
1 
2 
3 
4 
SOURCE: http://www.facit.org/FACITOrg/Questionnaires. 


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APPENDIX H 
SYSTEMIC LUPUS INTERNATIONAL COLLABORATIVE CLINICS/AMERICAN 
COLLEGE OF RHEUMATOLOGY DAMAGE INDEX 
 
(Sample provided in this appendix is for reference only.) 


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Systemic Lupus International Collaborative Clinics/American College of 
Rheumatology Damage Index 
 
 


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APPENDIX I 
CLINICAL CRITERIA FOR DIAGNOSING ANAPHYLAXIS 
 
(Sample provided in this appendix is for reference only.) 


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Clinical Criteria for Diagnosing Anaphylaxis 
 
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, 
generalized hives, pruritus or flushing, swollen lips-tongue-uvula) 
 
And at least one of the following: 
 
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope, 
incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient 
(minutes to several hours): 
a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula) 
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
c. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence) 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BPa 
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline 
a Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, less than (70 
mm Hg + [2 × age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years. 
 
PEF=peak expiratory flow; BP=blood pressure. 
SOURCE: Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF, Bock SA, Branum A, et al. Second 
symposium on the definition and management of anaphylaxis: Summary report—Second National Institute of 
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J All Clin Immunol 
2006;117(2):391–7. 
 
 
 
 
 
 
 

SAP_001.pdf: 
ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
Version date: 
Page 1 of 128 
28 MARCH 2018  
 
 
 
Statistical Analysis Plan 
 
IPP-201101/005 
 
A 52-Week, Randomized, Double-Blind, Parallel-Group, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of a 200-mcg 
Dose of IPP-201101 Plus Standard of Care in Patients With Systemic 
Lupus Erythematosus 
 
 
Prepared for: 
ImmuPharma 
 
Prepared by: 
ORION Clinical 
7 Bath Road, Slough 
Berkshire SL1 3UA UK 
Tel:  +44 (0) 1753 578080 
Fax:  +44 (0) 1753 578081 
 
 
CONFIDENTIAL 
 
 
Version  
Author 
Final Version 3 
Fahmeeda Sheikh, John Sullivan 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
Version date: 
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Statistical Analysis Plan 
 
IPP-201101/005 
 
A 52-Week, Randomized, Double-Blind, Parallel-Group, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of a 200-mcg 
Dose of IPP-201101 Plus Standard of Care in Patients With Systemic 
Lupus Erythematosus 
 
 
Author:  
Fahmeeda Sheikh, John Sullivan 
Version:  
Final Version 3 
 
 
The undersigned have reviewed and revised this SAP and find it to be consistent with the study 
requirements: 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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TABLE OF CONTENTS 1
 INTRODUCTION..................................................................................................................................9
 
1.1 
General ....................................................................................................................................................9 
1.2 
Changes from Protocol........................................................................................................................9 2
 STUDY OBJECTIVES........................................................................................................................9
 3
 STUDY DESIGN...................................................................................................................................9
 
3.1 
Overview .................................................................................................................................................9 
3.2 
Inclusion and Exclusion Criteria ..................................................................................................... 10 
3.3 
Study Treatment ................................................................................................................................. 10 
3.4 
Study Timepoints ................................................................................................................................ 10 
3.5 
Sample Size Considerations ............................................................................................................. 11 
3.6 
Randomisation ..................................................................................................................................... 11 4
 STUDY VARIABLES AND COVARIATES....................................................................................11
 
4.1 
Primary Efficacy Variable .................................................................................................................. 11 
4.2 
Secondary Efficacy Variables ............................................................................................................ 12 
4.3 
Exploratory Efficacy Variables ......................................................................................................... 13 
4.4 
Pharmacokinetic and Immunogenicity Variables ......................................................................... 13 
4.5 
Safety Variables ................................................................................................................................... 14 5
 DEFINITIONS......................................................................................................................................14
 6
 ANALYSIS SETS................................................................................................................................15
 
6.1 
Randomised Set .................................................................................................................................. 15 
6.2 
Safety Set .............................................................................................................................................. 15 
6.3 
Full Analysis Set .................................................................................................................................. 15 7
 SAFETY MONITORING....................................................................................................................15
 8
 INTERIM ANALYSES........................................................................................................................15
 9
 DATA....................................................................................................................................................15
 
9.1 
eCRF Data ............................................................................................................................................ 15 
9.2 
External Data ....................................................................................................................................... 16 
9.2.1 
Laboratory Data ................................................................................................................................. 16 
9.2.2 
Other non-CRF data ......................................................................................................................... 16 
9.3 
Randomisation list .............................................................................................................................. 16 
9.4 
Programming and Data Review ....................................................................................................... 16 


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 STATISTICAL METHODS................................................................................................................16
 
10.1 
General Principles .............................................................................................................................. 16 
10.2 
Stratification Adjustment .................................................................................................................. 17 
10.3 
Missing Data ......................................................................................................................................... 18 
10.3.1 Individual Questionnaire items ....................................................................................................... 18 
10.3.2 Sensitivity Analyses ............................................................................................................................ 18 
10.4 
Pooling of Sites .................................................................................................................................... 18 
10.5 
Statistical Issues................................................................................................................................... 18 11
 STATISTICAL OUTPUT...................................................................................................................18
 
11.1 
Patient Disposition ............................................................................................................................. 18 
11.2 
Patient Characteristics at Baseline ................................................................................................. 19 
11.2.1 Demographic and Baseline Characteristics ................................................................................. 19 
11.2.2 Medical History and Current Medical Conditions ..................................................................... 19 
11.2.3 Prior Medications .............................................................................................................................. 19 
11.2.4 SLE Disease History .......................................................................................................................... 19 
11.2.5 Other Baseline Characteristics ...................................................................................................... 20 
11.3 
Efficacy Analyses ................................................................................................................................. 20 
11.3.1 Primary Efficacy Variable .................................................................................................................. 20 
11.3.2 Secondary Efficacy Variables ........................................................................................................... 21 
11.3.3 Exploratory Efficacy Variables ........................................................................................................ 24 
11.4 
Pharmacokinetic and Immunogenicity Analyses .......................................................................... 24 
11.5 
Safety Analyses .................................................................................................................................... 24 
11.5.1 Adverse Events ................................................................................................................................... 24 
11.5.2 Adverse Events of Special interest ................................................................................................ 25 
11.5.3 Laboratory Data ................................................................................................................................. 26 
11.5.4 Vital Signs ............................................................................................................................................. 26 
11.5.5 Electrocardiogram ............................................................................................................................. 26 
11.5.6 Physical Examination ......................................................................................................................... 27 
11.5.7 Suicidality Assessment C-SSRS ....................................................................................................... 27 
11.5.8 Anaphylaxis Evaluation ..................................................................................................................... 27 
11.5.9 Concomitant Medication ................................................................................................................. 27 
11.6 
Study Termination .............................................................................................................................. 27 
11.7 
Study Drug Exposure ........................................................................................................................ 28 
11.8 
Procedures/Non-Drug Therapies................................................................................................... 28 12
 VALIDATION.....................................................................................................................................28
 13
 LITERATURE CITATIONS/REFERENCES.................................................................................28
 


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 LIST OF TABLES, FIGURES AND LISTINGS.............................................................................29
 
14.1 
List of Tables ....................................................................................................................................... 29 
14.2 
List of Listings ...................................................................................................................................... 32 15
 SHELLS FOR TABLES, FIGURES AND LISTINGS...................................................................33
 16
 APPENDICES...................................................................................................................................127
 
16.1 
Study Schedule .................................................................................................................................. 127 
 
 


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GLOSSARY OF ABBREVIATIONS 
 
%CV 
Coefficient of Variation 
ACR 
American College of Rheumatology 
AE 
Adverse Event 
ALT 
Alanine Transaminase  
AM 
Arithmetic Mean 
ANA 
Antinuclear antibody 
ANC 
Absolute Neutrophil Count  
ANCOVA 
Analysis of Covariance 
ANOVA 
Analysis of Variance 
Anti-dsDNA Ab 
Anti-double-stranded Deoxyribonucleic Acid Antibody 
Anti-Sm Ab 
Anti-Smith antibody 
Anti-U1-70K snRNP Ab 
Anti-uridine rich 70 kilodalton small nuclear ribonucleoprotein particle Ab 
AST 
Aspartate Transaminase  
ATC 
Anatomical Therapeutic Chemical 
BILAG A 
British Isles Lupus Assessment Group A  
BILAG B 
British Isles Lupus Assessment Group B 
BLQ 
Below the Limit of Quantification 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CRO 
Clinical Research Organisation 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTC 
Common Toxicity Criteria  
DBL 
Database Lock 
DMP 
Data Management Plan 


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DOB 
Date of Birth 
DRM 
Data Review Meeting 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
FACIT 
Functional Assessment of Chronic Illness Therapy 
FAS 
Full Analysis Set 
GM 
Geometric Mean 
GGT 
Gamma-Glutamyl-Transpeptidase 
ICH 
International Conference on Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IgA 
Immunoglobulin A 
IgE 
Immunoglobulin E 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IMP 
Investigational Medicinal Product 
IRT 
Interactive Response Technology 
IV 
Intravenous 
LDH 
Lactate Dehydrogenase 
LLQ 
Lower limit of quantification 
LOCF 
Last Observation Carried Forward 
LS Mean 
Least Squares Mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
ml 
Millilitre 
N 
Number of Patients 
n 
Number of Events 
NCS 
Not Clinically Significant 
PhGA 
Physician’s Global Assessment 
PK 
Pharmacokinetics 
PT 
Preferred Term 
QC 
Quality Control 
QoL 
Quality of Life 


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RBC 
Red Blood Cell  
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SC 
Subcutaneous 
SD 
Standard Deviation 
SDI 
SLICC/ACR Damage Index 
SDTM 
Study Data Tabulation Model 
SE 
Standard Error 
SELENA 
Safety of Estrogens in Lupus Erythematosus: National Assessment 
SF-36 
Medical Outcome Survey Short Form 36 
SFI 
SELENA Flare Index 
SLE 
Systemic Lupus Erythematosus 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLICC 
Systemic Lupus International Collaborative Clinics 
SOC 
System Organ Class 
SRI 
SLE Responder Index  
TEAE 
Treatment Emergent Adverse Event 
WBC 
White Blood Cell  
WHO 
World Health Organisation  
WHODD 
World Health Organisation Drug Dictionary 
μg 
Microgram 
 
 
 
 
 
  
 
 
 
 


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 1
 INTRODUCTION1.1
 GENERAL 
This statistical analysis plan (SAP) describes the statistical methods to be used during the reporting and 
analyses of data collected under ImmuPharma Protocol IPP-201101/005 and should be read in 
conjunction with the study protocol and electronic case report form (eCRF).   
This version of the plan has been developed using the protocol Version 2.5 dated 27JUL2016 for 
Germany and 01JUN2016 for all other countries and blank CRF Version 3.1 dated 06FEB2017. Any 
further changes to the protocol or eCRF will be reviewed for potential impact on the SAP which will 
be amended if it is deemed necessary. 
At the time of writing this version of the SAP, the study is ongoing. 1.2
 CHANGES FROM PROTOCOL
A tipping point sensitivity analysis has been added. 
A hierarchical testing procedure for the most important secondary endpoints will be used. 
Adverse events of special interest have been identified and will be investigated. 2
 STUDY OBJECTIVES
The primary objective of this study is to evaluate the efficacy of a 200 mcg dose of IPP-201101 every 4 
weeks for 48 weeks compared with placebo in patients with active Systemic Lupus Erythematosus 
(SLE) as assessed by the SLE Responder Index (SRI) at Week 52. An SRI response is defined as: 
 
a reduction from baseline in the Systemic Lupus Erythematosus Disease Activity Index 2000 
(SLEDAI-2K) score of at least 4 points; 
 
no worsening in Physician’s Global Assessment (PhGA) (with worsening defined as an increase 
in PhGA of more than 0.30 point from baseline); 
 
no new British Isles Lupus Assessment Group A (BILAG A) body system score and; 
 
no more than 1 new BILAG B body system score from baseline 3
 STUDY DESIGN3.1
 OVERVIEW
This is a Phase III, randomised, double-blind, parallel-group, placebo-controlled study which was 
conducted in 28 centres globally, over a period of 52 weeks. The study will enrol approximately 200 
men and women aged between 18 and 70, who have serologically active SLE with moderate disease 


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activity on the basis of a standard assessment of disease activity, validated for use as a measure in 
clinical studies.   
The purpose of the study is to evaluate the efficacy and safety of a 200 mcg dose of IPP-201101 plus 
standard of care compared with placebo plus standard of care. The study will evaluate the clinical 
response to treatment with IPP-201101 and will also include assessment of biomarkers and change in 
steroid use from baseline. Safety assessments will include monitoring of adverse events, clinical 
laboratory test results, vital signs measurements, 12-lead electrocardiogram (ECG) findings, suicidality 
assessments, anaphylaxis evaluations and concomitant medication use.  
Treatment assignment will be stratified by region (Europe or United States [US]), SLEDAI-2K 
screening total score (6 to 9, ≥ 10) and racial-ethnic classification (black/Hispanic or others). Within 
each stratum, eligible patients will be randomly assigned with a 1:1 ratio to receive either 200 mcg of 
IPP-201101 or placebo.  3.2
 INCLUSION AND EXCLUSION CRITERIA
To be eligible for inclusion into this study, each patient must fulfil all inclusion criteria and not violate 
any exclusion criteria (for the protocol under which they are entered) during screening prior to 
randomisation. Details of the inclusion and exclusion criteria are presented in the protocol and 
amendments. 3.3
 STUDY TREATMENT
Patients randomly assigned to IPP-201101 will be administered a dosage of 200 mcg subcutaneously 
(SC) every 4 weeks for 48 weeks, and those patients randomly assigned to placebo will be 
administered placebo SC every 4 weeks for 48 weeks. All patients will be administered a total of 13 
doses.  3.4
 STUDY TIMEPOINTS
The study consists of a screening period of up to 4 weeks, and a 48 week treatment period. Patients 
will return to the study centre 4 weeks after administration of the last dose of study drug and a final 
assessment will take place. Patients are expected to participate in the study for up to 54 weeks.  
Visits will be as follows: 
Visit 
 
Week 
1 
Screening 
Days -28 to -1 
2 
Baseline, Randomisation and Date of First 
Dose 
0 
3 
Blood sample for immunogenicity testing 
2 
4, 5, 6, 7, 8, 9, 10, 11, 
12, 13, 14, 15 
Treatment period  
4, 8, 12, 16, 20, 24, 28, 32, 36, 
40, 44, 48 
16 
Final assessment (or early termination)a 
52 
aIf a patient is withdrawn from the study before completion of 48 weeks of treatment (13 doses of study drug), final 
procedures and assessments will be performed at early termination visit. 


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If more than one visit occurs within a window, the nearest to the scheduled time will be presented 
within the summaries. 
See Section 16.1 for the Study Schedule of procedures and assessments.  3.5
 SAMPLE SIZE CONSIDERATIONS
The study is designed to estimate and assess the significance of the difference between a 200 mcg dose 
of IPP-201101 and placebo in the proportion of SRI responders at Week 52. It is anticipated that 
approximately 270 patients will be screened for participation in the study, and 200 of these patients 
will be enrolled in the study in order to provide 100 evaluable patients per treatment group.  
The study will have a 90% or greater power to detect a 25% or greater difference in the proportion of 
SRI responders between the IPP-201101 group and the placebo group, or to detect a 20% difference 
with an 80% power. This projection uses the 2-sided Pearson Chi-square test with alpha=0.05, and is 
based on an anticipated placebo effect at Week 52 of 40% to 45%. 3.6
 RANDOMISATION
Randomisation will be stratified for the following 3 baseline characteristics: 
 
Region (Europe, US) 
 
SLEDAI-2K screening total score (6 to 9, ≥ 10) 
 
Racial-ethnic group classification (black/Hispanic, others) 
Within each of the stratum, eligible patients will be randomly assigned with a 1:1 ratio to receive either 
200 mcg of IPP-201101 or placebo SC every 4 weeks for 48 weeks. 
The randomisation will be programmed by the unblinded statistician at Orion, who will send through 
randomisation and kit lists to Oracle to be loaded into the Interactive Response Technology (IRT).  
Upon receiving information for a new patient, the IRT will assign the new patient to the next available 
randomisation code with the randomisation stratum for the appropriate region, SLEDAI-2K screening 
score and racial-ethnic group classification.  
A more detailed description of the randomisation process can be found in the Randomisation Plan.   4
 STUDY VARIABLES AND COVARIATES4.1
 PRIMARY EFFICACY VARIABLE
The primary variable for statistical comparison between treatment groups will be the proportion of 
patients achieving a combined clinical response using the SRI at Week 52. An SRI is defined as: 
 
a reduction from baseline in the SLEDAI-2K score of at least 4 points; 
 
no worsening in PGA (with worsening defined as an increase in PhGA of more than 0.30 point 
from baseline); 
 
no new BILAG A body system score and; 


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 
no more than 1 new BILAG B body system score from baseline. 
The combined clinical response is intended to demonstrate an improvement in overall disease activity 
without worsening of disease in any organ system as determined by the investigator’s quantitative and 
qualitative assessments.   4.2
 SECONDARY EFFICACY VARIABLES
The following secondary efficacy variables and endpoints will be analysed:  
Most important secondary efficacy variables: 
 
Proportion of patients achieving a clinical SLEDAI-2K total score of 0 at Week 52 (remission) 
 
Proportion of patients who had an assessment of “no” for arthritis symptoms using SLEDAI-
2K at Week 52 and had an assessment of “yes” at randomisation 
 
Proportion of patients who achieved a BILAG C score at week 52 who had a BILAG A or 
BILAG B score in the BILAG body system score at randomisation 
 
Absolute change in fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue 
(FACIT-Fatigue) at Week 52 
 
Proportion of patients who achieved a combined clinical response using SRI (see Section 4.1 
Primary Efficacy Variable for definition) at Week 52 in the subgroup with screening SLEDAI-2K 
≥ 10 
Other secondary efficacy variables: 
 
SLEDAI-2K total score at each visit 
 
The SRI response at each visit during the study 
 
The reduction in the SLEDAI-2K total score by at least 4 points at each visit during the 
treatment period  
 
The effect of IPP-201101 on disease activity, as assessed by the BILAG-2004 disease activity 
index, at each visit during the treatment period 
 
The effect of IPP-201101 on the status of disease (PhGA scale) at each visit during the 
treatment period 
 
The reduction of the SLEDAI-2K total score by at least 5 points at each visit during the 
treatment period 
 
The reduction of the SLEDAI-2K total score by at least 6 points at each visit during the 
treatment period 
 
The SRI-5 response at each visit during the treatment period 
 
The SRI-6 response at each visit during the treatment period 
 
The SRI-7 response at each visit during the treatment period 
 
The SRI-8 response at each visit during the treatment period 
 
The SRI-9 response at each visit during the treatment period 


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 
The effect of IPP-201101 on arthritis, as assessed by the 28-joint count examination for pain 
and tenderness at each visit during the treatment period 
 
The effect of IPP-201101 on health-related quality of life, as assessed by completion of the 
Medical Outcome Survey Short Form 36 (SF-36) at visits at Weeks 12, 24, 36 and 52 (or final 
assessment) and change from baseline analysed at Week 52 
 
The reduction in the SLEDAI-2K total score by at least 4 points from baseline to Week 52  
 
The effect of IPP-201101 on disease activity, as assessed by the BILAG-2004 disease activity 
index, from baseline to Week 52  
 
The effect of IPP-201101 on the status of disease (PhGA scale) from baseline to Week 52 
 
The effect of IPP-201101 on the incidence of disease flares (i.e. Safety of Estrogens in Lupus 
Erythematosus: National Assessment [SELENA] Flare Index [SFI] and SLEDAI-2K score of 
greater than 15) at each visit during the treatment period 
 
The effect of IPP-201101 on the occurrence of SLE-induced organ damage (e.g. Systemic Lupus 
International Collaborative Clinics/American College of Rheumatology [SLICC/ACR] Damage 
Index [SDI] and adverse event inquiry) at visits at Weeks 24 and 52 (or final assessment) 
 
The effect of IPP-201101 on steroid dose over time throughout the study 4.3
 EXPLORATORY EFFICACY VARIABLES
The following exploratory efficacy variables and endpoints will be analysed:  
 
The effect of IPP-201101 on the biologic markers of disease activity, anti-double-stranded 
deoxyribonucleic acid antibody (anti-dsDNA Ab) complement components (C3 and C4), at 
each visit during the treatment period 
 
The effect of IPP-201101 on the following biologic markers of disease activity at Weeks 4, 12, 
24, 36 and 52 (or final assessment): 
o Antinuclear antibody (ANA) 
o Anti-uridine rich 70 kilodalton small nuclear ribonucleoprotein particle Ab (Anti-U1-
70K snRNP Ab) 
o Anti-Smith antibody (Anti-Sm Ab) 
o C-reactive protein (CRP) 
o Immunoglobulin G (IgG), Immunoglobulin M (IgM), Immunoglobulin E (IgE) and 
Immunoglobulin A (IgA)  
 
In vitro intracellular and cytokine response 4.4
 PHARMACOKINETIC AND IMMUNOGENICITY VARIABLES
A blood sample for measurement of the concentration of IPP-201101 will be obtained from all patients 
who have a serious adverse event and/or have an adverse event leading to withdrawal from the study. 
The immunogenicity of IPP-201101 will be assessed by any presence of anti-IPP-201101 antibodies 
(anti-IPP-201101 Ab) at visits at Weeks 2, 4, 12, 20, 28, 36, 44 and 52 (or final assessment). 


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 4.5
 SAFETY VARIABLES
The safety and tolerability of IPP-201101 will be evaluated by the following: 
 
Occurrence of adverse events throughout the study.  
 
Specified adverse events of special interest will be studied in more detail. These are: 
1. immune-mediated adverse reaction, 
2. hepatitis, 
3. pneumonitis, 
4. facial/face oedema or allergic oedema, 
5. nephritis or pyelonephritis, 
6. autoimmune haemolytic anaemia.  
 
Clinical laboratory parameters (serum chemistry, haematology and urinalysis) at each visit 
during the treatment period 
 
Vital signs (systolic and diastolic blood pressures, pulse, temperature and body weight) 
measurements at each visit during the treatment period 
 
12-lead ECG findings at Week 52 (or final assessment) 
 
Physical examination findings, including physical examination symptom directed findings, at 
specified time points at each visit during the treatment period 
 
Evaluation for suicidality at each visit during the treatment period using the Columbia-Suicide 
Severity Rating Scale (C-SSRS) 
 
Anaphylaxis assessment using the Clinical Criteria for Diagnosing Anaphylaxis 
 
Concomitant medication usage throughout the study 5
 DEFINITIONS
Study Drug. Study drug is taken to mean either IPP-201101 or placebo. 
Baseline. Baseline is defined by patient and by variable as the last non-missing value before the first 
dose of study drug. This will be the pre-dose assessment at Visit 2/Week 0. 
Study Day. Study day is the number of days since start of treatment where the date of first dose is 
counted as Day 1. 
Protocol Deviation: a deviation related to study inclusion or exclusion criteria, conduct of the trial, 
patient management or patient assessment. This refers to any change, divergence, or departure from 
the study design or procedures defined in the protocol. Deviations recorded by the Project Manager, 
CRA, Data Management or by Statistical programming checks will be identified and discussed at the 
Data Review Meeting (DRM) before database lock (DBL) to agree which should be included in the 
protocol deviation listing. 


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 6
 ANALYSIS SETS 
Membership of the analysis sets will be reviewed and agreed at a DRM before DBL. 6.1
 RANDOMISEDSET
The Randomised Set is defined as all patients who were randomised to a treatment at enrolment, 
regardless of whether or not they took any study drug. 
The Randomised Set will be used for all study population summaries.  6.2
 SAFETY SET
The Safety Set is defined as all patients who receive at least one dose of investigational drug.  
The Safety Set will be used for all safety analyses. Patients who receive the wrong treatment in error 
will be analysed as treated for safety analyses. 6.3
 FULL ANALYSIS SET 
The Full Analysis Set (FAS) will include all patients in the safety set. 
The FAS will be used for all efficacy analyses. Patients who receive the wrong treatment in error will 
be analysed as randomised for efficacy analyses. 7
 SAFETY MONITORING
No formal safety monitoring reports will be provided by Orion statistics department. 8
 INTERIM ANALYSES
No interim analysis is planned. 9
 DATA9.1
 ECRFDATA
eCRF data will be provided by Orion data management to the statistics department as SAS data sets in 
Orion standard format which will be used for programming the outputs. Populated data sets will be 
available when programming starts. These may contain dummy data if real data is not yet available.  
No laboratory results will be entered on the eCRF. 


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 9.2
 EXTERNAL DATA9.2.1
 Laboratory Data
Transfers of central laboratory data will be received in an agreed format and uploaded to a SAS dataset 
by Orion data management. Populated test transfers (using dummy data if necessary) will be received 
before programming can start.  
Laboratory samples and additional assays will be analysed centrally by the following laboratories: 
 
Seirian Laboratories (Simbec), UK 
 
Eurofins Central Laboratory, US  
Reference ranges will be recorded alongside each parameter as part of the transfer file.   9.2.2
 Other non-CRF data
Any PK concentration data will be received from Seirian Laboratories in an Excel spreadsheet in an 
agreed format. If any PK data is collected then the concentration spreadsheet will be uploaded to a 
SAS dataset for programming 
BILAG, SLEDAI-2K, flare index and PhGA data will be received from ADS-Limathon, UK in an agreed 
format, and will be uploaded to a SAS dataset for programming.  9.3
 RANDOMISATION LIST
The randomisation list will be uploaded to a SAS dataset following DBL. 9.4
 PROGRAMMING AND DATA REVIEW
Programming of analysis datasets, tables, figures and listings will be ongoing during the data 
management of the study. Blind outputs may be reviewed by ImmuPharma before DBL. 
When the final data is considered clean, key listings (to be agreed) will be run and distributed to the 
study team for review. A blind DRM will be held to discuss the outcome of this review and the 
protocol deviations. Once all data issues have been resolved and the analysis populations approved, 
the database will be locked. The randomisation codes will be opened and the final run of outputs and 
final quality control (QC) will then take place.  10
 STATISTICAL METHODS10.1
 GENERAL PRINCIPLES
All statistical methods will be based on the International Conference on Harmonisation (ICH) E9 
document “Statistical Principles for Clinical Trials”. 
Data will be summarised by treatment group.  A total column showing all patients will be included for 
baseline and safety summaries. Where appropriate, data will also be summarised by visit with 
summaries for each visit attended as scheduled and an additional summary for final (last scheduled visit 
or early withdrawal). The format of the summaries is defined in the shells at the end of this document. 


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In summary and analysis tables of continuous variables, standard descriptive statistics (N, mean, 
standard deviation [SD], median, minimum and maximum) will be presented.  Least Squares mean (LS 
mean), standard error (SE) and 95% confidence Interval (CI) will be presented in the statistical analysis 
outputs as appropriate. The minimum and maximum statistics will be presented in summary tables to 
the same number of significant figures as the original data.  The mean/AM, median, LS mean, CI, SD 
and SE will be presented to one more decimal place than the original data.   
For numeric data which includes non-numeric values (e.g. PK data reported as BLQ or lab results 
reported as < 10 or >100) the following principles will be applied when summarising the data: 
 
BLQ will be replaced with a value that is ½ of the lower limit of quantification (LLQ) 
 
Results reported as < x will be treated in the same way as BLQ  with LLQ=x 
 
Otherwise AM, SD, CI and %CV will not be calculated 
 
Whenever meaningful, minimum, median and maximum will be presented based on the 
reported data (e.g. minimum = <10, median = 20, maximum = >100) 
In summary tables of categorical variables, the number of non-missing observations by category will be 
presented with percentages. Categories for missing data will be presented if necessary. Unless 
otherwise specified, the denominator for each percentage will be the number of non-missing 
observations within the column. All percentages will be presented to one decimal place. 
If changes in severity for the same TEAE have been reported separately but with the same AE number, 
they will be collapsed to a single AE with maximum severity for the summary tables, but listed as 
reported. In AE summary tables, a patient will be counted only once in each preferred term or system 
organ class category, but all results will be listed. 
Classifications of medical history, concomitant medication and adverse events will be sorted 
alphabetically within the summary tables. 
If any laboratory assessments are repeated at the same visit, the result from the repeat assessment will 
be used in summaries. Both values will be listed. 
Data collected on the eCRF will be presented within data listings.  The data listings will be sorted by 
treatment group, patient number and visit/week/day. Treatment group will be as allocated 
(randomised). If any patients receive the wrong treatment this will be flagged in all listings. Visits 
outside the visit windows will be identified within the listings.  
The date format for all output presentations will be ‘ddMMMyyyy’. 
All statistical analysis will be performed using SAS 9.3 or higher. 
All hypothesis testing will be carried out at the 5% (2-sided) significance level unless stated otherwise.  
P-values will be rounded to four decimal places.  P-values less than 0.0001 will be reported as <0.0001 
in tables.   
If any of the assumptions underlying the formal statistical methods proposed are violated during the 
analysis of the final data, alternative statistical methods will be used and any changes documented in the 
statistical methods section of the clinical study report (CSR), including the rationale for use. 10.2
 STRATIFICATION ADJUSTMENT
Randomisation was stratified by region, SLEDAI-2K screening total score and racial-ethnic 
classification. The primary endpoint analysis will be adjusted for these stratification factors.  


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 10.3
 MISSING DATA10.3.1
 Individual Questionnaire items
For the purpose of efficacy analysis, missing or invalid values will be imputed using data from the 
previous visit for individual items and scores in the questionnaires and scales. For a derived score 
involving multiple items, the missing or invalid individual items will be imputed first before calculating 
the derived scores based on the complete individual item values. 
These rules only apply for visits in which the patient is currently in the study and some data or an 
individual item is missing. If an assessment is not done at a visit, the missing data will not be imputed.   10.3.2
 Sensitivity Analyses
Sensitivity analyses will be performed to investigate the possible impact of violations of assumptions 
about missing data on the reliability of the efficacy results. A tipping point analysis, where dropouts on 
IPP-201101 are assigned worse outcomes than those on placebo, will be performed. Additionally the 
last observation carried forward (LOCF) method will be used. For the continuous secondary endpoint 
FACIT-Fatigue multiple imputation will be used. See Section 11.3 Efficacy Analyses for more details.  10.4
 POOLING OF SITES
Sites will be pooled for all analyses. There will be no adjustment for centre effect or treatment by 
centre interaction. 10.5
 STATISTICAL ISSUES
There are no statistical issues. 11
 STATISTICAL OUTPUT
General principles for layout of the statistical output are described in Section 10.1, including 
specification of the table columns, and these are illustrated for each unique table in the table shells in 
Section 15. For clarity and brevity in this document the phrase “by treatment group” is understood for 
all summaries and is not included within the text of this section. 11.1
 PATIENT DISPOSITION
The patient disposition table will summarise the following data for all patients (Table 14.1.1): 
 
number of screened patients 
 
number of patients randomised 
 
number of patients who failed screening 
 
number of patients randomised but not treated  
 
The number (%) of patients in the FAS 
 
The number (%) of patients in the Safety Set 


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The number (%) of patients who complete the study and patients who withdraw from the study by the 
main reason for withdrawal will be summarised for the set of randomised patients (Table 14.1.2). 
A listing of all patients with protocol deviations will be presented. A data listing presenting the 
eligibility for the analysis sets for each patient will also be presented.  11.2
 PATIENTCHARACTERISTICS AT BASELINE
The main analysis set for the baseline summaries will be the set of randomised patients.  11.2.1
 Demographic and Baseline Characteristics
Age will be calculated using Date of Birth (DOB) and Date of Informed Consent and presented as age 
at last birthday as an integer. Height is recorded as part of the physical examination at screening visit 
only.  
Age, gender, ethnicity, race, height, weight and BMI will be summarised by stratification factor and 
overall (Table 14.1.3). 11.2.2
 Medical Historyand Current Medical Conditions
All conditions will be coded using the version of the Medical Dictionary for Regulatory Activities 
(MedDRA) defined in the Data Handling Manual. Past medical/surgical history and current medical 
conditions will be summarised by system organ class (SOC) and preferred term (PT). The number (%) 
of patients reporting each condition will be presented by stratification factor and overall (Table 14.1.4.1 
and 14.1.4.2). 11.2.3
 Prior Medications
All medications taken by patients on entry to the study or during the study will be recorded in the 
CRF. Medications will be classified using the version of the World Health Organisation Drug 
Dictionary (WHODD) coding dictionary defined in the Data Management Plan (DMP). The Anatomical 
Therapeutic Chemical (ATC) Classification and WHODD PT will be used to list and summarise the 
data.    
Prior medications are defined as medication that started and stopped before Visit 2 (week 0). Only 
medications where the stop date is prior to Visit 2 will be considered prior. If the stop date is 
unknown or incomplete and the medications cannot definitely be considered as stopped prior to Visit 
2 then the medications will be considered as concomitant medications.   
The number (%) of patients reporting the use of any prior medications by ATC classification and PT 
will be summarised by stratification factor and overall (Table 14.1.5). 11.2.4
 SLE Disease History
Date of diagnosis of SLE is recorded on the eCRF along with information about the patient’s last SLE 
flare and SLE-related hospitalisation. This information will be presented as time since diagnosis of SLE 
(years), time since last SLE flare (years) and time since SLE-related hospitalisation (years), and will be 
summarised using descriptive statistics by stratification factor and overall (Table 14.1.6). Time since 
diagnosis of SLE/ last SLE flare/ SLE-related hospitalisation is calculated as the difference between date 
of informed consent and date of diagnosis of SLE/ date of last SLE flare/ date of SLE-related 
hospitalisation.  


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 11.2.5
 Other Baseline Characteristics
Physical examination and 12-lead ECG will be performed at screening (Visit 1) and results will be 
summarised using descriptive statistics by stratification factor and overall (Table 14.1.7). 11.3
 EFFICACY ANALYSES
Treatment comparisons will be IPP-201101 vs placebo. The main analysis set for the efficacy analyses 
will be the FAS.  11.3.1
 Primary Efficacy Variable11.3.1.1
 Primary Analysis of the Primary Variable
The primary efficacy variable is the proportion of patients who achieve a combined clinical response 
using SRI assessed at Week 52. An SRI response is defined as: 
 
A reduction from baseline in the SLEDAI-2K score of at least 4 points; 
 
no worsening in PhGA (with worsening defined as an increase in PhGA of more than 0.30 
point from baseline); 
 
no new BILAG A body system score; 
 
and no more than 1 new BILAG B body system score from baseline.  
The SRI will be analysed using a logistic regression model with treatment and stratification factors as 
main factors and SRI is linked to the model factors through the logit function. Patients who withdraw 
from the study are classified as non-responders as measured by SRI at Week 52. Patients with no post-
baseline efficacy assessment are considered non-responders. The likelihood-ratio-based Chi-square 
statistics will be used to test treatment difference, at the 5% significance level. Odds ratio and 
associated 95% CI will be determined from the logistic regression model and presented for IPP-201101 
vs placebo (Table 14.2.1.1).  11.3.1.2
 SensitivityAnalyses of the Primary Variable
The primary analysis will be repeated using 4 different imputation methods to estimate missing SRI at 
Week 52 according to the reason for withdrawal.  
In the first method, patients who withdrew because of lack of efficacy will be classified as treatment 
failures assessed by SRI at Week 52. For patients who withdraw because of other reasons, their 
missing SRI at Week 52 will be estimated using the last observation carried forward (LOCF) multiple 
imputation (Table 14.2.1.2.1).  
In the second method, all missing SRI values at Week 52 will be imputed using the last observation 
carried forward (LOCF) method (Table 14.2.1.2.2). 
In the third method, patients who withdraw and those completers who used prohibited medication 
within 8 weeks from Week 52 will be classified as non-responders (Table 14.2.1.2.3). 
In the fourth method, a tipping point analysis, where dropouts on IPP-201101 are assigned worse 
outcomes than those on placebo, will be performed. IPP-201101 dropouts will be imputed as non-
responders and placebo dropouts will be imputed as responders. This tipping point analysis will be 
identical to the primary analysis described in Section 11.3.1.1, apart from placebo patients with missing 
assessments at Week 52 will be imputed as responders and IPP-201101 patients with missing 
assessments at Week 52 will be imputed as non-responders (Table 14.2.1.2.4). 


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 11.3.2
 Secondary Efficacy Variables11.3.2.1
 Most Important Secondary Endpoints
The most important secondary endpoints (in order of importance) are: 
 
Proportion of patients achieving a clinical SLEDAI-2K total score of 0 at Week 52 (remission). 
This will be summarised using descriptive statistics and analysed using logistic regression in the 
same way as the primary analysis of the primary variable (Table 14.2.2.1.1). Patients who 
withdraw early from the study are classified as non-responders at Week 52. 
 
Proportion of patients who had an assessment of “no” for arthritis symptoms using SLEDAI-
2K at Week 52 and had an assessment of “yes” at randomisation. This will be summarised 
using descriptive statistics and analysed using logistic regression in the same way as the primary 
analysis of the primary variable (Table 14.2.2.1.2). Patients who withdraw early from the study 
are classified as non-responders at Week 52. 
 
Proportion of patients who achieved a BILAG C score at Week 52 who had a BILAG A or 
BILAG B score in the BILAG body system score at randomisation. This will be summarised 
using descriptive statistics and analysed using logistic regression in the same way as the primary 
analysis of the primary variable (Table 14.2.2.1.3). Patients who withdraw early from the study 
are classified as non-responders at Week 52. 
 
Absolute change in fatigue using the FACIT-Fatigue at Week 52. The change from baseline at 
Week 52 will be descriptively summarised and analysed using an Analysis of Covariance 
(ANCOVA) model including fixed effects for treatment and the randomisation stratification 
factors region (Europe, US), SLEDAI-2K screening total score (6 to 9, ≥ 10) and racial-ethnic 
classification (black/Hispanic or others), and also the baseline fatigue score using the FACIT-
Fatigue as a covariate. The LOCF method will be used to impute missing values. LS mean 
estimates of the difference between the two treatment groups, together with 95% CIs, SE and 
the p-value, will be provided. (Table 14.2.2.1.4.1). 
 
Proportion of patients who achieved a combined clinical response using SRI (see Section 
11.3.1.1 Primary Analysis of the Primary Variable for definition) at Week 52 in the subgroup 
with screening SLEDAI-2K ≥ 10. This will be summarised using descriptive statistics and 
analysed using logistic regression in the same way as the primary analysis of the primary 
variable (Table 14.2.2.1.5). Patients who withdraw early from the study are classified as non-
responders at Week 52. 
To control for multiplicity a hierarchical testing approach will be used for the 5 most important 
secondary endpoints. The first will be tested at the 5% significance level. If this test is significant the 
second most important will be tested, then the third, and so on. This will continue until a test result is 
not statistically significant, at which point the process will stop. Sensitivity Analyses of the SecondaryEndpoint VariableFACIT-Fatigue
A multiple imputation method will be used to account for missing data at Week 52. The imputation 
values will be drawn from the categories formed by treatment group and randomisation stratum to 
which the patient belongs. This will be done as follows: 
1. The missing values are filled in m times to generate m complete data sets (using SAS PROC 
MI). A value of 5 will be used for m. 


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This is done by fitting m linear regression models using patients with observed values for the 
endpoint and further covariates. Based on the fitted regression model, a new regression model 
is simulated from the Bayesian posterior predictive distribution of the regression parameters 
and is used to impute the missing values; 
2. The m complete datasets are analysed by using the relevant statistical procedure (ANCOVA) 
for this endpoint; 
3. The results from the m analyses are combined for statistical inference (using SAS PROC 
MIANALYZE). 
Multiple imputation aims to allow for the uncertainty about the missing data by creating several 
different plausible imputed data sets and appropriately combining results obtained from each of them. 
The method assumes that missing values are ‘missing at random’ (MAR), such that any systematic 
difference between the missing values and the observed values can be explained by differences in 
observed data (Table 14.2.2.1.4.2).  11.3.2.2
 Other Secondary Endpoints
The following other secondary endpoints will be descriptively summarised only, unless otherwise 
specified: 
 
SLEDAI-2K total score at each visit (Table 14.2.2.2.1). 
 
Proportion of patients achieving an SRI response at each visit compared to baseline (Table 
14.2.2.2.2). 
 
Proportion of patients achieving a clinical SLEDAI-2K response at each visit compared to 
baseline, where a clinical response is defined as a reduction of at least 4 points in the SLEDAI-
2K clinical score (Table 14.2.2.2.3) 
 
Proportion of patients achieving a BILAG-2004 clinical response at each visit compared to 
baseline (an improvement in at least 1 category from a B score to a C or D score, with no 
worsening in any other category) (Table 14.2.2.2.4) 
 
Proportion of patients showing no worsening on a PhGA scale at each visit compared to 
baseline (Table 14.2.2.2.5). 
 
Proportion of patients achieving a reduction of 5 points in the SLEDAI-2K total score at each 
visit compared to baseline (Table 14.2.2.2.6) 
 
Proportion of patients achieving a reduction of 6 points in the SLEDAI-2K total score at each 
visit compared to baseline (Table 14.2.2.2.7) 
 
Proportion of patients achieving an SRI-5 response at each visit compared to baseline (Table 
14.2.2.2.8) 
 
Proportion of patients achieving an SRI-6 response at each visit compared to baseline (Table 
14.2.2.2.9) 
 
Proportion of patients achieving an SRI-7 response at each visit compared to baseline (Table 
14.2.2.2.10) 
 
Proportion of patients achieving an SRI-8 response at each visit compared to baseline (Table 
14.2.2.2.11) 


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 
Proportion of patients achieving an SRI-9 response at each visit compared to baseline (Table 
14.2.2.2.12) 
 
Proportion of patients showing an improvement from baseline in tender and swollen joint 
counts using the 28-joint count examination for pain and tenderness (Table 14.2.2.2.13). 
Tender and swollen joints are a significant cause of morbidity in patients with SLE and lupus 
arthritis will be evaluated using this assessment. 
 
Descriptive summary statistics for absolute and relative changes from baseline in the SF-36 
total score at Weeks 12, 24, 36 and 52 (or final assessment) will be presented (Table 
14.2.2.2.14). Assessments of the SF-36 with missing values will be omitted from the summaries. 
 
Proportion of patients achieving a reduction of at least 4 points in the SLEDAI-2K total score 
at Week 52 (Table 14.2.2.2.15). 
 
Proportion of patients achieving a BILAG-2004 response (no new BILAG A body system score 
and no more than 1 new BILAG B body system score from baseline) at Week 52 (Table 
14.2.2.2.16). 
 
Proportion of patients showing no worsening on a PhGA scale at Week 52 (Table 14.2.2.2.17). 
 
SFI time to first mild to moderate flare from time of randomisation to each visit (days), 
incidence of mild to moderate flare, incidence of severe flare and time to severe flare from 
time of randomisation to each visit (days) (Table 14.2.2.2.18) 
 
Proportion of patients with SLEDAI-2K score of greater than 15 at each visit (Table 
14.2.2.2.19) 
 
Changes in the SDI total score from screening to Week 24 and from screening to Week 52 
(or final assessment) (Table 14.2.2.2.20). The SDI assesses specific comorbidities associated 
with SLE and consists of 39 items covering 12 organ systems. 
 
Steroid dose will be evaluated to determine the proportion of patients taking a dose less than 
7.5 mg of prednisone equivalent/day, a dose of 7.5 mg prednisone equivalent/day or more, and 
none per day at baseline, Week 24 and Week 52 (Table 14.2.2.2.21.1). Proportion of patients 
with changes in steroid dose from baseline to Weeks 24 and 52 will be presented in a shift 
table (Table 14.2.2.2.21.2). 
 
A reduction from baseline in the SLEDAI-2K score of at least 4 points. This will be 
summarised using descriptive statistics and analysed using logistic regression in the same way 
as the primary analysis of the primary variable (Table 14.2.2.2.22). Patients who withdraw early 
from the study are classified as non-responders at Week 52. 
 
No worsening in PhGA (with worsening defined as an increase in PhGA of more than 0.30 
point from baseline). This will be summarised using descriptive statistics and analysed using 
logistic regression in the same way as the primary analysis of the primary variable (Table 
14.2.2.2.23). Patients who withdraw early from the study are classified as non-responders at 
Week 52.  
 
No new BILAG A body system score. This will be summarised using descriptive statistics and 
analysed using logistic regression in the same way as the primary analysis of the primary 
variable (Table 14.2.2.2.24). Patients who withdraw early from the study are classified as non-
responders at Week 52.  


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 
No more than 1 new BILAG B body system score from baseline. This will be summarised using 
descriptive statistics and analysed using logistic regression in the same way as the primary 
analysis of the primary variable (Table 14.2.2.2.25). Patients who withdraw early from the study 
are classified as non-responders at Week 52. 11.3.3
 Exploratory Efficacy Variables
The following exploratory efficacy variables will be descriptively summarised: 
 
Changes from baseline in the anti-dsDNA Ab, C3 and C4 biomarkers at each visit during the 
treatment period (Table 14.2.3.1). Biomarkers in SLE are often used for diagnosis but do not 
always correlate with changes in disease activity, so these will be evaluated to determine if a 
change in level correlates with a change in disease activity.  
 
Changes in the biomarkers ANA, anti-U1-70K snRNP Ab, anti-Sm Ab, CRP, IgG, IgM, IgA and 
IgE from baseline to Weeks 4, 12, 24, 36 and 52 (or final assessment) (Table 14.2.3.2). As 
above, these will be evaluated to determine if a change in level correlates with a change in 
disease activity.  
 
Blood samples (5 mL) for in vitro intracellular and cytokine response will be collected from 
patients at selected study centres via venipuncture or indwelling catheter prior to study drug 
administration at weeks 0, 4, 24, and 48. In vitro intracellular and cytokine response data will 
be summarised by time point (Table 14.2.3.3). 
 
The cumulative distribution of the decrease in the first item of the SRI responder definition (a 
reduction from baseline in the SLEDAI-2K score of at least 1, 2, 3 etc. points) showing the 
probability of attaining each decrease, or worse will be summarised (Table 14.2.3.4) and 
plotted by treatment on the FAS (Figure 1) at Week 52.    11.4
 PHARMACOKINETICAND IMMUNOGENICITY ANALYSES
A blood sample for measurement of the concentration of IPP-201101 will be obtained from all patients 
who have a serious adverse event and/or have an adverse event leading to withdrawal from the study. 
Any PK samples collected when a patient is withdrawn due to a SAE related to study treatment will be 
listed. 
Anti-IPP-201101 Ab testing will be performed at Weeks 0, 2, 4, 12, 20, 28, 36, 44 and 52 (or final 
assessment) prior to study drug administration. The immunogenicity of IPP-201101 will be evaluated by 
determining the presence of any anti-IPP-201101 at Weeks 2, 4, 12, 20, 28, 36, 44 and 52 (or final 
assessment). Results will be summarised by treatment and visit using the FAS (Table 14.2.4) and all 
results will be listed.  11.5
 SAFETY ANALYSES
The main analysis set for the safety analyses will be the safety set.  11.5.1
 Adverse Events
All adverse events (AE) will be classified using the version of the MedDRA coding dictionary specified 
in the DMP.  
Events will be classified as treatment-emergent if they started or increased in severity on or after the 
first date and time of medication dosing at Visit 2 and up to study closure or withdrawal date. If an 


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event start date is partial, then the start day, month, year or stop date will be used to determine if the 
event is treatment-emergent.  If the classification of the AE cannot be determined from the data 
available, then the event will be considered treatment-emergent. 
Treatment-emergent adverse events (TEAEs) will be further classified as follows: 
Severe TEAEs: Severity classified as ‘severe’ (Common Toxicity Criteria [CTC] grade 3 or 4) or 
missing. 
Serious TEAEs: Serious classified as ‘yes’ or missing. 
Drug-related TEAEs: Relationship to study drug classified as ‘related’ or missing. 
Serious drug-related TEAEs: Both serious and drug-related, as specified above. 
TEAEs leading to withdrawal from study: Action taken classified as ‘discontinued’. 
TEAEs overall and in each of the above classifications will be summarised by treatment group and 
overall. (Table 14.3.1.1). All TEAEs and drug-related TEAEs will also be summarised by severity within 
the same table.  
Summaries by SOC and PT will also be presented for treatment-emergent events (Table 14.3.1.2). 
Similar tables will be presented for each of the classifications of treatment-emergent events above 
(Tables 14.3.1.3 to 14.3.1.7).  
All AE summary tables will show the number (%) of patients having at least one event and the number 
of events in each treatment group and overall. Note: If a patient has multiple AEs with the same PT, 
these will be summarised once within the count for N (%) of patients, but each event will be counted 
within the number of reports n of each AE. Changes in severity of the same AE (if collected) will be 
counted only once within the number of reports n of each AE. 
The following will be presented in listing format within the data summaries: 
 
Deaths (Table 14.3.1.8.1) 
 
Serious Adverse Events (Table 14.3.1.8.2) 
 
Adverse Events which Led to Withdrawal (Table 14.3.1.8.3) 
All adverse events (including non-treatment-emergent events) recorded on the CRF will be listed 
within the data listings.  11.5.2
 Adverse Eventsof Special interest
The adverse events of special interest are: 
 
immune-mediated adverse reaction, 
 
hepatitis, 
 
pneumonitis, 
 
facial/face oedema or allergic oedema, 
 
nephritis or pyelonephritis, 
 
autoimmune haemolytic anaemia.  
A summary by SOC and PT will be presented for these adverse events of special interest (Table 
14.3.1.9).  


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 11.5.3
 Laboratory Data
Clinical laboratory tests (serum chemistry, haematology and urinalysis) will be carried out at screening 
(Visit 1), baseline/start of study drug treatment (Visit 2), throughout the treatment period, and at the 
final assessment.   
The laboratory tests will be performed using the central laboratory identified at the front of the 
protocol (and in the Laboratory Procedures Manual provided in the study file documents). Specific 
laboratory tests to be performed are listed below: 
 
Serum chemistry: calcium, phosphate, sodium, potassium, chloride, bicarbonate or carbon 
dioxide, glucose, blood urea nitrogen (BUN), creatinine, cholesterol, uric acid, alanine 
transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), gamma-
glutamyl transpeptidase (GGT), alkaline phosphatase, creatinine phosphokinase, total protein, 
albumin, total bilirubin and direct bilirubin 
 
Haematology: haemaglobin, haematocrit, platelet count, absolute neutrophil count (ANC), 
white blood cell (WBC) count and differential count (polymorphonuclear leukocytes 
[neutrophils], lymphocytes, eosinophils, monocytes, basophils, metamyelocytes) 
 
Urinalysis: protein, glucose, ketones, blood (haemoglobin), pH, specific gravity, spot protein-
creatinine ratio, creatinine clearance, eGFR and microscopic (bacteria, red blood cells [RBCs], 
WBCs, casts, crystals) 
The absolute values of each parameter and changes from baseline will be descriptively summarised at 
each visit by treatment and overall (Tables 14.3.2.1 to 14.3.2.3). 
If laboratory results are repeated at the same visit, the repeated result will be used in summaries 
(instead of the original one) provided the sample was taken within the visit window, otherwise the 
original result will be used. All values will be compared to pre-specified boundaries in order to identify 
clinically significant changes or values and will be highlighted in listings.  
Laboratory results at unscheduled visits will be included in the listings but will not be summarised. 
Serum pregnancy data will be listed only. 
A Coombs’ test will be obtained at screening. At subsequent visits, if hemolysis is suspected or 
confirmed, Coombs’ test, haptoglobin, and a peripheral smear will be obtained. Results of these tests 
will be listed only. 11.5.4
 Vital Signs
Systolic blood pressure, diastolic blood pressure, pulse and body temperature are collected at all visits.  
Weight is measured at all visits as part of the physical examination (complete and symptom directed) 
and will be descriptively summarised as part of vital signs. 
The absolute values of the vital signs and changes from baseline will be descriptively summarised at 
each visit (Tables 14.3.3). 11.5.5
 Electrocardiogram
A 12-lead ECG will be completed at Screening and at Week 52.  
The number and percentage of patients with Normal / Abnormal NCS / Abnormal CS ECG results at 
these visits will be summarised in a shift table (Table 14.3.4).  


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 11.5.6
 Physical Examination
A complete physical examination will be conducted at screening (Visit 1) and at the final assessment 
(or early termination). Symptom directed physical examination evaluations and the 28-joint count 
examination for pain and tenderness will be performed throughout the treatment period (Week 0 
through 52).  
All physical examination data will be listed and newly occurring physical examination abnormalities will 
be identified within the listings.  11.5.7
 Suicidality Assessment C-SSRS
Suicidality will be assessed using the C-SSRS at baseline and at each visit during the treatment period. 
The C-SSRS assesses suicidality from ideation to behaviours and monitors the potential emergence of 
suicidality in clinical studies.  
The C-SSRS Baseline version will be performed at baseline (Week 0) and the C-SSRS since Last Visit 
version will be performed at Weeks 4 to 52 (or final assessment). Cumulative positive C-SSRS 
outcomes during the study will be descriptively summarised (Table 14.3.5).   11.5.8
 Anaphylaxis Evaluation
Anaphylaxis is defined as a serious allergic reaction that is rapid in onset and may cause death. Any 
patient who experiences an adverse event that presents with signs and/or symptoms that are 
suggestive of an anaphylactic, anaphylactoid, or drug hypersensitivity reaction will be evaluated using 
the Clinical Criteria for Diagnosing Anaphylaxis at the DRM before database lock to agree which 
should be flagged within the adverse event data listing.  11.5.9
 Concomitant Medication 
Concomitant medications are defined as medications that started before Visit 2 (week 0) and either 
stopped on the day of Visit 2 or continued into the study. They will also include all medications taken 
while the patient is treated with study drug. Concomitant medications can be further classified as: 
 
Present at screening (started before Week 0 and stopped on date of Week 0) 
 
Ongoing at baseline (started before Week 0 and ongoing at Week 0) 
 
Started after first dose (started any time after Week 0 through to Week 52) 
Partial start dates where the medication cannot definitely be considered as starting prior to Week 0 
will lead to a categorisation of the medications as having started on or after Week 0. 
The number (%) of patients reporting the use of any concomitant medications in each of the above 
categories and the number (%) of patients taking each drug by ATC classification and PT will be 
summarised, by category (Table 14.3.6).   11.6
 STUDY TERMINATION
Time to study termination (days) is calculated as (date of study termination - date of informed 
consent).  
A Kaplan-Meier plot of time to study termination will be presented (Figure 2) and summarised using 
descriptive statistics (Table 14.3.7). 


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If there are sufficient numbers this will also be done by individual primary reason for withdrawal from 
study. 11.7
 STUDY DRUG EXPOSURE
Study drug exposure will be descriptively summarised by treatment and baseline stratification factors 
(Table 14.3.8). Exposure will be characterised by the duration of treatment and the number of 
injections received. Treatment duration is calculated as the total number of days from day of first dose 
to day of last dose.  11.8
 PROCEDURES/NON-DRUG THERAPIES
All prior procedures/therapies (started before date of first study drug intake) and current 
procedures/therapies (started during the treatment period) will be collected on the eCRF but will not 
be coded. All procedures/non-drug therapy data will be listed. 12
 VALIDATION
All tables, figures and listings will be subject to independent quality control and visual review. Unique 
tables will be independently programmed. Findings will be documented in a quality control form and 
actions taken will also be documented.  
The completed form will be reviewed and signed by both programmers and by the head of 
biostatistics. 13
 LITERATURE CITATIONS/REFERENCES
None 
  
 
 
 
 
 
 
 


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 14
 LIST OF TABLES, FIGURES AND LISTINGS14.1
 LIST OF TABLES
Demographic Data 
 
 
Table 14.1.1 
Patient Disposition 
All Enrolled Patients 
Table 14.1.2 
Study Termination and Primary Reason for 
Withdrawal 
All Randomised Patients 
Table 14.1.3 
Demographic Characteristics  
All Randomised Patients 
Table 14.1.4.1 
Medical History 
All Randomised Patients 
Table 14.1.4.2 
Current Medical Conditions 
All Randomised Patients 
Table 14.1.5 
Prior Medications 
All Randomised Patients 
Table 14.1.6 
SLE Disease History 
All Randomised Patients 
Table 14.1.7 
Other Baseline Characteristics 
All Randomised Patients 
 
Efficacy Data 
 
 
Table 14.2.1.1 
Primary Analysis of SRI Response at Week 52 
Full Analysis Set 
Table 14.2.1.2.1 
Sensitivity Analysis 1 of SRI Response at Week 52 
Full Analysis Set 
Table 14.2.1.2.2 
Sensitivity Analysis 2 of SRI Response at Week 52 
Full Analysis Set 
Table 14.2.1.2.3 
Sensitivity Analysis 3 of SRI Response at Week 52 
Full Analysis Set 
Table 14.2.1.2.4 
Sensitivity Analysis 4 of SRI Response at Week 52 
Full Analysis Set 
Table 14.2.2.1.1 
Analysis of Patients Achieving a Clinical SLEDAI-2K Total 
Score of 0 at Week 52 (remission) 
Full Analysis Set 
Table 14.2.2.1.2 
Analysis of Patients who had an Assessment of “No” for 
Arthritis Symptoms using SLEDAI-2K at Week 52 and had 
an Assessment of “Yes” at Randomisation 
Full Analysis Set 
Table 14.2.2.1.3 
Analysis of Patients Achieving a BILAG C Score at Week 
52 who had a BILAG A or BILAG B Score at 
Randomisation 
Full Analysis Set 
Table 14.2.2.1.4.1 
Analysis of Absolute Change in Fatigue using the FACIT-
Fatigue at Week 52 
Full Analysis Set 
Table 14.2.2.1.4.2 
Sensitivity Analysis of Absolute Change in Fatigue using 
the FACIT-Fatigue at Week 52  
Full Analysis Set 
Table 14.2.2.1.5 
Analysis of SRI Response at Week 52 in the Subgroup 
with Screening SLEDAI-2K ≥ 10 
Full Analysis Set 
Table 14.2.2.2.1 
Summary of SLEDAI-2K Total Score 
Full Analysis Set 


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Table 14.2.2.2.2 
Patients Achieving a SRI-Response 
Full Analysis Set 
Table 14.2.2.2.3 
Patients Achieving a SLEDAI-2K Clinical Response 
Full Analysis Set 
Table 14.2.2.2.4 
Patients Achieving a BILAG-2004 Clinical Response 
Full Analysis Set 
Table 14.2.2.2.5 
Patients Showing No Worsening on PhGA Scale 
Full Analysis Set 
Table 14.2.2.2.6 
Patients Achieving a Reduction of 5 Points in SLEDAI-2K 
Total Score 
Full Analysis Set 
Table 14.2.2.2.7 
Patients Achieving a Reduction of 6 Points in SLEDAI-2K 
Total Score 
Full Analysis Set 
Table 14.2.2.2.8 
Patients Achieving an SRI-5 Response 
Full Analysis Set 
Table 14.2.2.2.9 
Patients Achieving an SRI-6 Response 
Full Analysis Set 
Table 14.2.2.2.10 
Patients Achieving an SRI-7 Response 
Full Analysis Set 
Table 14.2.2.2.11 
Patients Achieving an SRI-8 Response 
Full Analysis Set 
Table 14.2.2.2.12 
Patients Achieving an SRI-9 Response 
Full Analysis Set 
Table 14.2.2.2.13 
Patients Showing an Improvement in Tender and Swollen 
Joints Count 
Full Analysis Set 
Table 14.2.2.2.14 
Summary of Medical Outcome Survey SF-36 
Full Analysis Set 
Table 14.2.2.2.15 
Patients with a Reduction in the SLEDAI-2K Total Score 
by at Least 4 Points from Baseline to Week 52 
Full Analysis Set 
Table 14.2.2.2.16 
Summary of BILAG-2004 Disease Activity Index 
Full Analysis Set 
Table 14.2.2.2.17 
Summary of Status of Disease (PhGA Scale) 
Full Analysis Set 
Table 14.2.2.2.18 
Summary of SFI Variables 
Full Analysis Set 
Table 14.2.2.2.19 
Proportion of Patients with SLEDAI-2K Score Greater 
than 15 at each Visit 
Full Analysis Set 
Table 14.2.2.2.20 
Summary of Changes in the SDI Total Score 
Full Analysis Set 
Table 14.2.2.2.21.1 
Summary of Steroid Dose 
Full Analysis Set 
Table 14.2.2.2.21.2 
Shift Table of Changes in Steroid Dose 
Full Analysis Set 
Table 14.2.2.2.22 
Reduction from Baseline in SLEDAI-2K Score of at Least 
4 Points 
Full Analysis Set 
Table 14.2.2.2.23 
No Worsening in PhGA 
Full Analysis Set 
Table 14.2.2.2.24 
No New BILAG A Body System Score 
Full Analysis Set 
Table 14.2.2.2.25 
No More than 1 New BILAG B Body System Score from 
Baseline 
Full Analysis Set 
Table 14.2.3.1 
Summary of Changes in Biomarkers: Anti-dsDNA Ab, C3 
and C4 
Full Analysis Set 
Table 14.2.3.2 
Summary of Changes in Other Biomarkers 
Full Analysis Set 
Table 14.2.3.3 
Summary of In Vitro Intracellular and Cytokine Response 
Full Analysis Set 


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Table 14.2.3.4 
Cumulative Distribution of the Reduction from Baseline 
to Week 52 in SLEDAI-2K Score 
Full Analysis Set 
 
Immunogenicity Data 
 
Table 14.2.4 
Immunogenicity Findings 
Full Analysis Set 
 
Safety Data 
 
 
Table 14.3.1.1 
Treatment-Emergent Adverse Events 
Safety Set 
Table 14.3.1.2  
Treatment-Emergent Adverse Events, by SOC and PT 
Safety Set 
Table 14.3.1.3 
Severe Treatment-Emergent Adverse Events, by SOC and 
PT 
Safety Set 
Table 14.3.1.4 
Serious Treatment-Emergent Adverse Events, by SOC 
and PT 
Safety Set 
Table 14.3.1.5 
Drug-Related Treatment-Emergent Adverse Events, by 
SOC and PT 
Safety Set 
Table 14.3.1.6 
Serious Drug-Related Treatment-Emergent Adverse 
Events, by SOC and PT 
Safety Set 
Table 14.3.1.7 
Treatment-Emergent Adverse Events Leading to 
Withdrawal from the Study, by SOC and PT 
Safety Set 
Table 14.3.1.8.1 
Listing of Deaths 
Safety Set 
Table 14.3.1.8.2 
Listing of Serious Adverse Events 
Safety Set 
Table 14.3.1.8.3 
Listing of Adverse Events which Led to Withdrawal 
Safety Set 
Table 14.3.1.9 
Adverse Events of Special Interest, by SOC and PT 
Safety Set 
Table 14.3.2.1 
Summary of Serum Chemistry Parameters 
Safety Set 
Table 14.3.2.2  
Summary of Haematology Parameters 
Safety Set 
Table 14.3.2.3  
Summary of Urinalysis Parameters 
Safety Set 
Table 14.3.3 
Vital Signs 
Safety Set 
Table 14.3.4 
Shift Table of 12-Lead ECG  
Safety Set 
Table 14.3.5 
Suicidality Assessment C-SSRS 
Safety Set 
Table 14.3.6 
Concomitant Medications 
Safety Set 
Table 14.3.7 
Time to Study Termination 
Safety Set 
Table 14.3.8 
Study Drug Exposure 
Safety Set 
 
Figures 
 
 
Figure 1 
Cumulative Distribution of the Reduction from Baseline Full Analysis Set 


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in SLEDAI-2K Score  
Figure 2 
Kaplan-Meier Plot of Time to Study Termination  
Safety Set 
 14.2
 LIST OF LISTINGS
Patient Data Listings 
 
Listing 16.2.1  
Discontinued Patients  
Listing 16.2.2  
Protocol Deviations  
Listing 16.2.3  
Analysis Datasets 
Listing 16.2.4 
Demographic Data  
Listing 16.2.5  
Study Drug Exposure and Compliance  
Listing 16.2.6  
Efficacy Response Data  
Listing 16.2.7  
Adverse Event Listing 
Listing 16.2.8.1 
Laboratory Measurements: Serum Chemistry 
Listing 16.2.8.2 
Laboratory Measurements: Haematology 
Listing 16.2.8.3 
Laboratory Measurements: Urinalysis 
 
Individual Patient Data Listings (Archive) 
Listing 16.4.1 
Final Status 
Listing 16.4.2  
Patient Visit Dates 
Listing 16.4.3.1  
Inclusion Criteria 
Listing 16.4.3.2 
Exclusion Criteria 
Listing 16.4.4.1 
Medical History   
Listing 16.4.4.2 
SLE Disease History  
Listing 16.4.4.3 
BILAG Historical Disease Assessment 
Listing 16.4.5.1 
Raw Efficacy Data: SRI 
Listing 16.4.5.2 
Raw Efficacy Data: 28 Joint Count Examination for Pain and Tenderness 
Listing 16.4.5.3 
Raw Efficacy Data: SDI 
Listing 16.4.5.4 
Raw Efficacy Data: SF-36 
Listing 16.4.5.5 
Raw Efficacy Data: FACIT Fatigue Scale 
Listing 16.4.5.6 
Raw Efficacy Data: BILAG 
Listing 16.4.5.7 
Raw Efficacy Data: SFI 
Listing 16.4.5.8 
Raw Exploratory Efficacy Data: Biomarkers 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Listing 16.4.5.9 
Raw Exploratory Efficacy Data: Cytokine Response 
Listing 16.4.6.1 
IPP-201101 Plasma Concentration 
Listing 16.4.6.2 
Immunogenicity Findings 
Listing 16.4.7 
Vital Signs 
Listing 16.4.8.1 
Complete Physical Examination 
Listing 16.4.8.2 
Symptom Directed Physical Examination 
Listing 16.4.9  
12-Lead ECG 
Listing 16.4.10.1 
Prior Medications 
Listing 16.4.10.2 
Concomitant Medications 
Listing 16.4.11 
Procedures/Non-Drug Therapies 
Listing 16.4.12.1 
Raw Suicidality Assessment C-SSRS: Baseline 
Listing 16.4.12.2 
Raw Suicidality Assessment C-SSRS: Since Last Visit  
Listing 16.4.13 
Urine Pregnancy Test 
Listing 16.4.14 
Hemolysis Testing 
Listing 16.4.15 
Laboratory Sample Collection 15
 SHELLS FOR TABLES, FIGURES AND LISTINGS
The intended layouts for tables, figures and listings are presented. However, it may be appropriate for 
the Orion programmer to change the layouts, upon review of the data available, for completeness and 
clarity.  
QCd output will be produced as Rich Text Format (.rtf) files for convenient inclusion in the CSR. 
Subject to this, the following will apply: 
 
Layout will be landscape, fixed width, font size 8.  
 
Each output will have the heading: 
IPP-201101/005 (left); date ddMMMyyyy (right) 
 
Table headings will define the analysis set used for the summary/analysis. 
 
All outputs will have a footer specifying the SAS program path and filename (left); page x/y 
(right) 
 
Tables will have a footer specifying the source listing 
 
Figures will have a footer specifying the source table or listing 
 
Additional footnotes will be included where appropriate for clarification. 
 
Treatment group and patient number and will be included in all listings. 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
 
 
 
 
 
 
 
 
 
 
 
 
 
ddMMMyyyy 
Table 14.1.1 Patient Disposition (All Enrolled Patients) 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
Total number of Enrolled 
 
 
xx  
   Failed screening 
 
 
xx (xx.x%) 
   Randomised 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Randomised but not treated  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Analysis Sets 
 
 
 
   Full Analysis Set 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Safety Set 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Enrolled ” entered on eCRF 
The denominator for each percentage is the number of enrolled subjects 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
  
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
 
Table 14.1.2 Study Termination and Primary Reason for Withdrawal (All Randomised Patients) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
Completed 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Early withdrawal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Main reason for early withdrawal 
 
 
 
    Adverse event 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    Etc 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
The denominator for each percentage is the number of randomised subjects within the column 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
 
Table 14.1.3 Demographic Characteristics (All Randomised Patients)  
 
Region UK, SLEDAI-2K Score 6-9, 
Race Black/ Hispanic 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Age (years) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Sex 
N 
xx 
xx 
xx 
 
Male 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Female 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Ethnicity 
N 
xx 
xx 
xx 
 
Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Race 
N 
xx 
xx 
xx 
 
White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 


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Statistical Analysis Plan 
 
 
 
 
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Black or African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
American Indian or Alaska Native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Native Hawaiian or Other Pacific Islander 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Height (m) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Weight (kg) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
BMI (kg/m2) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 


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Statistical Analysis Plan 
 
 
 
 
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SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
The denominator for each percentage is the number of non-missing observations within the column 
Age was calculated using DOB and date of informed consent and presented as age at last birthday. 
 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
Programming note: Start each strata on a new page. Order of strata: 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
Region UK, SLEDAI-2K Score 6-9, Race Other 
Region UK, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic  
Region UK, SLEDAI-2K Score ≥ 10, Race Other 
Region USA, SLEDAI-2K Score 6-9, Race Black/ Hispanic   
Region USA, SLEDAI-2K Score 6-9, Race Other 
Region USA, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score ≥ 10, Race Other 
Overall 
 
 
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
 
Table 14.1.4.1 Medical History (All Randomised Patients) 
 
 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
  Any medical history 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
  SOC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  PT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  PT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Etc 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
  SOC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  PT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  PT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Etc 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
  Etc 
 
 
 
 
 
 
 
 
 
 
 
The denominator for each percentage is the number of randomised patients within the column 
MedDRA version <XX.X> 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
Programming note: Start each strata on a new page. Order of strata: 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
Region UK, SLEDAI-2K Score 6-9, Race Other 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Region UK, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region UK, SLEDAI-2K Score ≥ 10, Race Other 
Region USA, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score 6-9, Race Other 
Region USA, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score ≥ 10, Race Other 
Overall 
 
 
This layout also applies to: 
Table 14.1.4.2 Current Medical Conditions (All Randomised Patients)  
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
 
 
 
 
 
 
 
 
 
 
 
 
 
ddMMMyyyy 
 
Table 14.1.5 Prior Medications (All Randomised Patients) 
 
 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
Any Prior Medications1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
X, xxxxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 X0N, xxxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  X0NXX, xxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   xxxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   xxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Etc 
 
 
 
 
 
 
 
  X0NXX, xxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    xxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Etc 
 
 
 
 Etc 
 
 
 
 
 
 
 
1 Medication that started and stopped prior to first study drug intake 
WHO-DDE version <XX.X> 
The denominator for each percentage is the number of randomised patients within the column 
 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
Programming note: Start each strata on a new page. Order of strata: 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 


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Statistical Analysis Plan 
 
 
 
 
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Region UK, SLEDAI-2K Score 6-9, Race Other 
Region UK, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region UK, SLEDAI-2K Score ≥ 10, Race Other 
Region USA, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score 6-9, Race Other 
Region USA, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score ≥ 10, Race Other 
Overall 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
 
Table 14.1.6 SLE Disease History (All Randomised Patients) 
 
 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Time since diagnosis of SLE (years) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Time since last SLE flare (years) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Time since SLE-related hospitalisation (years) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 


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Statistical Analysis Plan 
 
 
 
 
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Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
Time since diagnosis of SLE/ last SLE flare/ SLE-related hospitalisation is calculated as the difference between date of informed consent and 
date of diagnosis of SLE/ date of last SLE flare/ date of SLE-related hospitalisation 
 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
Programming note: Start each strata on a new page. Order of strata: 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
Region UK, SLEDAI-2K Score 6-9, Race Other 
Region UK, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region UK, SLEDAI-2K Score ≥ 10, Race Other 
Region USA, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score 6-9, Race Other 
Region USA, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score ≥ 10, Race Other 
Overall 
 
 
 
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
 
 
 
 
 
 
 
 
 
 
 
 
 
ddMMMyyyy 
 
Table 14.1.7 Other Baseline Characteristics (All Randomised Patients) 
 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Physical examination 
 
 
 
 
  General appearance 
N 
xx 
xx 
xx 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Abnormal NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
  Skin 
N 
xx 
xx 
xx 
 
Etc 
 
 
 
  Etc 
 
 
 
 
 
 
 
 
 
12-Lead ECG 
N 
xx 
xx 
xx 
 
Normal 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Abnormal NCS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
The denominator for each percentage is the number of non-missing observations within the column 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 


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Statistical Analysis Plan 
 
 
 
 
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Programming note: Start each strata on a new page. Order of strata: 
Region UK, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
Region UK, SLEDAI-2K Score 6-9, Race Other 
Region UK, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region UK, SLEDAI-2K Score ≥ 10, Race Other 
Region USA, SLEDAI-2K Score 6-9, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score 6-9, Race Other 
Region USA, SLEDAI-2K Score ≥ 10, Race Black/ Hispanic 
Region USA, SLEDAI-2K Score ≥ 10, Race Other 
Overall 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
 
Table 14.2.1.1 Primary Analysis of SRI Response at Week 52 (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Odds ratio  
(95% CI) 
p-value 
 
 
 
 
 
 
SRI Response at Week 52 
N 
xx 
xx 
 
 
   
Clinical SRI Response 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
No Clinical SRI Response 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
Logistic regression 
Responders 
xx 
xx 
 
 
 
Non-responders 
xx 
xx 
 
 
 
Treatment: IPP-201101 vs Placebo 
 
 
x.xx (x.xx, x.xx) 
x.xxxx 
 
Region 
 
 
 
x.xxxx 
 
SLEDAI-2K score at screening 
 
 
 
x.xxxx 
 
Racial-ethnic group classification 
 
 
 
x.xxxx 
 
 
 
 
 
 
The denominator for each percentage is the number of non-missing observations within the column 
 
Logistic regression model is fitted with treatment and stratification factors as main factors.  
Patients who withdrew early from the study are classified as non-responders at Week 52. 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
This layout also applies to: 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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28 MARCH 2018  
 
1. Sensitivity Analysis of Primary Variable: 
Table 14.2.1.2.1 Sensitivity Analysis 1 of SRI Response at Week 52 (Full Analysis Set) Programming note: Footnote 2 to read ‘Patients who 
withdrew early because of treatment failure are classified as non-responders. Patients who withdrew early because of other reasons have their 
missing SRI response at Week 52 imputed using the LOCF method.’ 
Table 14.2.1.2.2 Sensitivity Analysis 2 of SRI Response at Week 52 (Full Analysis Set) Programming note: Footnote 2 to read ‘All patients who 
withdrew early have their missing SRI response at Week 52 imputed using the LOCF method.’ 
Table 14.2.1.2.3 Sensitivity Analysis 3 of SRI Response at Week 52 (Full Analysis Set) Programming note: Footnote 2 to read ‘Patients who 
withdrew early and completers who used prohibited medication within 8 weeks from Week 52 are classified as non-responders.’ 
Table 14.2.1.2.4 Sensitivity Analysis 4 of SRI Response at Week 52 (Full Analysis Set) Programming note: Footnote 2 to read ‘Patients on IPP-
201101 who withdrew early are classified as non-responders at Week 52 and patients on Placebo who withdrew early are classified as responders 
at Week 52, as part of a tipping point analysis where dropouts on IPP-201101 are assigned worse outcomes than those on Placebo.’ 
 
2. Most important secondary endpoints: 
Table 14.2.2.1.1 Analysis of Patients Achieving a Clinical SLEDAI-2K Total Score of 0 at Week 52 (remission) (Full Analysis Set)  
Table 14.2.2.1.2 Analysis of Patients who had an Assessment of "No" for Arthritis Symptoms using SLEDAI-2K at Week 52 and had an Assessment 
of "Yes" at Randomisation (Full Analysis Set) 
Table 14.2.2.1.3 Analysis of Patients Achieving a BILAG C Score at Week 52 who had a BILAG A or BILAG B Score at Randomisation (Full Analysis 
Set) 
Table 14.2.2.1.5 Analysis of SRI Response at Week 52 in the Subgroup with Screening SLEDAI-2K ≥ 10 
 
3. Other secondary endpoints: 
Table 14.2.2.2.22 Reduction from Baseline in SLEDAI-2K Score of at Least 4 Points (Full Analysis Set) 
Table 14.2.2.2.23 No Worsening in PhGA (Full Analysis Set) 
Table 14.2.2.2.24 No New BILAG A Body System Score 
Table 14.2.2.2.25 No More than 1 New BILAG B Body System Score from Baseline (Full Analysis Set) 
 
 
 
 
 


ImmuPharma IPP-201101/005 
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Immupharma IPP-201101/005 
ddMMMyyyy 
 
Table 14.2.2.1.4.1 Analysis of Absolute Change in Fatigue using the FACIT-Fatigue at Week 52 (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
p-value 
 
 
 
 
 
 
Baseline 
N 
xx 
xx 
xx 
   
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Week 52 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
Etc 
 
 
 
 
 
 
 
 
Changes from baseline to Week 52 
N 
xx 
xx 
xx 
 
Etc 
 
 
 
 
 
 
 
 
ANCOVA Model1 
 
 
 
 
Treatment difference: IPP-201101 vs Placebo 
LS Mean 
 
 
xx.xx 
 
95% CI 
 
 
xx.x, xx.x 


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SE 
 
 
xx.xx 
 
p-value 
 
 
x.xxxx 
 
 
 
 
 
Fixed effects and covariates 
Treatment 
 
 
x.xxxx 
 
Region 
 
 
x.xxxx 
 
SLEDAI-2K screening total 
score 
 
 
x.xxxx 
 
Racial/ethnic 
classification 
 
 
x.xxxx 
 
Baseline fatigue using the 
FACIT-Fatigue total score 
 
 
x.xxxx 
 
 
 
 
 
Baseline is defined as the last non-missing value before the first dose of study drug. 
1The ANCOVA model analyses change from baseline in fatigue using the FACIT-Fatigue total score at Week 52 and includes fixed effects for 
treatment and randomisation factors (region, SLEDAI-2K screening score, racial/ethnic classification) and baseline fatigue using the FACIT-
Fatigue total score as covariates 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
This layout also applies to: 
Table 14.2.2.1.4.2 Sensitivity Analysis of Absolute Change in Fatigue using the FACIT-Fatigue at Week 52 (Full Analysis Set) Programming 
note: Add footnote ‘The multiple imputation method has been used to account for missing data at Week 52.’ 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
 
Table 14.2.2.2.1 Summary of SLEDAI-2K Total Score (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Baseline 
N 
xx 
xx 
xx 
   
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Week 4 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
Etc 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 


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Immupharma IPP-201101/005 
ddMMMyyyy 
Table 14.2.2.2.2 Patients Achieving a SRI Response (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Baseline to Week 4 
N 
xx 
xx 
xx 
 
Clinical SRI Response 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No Clinical SRI Response 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Baseline to Week 8 
N 
xx 
xx 
xx 
 
Clinical SRI Response 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No Clinical SRI Response 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
Baseline to Week 48 
Etc 
xx 
xx 
xx 
 
 
 
 
 
Baseline to Week 52 
Etc 
xx 
xx 
xx 
 
 
 
 
 
The denominator for each percentage is the number of non-missing observations within the column 
Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 
Path\Filename  


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Page x/y 
 
Programming Note: display all visits where SRI response is obtained 
 
This layout also applies to: 
 
Table 14.2.2.2.3 Patients Achieving a SLEDAI-2K Clinical Response (Full Analysis Set) 
Table 14.2.2.2.4 Patients Achieving a BILAG-2004 Clinical Response (Full Analysis Set) 
Table 14.2.2.2.5 Patients Showing No Worsening on PhGA Scale (Full Analysis Set) 
Table 14.2.2.2.6 Patients Achieving a Reduction of 5 Points in SLEDAI-2K Total Score (Full Analysis Set) 
Table 14.2.2.2.7 Patients Achieving a Reduction of 6 Points in SLEDAI-2K Total Score (Full Analysis Set) 
Table 14.2.2.2.8 Patients Achieving a SRI-5 Response (Full Analysis Set) 
Table 14.2.2.2.9 Patients Achieving a SRI-6 Response (Full Analysis Set) 
Table 14.2.2.2.10 Patients Achieving a SRI-7 Response (Full Analysis Set) 
Table 14.2.2.2.11 Patients Achieving a SRI-8 Response (Full Analysis Set) 
Table 14.2.2.2.12 Patients Achieving a SRI-9 Response (Full Analysis Set) 
Table 14.2.2.2.13 Patients Showing an Improvement in Tender and Swollen Joints Count (Full Analysis Set) 
Table 14.2.2.2.17 Summary of Status of Disease (PhGA Scale) (Full Analysis Set) 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.2.2.2.14 Summary of Medical Outcome Survey SF-36 (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Baseline 
N 
xx 
xx 
xx 
   
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Week 12 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
Etc 
 
 
 
 
 
 
 
 
Change from baseline to Week 12 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
Etc 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 


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Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
Programming note: display absolute and relative to baseline data for Weeks 12, 24, 36 and 52 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.2.2.2.16 Summary of BILAG-2004 Disease Activity Index (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Baseline to Week 52 
N 
xx 
xx 
xx 
 
BILAG-2004 Response 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No BILAG-2004 Response 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
The denominator for each percentage is the number of non-missing observations within the column 
Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 
Path\Filename  
 
Page x/y 
 
 
This layout also applies to: 
Table 14.2.2.2.15 Patients with a Reduction in the SLEDAI-2K Total Score by at Least 4 Points from Baseline to Week 52 (Full Analysis Set) 
 
 
 
 
 
 
 
 
 
 


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Table 14.2.2.2.18 Summary of SFI Variables (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Incidence of mild to moderate flare  
N 
xx 
xx 
xx 
 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Time to first mild to moderate flare (days) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Incidence of severe flare  
N 
xx 
xx 
xx 
 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Time to severe flare (days) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 


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SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Time to first mild to moderate flare/ time to severe flare is calculated as the difference between date of baseline visit and date of mild to 
moderate/severe flare  
The denominator for each percentage is the number of non-missing observations within the column 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.2.2.2.19 Proportion of Patients with SLEDAI-2K Score Greater than 15 at each Visit (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Baseline  
N 
xx 
xx 
xx 
 
Score >15 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Score ≤15 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Week 4 
N 
xx 
xx 
xx 
 
Score >15 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Score ≤15 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Etc 
 
 
 
 
 
 
 
 
 
Week 48 
Etc 
xx 
xx 
xx 
 
 
 
 
 
Week 52 
Etc 
xx 
xx 
xx 
 
 
 
 
 
The denominator for each percentage is the number of non-missing observations within the column 
Baseline is defined as the last non-missing value before the first dose of study drug. 
 
 
Source: Listing 16.x.x 
Path\Filename  


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Page x/y 
 
Programming Note: display all visits where SLEDAI-2K score is obtained 


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Immupharma IPP-201101/005 
 
 
 
 
 
 
 
 
 
 
 
 
 
ddMMMyyyy 
 
Table 14.2.2.2.20 Summary of Changes in the SDI Total Score (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Screening 
N 
xx 
xx 
xx 
   
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Week 24 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
Etc 
 
 
 
 
 
 
 
 
Change from Screening to Week 24 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
Etc 
 
 
 
 
 
 
 
 
Week 52 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 


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Etc 
 
 
 
 
 
 
 
 
Change from Screening to Week 52 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
Etc 
 
 
 
 
 
 
 
 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ddMMMyyyy 
 
Table 14.2.2.2.21.1 Summary of Steroid Dose (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Baseline 
N 
xx 
xx 
xx 
 
 None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 <7.5mg 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 ≥7.5mg  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Week 24 
N 
xx 
xx 
xx 
 
 None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 <7.5mg 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 ≥7.5mg  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Week 52 
N 
xx 
xx 
xx 
 
 None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 <7.5mg 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 ≥7.5mg  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Baseline is defined as the last non-missing value before the first dose of study drug. 
The denominator for each percentage is the number of non-missing observations within the column 
 


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Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ddMMMyyyy 
 
Table 14.2.2.2.21.2 Shift Table of Changes in Steroid Dose (Full Analysis Set) 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
Baseline 
Baseline 
Baseline 
 
   None       <7.5mg      ≥7.5mg 
   None       <7.5mg      ≥7.5mg 
   None       <7.5mg      ≥7.5mg 
 
 
 
 
 Week 24 
 
 
 
 None 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
 <7.5mg 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
 ≥7.5mg  
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
 
 
 
 
 Week 52 
 
 
 
 None 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
 <7.5mg 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
 ≥7.5mg  
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
xx (xx.x%)  xx (xx.x%)   xx (xx.x%) 
 
 
 
 
Baseline is defined as the last non-missing value before the first dose of study drug. 
The denominator for each percentage is the number of non-missing observations within the column 
 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 


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Table 14.2.3.1 Summary of Changes in Biomarkers: Anti-dsDNA Ab, C3 and C4 (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Anti-dsDNA Ab 
 
 
 
 
Baseline 
N 
xx 
xx 
xx 
   
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Week 1 
N 
xx 
xx 
xx 
   
Etc 
 
 
 
 
 
 
 
 
Changes from Baseline to Week 1 
N 
xx 
xx 
xx 
 
Etc 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 


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Path\Filename  
Page x/y 
 
Include all weeks in treatment period and start each parameter on a new page 
 
 
This layout also applies to: 
Table 14.2.3.2 Summary of Changes in Other Biomarkers (Full Analysis Set) Programming note: display Weeks 4, 12, 24, 36 and 52 
Table 14.2.3.3 Summary of In Vitro Intracellular and Cytokine Response (Full Analysis Set) Programming note: display Weeks 4, 24, and 48 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.2.3.4 Cumulative Distribution of the Reduction from Baseline to Week 52 in SLEDAI-2K Score (Full Analysis Set) 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
N 
Probability 
N 
Probability 
N 
Probability 
 
 
 
 
 
 
 
Reduction from Baseline to Week 52 
 
 
 
 
 
 
  Total 
xx 
 
xx 
 
xx 
 
  Less than or equal to 0 
xx 
x.xx 
xx 
x.xx 
xx 
x.xx 
  Less than or equal to 1 
xx 
x.xx 
xx 
x.xx 
xx 
x.xx 
  Less than or equal to 2 
xx 
x.xx 
xx 
x.xx 
xx 
x.xx 
  Less than or equal to 3 
xx 
x.xx 
xx 
x.xx 
xx 
x.xx 
  Less than or equal to 4 
xx 
x.xx 
xx 
x.xx 
xx 
x.xx 
  Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
The denominator for each probability is the number of non-missing observations within the column 
Baseline is defined as the last non-missing value before the first dose of study drug. 
A reduction of less than 0 signifies an increase in the score. 
 
 
Source: Listing 16.x.x 
Path\Filename  
 
Page x/y 
Programming note: continue table in one unit increases until all reductions are captured. 
 


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Immupharma IPP-201101/005 
ddMMMyyyy 
 
Table 14.2.4 Immunogenicity Findings (Full Analysis Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Presence of anti-IPP-201101 
 
 
 
 
  Baseline 
N 
xx 
xx 
xx 
 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
  Week 2 
N 
xx 
xx 
xx 
 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
  Week 4 
N 
xx 
xx 
xx 
 
Yes 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 


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Programming note: Baseline, Weeks 2, 4, 12, 20, 28, 36, 44 and 52 (or final assessment) should be presented in the table 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.3.1.1 Summary of Treatment-Emergent Adverse Events (Safety Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
Any Treatment-Emergent Adverse Events 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Severe Treatment-Emergent Adverse Events 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Serious Treatment-Emergent Adverse Events 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Drug-Related Treatment-Emergent Adverse Events 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Serious Drug-Related Treatment-Emergent Adverse Events 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Treatment-Emergent Adverse Events leading to withdrawal from the study 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Treatment-Emergent Adverse Events leading to death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
The denominator for each percentage is the number of subjects within the column 
 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
 
 
 
 
 
 
 


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Table 14.3.1.2 Treatment-Emergent Adverse Events, by SOC and PT (Safety Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
Any Treatment-Emergent Adverse Events 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
SOC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
PT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
PT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Etc 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
SOC 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
PT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
PT 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Etc 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
MedDRA version <XX.X> 
The denominator for each percentage is the number of subjects within the column 
 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
This layout also applies to: 


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Table 14.3.1.3 Severe Treatment-Emergent Adverse Events, by SOC and PT (Safety Set) 
Table 14.3.1.4 Serious Treatment-Emergent Adverse Events, by SOC and PT (Safety Set) 
Table 14.3.1.5 Drug-Related Treatment-Emergent Adverse Events, by SOC and PT (Safety Set) 
Table 14.3.1.6 Serious Drug-Related Treatment-Emergent Adverse Events, by SOC and PT (Safety Set) 
Table 14.3.1.7 Treatment-Emergent Adverse Events Leading to Withdrawal from the Study, by SOC and PT (Safety Set) 
Table 14.3.1.9 Adverse Events of Special Interest, by SOC and PT (Safety Set) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.3.1.8.1 Listing of Deaths 
 
 
Treatment 
Centre/ Patient number 
Date of start of treatment 
Date of death 
 
 
 
 
xxxxxxx 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
xxxxxxx 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
 
 
 
 
 
 
 
 
Etc 
Etc 
 
 
 
 
 
 
 
Path\Filename  
Page x/y 


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ddMMMyyyy 
 
Table 14.3.1.8.2 Listing of Serious Adverse Events 
 
IPP-201101 
Centre/ 
Patient 
number 
Adverse Event 
 Preferred Term 
  SOC Term 
Start 
date 
Study 
day 
Stop date 
/ongoing 
Duration 
of adverse 
event 
(days) 
Severity 
Action 
taken 
regarding 
study drug 
Concomitant 
therapy 
started 
due 
to AE 
Outcome 
Relationship 
to 
study 
drug 
Serious 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
 xxxx 
xxxxxxxxx 
 xxxxxxxx 
  xxxxxxx 
ddMMMyyyy 
xx 
ddMMMyyyy 
xx 
Mild 
/Moderate 
/etc 
None 
/Discontinued 
/Etc 
Yes /No 
Resolved 
/Etc 
Unrelated 
/Unlikely 
/Etc 
Yes /No 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxx 
 xxxxxxxx 
  xxxxxxx 
ddMMMyyyy 
xx 
ddMMMyyyy 
xx 
Mild 
/Moderate 
/etc 
None 
/Discontinued 
/Etc 
Yes /No 
Resolved 
/Etc 
Unrelated 
/Unlikely 
/Etc 
Yes /No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
 xxxx 
xxxxxxxxx 
 xxxxxxxx 
  xxxxxxx 
ddMMMyyyy 
xx 
ddMMMyyyy 
xx 
Mild 
/Moderate 
/etc 
None 
/Discontinued 
/Etc 
Yes /No 
Resolved 
/Etc 
Unrelated 
/Unlikely 
/Etc 
Yes /No 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Repeat for placebo 
Path\Filename  
Page x/y 
This layout also applies to: 


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Table 14.3.1.8.3 Listing of Adverse Events which Led to Withdrawal 


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Immupharma IPP-201101/005 
 
 
 
 
 
 
 
 
 
 
 
 
 
ddMMMyyyy 
 
Table 14.3.2.1 Summary of Serum Chemistry Parameters (Safety Set)  
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Calcium  
 
 
 
 
  Baseline 
N 
xx 
xx 
xx 
   
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
  Week 4 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
  Change from baseline to Week 4 
 
 
 
 
Etc 
 
 
 
 


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Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
Programming note: start each parameter on a new page and summarise any non-continuous data with number (%) instead of descriptive stats. 
 
This layout also applies to: 
Table 14.3.2.2 Summary of Haematology Parameters (Safety Set) 
Table 14.3.2.3 Summary of Urinalysis Parameters (Safety Set) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 14.3.3 Vital Signs (Safety Set)  
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Diastolic Blood Pressure 
 
 
 
 
  Baseline 
N 
xx 
xx 
xx 
   
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
  Week 4 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
  Change from baseline to Week 4 
 
 
 
 
Etc 
 
 
 
 


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Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Immupharma IPP-201101/005 
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Table 14.3.4 Shift Table of 12-Lead ECG (Safety Set)  
 
 
 
IPP-201101 (N=xxx) 
Placebo (N=xxx) 
 
Baseline 
Baseline 
 
Normal 
Abnormal NCS 
Abnormal CS 
Normal 
Abnormal NCS 
Abnormal CS 
 
 
 
 
 
 
 
Week 52 
 
 
 
 
 
 
Normal 
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%) 
Abnormal CS 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NCS=Not Clinically Significant; CS=Clinically Significant 
 
The denominator for each percentage is the number of non-missing observations within the column 
Baseline is defined as the last non-missing value before the first dose of study drug. 
 
 
Source: Listing 16.x.x 
Path\Filename  
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Table 14.3.5 Suicidality Assessment (Safety Set) 
 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
 
 
 
 
Baseline 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Week 4 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 


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Baseline is defined as the last non-missing value before the first dose of study drug. 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
Programming note: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 (or final assessment) should be presented in the table 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Immupharma IPP-201101/005 
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Table 14.3.6 Concomitant Medications (Safety Set) 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
Any Concomitant Medications 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Present at screening1 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Ongoing at baseline2 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Started after first dose3 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
Present at screening 
 
 
 
  X, xxxxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   X0N, xxxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
    X0NXX, xxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     xxxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     Etc 
 
 
 
 
 
 
 
    X0NXX, xxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     xxxxxxxxxxxx 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Etc 
 
 
 
 
 
 
 
1Medication that started prior to first study drug intake and stopped on the day of Week 0/baseline 
2Medication that started prior to first study drug intake and continued into the study  
3Medication that started any time after first study drug intake  
 
WHO-DDE version <XX.X> 
The denominator for each percentage is the number of patients within the column 
 
Source: Listing 16.x.x 


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Path\Filename  
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Table 14.3.7 Time to Study Termination (Safety Set)  
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Time to study termination (days) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Kaplan-Meier estimate (days) 
Median (95% CI) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
xx.xx (xx.xx, xx.xx) 
 
 
 
 
 
Time to study termination (days) is calculated as (date of study termination - date of informed consent). 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
 
 
 
 
 


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Table 14.3.8 Study Drug Exposure (Safety Set) 
 
 
 
 
IPP-201101 
(N=xxx) 
Placebo 
(N=xxx) 
Total 
(N=xxx) 
 
 
 
 
 
Duration of treatment (days) 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Number of injections 
N 
xx 
xx 
xx 
 
Mean 
xx.xx 
xx.xx 
xx.xx 
 
SD 
xx.xx 
xx.xx 
xx.xx 
 
Median 
xx.xx 
xx.xx 
xx.xx 
 
Minimum 
xx.x 
xx.x 
xx.x 
 
Maximum 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
Duration of treatment is calculated as (day of last dose - day of first dose). 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 


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Immupharma IPP-201101/005 
 
 
 
 
 
 
 
 
 
 
 
 
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Figure 1 Cumulative Distribution of the Reduction from Baseline to Week 52 in SLEDAI-2K Score (Full Analysis Set) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing 16.x.x 
Path\Filename  
Page x/y 
 
 
 
 


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Immupharma IPP-201101/005 
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Figure 2 Kaplan-Meier Plot of Time to Study Termination (Safety Set) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: Listing 16.x.x 
Path\Filename  
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Statistical Analysis Plan 
 
 
 
 
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Listing 16.2.1 Discontinued Patients 
 
Treatment 
Centre/ Patient number 
First dose date 
Last dose date 
Date of withdrawal 
Main reason for withdrawal 
 
 
 
 
 
 
xxxxxxx 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy 
xxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy 
xxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy 
xxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
ddMMMyyyy 
xxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
Path\Filename   
 
 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan 
 
 
 
 
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Listing 16.2.2 Protocol Deviations 
 
Treatment 
Centre/ Subject number 
Major deviation 
Description of deviation 
 
 
 
 
xxxxxxx 
xx/xx-xx 
Yes/No 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
Yes/No 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
 
Path\Filename  
 
 
 
 
 
 
 
 
 
 


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Listing 16.2.3 Analysis Datasets 
 
Treatment 
Centre/ Patient number 
Full Analysis Set 
Safety Set 
 
 
 
 
xxxxxx 
xxx-xxxx 
Yes/No 
Yes/No 
 
xxx-xxxx 
Yes/No 
Yes/No 
 
xxx-xxxx 
Yes/No 
Yes/No 
 
xxx-xxxx 
Yes/No 
Yes/No 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
Page x/y 
 
Path\Filename  
 
 


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Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.4 Demographic Data 
 
Treatment 
Centre/ 
Patient 
number 
Date of 
screening 
Date of 
birth 
Age* 
(years) 
Gender 
Ethnic 
origin 
Race 
Weight 
(kg) 
Height 
(cm) 
BMI (kg/m2) 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
xx 
xxxx 
xxxx 
xxxx 
xx.x 
xxx.x 
xx.x 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
xx 
xxxx 
xxxx 
xxxx 
xx.x 
xxx.x 
xx.x 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
xx 
xxxx 
xxxx 
xxxx 
xx.x 
xxx.x 
xx.x 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
xx 
xxxx 
xxxx 
xxxx 
xx.x 
xxx.x 
xx.x 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
xx 
xxxx 
xxxx 
xxxx 
xx.x 
xxx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Age calculated at Date of Screening 
 
 
 
Page x/y 
 
Path\Filename  
 


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Statistical Analysis Plan 
 
 
 
 
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Listing 16.2.5 Study Drug Exposure and Compliance 
Treatment 
Centre/ Patient 
number 
Visit 
200mcg dose 
administered 
Actual dose 
administered 
Reason for 
change in dose 
Treatment 
duration 
(weeks) 
Compliance 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
x 
Yes 
 
 
 
 
 
 
x 
Yes 
 
 
 
 
 
 
x 
No 
xxx mcg 
xxxxxx 
 
 
 
 
x 
Yes 
 
 
 
 
 
 
x* 
 
 
 
 
 
 
 
 
 
 
 
xx 
xxx.x% 
xxxxxx 
xxx-xxxx 
x 
Yes 
 
 
 
 
 
 
x 
No 
xxx mcg 
xxxxxx 
 
 
 
 
x 
Yes 
 
 
 
 
 
 
x 
Yes 
 
 
 
 
 
 
 
 
 
 
xx 
xxx.x% 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
Page x/y 
Path\Filename  
 
 


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Listing 16.2.6 Efficacy Response Data 
 
Treatment Centre/ 
Patient 
number 
Final 
Visit 
Reduction from 
baseline in the 
SLEDAI-2K score 
of atleast 4 
points 
No 
worsening 
in PGA* 
New BILAG A 
body system 
score 
More than 1 new 
BILAG B body 
system score 
from baseline 
Included in 
primary 
analysis? 
Responser at 
Week 52? 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-
xxxx 
Week X 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
 
xxx-
xxxx 
Week X 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
 
xxx-
xxxx 
Week X 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Worsening defined as an increase in PGA of more than 0.30 point from baseline 
Page x/y 
Path\Filename  
 
 
 


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Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Listing 16.2.7 Adverse Event Listing  
IPP-201101 
 
Centre/ 
Patient 
number 
Adverse Event 
 Preferred Term 
  SOC Term 
Date of 
onset 
Study 
day 
Resolution 
date 
/ongoing 
Duration 
of adverse 
event 
(days) 
Outcome 
Serious 
Severity 
Relationship 
to study 
drug 
Action taken 
Action taken 
with study 
drug 
 
 
 
 
 
 
 
 
 
 
 
 
xxx 
 xxxx 
xxxxxxxxx 
 xxxxxxxx 
  xxxxxxx 
ddMMMyyyy 
xx 
ddMMMyyyy 
xx 
Resolved 
/Etc 
Yes /No 
Mild 
/Moderate 
/etc 
Not 
related 
/Related 
None 
/Concomitant 
medication 
/Other 
None 
/Discontinued 
/Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxxxxx 
 xxxxxxxx 
  xxxxxxx* 
ddMMMyyyy 
xx 
ddMMMyyyy 
xx 
Resolved 
/Etc 
Yes /No 
Mild 
/Moderate 
/etc 
Not 
related 
/Related 
None 
/Concomitant 
medication 
/Other 
None 
/Discontinued 
/Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Adverse event classifed as an anaphylactic, anaphylactoid, or drug hypersensitivity reaction  
Repeat for Placebo 
 
Page x/y 
Path\Filename  
 
 


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Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
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Listing 16.2.8.1 Laboratory Measurements: Serum Chemistry 
Treatment 
Parameter 
Centre/ 
Patient 
number 
Visit 
Sample 
date 
Sample 
time 
Standard 
Result 
Standard 
Unit 
Reference range 
Is result outside reference 
range or is test not done? 
Clinically 
significant? 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
Calcium 
xxx-xxxx 
xxxx  
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
xxx.xx, xxx.xx 
Within range/ Outside range/ 
Test not done  
Yes/No 
 
 
 
xxxx 
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
xxx.xx, xxx.xx 
Within range/ Outside range/ 
Test not done  
Yes/No 
 
 
xxx-xxxx 
xxxx 
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
xxx.xx, xxx.xx 
Within range/ Outside range/ 
Test not done  
Yes/No 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phosphate 
xxx-xxxx 
xxxx  
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
xxx.xx, xxx.xx 
Within range/ Outside range/ 
Test not done  
Yes/No 
 
 
 
xxxx 
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
xxx.xx, xxx.xx 
Within range/ Outside range/ 
Test not done  
Yes/No 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window  
Page x/y 
Path\Filename  
 
 
This layout also applies to: 
Listing 16.2.8.2 Laboratory Measurements: Haematology 


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Listing 16.2.8.3 Laboratory Measurements: Urinalysis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Listing 16.4.1 Final Status 
 
Treatment 
Centre/ Patient number 
First dose date 
Last dose date 
Completed treatment 
Primary reason for discontinuation 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
Yes/No 
xxxxxxxxxxxxxxxxxxxx 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
Yes/No 
xxxxxxxxxxxxxxxxxxxx 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
Yes/No 
xxxxxxxxxxxxxxxxxxxx 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
Yes/No 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
 
Path\Filename  
 
 
 
 
 
 
 


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Listing 16.4.2 Visit Dates 
 
Treatment 
Centre/ Patient number 
Visit 
Date 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
ddMMMyyyy 
 
 
xx 
ddMMMyyyy 
 
 
xx* 
ddMMMyyyy 
 
 
xx 
ddMMMyyyy 
 
 
 
 
Etc 
 
 
 
 
 
 
 
*Outside the visit window 
 
 
 
Page x/y 
 
Path\Filename  
 
 
 
 


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Listing 16.4.3.1 Inclusion Criteria 
Criterion 
No. 
Definition of Criterion 
 
 
1 
The patient is a man or woman between 18 and 70 years of age with an established diagnosis of SLE as defined by ACR 
Classification Revised Criteria. The diagnosis is fulfilled provided that at least 4 criteria are met.  
2 
The patient has a positive test result for ANA at screening (titer must be at least 1:80 [by human epithelial cell tumor line 
(HEp-2) ANA assay]) and/or a positive test result for antidsDNA Ab at screening (value must be 30 IU/mL or more by enzyme-
linked immunosorbent assay [ELISA]). 
3 
Written informed consent is obtained. 
4 
Female and males receiving IPP-201101 and their female partners must use a highly effective contraceptive during treatment and 
for 30 days after discontinuation of study drug treatment. Women must be surgically sterile, 2 years postmenopausal, or, if of 
childbearing potential, use a highly effective method of contraception. Men and their partner must have highly effective 
accepted method of contraception, Single barrier/Double barrier and spermicides are not acceptable methods of contraception. 
Highly effective methods of contraception include, true abstinence, intrauterine device (IUD), or hormonal contraception 
associated with inhibition of ovulation (oral, transdermal, implanted, and injected), intrauterine hormone-releasing system 
(IUS), bilateral tubal occlusion, vasectomised partner. True abstinence is defined when this is in line with the preferred and 
usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), 
declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception] 
Etc 
 
 
 
Page x/y 
Path\Filename  
Programming Note: The list of criteria will be presented on the first page of the listing. Subject data will start on page 2. 
 
 


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Statistical Analysis Plan 
 
 
 
 
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Listing 16.4.3.1 Inclusion Criteria 
Treatment Centre/Patient 
number 
Visit 
Criteria 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xxxx 
Yes/No 
Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No 
 
xxx-xxxx 
xxxx* 
Yes/No 
Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No 
 
xxx-xxxx 
xxxx 
Yes/No 
Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No 
 
xxx-xxxx 
xxxx 
Yes/No 
Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No Yes/No 
 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
Page x/y 
 
Path\Filename  
 
 
 
This layout also applies to: 
Listing 16.4.3.2 Exclusion Criteria 
 
Programming Note: Adjust number of columns according to number in CRF.  If too many criteria to fit, split into listings Part 1 and Part 2 


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Statistical Analysis Plan 
 
 
 
 
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Listing 16.4.4.1 Medical History 
 
Treatment 
Centre/ 
Patient 
number 
Condition 
  SOC 
    PT 
Start date 
End date / 
Ongoing 
Currently 
treated? 
Severity 
Intermittent 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xxxxxxxxxxxxxx 
  xxxxxxxxxxxx 
    xxxxxxxxxx 
ddMMMyyyy 
ddMMMyyyy / 
Ongoing 
Yes/No 
Mild/ Moderate/ Severe/ 
Life-threatening 
Yes/No 
 
 
xxxxxxxxxxxxxx 
  xxxxxxxxxxxx 
    xxxxxxxxxx 
ddMMMyyyy 
ddMMMyyyy / 
Ongoing 
Yes/No 
Mild/ Moderate/ Severe/ 
Life-threatening 
Yes/No 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
 
Path\Filename  
 
 


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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.4.2 SLE Disease History 
 
Treatment 
Centre/ 
Patient 
number 
Date of SLE 
Diagnosis 
Date of last SLE flare 
known? 
Date of last SLE 
flare? 
Has patient been 
hospitalised for SLE 
related illnesss? 
Date of 
hospitalisation 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
ddMMMyyyy 
Yes/ No/ Not Applicable 
ddMMMyyyy 
Yes/No 
ddMMMyyyy 
 
xxx-xxxx 
ddMMMyyyy 
Yes/ No/ Not Applicable 
ddMMMyyyy 
Yes/No 
ddMMMyyyy 
 
xxx-xxxx 
ddMMMyyyy 
Yes/ No/ Not Applicable 
ddMMMyyyy 
Yes/No 
ddMMMyyyy 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
 
Path\Filename  
 
 
 
 
 
 
 


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Immupharma IPP-201101/005 
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Listing 16.4.4.3 BILAG Historical Disease Assessment 
 
Treatment 
Centre/ 
Patient 
number 
Date of 
assessment 
Cardiorespiratory 
score 
Constitutional 
score 
Gastrointestinal 
score 
Haematological 
score 
Mucocutaneous 
score 
Musculoskeletal 
score 
Neuropsychiatric 
score 
Ophthalmic 
score 
Renal 
score 
BILAG 
total 
numeric 
score 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-
xxxx 
ddMMMyyyy 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
xxx-
xxxx 
ddMMMyyyy 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
xxx-
xxxx 
ddMMMyyyy 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
 
Path\Filename  
 
This layout also applies to: 
Listing 16.4.5.6 Raw Efficacy Data: BILAG (Programming note: add column for ‘Visit’) 
 
Programming note: if column labels are not fitting on one page, abbreviate ‘Cardiorespiratory’ to CR, ‘Gastrointestinal’ to GI etc as 
necessary. All abbreviations should be included in a footnote e.g. CR = Cardiorespiratory; GI = Gastrointestinal; etc   
 
 


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Statistical Analysis Plan 
 
 
 
 
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Listing 16.4.5.1 Raw Efficacy Data: SRI 
 
Treatment 
Centre/ 
Patient 
number 
Visit 
SLEDAI-2K Score 
PGA Score 
New Bilag A 
Score from 
baseline  
More than 1 
BILAG B 
score from 
baseline 
SRI 
response 
SRI-5 
response 
SRI-6 
response 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
xx 
xx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
 
 
xx* 
xx 
xx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
 
 
xx 
xx 
xx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
 
 
xx 
xx 
xx 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
Yes/No 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
 
 
Page x/y 
 
Path\Filename  
 
 
 
 


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Listing 16.4.5.2 Raw Efficacy Data: 28 Joint Count Examination for Pain and Tenderness 
 
 
 
 
 
 
Right 
 
Left 
Treatment 
Centre/ 
Patient 
number 
Visit 
Was 28 joint count 
exam performed? 
Joint 
Tenderness 
Swelling  
Not 
done 
 
Tenderness 
Swelling  
Not 
done 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
Yes/No 
Shoulder 
Not Tender/ 
Tender 
None/ 
Detectable 
 
 
Not Tender/ 
Tender 
None/ 
Detectable 
 
 
 
 
 
Elbow 
Not Tender/ 
Tender 
None/ 
Detectable 
 
 
Not Tender/ 
Tender 
None/ 
Detectable 
 
 
 
 
 
Wrist 
Not Tender/ 
Tender 
None/ 
Detectable 
 
 
Not Tender/ 
Tender 
None/ 
Detectable 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xx* 
Yes/No 
Shoulder 
Not Tender/ 
Tender 
None/ 
Detectable 
 
 
Not Tender/ 
Tender 
None/ 
Detectable 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
Page x/y 
Path\Filename  
 
 


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Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.5.3 Raw Efficacy Data: SDI 
 
Treatment 
Centre/ 
Patient 
number 
Visit 
Was SDI 
performed? 
Date of 
assessment  
Any items 
present? 
Organ System 
Item 
Score 
Total Score 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
Yes/No 
ddMMMyyyy 
Yes 
xxxxxxxx 
xxxxxxxx 
xx 
 
 
 
 
 
 
 
xxxxxxxx 
xxxxxxxx 
xx 
 
 
 
 
 
 
 
 
 
 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xx 
Yes/No 
ddMMMyyyy 
No 
 
 
 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
xx 
Yes/No 
ddMMMyyyy 
Yes 
xxxxxxxx 
xxxxxxxx 
xx 
x 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
Page x/y 
Path\Filename 
Programming note: Only include organ systems/items where patient has answered yes 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.5.4 Raw Efficacy Data: SF-36  
 
Treatment 
Centre/ 
Patient 
number 
Question  
Baseline Week 1 
Week 12 
Week 24 
Week 36 
Week 52 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
Was SF-36 
performed? 
Yes/No  
Yes/No  
Yes/No  
Yes/No  
Yes/No  
 
 
Date 
ddMMMyyyy 
ddMMMyyyy* 
ddMMMyyyy 
ddMMMyyyy^ 
ddMMMyyyy 
 
 
1 
Excellent/ Very good/ 
Good/ Fair /Poor 
Excellent/ Very good/ 
Good/ Fair /Poor 
Excellent/ Very good/ 
Good/ Fair /Poor 
Excellent/ Very good/ 
Good/ Fair /Poor 
Excellent/ Very good/ 
Good/ Fair /Poor 
 
 
2 
Much better/ Somewhat 
better/ About the 
same/ Somewhat worse/ 
Much worse 
Much better/ Somewhat 
better/ About the 
same/ Somewhat worse/ 
Much worse 
Much better/ Somewhat 
better/ About the 
same/ Somewhat worse/ 
Much worse 
Much better/ Somewhat 
better/ About the 
same/ Somewhat worse/ 
Much worse 
Much better/ Somewhat 
better/ About the 
same/ Somewhat worse/ 
Much worse 
 
 
3a 
Yes, a lot / Yes, a 
little/ No 
Yes, a lot / Yes, a 
little/ No 
Yes, a lot / Yes, a 
little/ No 
Yes, a lot / Yes, a 
little/ No 
Yes, a lot / Yes, a 
little/ No 
 
 
3b 
Yes, a lot / Yes, a 
little/ No 
Yes, a lot / Yes, a 
little/ No 
Yes, a lot / Yes, a 
little/ No 
Yes, a lot / Yes, a 
little/ No 
Yes, a lot / Yes, a 
little/ No 
 
 
 
 
 
 
 
 
Etc 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
 
^Early termination visit has been mapped to the scheduled visit that occurs immediately after termination 


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Statistical Analysis Plan 
 
 
 
 
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Page x/y 
Path\Filename 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.5.5 Raw Efficacy Data: FACIT Fatigue Scale 
Treatment 
Centre/ 
Patient 
number 
Question  
Baseline Week 1 
Week 12 
Week 24 
Week 36 
Week 52 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
Was FACIT Fatigue Scale 
performed? 
Yes/No  
Yes/No  
Yes/No  
Yes/No  
Yes/No  
 
 
Date 
ddMMMyyyy 
ddMMMyyyy* 
ddMMMyyyy^ 
ddMMMyyyy 
ddMMMyyyy 
 
 
HI7 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
 
 
HI12 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
Not at all/ A 
little bit / 
Somewhat / Quite a 
bit / Very much 
 
 
An1 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
^Early termination visit has been mapped to the scheduled visit that occurs immediately after termination 
Page x/y 
Path\Filename 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.5.7 Raw Efficacy Data: SFI 
Treatment 
Centre/ Patient number 
Date of randomisation 
Date of assessment 
Visit 
Flare Classification 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
xxxx 
No flare/ Mild or moderate/ Severe/Not Done 
 
 
 
ddMMMyyyy 
xxxx 
No flare/ Mild or moderate/ Severe/Not Done 
 
 
 
ddMMMyyyy 
xxxx 
No flare/ Mild or moderate/ Severe/Not Done 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
ddMMMyyyy 
ddMMMyyyy 
xxxx 
No flare/ Mild or moderate/ Severe/Not Done 
 
 
ddMMMyyyy 
ddMMMyyyy 
xxxx 
No flare/ Mild or moderate/ Severe/Not Done 
Etc 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window  
Page x/y 
Path\Filename  
 
 
 
 
 
 
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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28 MARCH 2018  
 
Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.5.8 Raw Exploratory Efficacy Data: Biomarkers 
Treatment 
Parameter 
Centre/ Patient 
number 
Visit 
Sample date 
Sample time 
Result 
Unit 
 
 
 
 
 
 
 
 
xxxxxx 
ANA 
xxx-xxxx 
xxxx  
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
 
 
 
xxxx 
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
 
 
xxx-xxxx 
xxxx 
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anti-U1-70K snRNP 
Ab 
xxx-xxxx 
xxxx*  
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
 
 
 
xxxx 
ddMMMyyyy 
hh:mm 
xxx.xx 
xxxx 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window  
Page x/y 
Path\Filename  
 
 
This layout also applies to: 
Listing 16.4.5.9 Raw Exploratory Efficacy Data: Cytokine Response 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.6.1 PK Data: IPP-201101 Plasma Concentration 
 
Treatment 
Centre/ 
Patient number 
Visit 
Timepoint 
Sample 
taken 
Sample collection 
date 
Sample collection 
time 
Concentration 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
Pre-dose/5 mins post-dose/1 
hour post-dose/2 hours post-
dose/ 24 hours post-dose 
Yes/No 
ddMMMyyyy 
hh:mm 
xx.x 
 
 
xx 
Pre-dose/5 mins post-dose/1 
hour post-dose/2 hours post-
dose/ 24 hours post-dose 
Yes/No 
ddMMMyyyy 
hh:mm 
xx.x 
 
 
xx 
Pre-dose/5 mins post-dose/1 
hour post-dose/2 hours post-
dose/ 24 hours post-dose 
Yes/No 
ddMMMyyyy 
hh:mm 
xx.x 
 
 
xx* 
Pre-dose/5 mins post-dose/1 
hour post-dose/2 hours post-
dose/ 24 hours post-dose 
Yes/No 
ddMMMyyyy 
hh:mm 
xx.x 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
Page x/y 
 
Path\Filename  
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.6.2 Immunogenicity Findings 
Treatment 
Centre/ Patient number 
Visit 
Sample date 
Sample time 
Presence of any anti-
IPP-201101 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xxxx  
ddMMMyyyy 
hh:mm 
Yes/No 
 
 
xxxx 
ddMMMyyyy 
hh:mm 
Yes/No 
 
xxx-xxxx 
xxxx 
ddMMMyyyy 
hh:mm 
Yes/No 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
xxxx*  
ddMMMyyyy 
hh:mm 
Yes/No 
 
 
xxxx 
ddMMMyyyy 
hh:mm 
Yes/No 
Etc 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window  
Page x/y 
Path\Filename  
 
 
 
 
 
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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28 MARCH 2018  
 
Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.7 Vital Signs 
 
 
 
 
 
 
Blood pressure 
 
Pulse 
 
Body temperature 
Treatment 
Centre/ 
Patient 
number 
Visit 
Vital 
signs 
measured? 
Date of 
assessment  
Was 
blood 
pressure 
taken?  
Arm 
Systolic 
BP 
(mmHg) 
Diastolic 
BP (mmHg) 
 
Was 
pulse 
taken? 
Pulse 
(beats
/min) 
 
Was 
temperature 
taken? 
Temperature 
(°C)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx xx 
Yes/No 
ddMMMyyyy 
Yes/No 
Left/Right 
xxx 
xxx 
 
Yes/No 
xxx 
 
Yes/No 
xx.x 
 
 
xx 
Yes/No 
ddMMMyyyy 
Yes/No 
Left/Right 
xxx 
xxx 
 
Yes/No 
xxx 
 
Yes/No 
xx.x 
 
 
xx* 
Yes/No 
ddMMMyyyy 
Yes/No 
Left/Right 
xxx 
xxx 
 
Yes/No 
xxx 
 
Yes/No 
xx.x 
 
 
xx 
Yes/No 
ddMMMyyyy 
Yes/No 
Left/Right 
xxx 
xxx 
 
Yes/No 
xxx 
 
Yes/No 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
 
 
 
Page x/y 
 
Path\Filename  
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.8.1 Complete Physical Examination 
 
 
 
 
 
Weight 
 
Height 
 
 
 
 
Treatment Centre/ 
Patient 
number 
Visit Was physical 
examination 
performed? 
Was 
weight 
taken? 
Weight 
(kg) 
 
Was 
height 
measured? 
Height 
(cm) 
Date of 
assessment 
Body system 
Status 
Abnormality 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-
xxxx 
xx 
Yes/No 
(reason) 
Yes/No 
xxx.x 
 
Yes/No 
xxx.x 
ddMMMyyyy 
General appearance 
Normal/Abnormal 
NCS/ Abnormal 
CS/ Not done 
xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
Skin 
Normal/Abnormal 
NCS/ Abnormal 
CS/ Not done 
xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xx* 
Yes/No 
(reason) 
Yes/No 
xxx.x 
 
Yes/No 
xxx.x 
ddMMMyyyy 
General appearance 
Normal/Abnormal 
NCS/ Abnormal 
CS/ Not done 
xxxxxxxxxxxxxxx 
Etc 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
NCS=Not Clinically Significant; CS=Clinically Significant 
Page x/y 
Path\Filename  
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.8.2 Symptom Directed Physical Examination 
 
 
 
 
 
Weight 
 
 
 
 
Treatment 
Centre/ 
Patient 
number 
Visit 
Was physical 
examination 
performed? 
Was 
weight 
taken? 
Weight 
(kg) 
Date of 
assessment 
Body system 
Status 
Abnormality 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-
xxxx 
xx 
Yes/No 
(reason) 
Yes/No 
xxx.x 
ddMMMyyyy 
General appearance 
Normal/Abnormal 
NCS/ Abnormal CS/ 
Not done 
xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Skin 
Normal/Abnormal 
NCS/ Abnormal CS/ 
Not done 
xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xx* 
Yes/No 
(reason) 
Yes/No 
xxx.x 
ddMMMyyyy 
General appearance 
Normal/Abnormal 
xxxxxxxxxxxxxxx 
Etc 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
Page x/y 
Path\Filename 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.9 12-Lead ECG 
 
Treatment 
Centre/ Patient 
number 
Visit 
Was ECG 
performed? 
Date of 
assessment 
Result 
Abnormality 
Clinically 
significant? 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
Yes/No 
ddMMMyyyy 
Normal/ 
Abnormal 
xxxxxxxxxxx 
Yes/No 
 
 
xx 
Yes/No 
ddMMMyyyy 
Normal/ 
Abnormal 
xxxxxxxxxxx 
Yes/No 
 
 
xx* 
Yes/No 
ddMMMyyyy 
Normal/ 
Abnormal 
xxxxxxxxxxx 
Yes/No 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
 
Page x/y 
 
Path\Filename  
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.10.1 Prior Medications 
Treatment 
Centre/ 
Patient 
number 
Therapy 
  ATC Code 
    PT 
Type of 
treatment 
Dose 
Unit 
Frequency 
Route 
Start date 
(Stop date/ongoing) 
Indication 
Is treatment 
prophylactic? 
Related 
event(s) 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xxxxxxxxxxxxxxx 
  xxxxxxxxxxxxx 
    xxxxxxxxxxx 
SLE Treatment: 
Corticosteroids/ 
SLE Treatment: 
Other/ Other 
xx.x 
xxx 
xxx 
xxx 
ddMMMyyyy  
(ddMMMyyyy/ongoing) 
xxxxxxxxx 
Yes/No 
MH/AE  
 
 
xxxxxxxxxxxxxxx 
  xxxxxxxxxxxxx 
    xxxxxxxxxxx 
SLE Treatment: 
Corticosteroids/ 
SLE Treatment: 
Other/ Other 
xx.x 
xxx 
xxx 
xxx 
ddMMMyyyy  
(ddMMMyyyy/ongoing) 
xxxxxxxxx 
Yes/No 
MH/AE  
 
 
xxxxxxxxxxxxxxx 
  xxxxxxxxxxxxx 
    xxxxxxxxxxx 
SLE Treatment: 
Corticosteroids/ 
SLE Treatment: 
Other/ Other 
xx.x 
xxx 
xxx 
xxx 
ddMMMyyyy  
(ddMMMyyyy/ongoing) 
xxxxxxxxx 
Yes/No 
MH/AE  
 
 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
Path\Filename  
 
 
 
This layout also applies to: 
Listing 16.4.10.2 Concomitant Medications 


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Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.11 Procedures/ Non-Drug Therapies 
 
Treatment 
Centre/ 
Patient 
number 
Were there any 
procedures/non-drug 
therapies either prior 
to or during the study? 
Therapy 
   
 
Start date 
(Stop date/ongoing) 
Indication 
Is treatment 
prophylactic? 
Given for 
Adverse 
Event? 
Pre-existing 
condition? 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-
xxxx 
Yes/No 
xxxxxxxxxxxxxxx 
ddMMMyyyy (ddMMMyyyy/ ongoing) 
xxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
 
 
 
xxxxxxxxxxxxxxx 
ddMMMyyyy (ddMMMyyyy/ ongoing) 
xxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
 
 
 
 
 
 
 
 
 
 
xxx-
xxxx 
Yes/No 
xxxxxxxxxxxxxxx 
ddMMMyyyy (ddMMMyyyy/ ongoing) 
xxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
 
 
 
xxxxxxxxxxxxxxx 
ddMMMyyyy (ddMMMyyyy/ ongoing) 
xxxxxxxxx 
Yes/No 
Yes/No 
Yes/No 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
Path\Filename  
 
 
 
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.12.1 Raw Suicidality Assessment C-SSRS Baseline 
Treatment 
Centre/ 
Patient 
number 
Was C-SSRS 
performed? 
(Date) 
Category 
Question 
Response 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
Yes/No 
(ddMMMyyyy) 
Suicidal 
ideation 
Wish to be dead 
Yes (Reason)/ No 
 
 
 
 
Non-specific active suicidal thoughts 
Yes (Reason)/ No 
 
 
 
 
Active suicidal ideation with any methods 
(not plan) without intent to act 
Yes (Reason)/ No 
 
 
 
 
Active suicidal ideation with some intent to 
act, without specific plan 
Yes (Reason)/ No 
 
 
 
 
Active suicidal ideation with specific plan 
and intent 
Yes (Reason)/ No 
 
 
 
Intensity of 
ideation 
Most severe ideation type (description) 
1/2/3/4/5 (xxxxxxxxxx) 
 
 
 
 
Frequency of thoughts 
Less than once a week/ Once a week / 2-5 
times in week / Daily or almost daily/ 
Many times each day 
Etc 
 
 
 
 
 
 
 
 
 
 
 
Page x/y 
Path\Filename  
 
 
This layout also applies to: Listing 16.4.12.2 Raw Suicidality Assessment C-SSRS Since Last Visit (Programming note: Include a Visit column 
after Centre/ Patient number column) 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.13 Urine Pregnancy Test 
 
Treatment 
Centre/ Patient 
number 
Visit 
Date of test 
Test done 
Reason 
Result 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
ddMMMyyyy 
Yes/No/Not applicable 
xxxxxxxxxxxxx 
Positive/ Negative 
 
 
xx 
ddMMMyyyy 
Yes/No/Not applicable 
xxxxxxxxxxxxx 
Positive/ Negative 
 
 
xx* 
ddMMMyyyy 
Yes/No/Not applicable 
xxxxxxxxxxxxx 
Positive/ Negative 
 
 
xx 
ddMMMyyyy 
Yes/No/Not applicable 
xxxxxxxxxxxxx 
Positive/ Negative 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
 
 
 
Page x/y 
 
Path\Filename  
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.14 Hemolysis Testing  
Treatment 
Centre/ 
Patient 
number 
Visit 
Was sample 
taken? 
Sampling 
date 
Sampling 
time 
Is 
hemolysis 
suspected/ 
confirmed? 
Coomb’s Test  
Haptoglobin 
(units) 
Peripheral 
Smear  
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
Yes/No 
ddMMMyyyy 
hh:mm 
Yes/No 
Positive/Negative 
 
 
 
 
xx 
Yes/No 
ddMMMyyyy 
hh:mm 
Yes/No  
Positive/Negative 
xxxx 
xxxx 
 
 
xx* 
Yes/No 
ddMMMyyyy 
hh:mm 
Yes/No 
Positive/Negative 
xxxx 
xxxx 
 
 
xx 
Yes/No 
ddMMMyyyy 
hh:mm 
Yes/No 
Positive/Negative 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
xx 
Yes/No 
ddMMMyyyy 
hh:mm 
Yes/No 
Positive/Negative 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxx-xxxx 
xx 
Yes/No 
ddMMMyyyy 
hh:mm 
Yes/No 
Positive/Negative 
 
 
 
 
xx 
Yes/No 
ddMMMyyyy 
hh:mm 
Yes/No 
Positive/Negative 
xxxx 
xxxx 
 
 
 
 
 
 
 
 
 
 
Etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
Page x/y 
Path\Filename  
 
 
Programming note: Coombs’ test should be populated for all screening visits, but for subsequent visits Coombs’ test, haptoglobin and 
peripheral smear will only be measured if hemolysis was suspected. Therefore, some patients will only have screening results. 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Immupharma IPP-201101/005 
ddMMMyyyy 
Listing 16.4.15 Laboratory Sample Collection  
Treatment 
Centre/ Patient 
number 
Visit 
Analyte 
Sample taken 
Sampling date 
Sampling time 
 
 
 
 
 
 
 
xxxxxx 
xxx-xxxx 
xx 
Serum Chemistry 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
Haematology 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
Urinalysis 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
HBsAg, HCV Ab 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
Serology 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
Immunogenicity 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
Cytokine response 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
 
 
 
 
 
 
xx 
Serum Chemistry 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
Haematology 
Yes/No 
ddMMMyyyy 
hh:mm 
 
 
 
 
 
 
 
 
 
xx* 
 
 
 
 
Etc 
 
xx 
 
 
 
 
 
 
 
 
 
 
 
*Outside the visit window 
Page x/y 
Path\Filename  
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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Programming note: Analytes include Serum Chemistry; Haematology; Urinalysis; HBsAg and HCV Ab; Serology tests; Immunogenicity; Cytokine 
response. Note that not all are collected at all visits.  
 
 
 
 
 
 
 
 
 
 
 
 
 


ImmuPharma IPP-201101/005 
Statistical Analysis Plan 
 
 
 
 
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 16
 APPENDICES16.1
 STUDY SCHEDULE
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Statistical Analysis Plan 
 
 
 
 
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