Clinical trial NCT03037489
Conditions: Osteoarthritis, Knee
Sponsor: Medivir
Start date: 2016-09-01; Completion date: 2017-11-28
Enrollment: 50 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a multicentre, open-label, one-arm Phase II extension study to evaluate the safety and tolerability of MIV-711 in patients with knee joint osteoarthritis (OA).

Detailed description:

Arms: arm 1: MIV-711 for a total of 26 weeks
Interventions: intervention 1: MIV-711
Intervention descriptions: intervention 1: MIV-711 administered orally once daily

Protocol documents:
Prot_000.pdf: 
An Open-Label, One-Arm Phase II Extension Study to Evaluate Safety 
and Tolerability of MIV-711 in Patients with Knee Joint Osteoarthritis
Sponsor:
Medivir AB
Blasieholmsgatan 2,
111 48 Stockholm, Sweden
Clinical Research Organization:
PAREXEL International (IRL) Limited,
70 Sir John Rogerson’s Quay, Dublin 2, Ireland.
Principal/Global Coordinating 
Investigator
Prof. Philip Conaghan
University of Leeds
Leeds Institute of Rheumatic and Musculoskeletal 
Medicine
Chapel Allerton Hospital
Chapeltown Road
Leeds LS7 4SA, United Kingdom
Sponsor Protocol No.:
MIV-711-202
EudraCT No.:
2016-001096-73
Study Drug Name:
MIV-711
Development Phase:
Phase II
Date of Protocol:
01 July 2016
The study will be conducted according to the protocol and in compliance with Good 
Clinical Practice (GCP), with the Declaration of Helsinki [1] and with other applicable 
regulatory requirements.
CONFIDENTIAL
This document contains confidential information of Medivir AB.
Do not copy or distribute without written permission from the Sponsor.






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Declaration of the Investigator
Title: An Open-Label, One-Arm Phase II Extension Study to Evaluate Safety and Tolerability 
of MIV-711 in Patients with Knee Joint Osteoarthritis
All documentation for this study that is supplied to me and that has not been previously 
published will be kept in the strictest confidence. This documentation includes this study 
protocol, Investigator's Brochure, electronic Case Report Form (eCRF), Patient-Reported 
Outcomes (PRO),patient diaries and other scientific data.
The study will not be commenced without the prior written approval of a properly constituted 
Independent Ethics Committee (IEC). No changes will be made to the study protocol without 
the prior written approval of the Sponsor and the IEC, except where necessary to eliminate an 
immediate hazard to the patients.
I have read and understood and agree to abide by all the conditions and instructions contained 
in this protocol.
Responsible Investigator of the local study centre
Signature
Date
Name (block letters)
Title (block letters)
Institution (block letters)
Country


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PROTOCOL SYNOPSIS
Title
An Open-Label, One-Arm Phase II Extension Study to Evaluate 
Safety and Tolerability of MIV-711 in Patients with Knee Joint 
Osteoarthritis
Sponsor Study No.
MIV-711-202
Phase
Phase II
Sponsor
Medivir AB
Blasieholmsgatan 2, 111 48 Stockholm, Sweden
Principal or Global 
Coordinating 
Investigator
Prof. Philip Conaghan
University of Leeds
Leeds Institute of Rheumatic and Musculoskeletal Medicine
Chapel Allerton Hospital
Chapeltown Road, Leeds LS7 4SA, United Kingdom
Study Centers
Five sites distributed in 5 European countries.
1) PAREXEL Berlin Early Phase Clinical Unit, PAREXEL 
International GmbH, Spandauer Damm 130, 14050 Berlin, 
Germany
2) MC Comac Medical, 13 Urvich Str, 1612 Sofia, Bulgaria
3) LLC ARENSIA Exploratory Medicine, Research Institute of 
Clinical Medicine, 13a, Tevdore Mgvdeli Str. 0112 Tbilisi,
Georgia
4) LLC ARENSIA Exploratory Medicine, Republican Clinical 
Hospital, 29 Testemitanu Str. 2025 Chisinau,
Republic of Moldova
5) SC ARENSIA Exploratory Medicine SRL
Spitalul Clinic Colentina, Sectia de Medicina Interna III, Sos. 
Stefan cel Mare Nr. 19-21,
Sector 2 Bucharest 020125, Romania
Objective
The primary objective is to assess the safety and tolerability of 
200 mg MIV-711 q.d. over 52 (26+26) weeks in patients with 
symptomatic and radiographic knee osteoarthritis (OA).
Design
This is a multicentre, open-label, one-arm Phase II extension study to evaluate the safety 
and tolerability of MIV-711 for up to 52 (26+26) weeks in patients with knee joint OA.
Patients to be enrolled will be selected from the patients in Study MIV-711-201 (a 
randomised, double-blind, placebo-controlled Phase IIa study to evaluate efficacy, safety 
and tolerability of MIV-711 in knee joint osteoarthritis). 
Patients treated with 200 mg MIV-711 once daily (q.d.) in Study MIV-711-201 whose 
symptoms did not clinically significantly deteriorate as defined by a numeric rating scale 
(NRS) increase of ø4" eqorctgf" vq" Daseline will be offered to roll over for 26 weeks’
extended treatment primarily evaluating longer term safety and tolerability. The 
52 (26+26) weeks total treatment also allows for a more suitable treatment length for the 
exploratory study of any structural effects of MIV-711 on joint cartilage thickness. In this 
protocol, this population is referred to as Study Population A.
The second objective of this study is the exploratory assessment of the treatment effect in a 


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group of OA patients that has confirmed symptom progression over the last 6 months. This
means that patients receiving placebo in Study MIV-711-201 and that had experienced a 
clinical worsening as defined by increased NRS versus Bcugnkpg" qh" œ4"will be offered to 
receive 200 mg MIV-711 q.d. for the next 6 months. In this protocol, this population is 
referred to as Study Population B. The safety and tolerability in Study Population B
constitutes a secondary objective whereas all other analyses are exploratory.
All patients in Study MIV-711-201 (Eudract No. 2015-003230-26) at the participating sites 
included in Study MIV-711-202 will be given the opportunity to participate provided that 
they meet the eligibility criteria.
To ensure the patients will have sufficient time to consider their participation in the study 
the informed consent form will be given to the patients prior to Visit 8 in Study 
MIV-711-201. Visit 8 of Study MIV-711-201 will ideally be conducted on the same day as 
Visit 1 of the present study. If these visits are conducted on the same day, the results of the 
following assessments will be recorded in the electronic case report form (eCRF) for both 
studies; urine and blood sampling for safety, vital signs, physical examination and 
electrocardiogram (ECG).
A central person, independent from the study, with access to the randomisation list and the 
eCRF for the MIV-711-201 study will confirm Inclusion Criterion 1. The confirmation will 
be communicated to the site staff and the study team via fax/email without revealing the 
treatment in MIV-711-201 or the change in NRS score.
All enrolled patients will receive 200 mg q.d. oral dose of MIV-711 for 26 weeks in 
addition to their current medication. MIV-711 200 mg will be provided as identical 
capsules to those used in Study MIV-711-201.
The patients will take the last dose of IMP in Study MIV-711-201 at Visit 8 and dosing in 
the present study will be started at Visit 2 after a screening period of 10±5 days.
Patients who are not eligible to participate in the present study will return for the safety 
follow up visit (Visit 9) in Study MIV-711-201. 
Patients will be permitted to remain on their current analgesic regimen with any changes in 
concomitant medications reported and recorded at study visits as well as in a 
patient-reported daily e-diary for two 2-week periods prior to Visit 4 and Visit 5.
The study consists of a Screening period of approximately 2 weeks (Visit 1), eligibility at 
Visit 2, an open-label treatment period of 26 weeks from Visit 2 through Visit 5, and a 
follow-up period of 4 weeks (Visit 6) after the last dose of study treatment is administered.
Telephone calls will be made 5-9 days after all dosing visits for safety and tolerability.
There will be additional phone calls at Week 10 and Week 20 for safety and tolerability.
A Data Monitoring and Ethics Committee will meet to review the unblinded safety and 
tolerability data after the first 25 patients complete Visit 4 and Visit 5.
Treatment
All patients will receive a 200 mg oral dose of MIV-711 q.d. for 
26 weeks in addition to their current medication.
Number of Patients
All patients in Study MIV-711-201 at the participating sites 
included in Study MIV-711-202 will be given the opportunity to 
participate provided that they meet the eligibility criteria. However, 
based on the inclusion and exclusion criteria it is anticipated that 
50-80 patients will be eligible for participation. The patients will be 
recruited from up to 5 centres in up to 5 countries for this study. 
Population
The study population will consist of patients with symptomatic and 
radiographic knee joint OA who have participated in Study 
MIV-711-201. Patients must be able to provide written consent, be 


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approved by the investigator for eligibility as well as meeting all the 
inclusion criteria and none of the exclusion criteria.
Criteria for inclusion and exclusion
Inclusion:
Patients must meet all of the following criteria to be eligible for enrolment in this study:
1. Previously enrolled in the MIV-711-201 study including completion of Visit 8 either by 
‚
Receiving MIV-711 200 mg and had non-significant clinical worsening on the 
primary endpoint as defined by NRS increase of ø2
OR by
‚
Receiving placebo and had a clinically significant worsening on the primary 
endpoint as defined by NRS increase of œ4
The NRS result will be derived using the primary endpointfrom Study MIV-711-201: NRS average knee 
pain in the target knee with 7days recall: increase from Baseline (Visit 2 of Study MIV-711-201) to 
Visit 8 of Study MIV-711-201.
2. Female patients must be non-pregnant, non-lactating and of non-childbearing potential 
either as naturally (spontaneously) post-menopausal or due to hysterectomy and/or 
bilateral oophorectomy/salpingo-oophorectomy (as determined by patient medical 
history). Naturally (spontaneously) post-menopausal is defined as being amenorrhoeic 
for 12 months without an alternative medical cause and with a Screening follicle 
stimulating hormone test indicating post-menopausal state.
3. Male patients should avoid fathering a child by either of the following methods:
‚
True sexual abstinence: meaning that heterosexual abstinence is in line with the 
preferred and usual lifestyle of the patient (periodic abstinence such as that based 
on calendar, ovulation, symptothermal, post-ovulation methods, declaration of 
abstinence for the duration of a trial, or withdrawal/coitus interruptus are not 
acceptable methods of contraception).  
‚
Willingness to use two effective means of contraception with their partner from 
the time of first IMP administration until 3 months after the last dose of IMP. Two 
or more of the following methods are acceptable and must include at least one 
barrier method: i) Surgical sterilisation (i.e., bilateral tubal ligation for female 
partners; vasectomy for male), ii) placement of an intrauterine device or 
intrauterine system, iii) hormonal contraception (implantable, patch, oral), iv) 
barrier methods including condom or occlusive cap (diaphragm or cervical/vault 
caps) with spermicidal foam/gel/film/cream/suppository. Male patients who have 
been sterilised are required to use one barrier method of contraception (condom).
4. The patient’s usual analgesic regimen (in case of use) should remain the same as for 
Visit 8 in the MIV-711-201 study (i.e., Visit 1 in the MIV-711-202 study).
NOTE: If a patient is experiencing increased or decreased pain and requires an increase or a decrease in 
the dose of analgesics, or an occasional change of analgesics medication during his/her participation in 
the study, then this will be allowed and should be properly documented in the patient file and the eCRF.
5. Needs to be able to communicate well with the investigators and staff.
6. Able to comply with the requirements of the study procedures and provide written 
informed consent prior to any study related procedures.


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Exclusion:
Patients will be excluded from enrolment in this study if they meet any of the following 
criteria:
1. The presence of any inflammatory arthritis (e.g., gout, reactive arthritis, rheumatoid 
arthritis, psoriatic arthritis, seronegative spondylarthropathy) or any underlying 
condition, other than OA, that may result in abnormal cartilage and bone metabolism.
2. Any generalised pain condition that may interfere with the evaluation of the target knee 
pain (e.g., fibromyalgia) as judged by the investigator.
3. Ongoing or a history of atrial fibrillation.
4. Currently receiving medication that affects cartilage or bone metabolism (other than 
study drug; hormone replacement therapy taken for more than 6 months is allowed).
5. Current or recurrent disease that could affect the action, absorption or disposition of 
MIV-711, or could affect clinical assessments or clinical laboratory assessments.
6. Any clinically severe or significant uncontrolled concurrent illness, which, in the 
opinion of the Investigator, would impair ability to give informed consent or take part in 
or complete this clinical study.
7. Any medical condition, adverse event (AE), clinical or laboratory finding from 
Study MIV-711-201 that, in the opinion of the Investigator, would preclude inclusion in
the present clinical study.
8. Known or suspected intolerance or hypersensitivity to the investigational medicinal 
product, closely related compounds, or any of the stated ingredients.
9. History of alcohol or other substance abuse within the last year.
10. Use of an investigational product other than MIV-711 during participation in the 
MIV-711-201 study and /or active enrolment in another drug or vaccine clinical study.
11. Significant target knee injury or surgery during participation in the MIV-711-201 study.
12. A history of partial or complete joint replacement surgery in the target knee at any time, 
listed for knee surgery, or anticipating knee surgery during the study period.
13. Any factor which, in the opinion of the investigator, would jeopardise the evaluation or
safety of the patient or be associated with poor adherence to the clinical study protocol
(e.g., inability to complete study diary, poor tolerability of venepuncture or lack of 
adequate venous access for required blood sampling during the study period).
14. Use of intra-articular hyaluronic acid in the target knee during participation in the 
MIV-711-201 study.
15. Use of intra-articular, intra-muscular or oral corticosteroids during participation in the 
MIV-711-201 study.
16. Commencement of non-pharmacological OA interventions during participation in the 
MIV-711-201 study. 
17. Vulnerable patients, e.g., patients kept in detention, soldiers, and employees of the 
sponsor or the Contract Research Organisation (CRO) with direct involvement in the 
proposed study or other studies under the direction of the investigator or the CRO, as 
well as family members of the employees or the investigator.
18. Lack of MRI of the knee from Visit 8 in the MIV-711-201 study due to special 
circumstances, such as claustrophobia or difficulties to fit the knee coil.
19. Patients with contra-indication to MRI of the knee.


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Outcome variables
Safety:
The primary outcome variables for this study are related to safety:
•
Incidence and severity of adverse events 
•
Incidence and severity of clinical laboratory abnormalities
•
Physical examination findings by the patient
•
Incidence and severity of ECG abnormalities
•
Mean change from Baseline (Visit 2 of Study MIV-711-201) in vital signs (blood 
pressure, heart rate, temperature) and oxygen saturation
•
Categorical summary of observed vital signs and vital sign changes compared to 
Baseline (Visit 2 of Study MIV-711-201), by patient
Efficacy:
The secondary outcome variables are related to efficacy:
•
The effect of MIV-711 on MRI cartilage thickness loss
•
The effect of MIV-711 on MRI bone marrow lesion volume
•
The effect of MIV-711 in the semi quantitative MRI Osteoarthritis Knee Score 
(MOAKS) parameters
•
To assess the effect of MIV-711 on MRI knee joint bone area.
Note: all MRI assessments refer to the target knee unless stated otherwise.
Exploratory outcome variables:
•
The effect of MIV-711 on worst target knee pain (1 week recall)
•
The effect of MIV-711 on average contralateral knee pain (1 week recall)
•
The effect of MIV-711 on constant and intermittent OA pain
•
The effect of MIV-711 on global improvements in knee problem, knee pain and knee 
function
•
The effect of MIV-711 on knee joint OA symptoms (function, pain, stiffness) 
•
The effect of MIV-711 on global disease activity 
•
The effect of MIV-711 on quality of life (QoL)
•
The effect of MIV-711 on patient reported e-diary daily recall knee joint pain
•
The effect of MIV-711 on patient reported e-diary daily recall analgesics use
•
Serum and urinary biomarkers (C-terminal telopeptide of collagen type I [CTX-I], 
procollagen type I N-terminal propeptide [PINP],bone specific alkaline phosphatase
[BSAP], C-terminal telopeptide of collagen type II [CTX-II], N-terminal telopeptide 
of collagen type I [NTX-I], gCTX-I and tartrate-resistant acid phosphatase 5b
[TRAP5b])
•
Compound index of MRI bone area and cartilage volume
•
Pharmacokinetics: MIV-711 Pharmacokinetic (PK) parameters and their relationship 
to covariates such as age, weight, gender, liver function and concomitant 
medications.
All of the above denoted secondary and exploratory parameters are considered as 
exploratory objectives in Study Population B and will be evaluated over 26 weeks.


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Statistical Methods
Primary Analysis
The primary outcome will be to study the safety and tolerability of MIV-711 in OA patients 
who have received treatment for up to 52 (26+26) weeks. Safety and tolerability will be 
assessed descriptively in summary tables presented over time. All data presentations 
addressing the primary outcome will use Study Population A.
Secondary Analysis
For Study Population B, the safety and tolerability of 200 mg MIV-711 will be studied for 
26 weeks. Safety and tolerability will be assessed descriptively in summary tables presented 
over time. 
All other secondary analyses will be undertaken using Study Population A while they will 
be undertaken as exploratory analyses on Study Population B.
For Study Population A all secondary outcome variables will be analysed using descriptive 
summary tables presenting statistics for, number of non-missing values means, medians, 
standard deviations, minimum and maximum values. Frequency tables (counts and 
percentages) will be presented in tables where appropriate. Figures of secondary response 
over time will be presented as appropriate.
For all outcome variables analysed using a linear model, distributional assumptions will be 
checked using examination of empirical distributions and model residuals. If necessary, 
data will be transformed prior to analysis if this improves the model fit, or normalises the 
distribution of the residuals. Non-parametric methods may be applied if appropriate.
For the analysis of secondary endpoints, alternate statistical methods maybe considered that 
will include the use of generalised linear models that account for the response variable 
having a “non-normal” distribution.  Additional details will be provided in the Statistical 
Analysis Plan.
All secondary outcomes will be summarised descriptively (mean, SD, median, minimum 
and maximum for continuous data and counts and percentages for categorical data). 
No comparisons between Study Populations A and B will be undertaken.
Exploratory Analysis
The exploratory analysis of patient-reported outcomes, bone and cartilage biomarkers, MRI 
imaging and PK assessments will be listed and summarised using descriptive statistics only
or presented in separate reports. The pharmacokinetic measurements in this study will be 
performed using sparse sampling in which the date/time of sample collection as well as the 
date/time of the most recent dose will be collected in the eCRF to allow for a future 
population pharmacokinetic analysis of these data. For the purpose of this study, the plasma 
concentrations of parent and potential metabolites of MIV-711 will be an additional 
exploratory endpoint and will be reported as outlined above. In the analysis of biomarkers
that are sampled at multiple visits, all sampled time points will be considered for change 
from Baseline in the respective cases. In applicable cases PK and biomarker data may be 
analysed using area under the curve calculations.


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LIST OF STUDY PERSONNEL
Sponsor
Medivir AB
Blasieholmsgatan 2
111 48 Stockholm, Sweden
Principal or Global 
Coordinating Investigator
Prof. Philip Conaghan
University of Leeds
Leeds Institute of Rheumatic and Musculoskeletal 
Medicine
Chapel Allerton Hospital
Chapeltown Road
Leeds LS7 4SA, United Kingdom
Contract Research 
Organization
PAREXEL International (IRL) Limited,
70 Sir John Rogerson’s Quay, Dublin 2, Ireland.
Adverse Event Reporting
PAREXEL International
Medical Monitor: Francois Burger
Medical hotline: +49 30 30685 274
SAE Fax: +49 30 315118 7777 (24-hour service)
Email: Medical_Berlin@parexel.com
Central Imaging Reader
Imorphics
Kilburn House, Lloyd Street North, Manchester Science 
Park, Manchester M15 6SE,United Kingdom
Laboratory for safety 
testing and urinalysis
ACM Global Central Laboratory
23 Hospital Fields Road
York, YO10 4DZ, United Kingdom
Laboratory for biomarker 
analysis
Nordic Bioscience Laboratory A/S
Herlev Hovedgade 207
2730 Herlev, Denmark
Laboratory for drug 
concentration  analysis
York Bioanalytical Solutions
Cedar House, Northminster Business Park
Upper Poppleton
York, YO26 6QR, United Kingdom
eDiary provider:
CRF Health
Brook House - 3rd Floor
229-243 Shepherds Bush Road Hammersmith
London, W6 7AN, United Kingdom


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TABLE OF CONTENTS
PROTOCOL SYNOPSIS............................................................................................5 
LIST OF STUDY PERSONNEL..............................................................................11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS............................15 
1 
ABSTRACT...................................................................................................18 
2 
INTRODUCTION.........................................................................................19 
2.1 
Background...............................................................................................19 
2.2 
Pharmacokinetic, Pharmacodynamic and Safety results from MIV-711
First Time in Man Study and Blinded Safety and Tolerability Summary 
from MIV-711-201 ....................................................................................20 
2.3 
Study Rationale .........................................................................................21 
2.4 
Study Design and Dosing Rationales.........................................................22 
2.5 
Risk-Benefit Assessment...........................................................................23 
3 
STUDY OBJECTIVES..................................................................................25 
3.1 
Primary Objective Study Population A* ..................................................25 
3.2 
Secondary Objectives Study Population A................................................25 
3.3 
Secondary Objective Study Population B* ...............................................25 
3.4 
Exploratory Objectives Study Population A.............................................25 
3.5 
Exploratory Objectives Study Population B.............................................26 
4 
OVERALL DESIGN AND PLAN OF THE STUDY....................................27 
5 
STUDY POPULATION ................................................................................29 
5.1 
Inclusion Criteria......................................................................................29 
5.2 
Exclusion Criteria.....................................................................................30 
5.3 
Patient Withdrawal and Replacement......................................................31 
5.4 
Planned Sample Size and Number of Study Centres................................32 
5.5 
Patient Identification.................................................................................32 
5.5.1 
Patient Identification....................................................................... 32 
5.5.2 
Investigational Drug Administration Scheme................................... 32 
5.5.3 
Allocation of Patients to Treatment ................................................. 32 
5.5.4 
Procedures for Handling of Incorrectly Included Patients................. 33 
6 
STUDY DRUG ..............................................................................................34 
6.1 
Investigational Drug..................................................................................34 
6.2 
Administration..........................................................................................34 
6.3 
Packaging, Labelling and Storage.............................................................34 
6.4 
Drug Accountability..................................................................................35 
6.5 
Compliance ...............................................................................................35 
6.6 
Other Medications.....................................................................................35 
6.6.1 
Rescue Medication ......................................................................... 35 
6.6.2 
Concomitant Medications ............................................................... 35 
6.6.3 
NSAIDs and other analgesics.......................................................... 36 
6.6.4 
Prohibited Concomitant Medications............................................... 36 
6.6.5 
Chondroitin and Glucosamine ......................................................... 36 
6.7 
RESTRICTIONS......................................................................................36 
7 
ENDPOINT AND METHODS OF ASSESSMENT......................................37 
7.1 
Primary Endpoint (Study Population A) ..................................................37 


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7.2 
Secondary Endpoints (Study Population A) .............................................37 
7.3 
Secondary Endpoints (Study Population B)..............................................38 
7.4 
Exploratory Endpoints..............................................................................38 
7.4.1 
Exploratory Endpoints (Study Population A)................................... 38 
7.4.2 
Exploratory Endpoints (Study Population B) ................................... 39 
7.5 
Physical Examination................................................................................40 
7.6 
Vital Signs .................................................................................................40 
7.7 
12-lead Electrocardiograms (ECG)...........................................................40 
7.8 
Imaging Assessments.................................................................................40 
7.9 
Self-report Parameters..............................................................................41 
7.10 
Pharmacokinetic Sampling .......................................................................42 
7.11 
Biomarker Sampling .................................................................................42 
7.12 
Optional Pharmacogenomics Sampling ....................................................43 
7.13 
Adverse Events..........................................................................................43 
7.13.1 
Definitions of Adverse Events (AEs)............................................... 43 
7.13.2 
Assessment of Adverse Events........................................................ 43 
8 
STUDY CONDUCT.......................................................................................48 
8.1 
Study Schedule..........................................................................................48 
8.1.1 
Screening Visit (Visit 1, Day -10 ± 5 days)...................................... 48 
8.1.2 
Enrolment (Visit 2, Day 1).............................................................. 49 
8.1.3 
Safety Visit (Visit 3 [Week 4 ± 2 days]) .......................................... 49 
8.1.4 
Safety and Treatment Visit (Visit 4 [Week 14 ± 7 days], and Visit 5
[Week 26 ± 7 days]) ....................................................................... 49 
8.1.5 
Additional Telephone Calls to Assess Safety and Tolerability .......... 50 
8.1.6 
Safety Follow-up Visit (Visit 6, Week 30 ± 7 days) ......................... 50 
8.2 
Early Termination Visit............................................................................55 
8.3 
Discontinuation of the Study.....................................................................55 
9 
STATISTICAL METHODS..........................................................................56 
9.1 
Study Patients ...........................................................................................56 
9.1.1 
Disposition of Patients.................................................................... 56 
9.1.2 
Protocol Deviations ........................................................................ 56 
9.1.3 
Analysis Sets.................................................................................. 56 
9.2 
General Consideration..............................................................................57 
9.2.1 
Power and Sample Size Consideration............................................. 57 
9.2.2 
Analysis and Data Conventions:...................................................... 57 
9.3 
Demographics, Medical History, Baseline Characteristics, and 
Concomitant Medications .........................................................................57 
9.4 
Treatment Compliance .............................................................................57 
9.5 
Statistical Methodology.............................................................................58 
9.5.1 
Primary Endpoint (Study Population A) .......................................... 58 
9.5.2 
Secondary Endpoints ...................................................................... 58 
9.5.3 
Exploratory Endpoints .................................................................... 59 
9.5.4 
Safety............................................................................................. 59 
9.6 
Interim Analyses.......................................................................................60 
10 
ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS ........................61 
10.1 
Data Quality Assurance ............................................................................61 
10.1.1 
Database Management and Quality Control..................................... 61 
10.2 
Case Report Forms and Source Documentation.......................................61 
10.2.1 
Data Collection .............................................................................. 61 


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10.3 
Access to Source Data ...............................................................................62 
10.4 
Data Processing.........................................................................................62 
10.5 
Data Monitoring........................................................................................62 
10.6 
Safety Monitoring Plan .............................................................................63 
10.7 
Archiving Study Records..........................................................................63 
10.8 
Good Clinical Practice ..............................................................................63 
10.9 
Informed Consent.....................................................................................63 
10.10 Protocol Approval and Amendment.........................................................63 
10.11 Duration of the Study................................................................................64 
10.12 Confidentiality ..........................................................................................64 
10.13 Other Ethical and Regulatory Issues........................................................64 
10.14 Liability and Insurance.............................................................................64 
10.15 Publication Policy......................................................................................64 
11 
REFERENCE LIST.......................................................................................65 
12 
APPENDICES...............................................................................................68 
12.1 
APPENDIX 1: Total Blood Volumes ........................................................69 
Tables in Text
Table 1: Clinical Laboratory Testing......................................................................... 50 
Table 2: Study Schedule ........................................................................................... 52 
Figure in Text
Figure 1: Transition from Study MIV-711-201 to Study MIV-711-202......................... 27 
Figure 2: Study Design ............................................................................................... 28 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
The following abbreviations and special terms are used in this Clinical Study Protocol.
g"EVZ-I
g C-terminal telopeptide of collagen type I
AE
Adverse event
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
AUC0-24h
Area under the concentration-time curve from zero to 24 hours
AUCı
Area under the concentration-time curve from zero to infinity
BSAP
Bone specific alkaline phosphatase
BML
Bone marrow lesions
DMEC
Data Monitoring and Ethics Committee
DMOAD
Disease modifying OA drug
CI
Confidence interval
Cmax
Observed maximum measured plasma concentration
CRA
Clinical research associate
CRO
Contract research organisation
CTX-I
C-terminal telopeptide of collagen type I
CTX-II
C-terminal telopeptide of collagen type II
eCRF
Electronic case report form
ECG
Electrocardiogram
EOT
End of Treatment
EQ-5D-5L
EQ-5D is a standard measure of health status developed by the EuroQol
Group in order to provide a simple, generic measure of health for clinical 
and economic appraisal
FTIM
First time in man
FSE
Fast spin echo
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
IB
Investigator’s brochure
ICF
Informed consent form
ICOAP
Intermittent and constant osteoarthritis pain
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IMP
Investigational medicinal product
IRT
Interactive Response Technology
IWRS
Interactive Web Response System


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LSmeans
Least square means
MedDRA
Medical Dictionary for Regulatory Activities
MOAKS
MRI Knee Osteoarthritis Score
MRI
Magnetic resonance imaging
mITT
modified intention to treat
NSAID
Nonsteroidal anti-inflammatory drug
NOAEL
No observed adverse effect level
NRS
Numeric rating scale
NTX-I
N-terminal telopeptide of collagen type I
OA
Osteoarthritis
OARSI
Osteoarthritis Research Society International
OMERACT
Outcome Measures in Rheumatoid Arthritis Clinical Trials
PD
Proton density
PINP
Procollagen type I N-terminal propeptide
PK
Pharmacokinetic
PPS
Per-Protocol Set
PRO
Patient-reported outcomes
q.d.
Once daily
QoL
Quality of Life
QTcF
QTc interval (Fridericia’s correction)
SAE
Serious adverse event
SAF
Safety analysis set
SAP
Statistical analysis plan
SD
Standard Deviation
PINP
Procollagen type I N-terminal propeptide
SUSAR
Suspected unexpected serious adverse reaction
Target Knee
Identified by knee pain on a numeric rating scale and Kellgren and 
Lawrence classification grade. If patients have knee pain in both sides
with equal regard to these two criteria, the right knee should always be 
prioritized.
TE
Time-to-echo
TEAE
Treatment-emergent adverse event
TRAP5b
Tartrate-resistant acid phosphatase 5b
TSC
Trial Steering Committee
ULN
Upper limit of normal
UV
Ultra violet


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WOMAC
Western Ontario and McMaster Universities Osteoarthritis Index


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1
ABSTRACT
Knee osteoarthritis (OA) represents a major health burden with few effective analgesic 
therapies and no approved structure modification drugs. The subchondral bone is integral to 
the OA process with modern imaging studies showing that subchondral bone pathology is 
associated with both the symptoms and progressive loss of cartilage in knee OA. The 
available data support the hypothesis that a potent and selective inhibitor of cathepsin K such 
as MIV-711 will have both anti-resorptive effects on subchondral bone and protective effects 
on cartilage and animal models demonstrate reduced structural joint degradation. One Phase I 
study with MIV-711 is completed and a three-arm, 240 patient, 6 month, Phase IIa, 
randomised, placebo-controlled study to assess the efficacy of MIV-711 in treating painful, 
radiographic knee OA, both in terms of symptoms and structural progression is currently in 
progress. The present protocol details the intention to conduct an extension of the ongoing 
Phase IIa study. The purpose is to establish 52 weeks safety and tolerability data in a subset of 
the study population. 


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2
INTRODUCTION
2.1
Background
Osteoarthritis is the fastest growing chronic pain disease worldwide.[2, 3] Radiographic knee 
OA is the most frequent site and affects about one in four middle age and older men and 
women.[4] Symptomatic knee OA (defined as frequent knee pain and an X-ray showing OA) 
affects about 12% of persons aged 55 years and over. Current treatments for OA are aimed at 
controlling pain, and all major contemporary evidence-based guidelines recommend a range 
of pharmacological and non-pharmacological therapies.[5, 6, 7, 8] Other than surgery, there 
are no current safe, long-term, effective analgesic treatments for established OA; 
consequently 70% of people with OA report to being in constant pain and 12.5% live with 
daily unbearable pain. [5, 9, 10]
A growing literature has suggested benefits for agents targeting OA subchondral 
bone.[11, 12] Bisphosphonates are commonly used for treating conditions with exaggerated 
osteoclastic bone resorption including osteoporosis, but also indicate beneficial effects in 
OA.[13, 14, 15] Treatment with strontium ranelate, another anti-resorptive bone acting agent 
which enhances pre-osteoblast replication, promotes osteoblastic differentiation and inhibits 
osteoclastic activity, was associated with a significant effect on structure, with a smaller loss 
of joint space width over 3 years compared with placebo.[16, 17, 18] Current studies of 
structure modification for regulatory approval typically use radiographic joint space width as 
the primary outcome which requires large numbers of patients over long periods of time.
Magnetic resonance imaging (MRI) has provided new insights into the multi-tissue pathology 
underlying typical clinical OA, and has also provided novel imaging biomarkers.[19, 20, 21]
While cartilage quantification and morphology have been well studied, semi-quantitative 
measures of other tissues are slowly accruing evidence for their metric properties in clinical 
studies.[22] Recently, a publication showed that accurate 3D quantification of MRI bone area 
provides a valid and highly responsive measure of OA progression and in a small study which 
selected for typical clinical study patients, bone area was more responsive to change at 3 and 
6 months than quantitative cartilage measures.[23, 24, 25]
Cathepsin K is a cysteine protease predominantly expressed in the osteoclast and intimately 
involved in bone resorption. It is also expressed in chondrocytes and synovial fibroblasts. 
Under normal physiological conditions, cathepsin K degrades key bone matrix proteins such 
as type I collagen. Cathepsin K is also expressed in chondrocytes in cartilage where it is able 
to cleave collagen type II and aggrecan, the main components of the cartilage matrix, leading 
to cartilage destruction. Consistent with these observations, transgenic mice that over-express 
cathepsin K spontaneously develop synovitis and cartilage degeneration.[26] Some fragments 
resulting from cathepsin K cleavage serve as biomarkers for its activity both in vitro and 
in vivo as further described below.
Cleavage of type I collagen results in release of the C-terminal telopeptide of collagen type I
(CTX-I), a biomarker that has been used extensively as a surrogate measure of bone 
resorption.[27] Cartilage degradation can be assessed by measuring the C-terminal telopeptide 
of collagen type II (CTX-II), which is a fragment released during cartilage degeneration in 
OA. In OA patients, increased CTX-II levels are associated with loss of cartilage integrity and 
are linked to disease burden, progression and radiographic scoring.[12, 28, 29] Bone-acting 
agents do not solely affect CTX-I but also CTX-II, most likely indirectly due to their 
anti-resorptive effects on subchondral bone. Reductions in CTX-II levels of 20-40% by 
anti-resorptive drugs are associated with attained pain and structural primary endpoints in OA 
patient studies.[14, 16, 30, 31] To summarise the relevance of these two biomarkers, the 


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reduction of CTX-I and CTX-II in blood and urine are used as indicators of reduced bone 
resorption and cartilage degradation, respectively, which are believed to translate into 
beneficial effects counteracting joint degeneration in OA.
Besides effects on biomarkers under physiological conditions, pharmacological studies 
performed in surgically-induced OA models in vivo have demonstrated that cathepsin K 
inhibition reduces cartilage degeneration, prevents subchondral bone loss and attenuates 
osteophytosis in rabbits subjected to anterior cruciate ligament transection. [32] In addition, 
cathepsin K inhibition reduces cartilage degeneration in dogs subjected to partial medial 
meniscectomy, another experimental model of OA.[33] Cathepsin K inhibition also reduces 
the mechanosensitivity of knee afferent nerve activity in a guinea pig model of spontaneous 
OA, thus suggesting a role for cathepsin K in joint nociception during disease 
progression.[34]
The investigational product intended for the present study, MIV-711, is a potent, selective and 
reversible inhibitor of the cathepsin K enzyme with an attractive preclinical profile. A 
consistent relationship is observed between the magnitude of MIV-711-evoked reductions on 
CTX-I and CTX-II and effects on disease progression in different animal models of 
OA.[32, 33] The MIV-711 biomarker results in man (described briefly in Section 2.2,
Section 2.4 and Section 2.5), show changes in CTX-I and CTX-II levels of similar 
magnitudes to those that are associated with disease modification in the animal models of OA. 
Hence, a positive effect of MIV-711 treatment on structurally relevant readouts in OA may be 
expected. More detailed information of MIV-711’s pharmacology, pre-clinical studies 
including OA animal models and Phase I clinical testing are included in the Investigator’s 
Brochure (IB).
2.2
Pharmacokinetic, Pharmacodynamic and Safety results from MIV-711 First 
Time in Man Study and Blinded Safety and Tolerability Summary from 
MIV-711-201
A First Time in Man (FTIM) study with MIV-711 has been conducted in male and female 
healthy volunteers including single doses up to 600 mg, multiple doses up to 200 mg 
once-daily (q.d.) for 7 days and in healthy post-menopausal female volunteers at multiple 
doses of 100 mg q.d. for 28 days. The single dose part enrolled 18 males and 9 females with 
an age range of 19-64 years. The multiple dose parts enrolled 15 males and 24 females with 
an age range of 18-65 years. The primary objective was to determine the safety and 
tolerability of ascending single and multiple oral doses of MIV-711 in healthy volunteers.
MIV-711 was rapidly absorbed after oral administration with peak concentrations typically 
occurring 1 hour after administration. A high fat meal prolonged the absorption but had no 
apparent effect on systemic exposure measured by area under the concentration-time curve 
from zero to infinity (AUCı) of MIV-711. The mean terminal half-life was 3.3 to 5.2 hours 
over the 20 to 200 mg dose range. Observed maximum measured plasma concentration (Cmax)
and AUCı increased in close proportion to dose over the single dose range 100-600 mg. 
Following multiple oral administration of 50 to 200 mg q.d. for 7 days or 100 mg q.d. for 28 
days, no accumulation of MIV-711 was observed. MIV-711 was indicated to be extensively
metabolised with less than 1% excreted unchanged by the kidney. No gender differences in 
dose normalised Cmax or AUCı for MIV-711 were observed. Further details on MIV-711 
metabolism can be found in the IB.
A dose-dependent reduction in the biomarkers serum CTX-I and urinary CTX-II was 
observed after single and multiple doses of MIV-711, by down to 55 and 72% from Baseline 
respectively at multiple dosing (for further details see Section 2.4, Section 2.5 and the IB).


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No clinically meaningful effects on vital signs, laboratory parameters or electrocardiogram 
(ECG) time intervals: including QTc interval (Fridericia’s correction; QTcF) were observed. 
Adverse events (AEs) assessed as related to investigational medicinal product (IMP) had a 
similar incidence for active treatment and for placebo. One subject was found on a per 
protocol ECG to have asymptomatic atrial fibrillation after 3 q.d. doses of MIV-711 200 mg. 
Spontaneous conversion to sinus rhythm occurred within 24 hours after the last dose. 
Investigations by an independent cardiologist supported that the post-dose atrial fibrillation 
observed was possibly drug induced. Further details of the results of the FTIM study are 
provided in the IB.
The ongoing MIV-711-201 study, from which the patients in the current protocol will be 
recruited, will include 240 patients under 1:1:1 randomisation to placebo: 100 mg MIV-711: 
200 mg MIV-711. The first patient was randomised in March 2016 and recruitment is 
ongoing; as of 21 June 2016, 102 patients have been enrolled. No treatment-related serious 
adverse events (SAEs) have been reported to date. One unrelated SAE was reported before the 
start of dosing. Seven patients were withdrawn from the study due to the following reasons: 
increased liver function tests; severe polymyalgia; suspected macular-papular rash; 
angioedema; non-compliance; lost to follow-up; withdrawal of consent. No safety-related 
trends have been identified in the ongoing Study MIV-711-201 and it is believed that 
MIV-711 has acceptable safety and tolerability based on blinded results in OA patients.
2.3
Study Rationale
As stated in Section 2.1, there are no pharmacological treatments available today that provide 
long term relief of OA symptoms nor are there any treatments that counteract its structural 
progression. Disease modifying OA drugs (DMOADs) would potentially address both these 
features which highlights the importance of evaluating candidate drugs such as MIV-711.
The available data support the hypothesis that a potent and selective inhibitor of cathepsin K 
such as MIV-711 will have both anti-resorptive effects on subchondral bone and protective 
effects on cartilage; this is supported by relevant animal models which demonstrate reduced 
structural joint degradation after treatment with MIV-711.
Whilst the first study of MIV-711 in patients, Study MIV-711-201, has the potential to 
establish a first indication of disease modifying efficacy for MIV-711 in OA, it is also 
important to consider the chronic nature of OA which often leads to life-long disease 
symptoms from the time of diagnosis. The life-long course of OA highlights the need to 
assess long-term safety for a prospective DMOAD, which is therefore the main rationale of 
the current extension study.  While further outlining the current study MIV-711-202 in the 
following sections, the study population pertaining to the 12 month safety assessment in 
Study MIV-711-202 is henceforth described as Study Population A.
There are two further rationales for this study:
‚
It is known that cartilage structural changes are not expected to be apparent over a 
6-month period using MRI [35] which constitutes the reason for using knee joint bone 
area as the main structural read-out in Study MIV-711-201. In the current study, 
patients will be treated for 52 (26+26) weeks (Study Population A) which will enable 
the secondary analysis of cartilage changes versus Baseline in Study MIV-711-201. 
‚
Furthermore, there is no available method to predict OA progression. In 
Study MIV-711-201 there is a potential to identify patients treated with placebo that
exhibit signs of clinical progression over the course of 26 weeks. Patients with
manifest symptomatic progression of OA would constitute the most justifiable patient 
population to receive a DMOAD. It is believed that the proposed extension study 
would be the first opportunity to explore the effects of a potential DMOAD in OA 


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patients with verified progressive symptoms (based on symptoms reported from Study
MIV-211-201). While further outlining study MIV-711-202 in the following sections,
the study population pertaining to the 6 month treatment assessment in patients with 
progressive symptoms is henceforth described as Study Population B.
2.4
Study Design and Dosing Rationales
The present study is a 6-month open-label one-arm extension study evaluating safety and 
tolerability as well as the efficacy of 200 mg MIV-711 q.d. in two separate patient populations
denoted as Study Populations A and B. 
Study Population A will be recruited from patients treated with 200 mg MIV-711 q.d. in 
Study MIV-711-201 and whose symptoms did not clinically significantly deteriorate as 
defined by an increase in the numeric rating scale (NRS) of ø4"eqorctgf"vq"Baseline. Patients 
eligible for Study Population A will be offered to roll over for 6 months’ extended treatment,
primarily evaluating longer term safety and tolerability. The total treatment duration of 
52 weeks also allows a more suitable treatment length for the exploratory study of any 
structural effects of MIV-711 on joint cartilage thickness. [23, 24, 25].
There will be no continuation of the 100 mg dose from Study MIV-711-201 because from a 
safety and tolerability perspective, using the 200 mg dose in this extension study allows
exposure to the highest dose previously tested for MIV-711. MIV-711 has also shown a 
higher reduction in CTX-II excretion at 200 mg compared with 100 mg q.d. Based on the 
established link between CTX-II and the levels that are predictive for structural effects on
bone only, and the higher levels that are indicative of cartilage protection (see Section 2.1), it 
is judged that the 200 mg dose should be studied in this extension study since it has the 
highest potential to contribute to a disease modifying effect in OA. Extending the 200 mg 
dose in those patients that did not significantly deteriorate clinically in their OA on that dose 
during the first 26 weeks, allows a balanced assessment of the 52-week safety and tolerability 
of MIV-711 while at the same time maximizing the opportunity of measuring structural 
change on joint cartilage thickness versus Baseline. Joint cartilage thickness is believed to 
require an observational period of at least 12 months as described in the literature.[23, 24, 25]
A further rationale of this study is to explore the treatment effect in a group of OA patients 
that have confirmed symptom progression over the last 6 months (Study Population B). Study 
Population B will be recruited from patients receiving placebo in Study MIV-711-201 having
experienced a clinical worsening as defined by an increase in PTU" qh" œ4 versus Baseline.
Patients eligible for Study Population B will be offered 200 mg MIV-711 q.d. for the next 
26 weeks. In addition to offering the treatment to appropriate patients, this also enables the 
assessment of the effects of MIV-711 based on MRI imaging, symptoms and biomarkers in 
patients with progressing symptoms and, as such, has the potential to provide valuable 
information for future patient selection in OA trials. Similar to Study MIV-711-201, the joint 
structural endpoint of choice over 6 months treatment constitutes MRI joint bone surface 
measurement (see Section 7.2).[23] All analyses, with the exception of safety and tolerability, 
will be conducted as exploratory with regards to Study Population B.
All patients in Study MIV-711-201 at the participating sites included in Study MIV-711-202 
will be given the opportunity to participate. Patients, investigators and site staff will not be 
made aware of the preceding treatment allocation in Study MIV-711-201 and treatment will 
remain blinded until database lock of study MIV-711-201. The actual roll-over of individual 
patients to Study MIV-711-202 is based on the criteria for Study Populations A and B 
detailed above and is executed by a central person independent from the study with access to 
the randomisation list and eCRF for Study MIV-711-201. The patients will be considered for 
roll-over one by one as they complete the last treatment visit in Study MIV-711-201 and upon 
blinded approval of the investigator as well as provision of informed consent. Based on the 


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selection criteria for Study Population A and B described earlier in this section, it is 
anticipated that 50-80 patients will be eligible for participation. Patients will be recruited from 
up to 5 centres in up to 5 countries for this study. Recruitment may be terminated if 
considered appropriate or necessary by the sponsor.
The analysis of data from the proposed study will not be based on a formal statistical analysis 
since the primary endpoint constitutes safety and tolerability. All efficacy parameters 
measured in Study MIV-711-201 will also be measured in the proposed study. However, the 
important difference is that any comparisons will be made from baselines within but not 
between Study Population A and B. In contrast, in Study MIV-711-201, comparisons will be 
made between treatment groups with a formally powered analysis regarding the primary 
endpoint.
2.5
Risk-Benefit Assessment
The presently proposed Phase II study (MIV-711-202) is the third clinical study with 
MIV-711 and as such it has the potential to determine the 12 month safety of MIV-711 in 
treating painful, radiographic knee OA, as well as the effect over 6 months in patients with 
progressing symptomatology.
The toxicity of MIV-711 has been studied in mouse and monkey up to 6 months. In the mouse
6 month study, MIV-711 was well tolerated to systemic exposures of 58 µM x h (mean) in 
terms of AUC0-t with no treatment-related microscopic findings. In the 6-month cynomolgus 
monkey study, the majority of the observed findings were related to MIV-711 pharmacology 
and the systemic exposure at the no observed adverse effect level (NOAEL) was 15 µM x h
(mean) in terms of AUC0-24. Further data is provided in the IB.
The single dose ranges 20-600 mg and multiple dose ranges 50-200 mg of MIV-711 given 
q.d. for 7 days have been explored in healthy volunteers. In addition, the 100 mg dose was 
administered q.d. in a 28-day open care cohort consisting of healthy post-menopausal female 
volunteers. In these settings, MIV-711 showed acceptable safety and tolerability in
conjunction with no clinically significant changes in haematology, clinical chemistry, vital 
signs or ECG parameters. The study of 200 mg MIV-711 q.d. in man, which constitutes the 
highest dose in Study
MIV-711-201 as well as the only dose administered in
Study MIV-711-202 resulted in a 2.4 µM x h average AUC0-24 which corresponds to an 
expected 6 times margin to the NOAEL level in the cynomolgus monkey.
MIV-711 has consistently shown biomarker effects in the Phase I study that correlates
strongly with efficacy on joint structure in the pre-clinical models. The doses of MIV-711 
used in Study MIV-711-201 were estimated to provide an exposure sufficient to produce an 
improvement in joint structure and symptoms, as has been shown for other bone-acting agents
(see Section 2.1). There is further potential symptom and structure improvement benefit for 
patients in Study Population A in the present study as the treatment length is extended to a 
total of 52 (26+26) weeks on 200 mg q.d. MIV-711. This potentially allows measurable 
changes in cartilage to occur. Furthermore, patients in Study Population B are selected based 
on clinically significant symptom progression and may therefore benefit more from a 
potential DMOAD compared to stable patients. The potential for benefit together with the
hitherto favourable safety and toxicology profile converge into a favourable Benefit/Risk 
assessment for the present study.
No safety-related trends have been identified in the ongoing Study MIV-711-201 and it is 
believed that MIV-711 has acceptable safety and tolerability in OA patients based on the 
blinded results so far. By the start of enrolment into the present study, at least one Data 
Monitoring and Ethics Committee (DMEC) meeting reviewing the safety data of 


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Study MIV-711-201 will have been finalized. For the present study, the DMEC will
reconvene to review the unblinded safety and tolerability data after the first 25 patients 
complete Visit 4 and Visit 5.
With regard to previous clinical experience (see IB for further information), there are at
present time no approved cathepsin K inhibitors on the market, although several have 
been/are in clinical stages of development. The clinical data on these other compounds are 
only available in part from meeting abstracts and published progress reports. However it is 
judged that there is no indication of any class effect, or otherwise collectively significant 
findings in the available data that would infer any added risk to the Benefit/Risk assessment 
for the present study.
On the basis of the pre-clinical and clinical data on MIV-711 to date and the favourable
Benefit/Risk balance, it is considered appropriate to proceed with the Phase II extension study 
which is proposed in the present protocol.


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3
STUDY OBJECTIVES
3.1
Primary Objective Study Population A*
To assess the safety and tolerability of 200 mg MIV-711 q.d. over 52 (26+26) weeks in 
patients with symptomatic and radiographic knee osteoarthritis.
* Study Population A will be recruited from patients treated with 200 mg MIV-711 q.d. in Study MIV-711-201 
and whose symptoms did not clinically significantly deteriorate as defined by an increase in PTU" qh" ø4"
compared to Baseline.
3.2
Secondary Objectives Study Population A
To assess, in patients with symptomatic and radiographic knee OA, over 52 (26+26) weeks:
•
The effect of MIV-711 on MRI cartilage thickness loss
•
The effect of MIV-711 on MRI bone marrow lesion volume
•
The effect of MIV-711 in the semi quantitative MRI Osteoarthritis Knee Score 
(MOAKS) parameters
•
To assess the effect of MIV-711 on MRI knee joint bone area.
Note: all MRI assessments refer to the target knee unless stated otherwise.
Target knee is identified by knee pain on a numeric rating scale and Kellgren and Lawrence classification 
grade. If patients have knee pain in both sides with equal regard to these two criteria, the right knee should 
always be prioritized. The target knee in Study MIV-711-202 must be the same as in Study MIV-711-201.
3.3
Secondary Objective Study Population B*
To assess the effect of 200 mg MIV-711 q.d. on safety and tolerability over 26 weeks in 
patients with symptomatic and radiographic knee osteoarthritis.
* Study Population B will be recruited from patients receiving placebo in Study MIV-711-201 having 
gzrgtkgpegf"c"enkpkecn"yqtugpkpi"cu"fghkpgf"d{"cp"kpetgcug"kp"PTU"qh"œ4"xgtuwu"Dcugline.
3.4
Exploratory Objectives Study Population A
In addition, the study will address the following exploratory parameters:
•
The effect of MIV-711 on worst target knee pain (1 week recall)
•
The effect of MIV-711 on average contralateral knee pain (1 week recall)
•
The effect of MIV-711 on constant and intermittent OA pain
•
The effect of MIV-711 on global improvements in knee problem, knee pain and knee 
function
•
The effect of MIV-711 on knee joint OA symptoms (function, pain, stiffness) 
•
The effect of MIV-711 on global disease activity 
•
The effect of MIV-711 on quality of life (QoL)
•
The effect of MIV-711 on patient reported e-diary daily recall knee joint pain
•
The effect of MIV-711 on patient reported e-diary daily recall analgesics use
•
Assessment of the effect of MIV-711 on exploratory serum and urinary biomarkers of 
relevance for OA including but not limited to procollagen type I N-terminal propeptide
(PINP), bone specific alkaline phosphatase (BSAP), N-terminal telopeptide of collagen 
type I (NTX-I), CTX-K."gEVZ-I, CTX-II and tartrate-resistant acid phosphatases
(TRAP5b).
•
Baseline and steady state treatment blood and urinary samples will be stored for 
patients who sign a separate voluntary Informed Consent Form (ICF) for potential 


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future pharmacogenomics and disease-related proteomics, genomics, metabolomics and 
lipidomics analyses.
•
The effect of MIV-711 on a compound index of MRI bone area and cartilage thickness
•
The pharmacokinetics of MIV-711 and the relationship to patient factors and 
concomitant medications
3.5
Exploratory Objectives Study Population B
All of the above denoted secondary and exploratory parameters described in Section 3.2 and 
Section 3.4 for Study Population A, are considered as exploratory objectives in Study 
Population B and will be evaluated over 26 weeks.


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4
OVERALL DESIGN AND PLAN OF THE STUDY
This is a multicentre, open-label, one-arm Phase II extension study to evaluate the safety and 
tolerability of MIV-711 in patients with knee joint OA. 
The clinical study, which involves the use of an IMP, has been designed and will be run in 
accordance with the principles of Good Clinical Practice (GCP) and the current regulatory 
requirements as detailed in the Clinical Trial Directive 2001/20EC and any subsequent 
amendments of the clinical study regulations.
All patients in Study MIV-711-201 (Eudract No. 2015-003230-26) at the participating sites 
included in Study MIV-711-202 will be given the opportunity to participate provided that 
they meet the eligibility criteria. The transition from Study MIV-711-201 to MIV-711-202 is 
shown in Figure 1.
Figure 1: Transition from Study MIV-711-201 to Study MIV-711-202
To ensure the patients will have sufficient time to consider their participation in the study the 
informed consent form will be given to the patients prior to Visit 8 in Study MIV-711-201. 
Visit 8 of Study MIV-711-201 will ideally be conducted on the same day as Visit 1 of the 
present study. If these visits are conducted on the same day the results of the following 
assessments will be recorded in the electronic Case Report Form (eCRF) for both studies; 
urine and blood sampling for safety, vital signs, physical examination and ECG. See 
Section 8.1.1 for a full list of assessments required at Visit 1.
A central person, independent from the study, with access to the randomisation list and the
eCRF for Study MIV-711-201 study will confirm Inclusion Criterion 1. The confirmation will 
be communicated to the site staff and the study team via fax/email without revealing the 
treatment in MIV-711-201 or the change in NRS score.
All enrolled patients will receive 200 mg q.d. oral dose of MIV-711 for 26 weeks in addition 
to their current medication. MIV-711 200 mg will be provided as identical capsules to those 
used in Study MIV-711-201.
The patients will take the last dose of IMP in Study MIV-201-711 at Visit 8 and dosing in the 
present study will be started at Visit 2 after a screening period of 10±5 days. Patients who are 


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not eligible to participate in the present study will return for the safety follow up visit (Visit 9) 
in Study MIV-711-201. 
Patients will be permitted to remain on their current analgesic regimen with any changes in 
concomitant medications reported and recorded at study visits as well as in a patient reported 
daily e-diary for two 2-week periods prior to Visit 4 and Visit 5.
The study consists of a Screening period of approximately 2 weeks (Visit 1), eligibility at 
Visit 2, an open-label treatment period of 26 weeks from Visit 2 through Visit 5, and a 
follow-up period of 4 weeks (Visit 6) after the last dose of study treatment is administered.
Telephone calls will be made 5-9 days after all dosing visits for safety and tolerability. There 
will be additional phone calls at Week 10 and Week 20 for safety and tolerability.
A DMEC will meet to review the unblinded safety and tolerability data after the first
25 patients complete Visit 4 and Visit 5.
The study design is summarised in Figure 2.
Figure 2: Study Design


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5
STUDY POPULATION
The study population will consist of patients with symptomatic and radiographic knee joint 
OA who have participated in Study MIV-711-201. Patients must be able to provide written 
consent and meet all the inclusion criteria and none of the exclusion criteria.
5.1
Inclusion Criteria
Patients must meet all of the following criteria to be eligible for enrolment in this study:
1. Previously enrolled in Study MIV-711-201 including completion of Visit 8 either by 
‚
Receiving MIV-711 200 mg and had non-significant clinical worsening on the 
primary endpoint as defined by NRS increase of ø2
OR by
‚
Receiving placebo and had a clinically significant worsening on the primary 
endpoint as defined by NRS increase of œ2
The NRS result will be derived using the primary endpointfrom Study MIV-711-201: NRS average knee 
pain in the target knee with 7days recall: increase from Baseline (Visit 2 of Study MIV-711-201) to Visit 8 
of Study MIV-711-201.
2. Female patients must be non-pregnant, non-lactating and of non-childbearing potential 
either as naturally (spontaneously) post-menopausal or due to hysterectomy and/or 
bilateral oophorectomy/salpingo-oophorectomy (as determined by patient
medical 
history). Naturally (spontaneously) post-menopausal is defined as being amenorrhoeic for 
12 months without an alternative medical cause and with a Screening follicle stimulating 
hormone test indicating post-menopausal state.
3. Male patients should avoid fathering a child by either of the following methods:
‚
True sexual abstinence: meaning that heterosexual abstinence is in line with the 
preferred and usual lifestyle of the patient (periodic abstinence such as that based on 
calendar, ovulation, symptothermal, post-ovulation methods, declaration of 
abstinence for the duration of a trial, or withdrawal/coitus interruptus are not 
acceptable methods of contraception).  
‚
Willingness to use two effective means of contraception with their partner from the 
time of first IMP administration until 3 months after the last dose of IMP. Two or 
more of the following methods are acceptable and must include at least one barrier 
method: i) Surgical sterilisation (i.e., bilateral tubal ligation for female partners; 
vasectomy for male), ii) placement of an intrauterine device or intrauterine system, 
iii) hormonal contraception (implantable, patch, oral), iv) barrier methods including 
condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal 
foam/gel/film/cream/suppository. Male patients who have been sterilised are 
required to use one barrier method of contraception (condom).
4. The patient’s usual analgesic regimen (in case of use) should remain the same as for 
Visit 8 in Study MIV-711-201 (i.e., Visit 1 in Study MIV-711-202).
NOTE: If a patient is experiencing increased or decreased pain and requires an increase or 
a decrease in the dose of analgesics, or an occasional change of analgesics medication 
during his/her participation in the study, then this will be allowed and should be properly 
documented in the patient file and the CRF.
5. Needs to be able to communicate well with the investigators and staff.


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6. Able to comply with the requirements of the study procedures and provide written 
informed consent prior to any study related procedures.
5.2
Exclusion Criteria
Patients will be excluded from enrolment in this study if they meet any of the following 
criteria:
1. The presence of any inflammatory arthritis (e.g., gout, reactive arthritis, rheumatoid 
arthritis, psoriatic arthritis, seronegative spondylarthropathy) or any underlying condition, 
other than OA, that may result in abnormal cartilage and bone metabolism.
2. Any generalised pain condition that may interfere with the evaluation of the target knee 
pain (e.g., fibromyalgia) as judged by the investigator.
3. Ongoing or a history of atrial fibrillation.
4. Currently receiving medication that affects cartilage or bone metabolism (other than study 
drug; hormone replacement therapy taken for more than 6 months is allowed).
5. Current or recurrent disease that could affect the action, absorption or disposition of 
MIV-711, or could affect clinical assessments or clinical laboratory assessments.
6. Any clinically severe or significant uncontrolled concurrent illness, which, in the opinion 
of the Investigator, would impair ability to give informed consent or take part in or 
complete this clinical study.
7. Any medical condition, AE, clinical or laboratory finding from Study MIV-711-201 that,
in the opinion of the Investigator, would preclude inclusion in the present clinical study.
8. Known or suspected intolerance or hypersensitivity to the investigational medicinal 
product, closely related compounds, or any of the stated ingredients.
9. History of alcohol or other substance abuse within the last year.
10. Use of an investigational product other than MIV-711 during participation in Study
MIV-711-201 and /or active enrolment in another drug or vaccine clinical study.
11. Significant target knee injury or surgery during participation in Study MIV-711-201.
12. A history of partial or complete joint replacement surgery in the target knee at any time, 
listed for knee surgery, or anticipating knee surgery during the study period.
13. Any factor which, in the opinion of the investigator, would jeopardise the evaluation or 
safety of the patient or be associated with poor adherence to the clinical study protocol
(e.g., inability to complete study diary, poor tolerability of venepuncture or lack of 
adequate venous access for required blood sampling during the study period).
14. Use of intra-articular hyaluronic acid in the target knee during participation in Study
MIV-711-201.
15. Use of intra-articular, intra-muscular or oral corticosteroids during participation in Study
MIV-711-201.
16. Commencement of non-pharmacological OA interventions during participation in Study
MIV-711-201. 
17. Vulnerable patients, e.g., patients kept in detention, soldiers, and employees of the sponsor 
or the Contract Research Organisation (CRO) with direct involvement in the proposed 
study or other studies under the direction of the investigator or the CRO, as well as family 
members of the employees or the investigator.


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18. Lack of MRI of the knee from Visit 8 in Study MIV-711-201 due to special 
circumstances, such as claustrophobia or difficulties to fit the knee coil.
19. Patients with contra-indication to MRI of the knee.
5.3
Patient Withdrawal and Replacement
In accordance with the Declaration of Helsinki, GCP, and International Conference on 
Harmonisation (ICH) Guidelines and applicable regulations governing human subject 
protections, individual patients have the right to withdraw consent at any time without 
prejudice. At the time of withdrawal of consent, a full efficacy and safety evaluation will be 
performed if the patient consents. 
Patients who withdraw will be asked about the reason(s) for withdrawal, and the presence of 
any AEs and will be asked to return for a follow-up visit (similar to Visit 6) within 4 weeks 
following the withdrawal. An MRI scan should be completed if withdrawal is after Visit 4.
If a patient is being withdrawn due to a suspected infection, no biological samples from this 
patient are allowed to be sent to the laboratory. Samples will be managed according to 
standard routines at the study site. 
In case of discontinuation, the clinical research associate (CRA) should be informed as soon 
as possible.
If the patient has not yet received any IMP in the current protocol and discontinues from the 
study, the patient should not participate in any further study related procedure.
Patients who withdraw will return to routine care.
Patients must also be removed from the study by the Sponsor or Investigator for any of the 
reasons listed below:
‚
The occurrence of pregnancy in a patient.
‚
Use of a non-permitted concomitant drug, as defined in Section 6.6.4 where the 
predefined consequence is withdrawal from the IMP.
‚
Taking another investigational medicinal agent during patients involvement in the study 
i.e., from qualification to end of treatment (EOT).
‚
Any violation of, or deviation from study protocol procedures which, in the judgment of 
the responsible physician, could adversely affect the patients or the integrity of the study 
including missing more than 7 consecutive doses or other evidence of significant non-
compliance (excluding drug holidays or interruptions that were medically warranted).
‚
Any clinical AE, laboratory abnormality, inter-current illness or significant worsening of 
inter-current illness which, in the opinion of the investigator, indicates that continued 
participation in the study is not in the best interest of the patient.
‚
Patients who undergo target knee joint replacement during the treatment period will be 
withdrawn from the study and classified as treatment failures.
‚
Serum transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase 
[AST]) > 3 x upper limit of normal (ULN) AND total bilirubin > 2 x ULN (confirmed 
by subsequent repeat).
‚
ALT or AST > 3 x ULN (confirmed by repeat visit) with the appearance or worsening of 
symptoms felt by the Investigator to be potentially related to hepatic inflammation, such 
as fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or 
eosinophilia.
‚
QTcF > 500 ms or increase > 60 ms from time matched baseline (confirmed by repeat 


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ECG).
‚
Occurrence of an exclusion criterion which is clinically relevant and affects the patient’s 
safety, if discontinuation is considered necessary by the Principal Investigator and/or 
Sponsor.
In order to perform the modified intention to treat (mITT) analysis, and to enable safety 
analyses, all patients who discontinue their medication will be asked to still complete their 
follow-up visit (Visit 6) as outlined in the study schedule. 
Patients who withdraw from the study will not be replaced.
In all cases, the reason(s) for withdrawal must be recorded on the electronic CRF (eCRF).
5.4
Planned Sample Size and Number of Study Centres
All patients in Study MIV-711-201 at the participating sites in Study MIV-711-202 will be 
given the opportunity to participate provided that they meet the eligibility criteria.
It is expected that approximately 50-80 patients based on the normal progression rate of OA
symptoms, as well as the study selection criteria, will be eligible for participation. However 
due to unpredictable factors such as perceived benefits or burdens for the patients 
participating in the study the estimated total number of patients may deviate from the range 
above.
The patients will be recruited from up to 5 centres in up to 5 countries for this study. 
Recruitment could be terminated if considered appropriate.
5.5
Patient Identification 
5.5.1
Patient!Identification
The Principal Investigator or qualified designee will obtain signed, informed consent from the 
potential study patient before any study-specific procedures are performed.
After written informed consent has been obtained, each patient will receive a unique patient 
number. Screened patients who drop out of the study before the first administration of IMP in 
Study MIV-711-202 will retain their patient number. The MIV-711-202 study will be an 
open-label study and distribution of IMP will proceed through the use of an Interactive 
Response Technology (IRT) System [Interactive Web Response System (IWRS)].
5.5.2
Investigational!Drug!Administration!Scheme
From the patients with knee joint OA participating in Study MIV-711-201, those who meet 
the eligibility criteria for the extension study and who provide written informed consent will 
be included in the extension study. In Study MIV-711-202, all patients will receive 200 mg
q.d. oral dose of MIV-711 for 26 weeks in addition to their current medication. MIV-711 
200 mg will be provided as identical capsules to those used in Study MIV-711-201.
The study site will obtain the patient number and container number assignment from the IRT 
system. The date on which the patient number was assigned will be recorded on the eCRF.
Once patient numbers and container numbers have been assigned, they cannot be reassigned.
5.5.3
Allocation!of!Patients!to!Treatment
Allocation of patients to treatment will occur at Visit 2 (Enrolment) after the patient has 
signed the informed consent form and the Investigator has confirmed the patient’s eligibility 
based on screening procedures performed. All patients will receive a unique patient number. 
The patient number allocated to any patient will not be reallocated to other patients if he/she
terminates the study participation for any reason, regardless of whether IMP was taken or not.


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5.5.4
Procedures!for!Handling!of!Incorrectly!Included Patients
Patients who fail to meet the inclusion/exclusion criteria for this study should not, under any 
circumstances, be enrolled into the study. There can be no exceptions to this rule. 
Where patients who do not meet the study criteria are enrolled in error or where patients 
subsequently fail to meet the criteria for the study post enrolment, the procedures in the 
protocol for the discontinuation of such patients must be followed (see Section 5.3).
Once the error is identified a discussion must occur between the Sponsor, the Medical 
Monitor and the Investigator regarding whether to continue or discontinue the patient from the 
study. It needs to be ensured that all such decisions are appropriately documented.


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6
STUDY DRUG
6.1
Investigational Drug
MIV-711 is provided as the hydrochloride (HCl) salt. The pre-clinical development laboratory 
code was MV076159. MIV-711 is manufactured by NCK A/S, Farum, Denmark.
MIV-711 is formulated in hard gelatin capsules (size 0) at the strength of 200 mg, expressed 
as MIV-711 free base. The included excipients are microcrystalline cellulose; Starcap 1500; 
magnesium stearate and anhydrous colloidal silica. The capsule formulation is manufactured 
by Galenica AB, Malmö, Sweden.
6.2
Administration
Patients will receive q.d. 200 mg oral dose of MIV-711 for 26 weeks in addition to their 
current medication.
The IMP should be taken q.d. in the morning approximately 24 hours apart and swallowed 
whole together with a glass of water (approximately 200 ml) before breakfast; breakfast can 
be taken approximately one hour later. The first dose in Study MIV-711-202 is administered 
at the site during Visit 2 (Enrolment). All patients must stay at the site 2 hours after 
administration of the first dose.
IMP should be dispensed during the Visits 2 and 4 and returned by the patients for drug 
accountability at Visit 4 and Visit 5.
On days when the patient is visiting the site the IMP must be taken at the site under fasting
conditions (and not at home) and the time of the intake must be recorded in the source 
documents.
6.3
Packaging, Labelling and Storage
The capsules will be packaged in the white Duma high-density polyethylene containers with 
polypropylene caps.
The packaging and labelling of the patient packages will be performed in accordance with 
Good Manufacturing Practice (GMP) and national requirements. The labelling will fulfil 
GMP Annex 13 requirements and be translated into local language.
The label will include the following information:
-
Name and address of the sponsor (Medivir) 
-
Dosage form, route of administration and quantity of dosage units
-
Study code
-
Kit ID
-
Directions for use
-
The name of the Investigator 
-
Storage conditions
-
Batch number
-
Expiry date
-
The following standard statements:
ｗfor clinical study use only”
ｗkeep out of reach of children”
Additional local requirement will be adhered to the country-specific labels in accordance with 
local regulations for each participating countries.


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The proposed shelf life for the IMP in this packaging is 24 months at room temperature 15 to
25°C.
A temperature record must be maintained and the max/min temperature must be recorded 
during working days.
The investigator must immediately inform the CRA in case of any temperature excursions.
Shorter (ø 24 hours) periods of storage outside the 15°C to 25°C range is accepted if 
maximum temperature does not exceed 40°C.
6.4
Drug Accountability
The Investigator is responsible for maintaining accurate IMP accountability records 
throughout the study. The CRA will review the accountability records.
Each dispensing of IMP will be documented in the eCRF system.
The drug accountability log will include information such as amount dispensed and amount 
returned to the site. IMP returned to the site will be stored as outlined in Section 6.3. The 
returned products should be marked as “returned” and kept separate from the IMP not yet 
dispensed.
The destruction of IMP will be performed according to local requirements following sponsor 
approval.
6.5
Compliance
The administration of all medication (including IMP) must be recorded in the appropriate 
sections of the eCRF. The Investigator is responsible for discussing the treatment compliance 
with the patient before enrolment in the study. Drug accountability will be performed and 
compliance of drug accountability will also be discussed with the patient.
Treatment compliance will be analysed via capsule count. More details will be given in the 
Statistical Analysis Plan (SAP).
6.6
Other Medications
6.6.1
Rescue!Medication
Where possible, patients
will be asked to continue with the same analgesic or 
anti-inflammatory medication they are taking at Screening throughout the study. However, if 
a patient is experiencing increased or decreased pain and requires an increase or a decrease in 
the dose of analgesics, or an occasional change of analgesics medication, then this will be 
allowed, but the reason for the dose change, the new dose and or medication used, must be 
documented in the eCRF. 
6.6.2
Concomitant Medications
In vitro studies have shown no significant inhibition of drug metabolic CYP enzymes at 
MIV-711 concentrations up to 10 µM. In a previous clinical study, mean Cmax at steady-state 
for the dose 200 mg q.d. was 0.58 µM and the highest individual value was 0.80 µM. It is 
therefore considered unlikely that MIV-711 will affect the metabolism of other drugs through 
CYP inhibition and there are no specific restrictions on concomitant medications for 
pharmacokinetic (PK) reasons.
Furthermore, clinical data indicate that MIV-711 is 
extensively metabolised potentially by several routes, making it less likely that other drugs 
should significantly affect the elimination of MIV-711.
In addition to the periodical e-diary, use of concomitant medication and any 
non-pharmacological interventions will be recorded in the source documents and eCRF. All 


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concomitant medications taken during the study will be recorded with generic name, 
indication, daily dose, and start and stop dates of administration at each visit. For this study, 
prescription medicines, other than those prohibited by the study protocol are permitted as 
concomitant medications to manage ongoing or chronic, stable medical conditions. 
Medications taken at the time of Visit 1 will be documented as prior medication. Medication 
taken after the first dose of IMP in the current (MIV-711-202) study will be documented as 
concomitant medication. All patients will be asked about concomitant medication use and any 
changes to use of concomitant medications at all study visits. Patients will be permitted to 
reinstate prohibited concomitant medications on completion of their follow up study visit.
6.6.3
NSAIDs!and!other!analgesics
Patients will be allowed to continue any analgesic medication they are taking at the Screening 
visit for the duration of the study. The patients’ usual analgesics regimen should remain the 
same as at Visit 8 in Study MIV-711-201. Typical OA analgesics are allowed such as: 
nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol and tramadol, as well as 
NSAID and paracetamol combinations with mild opioids such as codeine and 
dextropropoxyphene. In addition to the periodical e-diary, use of concomitant medication will 
be recorded in the source document at each visit.
6.6.4
Prohibited!Concomitant!Medications
Patients should not use any form of steroids (oral, intravenous, intra-articular or intra-
muscular) during the study period; except for inhaled/intranasal steroids for the treatment of 
allergic rhinitis and/or asthma and topical steroids for the treatment of eczema. Medications 
purposed to affect bone or cartilage metabolism are also prohibited as exemplified (albeit not 
exhaustively) by antiresorptive medications such as bisphosphonates, receptor activator of 
nuclear factor kappa-B ligand inhibiting antibodies and calcitonin. Apart from combinations 
with mild opioids as specified in Section 6.6.3, all opioids are prohibited unless for occasional 
rescue medication purposes. In case of uncertainty regarding prohibited medications please 
contact the medical monitor.
6.6.5
Chondroitin! and!Glucosamine
Patients will be permitted to continue current use of chondroitin and glucosamine; however
their use must be clearly documented in the eCRF. Chondroitin or glucosamine therapy may 
not be started during the study.
6.7
RESTRICTIONS
The present study, MIV-711-202 is an extension to the main study MIV-711-201. The main 
study was started with limited available data on phototoxicity for the study drug MIV-711 
which necessitated protective sunlight measures for participating patients. Further evaluation 
of MIV-711 in laboratory tests have since been undertaken which concluded that there is no 
phototoxicity risk for patients taking MIV-711. However, since the present study is an 
extension, it is advised that patients follow similar sunlight protective measures in order to 
maintain consistency in study conditions for patients in the two studies. Such sun and ultra 
violet (UV)-light protective measures include avoiding indoor tanning and direct sun 
exposure, especially between 10 am and 4 pm. If sun/UV light cannot be avoided, suitable 
protective clothing and use of appropriate sunscreen on uncovered areas of the skin are 
advised.


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7
ENDPOINT AND METHODS OF ASSESSMENT
7.1
Primary Endpoint (Study Population A)
The primary objective is to study the safety and tolerability of MIV-711 in OA patients who 
have received treatment for up to 52 (26+26) weeks.
Safety endpoints:
•
Incidence and severity of AEs
•
Incidence and severity of clinical laboratory abnormalities
•
Physical examination findings by patient
•
Incidence and severity of ECG abnormalities
•
Mean change from Baseline (Visit 2 of Study MIV-711-201) in vital signs (blood 
pressure, heart rate, temperature) and oxygen saturation
•
Categorical summary of observed vital signs and vital sign changes compared to
Baseline (Visit 2 of Study MIV-711-201), by patient
7.2
Secondary Endpoints (Study Population A)
Bone parameters will be measured from MRIs of the bone area taken at Visit 2 (Enrolment)
and Visit 8 of Study MIV-711-201 as well as the MRI of the bone area taken at Visit 5 in 
Study MIV-711-202.
MRIs will be analysed semi-quantitatively by a central experienced musculoskeletal 
radiologist using the MOAKS [36] and quantitatively using statistical shape modelling (SSM, 
Imorphics Ltd) for the features below. [23, 37, 38]
MOAKS scoring will be used to assess the following features:
-
Bone marrow lesions (BMLs) and cysts: 15 sub-regions graded for BML (including 
ill-defined lesions and cysts) size in regard to the total volume of the sub-region 
occupied by BML(s). Grade 0=none, grade 1<33% of sub-regional volume, 
grade 2=33–66% of sub-regional volume and grade 3>66% of sub-regional volume. 
-
Articular cartilage: 14 articular cartilage regions graded for size of any cartilage loss 
(including partial and full thickness loss) as a % of surface area as related to the size of 
each individual region surface and % of loss in this sub-region that is full-thickness 
loss.
-
Osteophytes: 12 sites scored for presence and size of osteophytes. Grade 0=none; 
Grade 1=small; Grade 2= medium; Grade 3= large.
Bone shape modelling of MRI will be used to assess:
-
Mean cartilage thickness (mm) for each of the anterior, posterior and central regions, 
with areas denuded of cartilage included as having zero thickness [39]
-
Bone marrow lesion volume (mm3) by anatomical region: medial and lateral 
femorotibial region of femur, medial and lateral patellofemoral region of femur,
medial and lateral tibia, and patella
-
Bone area (mm2) for anatomical regions: lateral and medial femur (patellofemoral); 
lateral and medial femur (femorotibial); lateral and medial patella, lateral and medial 
tibial condyle
-
Bone shape by distance along an OA shape vector for femur, tibia and patella
-
Index bone area/cartilage thickness.


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7.3
Secondary Endpoints (Study Population B)
These are the same as the primary endpoints for Study Population A (see Section 7.1).
7.4
Exploratory Endpoints
7.4.1
Exploratory!Endpoints!(Study!Population!A)
Patient-reported outcomes (PROs)
At Visit 4 and 5 the following PROs will be recorded using questionnaires as specified in 
Table 2.
•
Average overall knee pain severity in the target knee over the past 1 week (0-10 NRS)
•
Worst knee pain severity in the target knee over the past 1 week (0-10 NRS)
•
Global disease activity over the past 1 week (0-10 NRS)
•
Average overall knee pain severity in the contralateral knee over the past 1 week (0-10
NRS)
•
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 3.1 [40] -
a 24-item OA-specific, tri-dimensional self-administered questionnaire, for assessing 
health status and health outcomes in OA of the knee. The response to each question is 
scored as 0=none, 1=mild, 2=moderate, 3=severe, 4=extreme. The 24 questions are 
divided into 3 subscales; pain (questions 1-5, score range 0-20), stiffness (questions 6 
and 7, score range 0-8) and physical function (questions 8-24, score range 0-68). 
Higher scores indicate worse pain, stiffness and physical function. The subscale scores 
are derived by summing the assigned values on component items. The study joint 
referred in the WOMAC questionnaire corresponds to the target knee (as referenced 
elsewhere in this protocol).
•
Osteoarthritis Research Society International (OARSI)-OMERACT Responder index 
[41, 42] will be calculated using the WOMAC pain and function subscales and the 
patient’s global assessment score. Response will be defined as:
1) Improvement in pain or function œ72'"cpf"cduqnwvg"ejcpig œ42"qt"
2) Improvement in at least two of the following:
i) pain œ42'"cpf"cduqnwvg" ejcpig œ32."
ii) function œ42'"cpf"cduqnwvg"ejcpig œ32"cpf"
iii) patients’ global assessment œ42'"cpf"cduqnwvg" ejcpig œ32
•
Intermittent and constant osteoarthritis pain (ICOAP) [42] - an 11-item tool designed to 
assess constant and intermittent OA pain. The tool will be self-reported. (The tool was 
designed for telephone or interview administration but self-reporting is allowed.) The 
questions will be scored according to the User Manual [43] into a constant pa in 
subscale, intermittent pain subscale and total pain score. These scores will be 
transformed to a 0-100 scale for analysis.
•
Global improvements in knee problem, knee pain and knee function recorded on a 
6-point likert scale: completely better, much better, better, no change, worse, much 
worse.
•
EuroQol-5 Dimensions (EQ-5D-5L) [44] (Visit 5 only) - a generic measure of self-
reported health status that defines health status in terms of five dimensions – mobility; 
self-care; usual activity; pain or discomfort; and anxiety or depression [45]. EQ-5D-5L
has been extensively validated and shown to be sensitive, internally consistent, and 
reliable in the general population and other patient groups, including for inflammatory 
arthritis.[46]


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•
In an e-diary format, a patient knee pain diary (NRS) and analgesia questionnaire will 
be completed daily during two 2-week periods prior to Visit 4 and Visit 5. Baseline 
(Visit 2 of Study MIV-711-201) will be defined as the last observation prior to the first 
dose of investigational product. The assessments in the e-diary comprise.
1) Average overall knee pain severity in the target knee over the past 12 h (0-10
NRS)
2) Worst knee pain severity in the target knee over the past 12 h (0-10 NRS)
3) Adherence to usual analgesics regimen
4) Intake of IMP
Biomarkers, imaging and pharmacokinetics:
•
Serum and urinary biomarkers (CTX-I, PINP, BSAP and TRAP5b in serum and NTX-I, 
CTX-K."gEVZ-I, and CTX-II in urine).
•
Compound index of MRI bone area and cartilage volume
•
Pharmacokinetics: MIV-711 PK parameters and their relationship to covariates such as 
age, weight, gender, liver function and concomitant medications.
7.4.1.1
Biomarkers and biobanking
Blood and urine samples will be taken at Visits 2, 4, 5 and 6, for analysis of exploratory bone 
and cartilage markers of relevance for OA disease, such as CTX-I, PINP, BSAP and TRAP5b
in serum and NTX-I, CTX-I, gEVZ-I and CTX-II in urine.
A blood and urine sample from Visit 5 will be collected and stored in a biobank according to 
local biobanking regulations and under a separate voluntary ICF, to enable further profiling 
(pharmacogenomics, proteomics, genomics, metabolomics and lipidomics). In addition, 
potential susceptibility genes and genes related to underlying disease may be explored using 
the same samples. Aliquots of each sample will be retained for up to 5 years by the sponsor or 
its subcontractor for biobank storage, in line with GCP/Good laboratory practice and 
biobanking policies. Biological samples used for possible exploratory analysis may be 
retained at Medivir, Huddinge, Sweden, or at an affiliated storage location detailed in the 
Laboratory Manual, for a maximum of 5 years following the finalisation of the Clinical Study 
Report. The results from such analysis will be reported separately from the Clinical Study 
Report.
7.4.1.2
Imaging
Change from Visit 8 in Study MIV-711-201 to Visit 5 in the current study in a calculated 
compound index of MRI bone area (key secondary endpoint) and cartilage thickness.
7.4.1.3
Pharmacokinetics
The pharmacokinetics and potential metabolites of MIV-711 and their relationship to patient 
factors and concomitant medications will be analysed following the sampling procedures as 
described in Section 7.10.
7.4.2
Exploratory!Endpoints!(Study!Population!B)
All secondary and exploratory endpoints described in Section 7.2 and Section 7.4.1,
respectively, for Study Population A will be assessed as exploratory endpoints for Study 
Population B and will be evaluated over 26 weeks.


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7.5
Physical Examination
A standard complete physical examination will be performed at Visit 1 (Screening), Visit 2
(Enrolment), Visit 3, Visit 4 and Visit 5. The following parameters and body systems will be 
examined and any abnormalities will be described: general appearance, skin (presence of 
rash), head, eye, ears, nose, and throat, lungs (auscultation), heart (auscultation for presence 
of murmurs, gallops, rubs), extremities exam for the presence of peripheral oedema,
abdominal (palpation and auscultation), neurologic (mental status, station, gait, reflexes, 
motor and sensory function, coordination) and lymph nodes. 
A standard clinical examination of both knees will be undertaken at all visits. Any clinically 
significant changes from Visit 2 (Enrolment) should be recorded as AEs.
7.6
Vital Signs 
Vital signs (body temperature, heart rate, blood pressure, oxygen saturation) will be 
performed at all clinic visits prior to IMP dosing.
Blood pressure and heart rate measurements will be performed after the patient has been 
resting in a supine position for at least 5 minutes.
Weight will be measured at Visit 1 (Screening).
7.7
12-lead Electrocardiograms (ECG)
A 12-lead ECG will be performed at all clinic visits. 12-lead serial ECGs will be recorded at 
Visit 2 (Enrolment) pre-dosing and after 30 minutes, 1 hour and 2 hours post-dosing 
(± 10 minutes).
On dosing days, ECG should be performed 30 minutes after dosing (± 10 minutes).
The 12-lead ECG will be performed after the patient has been resting in a supine position for 
at least 10 minutes.
All ECGs will be assessed by the investigator, and the data will be recorded in the eCRF. The 
clinical significance of ECG results will be determined by the investigator after review of the 
ECG report in relation to the patient’s medical history, physical examination findings, and 
concomitant medications.
7.8
Imaging Assessments
At Visit 5 MRI acquisition will be performed on the bone area using 1.5/3T systems using the 
following sequences, which have been optimised for visualization of bone, cartilage and 
BML:
•
High resolution 3D sagittal proton density (PD) fast spin echo (FSE) with fat saturation
•
Sagittal PD FSE intermediate-weighted with fat-saturation
•
Sagittal PD FSE without fat-suppression.
The total scanning time for this set of sequences is approximately 15 minutes. 
When obtaining the MRI scan the sites must use the same scanner and coil as used during 
Visit 2 and Visit 8 in Study MIV-711-201.
Based on experience from Study MIV-711-201 it will be the responsibility of each site to 
ensure robustness of MRI acquisition. At each centre, phantoms will be scanned and visually 
assessed for distortion, warping and double shadowing along with protocol compliance prior 
to study initiation and then regularly re-tested. Each set of images will be quality controlled to 
allow for a repeat MRI to be captured if required. It is the responsibility of the sites to perform 
these phantom scans on a regular basis throughout the study and these scans will not be
evaluated centrally. In case of image quality issues the central reader may request the 


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phantom scans. If a site has an upgrade (hardware/software) then a phantom scan will be 
requested before and after upgrade to confirm the protocol has not changed.
Further details are provided in the imaging acquisition guidelines provided to each site.
Upon study completion the MRI measures from the images gathered for this study will be 
repeated using automated image analysis to enable future methodological improvements.
7.9
Self-report Parameters
Patient-reported outcomes will be recorded using questionnaires at Visit 4 and at Visit 5, as 
follows:
Pain, function and disease activity
•
11-point NRS scales for: 
-
Average overall knee pain severity in the target knee over the past 1 week
-
Average overall knee pain severity in the contralateral knee over the past 1 week
-
Worst knee pain severity in the target knee over the past 1 week 
-
Global disease activity over the past 1 week 
•
ICOAP – an 11-item tool designed to assess constant and intermittent pain
•
WOMAC 3.1 – a 24-item OA - specific, tri-dimensional self-administered 
questionnaire, for assessing health status and health outcomes in OA of the knee 
•
In an e-diary format, a patient pain diary and analgesia questionnaire will be completed 
daily during two 2-week periods prior to Visit 4 and prior to Visit 5.
Using a 6-point Likert scale (completely better, much better, better, no change, worse, much 
worse) we will record patient-reported:
•
Global improvement in knee problem at follow-up
•
Global improvement in knee pain at follow-up
•
Global improvement in knee function at follow-up
Quality of life 
EuroQol-5 Dimensions (EQ-5D-5L) - a generic measure of self-reported health status that 
defines health status in terms of five dimensions – mobility; self-care; usual activity; pain or 
discomfort; and anxiety or depression. This will be performed at Visit 5 only.
Clinical Safety Evaluation/Adverse Events
During each visit patients will be monitored and questioned by a member of the clinical staff 
for the occurrence of new AEs since the last visit, or the outcome of any AEs reported at 
previous visits. Incidence, severity, expectedness, relation to the study intervention and 
outcome of each adverse event will be documented and reported.
Adherence to Study Medication and Concomitant Medication
Patients will be asked to return any unused study medication at Visit 4 and Visit 5 and drug
accountability will be conducted. The Brief Medication Questionnaire self-reported measure 
[47] for the use of concomitant medication will be included at Visit 4 and Visit 5.


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7.10
Pharmacokinetic Sampling
Three blood samples will be collected at Visit 5 to measure plasma concentrations of 
MIV-711 and potential metabolites. On this visit, one of these three samples will be collected
at pre-dose and the other two samples will be collected post-dose. The two post-dose samples 
should be separated by two of the following time intervals, if possible; 0.25-1h, 1-2h, 2-4h, 
4-6h, 6-8h and 8-10h. For example, if the first post-dose sample is taken at 1-2h the second 
should be taken at 6-8h.
The 3 blood samples (approximately 5 mL each) will be taken by venipuncture or cannulation 
from a forearm vein(s) and collected into lithium heparin tubes, and will be mixed. After 
mixing, blood samples will be placed in a cool box containing crushed ice/water. The samples 
will be centrifuged, within 1 hour of collection, at 1500 g for 10 minutes at approximately 
4°C.
For each sample, the separated plasma will be equally split into 2 aliquots and transferred into 
2 suitably labelled polypropylene tubes, and stored within 2 hours of collection at at 
least -70°C until shipped on dry-ice. The 2 aliquots should be shipped in two separate 
shipments to the Bioanalytical Laboratory for further shipment and analysis of MIV-711 and
for potential metabolite analysis. Refer to the Laboratory Manual for further details.
The date/time of sample collection as well as the date/time of the most recent dose will be 
collected in the eCRF. A separate sub-protocol for the Population pharmacokinetics (PK)
analysis will be established aiming at analysing MIV-711 PK parameters and their 
relationship to covariates such as age, weight, gender, liver function, and concomitant 
medications. Exploratory PK-Pharmacodynamic
analyses for efficacy variables and 
biomarkers may be performed based on the study results. 
Further details on the provider and handling of the pharmacokinetic samples will be provided 
in the Laboratory Manual.
7.11
Biomarker Sampling
Blood and urine samples will be taken at Visits 2, 4, 5 and 6 for analysis of exploratory bone 
and cartilage biomarkers of relevance for OA disease, such as CTX-I, PINP, BSAP and 
TRAP5b in serum and NTX-I, CTX-I, gEVZ-I and CTX-II in urine. Patients should be fasted 
overnight (no meals after 11 pm, but water allowed) and restrained from extensive exercise 
and smoking the previous day. Blood and urine samples will be collected at pre-dose in the 
morning (between 7-10 am) on the visit.
Blood samples (approximately 15 mL) will be taken by venipuncture or cannulation from a 
forearm vein(s) and collected into serum separator tubes. The samples will be centrifuged, 
within 1 hour of collection, at 1800g for 10 minutes at room temperature. For each sample the 
separated serum will be divided into 3 aliquots and transferred into suitably labelled
polypropylene tubes and stored within 1.5 hours of collection at at least -70°C until analysis.
The first void of morning urine should have occurred before the urine sample (approximately 
10 mL) is taken from a later void. The urine samples will be divided into 3 aliquots into 
suitably labelled polypropylene tubes. The samples will be stored within 1.5 hours of 
collection at at least -70°C until analysis.
The date/time of sample collection as well as the date/time of the most recent dose will be 
collected in the eCRF.
Aliquot 1 and 2 of each blood and urine sample should be shipped together to the Central 
Laboratory. The third aliquot should remain at the site and be shipped separately.
Further details on the provider and handling of the biomarker samples will be provided in the 
Laboratory Manual.


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7.12
Optional Pharmacogenomics Sampling
Blood and urine samples will be collected at Visit 5
under voluntary ICF for 
pharmacogenomics, proteomics, genomics, metabolomics and lipidomics.
Blood samples (approximately 19 mL) will be taken by venipuncture or cannulation from a 
forearm vein(s) and collected into a DNA PAXgene (approximately 8.5 mL), RNA PAXgene 
(approximately 2.5 mL) or EDTA tube (approximately 8 mL) for preparation of DNA, RNA 
and protein, respectively. The DNA and RNA PAXgene tubes will be frozen and stored at at 
least -70°C until analysis. The EDTA tube will be processed into plasma by centrifugation 
within 1 hour of collection, at 1500 g for 10 minutes at approximately 4°C. The plasma will 
be separated into 2 aliquots and transferred into suitably labelled cryovials and stored at at 
least -70°C until analysis. 
A urine sample (approximately 5 mL) will be collected for protein isolation. The urine sample 
is centrifuged within 1 hour of collection at 1500 g for 5 min at approximately 4°C and the 
sample is separated into 2 aliquots and transferred into suitably labelled cryovials and stored 
at at least -70°C until analysis.
The 2 aliquots of each blood and urine sample should be shipped in two separate shipments to 
the Central Laboratory.
7.13
Adverse Events
7.13.1 Definitions of!Adverse!Events (AEs)
An AE is any untoward medical occurrence that occurs in a patient or clinical investigation 
patient administered a pharmaceutical product, and which does not necessarily have to have a 
causal relationship with this treatment. An AE can therefore be any unfavourable and 
unintended sign (including abnormal laboratory finding), symptom, or disease temporally 
associated with the use of an investigational product, whether or not considered related to the 
product.
All AEs, including undercurrent illnesses, occurring during the study will be documented in 
the eCRF system. Concomitant illnesses, which existed before entry into the study, will not be 
considered AEs unless they worsen during the treatment period. All AEs, regardless of the 
source of identification (e.g., physical examination, laboratory assessment, ECG, reported by 
patient), must be documented. Worsening of the underlying disease is not considered an AE
and should be reported as such only if deemed by the Investigator to be beyond the expected 
progression for OA.
Pre-existing conditions will be recorded in the eCRF system on the Medical History page.
A treatment-emergent AE (TEAE) will be defined as an AE that begins or that worsens in 
severity after at least one dose of IMP has been administered.
7.13.2 Assessment!of!Adverse!Events
Each AE will be assessed by the Investigator with regard to the following categories.
7.13.2.1 Seriousness
An SAE is defined as any untoward medical occurrence that at any dose:
•
Results in death
•
Is life-threatening
This means that the patient is at risk of death at the time of the event; it does not mean 
that the event hypothetically might have caused death if it were more severe.
•
Requires inpatient hospitalization or prolongation of existing hospitalization


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•
Results in persistent or significant disability or incapacity
•
Is a congenital anomaly or birth defect
•
Is an important medical event(s) that may not be immediately life-threatening or result 
in death or hospitalization but that may jeopardise the patient or require intervention to 
prevent one of the above outcomes.
Medical and scientific judgment should be exercised in deciding whether a case is serious 
and whether expedited reporting is appropriate.
7.13.2.2 Intensity
The intensity of each AE must be assessed by the Investigator using one of the following 
categories, and recorded in the eCRF system:
•
Mild: An AE that is easily tolerated and does not interfere with usual activities;
•
Moderate: An AE that interferes with usual activities;
•
Severe: An AE that prevents usual activities.
7.13.2.3 Causality
The Investigator will assess the causality/relationship between the AE and the IMP as well as 
the study procedure and record that assessment in the eCRF system.
The causal relationship of the AE to IMP will be described in terms of:
•
Related
•
Unrelated
7.13.2.4 Adverse Events of Special Interest
No Adverse Events of Special Interest monitoring is applicable for this study.
7.13.2.5 Recording Adverse Events
All AEs and SAEs must be recorded, whether or not considered causally related to the IMP or 
to the study procedure(s). All AEs and SAEs will be recorded in the eCRF system from the 
date the Informed Consent Form is signed (Visit 1) until the safety follow-up visit (Visit 6) is 
completed. All AE reports should contain a brief description of the event, date and time of 
onset, date and time of resolution, intensity, treatment required, relationship to IMP, action 
taken with the IMP, outcome, and whether the event is classified as serious. The information 
related to the AEs will be captured in the eCRF within the normal data entry timelines.
Whenever feasible, AEs should be documented as medical diagnoses. When AEs do not 
appear clearly inter-related, individual signs or symptoms may be reported as separate AEs.
7.13.2.6 Reporting Serious Adverse Events
The Investigator will complete the SAE report and will evaluate the seriousness and the 
causal relationship of the event to study treatment. In addition, sponsor will evaluate the 
relatedness and expectedness according to the reference document (IB). Based on the 
Investigator and sponsor’s assessment of the event, a decision will be made concerning the 
need for further action.
All SAEs that occur from the time of signature of informed consent until 4 weeks (Visit 6)
after the last dose of IMP, whether considered to be associated with the IMP or not, must be 
reported within 24 hours of awareness to the PAREXEL Safety Contact using the numbers in 
the List of Study Personnel.
SAEs occurring after the end of the study should be reported to the sponsor by the 
Investigator, if the Investigator considers there is a causal relationship with the IMP.


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The following information is required for a valid report:
•
An identifiable reporter (i.e., name, address of Investigator)
•
An identifiable patient (i.e., patient number, but NOT patient name)
•
A suspect IMP or clinical study procedure
•
A serious adverse event or outcome associated with the use of IMP or clinical study
procedure
As far as possible all points on the SAE report form should be covered in the initial report, or 
the completed SAE form itself must be faxed to the PAREXEL Safety Contact. If important 
relevant information is missing, PAREXEL will immediately initiate follow-up. The 
investigator or other site personnel must inform PAREXEL of any follow-up information on a 
previously reported SAE within 24 hours of when he or she becomes aware of it. The original 
SAE form must then be sent by mail to the PAREXEL Safety Contact. In addition, the event 
must be documented in the eCRF system.
In the event that the Investigator is unable to enter the SAE in the eCRF or to complete the 
paper SAE form to report the event within 24 hours of their awareness of the event, the 
investigator may report the SAE over the telephone via the SAE answering service, and then 
provide the completed paper SAE form via fax/email. In any case the Investigator also has to 
record the event in the eCRF. If questions arise regarding the reporting procedures or the 
specifics of the reporting of an event, sites may call utilizing the numbers specified in the list 
of Study Personnel.
After receipt of the initial report, the safety centre will review the information and, if 
necessary, contact the Investigator, to obtain further information for assessment of the event. 
PAREXEL will be responsible for all information processing and reporting according to local 
legal requirements. 
PAREXEL International
Medical Monitor: Francois Burger
Medical hotline: +49 30 30685 274
SAE Fax: +49 30 315118 7777 (24-hour service)
Email: Medical_Berlin@parexel.com
7.13.2.7 Follow-up of Adverse Events
All AEs experienced by a patient, irrespective of the suspected causality, will be monitored 
until the AE has resolved, any abnormal laboratory values have returned to baseline or 
stabilized at a level acceptable to the Investigator and Medical Monitor, until there is a 
satisfactory explanation for the changes observed, until the patient is lost to follow-up, or until 
the patient has died.
The Sponsor will actively follow-up and collect information on any AE that occurs during the 
course of a clinical study, however while this activity will continue for any serious AEs until 
stabilization or until the outcome is known, it will be discontinued at the time of database lock 
for non-serious AEs.
7.13.2.8 Suspected Unexpected Serious Adverse Reactions
Any adverse event that is serious, associated with the use of the IMP, and suspected 
unexpected serious adverse reaction (SUSAR) has additional reporting requirements, as 
described below. For the assessment of expectedness, further information is found in the IB 
Section 6 ‘Summary of Data and Guidance for the investigator’.


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•
If the SUSAR is fatal or life-threatening Regulatory Authorities and Independent Ethics 
Committees (IECs) will be notified within 7 calendar days after PAREXEL learns of 
the event. Additional follow-up (cause of death, autopsy report, and hospital report) 
information should be reported within an additional 8 days (15 days total).
•
If the SUSAR is not fatal or life-threatening Regulatory Authorities and IECs will be 
notified within 15 calendar days after PAREXEL learns of the event.
The Sponsor will notify the Investigators in a timely fashion of relevant information about 
SUSARs that could adversely affect the safety of patients. Follow-up information may be 
submitted if necessary. 
The Sponsor will also provide annual safety updates to the Regulatory Authorities and IECs
responsible for the study. These updates will include information on SUSARs and other 
relevant safety findings.
7.13.2.9 Pregnancy
Women of childbearing potential are not allowed to be included in this study. Should a 
pregnancy still occur during study treatment, the patient must be discontinued from the study 
immediately and the pregnancy must be reported to the sponsor by providing the completed 
Pregnancy Reporting and Outcome Form within 24 hours of awareness and followed until 
outcome (completion/termination) of the pregnancy.
7.13.2.10 Paternal Exposure
Pregnancy of the patient's partner is not considered to be an AE. However, the outcome of all 
pregnancies from the date of the first dose until 6 month after the last dose must be reported to 
the Sponsor and, be followed and documented by completion of the Pregnancy Reporting and 
Outcome Form.
Any pregnancy must be reported to the Sponsor according to the SAE reporting procedure 
whether or not associated with an AE/SAE as described in section 7.13.2.6.
7.13.2.11 Abuse, Misuse, Overdose or Medication Error
Any abuse, misuse, overdose, or medication error must be reported to the Sponsor according 
to the SAE reporting procedure whether or not associated with an AE/SAE as described in 
Section 7.13.2.6.
Note: The 24 hour reporting requirement for SAEs does not apply to reports of abuse, misuse, 
overdose, or medication errors unless these result in an SAE.
The categories below are not mutually exclusive; the event can meet more than 1 category.
•
Abuse – Persistent or sporadic intentional intake of IMP when used for a non-medical 
purpose in a manner that may be detrimental to the individual and/or society.
•
Misuse – Intentional use of IMP other than as directed or indicated at any dose (Note: 
this includes a situation where the investigational product is not used as directed at the 
dose prescribed in this protocol). 
•
Overdose – Intentional or unintentional intake of a dose of an investigational product 
exceeding 15% over the total daily mg of MIV-711 as defined in the dosing charts 
developed per protocol. 
•
Medication Error – An error made in prescribing, dispensing, administration, and/or 
use of an IMP. Medication errors should be collected/reported for all investigational 
products under investigation.
The following medication errors are defined as reportable to the sponsor in this study:


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-
The administration and/or use of an expired product should be considered as a 
reportable medication error.
A blood sample for determination of plasma MIV-711 concentration should be obtained, if at 
all possible, as soon as possible after Investigator becomes aware of any above, if associated 
with an AE.
The information related to abuse, misuse, overdose, or medication error will be captured in 
the eCRF within the normal data entry timelines.


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8
STUDY CONDUCT
8.1
Study Schedule
Patients with symptomatic knee OA participating in Study MIV-711-201 will be invited to 
participate in the present study.
Visit 1 of the present study coincides with Visit 8 of Study MIV-711-201. To ensure the 
patients will have sufficient time to consider their participation in the study, the informed 
consent form will be given to the patients prior to Visit 8 in Study MIV-711-201. During 
Visit 1 of the present study the patient information will be discussed. Any questions from the 
patient will be answered. The Screening Phase will last for a maximum of 10±5 days, during 
which patients will be checked for eligibility by the investigator. The patient’s eligibility will 
be determined by the laboratory results obtained during the Screening visit (Visit 1). The 
study will include 26 weeks of treatment, with patients followed for 30 weeks as per Study 
Schedule (Table 2).
8.1.1
Screening!Visit!(Visit 1,!Day -10 ± 5 days)
The activities below are those performed at the Screening visit which will be documented in 
eCRF:
•
Obtaining written informed consent. Study details, risks and benefits will be reviewed 
and patients will be encouraged to ask questions and clarify any concerns. The patient
will have been provided with the consent form to read prior to Visit 8 in Study 
MIV-711-201.
•
Assessing inclusion and exclusion criteria
•
Obtaining demographic data (including age, gender and race)
•
Obtaining medical and surgical history 
•
Performing complete physical examination (assessed at Visit 8 in MIV-711-201, must 
only be re-assessed if Visit 8 does not occur on the same day as Visit 1 in the present 
study)
•
Performing vital signs assessments including weight and oxygen saturation (assessed at 
Visit 8 in MIV-711-201, must only be re-assessed if Visit 8 will not occur on the same 
day as Visit 1 in the present study)
•
Performing 12-lead electrocardiogram assessment (assessed at Visit 8 in MIV-711-201, 
must only be re-assessed if Visit 8 will not occur on the same day as Visit 1 in the 
present study)
•
Sampling for urinalysis (assessed at Visit 8 in MIV-711-201, must only be re-assessed 
if Visit 8 will not occur on the same day as Visit 1 in the present study)
•
Sampling for urine drug screen
•
Sampling for blood clinical chemistry and haematology testing (assessed at Visit 8 in 
MIV-711-201, must only be re-assessed if Visit 8 will not occur on the same day as 
Visit 1 in the present study)
•
Sampling for blood post-menopausal assessments (only post-menopausal or sterile 
women will be enrolled)
•
Dispensing new Patient Emergency Card
•
Monitoring for AEs, SAEs
•
Performing registration in the Interactive Web Response System (IWRS)


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8.1.2
Enrolment!(Visit 2,!Day 1)
The activities below are those performed at the enrolment visit which will be documented in 
eCRF:
•
Confirming inclusion and exclusion criteria
•
Monitoring for AEs, SAEs and concomitant medication
•
Performing complete physical examination
•
Performing vital signs assessments
•
Performing 12-lead serial ECGs at Visit 2 (Enrolment) pre-dosing and after 30 minutes, 
1 hour and 2 hours post-dosing (± 10 minutes)
•
Sampling for blood and urine biomarker testing
•
Sampling for blood clinical chemistry, haematology and urine testing
•
Dispensing the first IMP at the site. Patient must stay at the clinic for 2 hours after 
taking the IMP.
•
Dispense e-diary. Re-training of patients if required.
•
Obtaining optional ICF for pharmacogenomics, proteomics, genomics, metabolomics 
and lipidomics.
•
Phone call to assess safety and tolerability (completed 5-9 days after the visit)
8.1.3
Safety!Visit!(Visit!3![Week!4!±!2!days])
The activities below are those performed at the safety visit which will be documented in 
eCRF: 
•
Monitoring for AEs, SAEs and concomitant medication
•
Performing vital signs assessments  
•
Performing physical examination 
•
Performing 12-lead electrocardiogram assessment 30 minutes post-dose 
•
Sampling for urinalysis  
•
Sampling for blood clinical chemistry and haematology testing
•
Phone call to assess safety and tolerability (completed 5-9 days after the visit)
8.1.4
Safety!and!Treatment!Visit!(Visit 4 [Week 14 ±!7!days],!and!Visit 5 [Week 26 ±!
7 days])
The activities below are those performed at the safety and treatment visits which will be 
documented in eCRF:
•
Monitoring AEs, SAEs and concomitant medication
•
Performing vital signs assessments
•
Performing complete physical examination
•
Performing 12-lead electrocardiogram assessment 30 minutes post-dose (± 10 minutes)
•
Sampling for urinalysis 
•
Sampling for blood and urine biomarker testing
•
Sampling for blood clinical chemistry and haematology testing 
•
Sampling for blood PK assessment (at Visit 5 only)
•
Obtaining optional blood sample for pharmacogenomics, proteomics, genomics, 
metabolomics and lipidomics and urine sample for proteomics and metabolomics (at 
Visit 5 only)
•
Performing knee MRI (at Visit 5 only) ±5 days


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•
Completion of NRS, WOMAC, ICOAP, Global Improvement Questionnaire and Brief 
Medication Questionnaire
•
Completion of Quality of Life questionnaire: EuroQoL EQ-5D-5L (at Visit 5 only)
•
Dispense IMP at the site (the capsule should be taken from the bottle currently in use 
by the patient) (Visit 4 only)
•
Drug accountability
•
Review e-diary completion which has been done for a two-week period prior to the 
visits
•
Phone call to assess safety and tolerability (completed 5-9 days after the visits)
•
Return of e-diary (at Visit 5 only)
8.1.5
Additional!Telephone!Calls to!Assess!Safety!and!Tolerability
Additional telephone calls to assess safety and tolerability will be performed at Week 10 and 
Week 20.
8.1.6
Safety!Follow-up Visit (Visit 6,!Week 30 ±!7 days)
The activities below are those performed at the safety follow-up visit which will be 
documented in eCRF:
•
Monitoring AEs, SAEs and concomitant medication
•
Performing vital signs assessments 
•
Performing 12-lead electrocardiogram assessment 
•
Sampling for blood and urine biomarker testing
•
Sampling for blood clinical chemistry, haematology and urine testing 
The end of the study is defined as the last Visit 6 (Week 30) of the last patient.
Table 1:
Clinical Laboratory Testing
Post-menopausal determination:Follicle stimulation hormone (FSH) 
Female patients mustbe of non-childbearing potential either as naturally (spontaneously) post-menopausal 
or due to hysterectomy and/or bilateral oophorectomy/salpingo-oophorectomy (as determined by patient 
medical history). Naturally (spontaneously) post-menopausal is defined as being amenorrheic for 
12 months without an alternative medical cause and with a Screening FSH indicating post-menopausal 
state.
Fasting samples are required at all study visits as fasting glucose is required as part of the chemistry 
samples.
Haematology: WBC and differential, % and absolute for: neutrophils, lymphocytes, monocytes, 
eosinophils, basophils; haemoglobin,haematocrit, RBC, RBC indices (MCV, MCH and MCHC) and 
morphology, platelet count
Chemistry:urea nitrogen, creatinine, calcium, sodium, potassium, bicarbonate, chloride, total protein, 
fasting glucose, total bilirubin, direct bilirubin and indirect bilirubin, ALT, AST, alkaline phosphatase, 
GGT, CPK, CRP 
Urinalysis:with microscopic: specific gravity, pH , protein, glucose, ketones, nitrites, blood and leukocyte 
esterase
Urine Drug Screen:Amphetamine, Benzodiazepines, THC, Cocaine, Oxycodone and Opiate
PTH (parathyroid hormone)


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The above parameters will be analysed by a Central Laboratory. Total blood volumes to be 
collected are detailed in Appendix 1. Further details on the provider and handling of 
laboratory samples will be provided in the Laboratory Manual.
The study schedule is summarised in Table 2.


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Table 2:
Study Schedule
Study Visit
V1
V2
V3
V4
V5
V6
Weeks
-2
1
4 ±2 days
14 ±7 days
26 ± 7 days
30 ± 7 days
Day
-10 ± 5 days
Day 1
28 ±2 days
98 ±7 days
182 ± 7 days
210 ± 7 days
Visit Description
ScreeningA
Enrolment
Safety
Safety and Treatment
Safety follow-up
Signed informed consent
X
XB
Inclusion/exclusion criteria
X
X
Demographics
X
Weight
X
Medical & Surgical history
X
Physical examination
XC
X
X
X
X
Vital signs, including body 
temperature
XC
X
X
X
X
X
12-Lead ECGD
XC
XE
X
X
X
X
Clinical chemistry/Haematology
XC
X
X
X
X
X
UrinalysisF
XC
X
X
X
X
X
Urine drug screen
X
Post-menopausal assessment
(females only)
X
e-diary dispensing and training
X
e-diary for pain and analgesicG
X
X
Patient Emergency Card 
Dispensing
X
MRI of the bone area
XH


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Study Visit
V1
V2
V3
V4
V5
V6
Weeks
-2
1
4 ±2 days
14 ±7 days
26 ± 7 days
30 ± 7 days
Day
-10 ± 5 days
Day 1
28 ±2 days
98 ±7 days
182 ± 7 days
210 ± 7 days
Visit Description
ScreeningA
Enrolment
Safety
Safety and Treatment
Safety follow-up
Registration in the IWRS
X
NRS, ICOAP, WOMAC
X
X
Global improvement (6-point 
Likert scale)
X
X
EuroQoL EQ-5D-5L
X
Brief Medication Questionnaire
X
X
Dispense IMPI
XJ
X
Drug accountability
X
X
e-diary return
X
PK sampling (blood)
X
Biomarker samplesK
X
X
X
X
AEs/SAEs monitoring
X
X
X
X
X
X
Concomitant Medication
X
X
X
X
X
Phone call to assess safety and 
tolerabilityL
X
X
X
X
Blood sample for 
pharmacogenomics, proteomics, 
genomics, metabolomics and 
lipidomics and urine sample for 
proteomics and metabolomics
XM


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Study Visit
V1
V2
V3
V4
V5
V6
Weeks
-2
1
4 ±2 days
14 ±7 days
26 ± 7 days
30 ± 7 days
Day
-10 ± 5 days
Day 1
28 ±2 days
98 ±7 days
182 ± 7 days
210 ± 7 days
Visit Description
ScreeningA
Enrolment
Safety
Safety and Treatment
Safety follow-up
Abbreviations: AE=adverse event; ECG=electrocardiogram; eCRF=electronic case report form; DNA=deoxyribose nucleic acid;  EuroQoL EQ-5D-5L= a standard measure of 
health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal; FSH=follicle stimulating hormone; 
ICF=informed consent form; ICOAP=intermittent and constant osteoarthritis pain; IMP=investigational medicinal product; IWRS= Interactive Web Response System;
MRI=magnetic resonance imaging; NRS=numeric rating scale; PK=pharmacokinetic; PRO=patient-reported outcomes; RNA=ribonucleic acid; SAE=serious adverse event; 
WOMAC= Western Ontario and McMaster Universities Osteoarthritis Index
A) The Screening visit (Visit 1) will coincide with 26-week End of Treatment visit of Study MIV-711-201 (Visit 8).
B) Optional ICF to be provided and signed at Visit 2.
C) Assessed at Visit 8 in Study MIV-711-201. Only need to be re-assessed if Visit 8 does not occur on the same day as Visit 1 in Study MIV-711-202
D) 30 minutes post-dose (± 10 minutes).
E) 12-lead serial ECGs will be recorded at Visit 2 (Enrolment) pre-dosing and after 30 minutes, 1 hour and 2 hours post-dosing (± 10 minutes).
F) If urinalysis is positive for blood, nitrites, leukocyte esterase, and/or protein, additional microscopic analysis may be performed.
G) To be completed at home during the 2 weeks leading up to the marked visit with final recording the day before.
H) ± 5 days
I) Patients take IMP in the clinic in a fasting state. Breakfast can be eaten 1 hour after IMP intake. The last dose of the IMP will be taken at the site during Visit 5.
J) The first dose of IMP will be dispensed to the patient at the site and the patient must stay at the clinic for 2 hours after intake of IMP. Date and time should be recorded in the 
eCRF. The first dose should be given to the patient after all assessments at Enrolment have been performed. 
K) Both blood and urine sample will be collected for biomarker. The first void of morning urine should have occurred before the urine sample is taken from a later void. The 
patients must be fasting when all biomarker samples are taken.
L) The phone call should be made 5-9 days after all dosing visits. There will be additional phone calls at Week 10 and Week 20. 
M) Blood will be collected for pharmacogenomics, proteomics, genomics, metabolomics and lipidomics and urine will be collected for proteomics and metabolomics pre-dose at 
Visit 5 from patients who provide additional written consent.


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8.2
Early Termination Visit
All patients who discontinue the IMP because of an AE, or for any other reason, will be asked 
to complete the safety follow-up visit (Visit 6) as outlined in the study schedule (Table 2). In 
addition to the assessments described in Section 8.1.6, the following should also be 
completed:
•
Drug accountability
•
Return of eDiary
•
Physical examination
•
Performing knee MRI (±5 days) (if withdrawal is after Visit 4)
•
Obtaining optional blood samples for pharmacogenomics, proteomics, genomics, 
metabolomics and lipidomics and urine samples for proteomics and meabolomics.
8.3
Discontinuation of the Study
No formal interim analysis to allow early stopping of the study on the basis of demonstrating 
efficacy or futility is planned.
The study will be monitored by the independent DMEC. Any SAE will be reported to the 
committee who may recommend stopping the study for safety reasons. Interim safety analyses 
(i.e. no efficacy analyses) will be undertaken after the first 25 patients have completed Visit 4
and 5. No formal statistical tests will be undertaken but AEs will be summarised and tabulated 
for each group separately. If, in the view of the DMEC, the number or severity of adverse 
events is of concern, consideration will be given to the future conduct and design of the study,
and to whether further formal interim analyses are required.
The study will be discontinued due to events such as exemplified below:
•
The Sponsor (following DMEC recommendation or in absence of such 
recommendation) judges it necessary for medical, safety, regulatory or any other 
reasons consistent with applicable laws, regulations and GCP.
•
If SAEs are assessed as causally related to IMP or in presence of other significant 
medical events as judged by the sponsor.
•
New information leading to unfavourable risk-benefit judgment of the IMP, as judged 
by the investigator and/or sponsor, e.g., due to:
1) Occurrence of significant previously unknown adverse reactions or 
unexpectedly high intensity or incidence of known adverse reactions, or
2) Other unfavourable safety findings.
•
If events are not considered to be consistent with continuation of the study.
•
Poor enrolment of patients making completion of the trial within an acceptable time 
frame unlikely.
•
Discontinuation of development of the sponsor’s IMP.


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9
STATISTICAL METHODS
The statistical considerations summarised in this section outline the plan for data analysis of 
this study. 
Before database lock, a separate SAP will be finalised, providing detailed methods for the 
analyses outlined below. 
Any deviations from the planned analyses will be described and justified in the final 
integrated study report.
9.1
Study Patients
9.1.1
Disposition!of!Patients
The number and percentage of patients entering and completing each phase of the study will 
be presented overall. Reasons for withdrawal pre- and post-randomisation will also be 
summarised.
The disposition of patients will also include information on the number and percentage of 
patients who:
•
Completed IMP and follow-up,
•
Withdrew from IMP but completed follow-up,
•
Withdrew from IMP and from follow-up.
9.1.2
Protocol!Deviations
Deviations from the protocol including violations of inclusion/exclusion criteria will be 
assessed as “minor” or “major” in cooperation with the sponsor. Major deviations from the 
protocol will lead to the exclusion of a patient from the Per Protocol Set (PPS). Deviations 
will be defined prior to data base hard lock.
9.1.3
Analysis!Sets
Study Population A
Patients treated with 200 mg MIV-711 q.d. in Study MIV-711-201 whose symptoms did not 
clinically significantly deteriorate as defined by an NRS increase of ø4"eqorctgf"vq"Daseline.
Study Population B
Patients receiving placebo in Study MIV-711-201 and that had experienced a clinical 
worsening as defined by increased NRS versus Bcugnkpg" qh"œ40
No comparisons between Study Populations A and B will be undertaken.
Major protocol violators and exclusions from the analysis sets will be identified by a panel,
including the clinical project manager, study statistician, and other appropriate clinical study 
team members.
The following criteria will be used to exclude a patient from the analysis set:
•
Incorrect diagnosis
•
Any of the prohibited interventions/injuries for the target knee
•
Missing more than 7 doses of MIV-711
The panel will review these criteria using soft-locked data prior to data analysis.
The safety analysis set (SAF): all patients receiving at least one dose of either MIV-711.
The primary analysis will be based on Study Population A.


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The secondary analysis will be based on Study Population B.
All safety analyses will be based upon the SAF.
Demographic and Baseline characteristics will be evaluated for the SAF.
9.2
General Consideration
Continuous data will be summarised using descriptive statistics (number, mean, median, 
standard deviation [SD], minimum, and maximum). Categorical data will be summarized by 
treatment group using frequency tables (frequencies and percents).
9.2.1
Power!and!Sample!Size!Consideration
This study is not powered for any confirmatory analyses.
9.2.2
Analysis!and!Data!Conventions:
Visit windows
Assessments taken outside of protocol allowable windows will be displayed according to the 
eCRF assessment recorded by the investigator.
Unscheduled assessments
Extra (repeat) assessments (laboratory data or vital signs associated with non-protocol clinical 
visits or obtained in the course of investigating or managing adverse events) will be included 
in data listings.
For repeat/unscheduled assessments collected prior to first dose administration, the last 
assessment taken for a time point will be used in data summaries (summary tables, figures, 
and statistical analysis). For repeat/unscheduled collected after the first dose administration 
the original assessment for any given time point will be used in the data summaries (summary 
tables, figures, and statistical analysis).
It is noted that invalid laboratory data may not be used (from haemolysed samples, 
mishandled samples, quantity not sufficient or other conditions that would render values 
invalid). 
Missing data conventions
In general, data will not be imputed for safety analysis. Efficacy analysis imputations will use 
last observation carried forward (LOCF) for patients in analysis populations as described. 
Additional details will be in the SAP.
Any outliers that are detected during the blind review of the data will be investigated. If 
necessary, queries will be issued to the Investigator to either correct or confirm the outlier.
9.3
Demographics, Medical History, Baseline Characteristics, and Concomitant 
Medications
Demographic data, medical history, concomitant disease, and concomitant medication will be 
summarised by means of descriptive statistics (n, mean, SD, median, minimum and 
maximum) or frequency tables, presented overall.
9.4
Treatment Compliance
Treatment compliance as measured in Section 6.5 will be summarised by means of descriptive 
statistics (n, mean, SD, median, minimum, and maximum) and/or frequency tables presented 
overall.


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9.5
Statistical Methodology
9.5.1
Primary!Endpoint (Study!Population A)
The primary outcome will be to study the safety and tolerability of 200 mg MIV-711 q.d. over 
52 (26+26) weeks in patients with symptomatic and radiographic knee OA.
Safety endpoints:
•
Incidence and severity of AEs
•
Incidence and severity of clinical laboratory abnormalities
•
Physical examination findings by patient
•
Incidence and severity of ECG abnormalities
•
Mean change from Baseline (Visit 2 of Study MIV-711-201) in vital signs (blood 
pressure, heart rate, temperature) and oxygen saturation
•
Categorical summary of observed vital signs and vital sign changes compared to
Baseline (Visit 2 of Study MIV-711-201), by patient
Safety and tolerability will be assessed descriptively in summary tables presented over time. 
All data presentations addressing the primary outcome will use Study Population A.
9.5.2
Secondary!Endpoints
9.5.2.1
Definition of Baseline for Secondary Endpoints
For the efficacy parameters, for Study Population A, changes from Baseline will be assessed 
using the Visit 2 baseline data from MIV-711-201. For Study Population B, changes from 
Baseline will be assessed using the Visit 2 data from Study MIV-711-202.
9.5.2.2
Study Population A
The secondary endpoints are related to efficacy:
•
The effect of MIV-711 on MRI cartilage thickness loss
•
The effect of MIV-711 on MRI bone marrow lesion volume
•
The effect of MIV-711 in the semi quantitative MRI Osteoarthritis Knee Score 
(MOAKS) parameters
•
To assess the effect of MIV-711 on MRI knee joint bone area.
Note: all MRI assessments refer to the target knee unless stated otherwise.
9.5.2.3
Study Population B
The secondary endpoint for Study Population B is the same as the primary endpoint for Study 
Population A (see Section 9.5.1).
9.5.2.4
Statistical Methodology for Secondary Endpoints
For Study Population B, the safety and tolerability of 200 mg MIV-711 for 26 weeks will be 
studied in OA patients with clinical worsening during the placebo treatment in the 
MIV-711-201 study. Safety and tolerability will be assessed descriptively in summary tables 
presented over time. 
All other secondary analyses will be undertaken using Study Population A, while they will be 
undertaken as exploratory analyses on Study Population B.
For Study Population A all secondary outcome variables will be analysed using descriptive 
summary tables presenting statistics for, number of non-missing values means, medians, 
standard deviations, minimum and maximum values. Frequency tables (counts and 


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percentages) will be presented in tables where appropriate. Figures of secondary response 
over time will be presented as appropriate.
For all outcome variables analysed using a linear model, distributional assumptions will be 
checked using examination of empirical distributions and model residuals. If necessary, data 
will be transformed prior to analysis if this improves the model fit, or normalises the 
distribution of the residuals. Non-parametric methods may be applied if appropriate.
For the analysis of secondary endpoints, alternate statistical methods maybe considered that 
will include the use of generalised linear models that account for the response variable having 
a “non-normal” distribution.  Additional details will be provided in the SAP.
All secondary outcomes will be summarised descriptively (mean, SD, median, minimum and 
maximum for continuous data and counts and percentages for categorical data). 
9.5.3
Exploratory!Endpoints
The exploratory endpoints are detailed in Section 7.4.1 for Study Population A and 
Section 7.4.2 for Study Population B.
9.5.3.1 Definition of Baseline for Exploratory Endpoints
For the efficacy parameters, for Study Population A, changes from Baseline will be assessed 
using the Visit 2 baseline data from MIV-711-201. For Study Population B, changes from 
Baseline will be assessed using the Visit 8 data from Study MIV-711-201 which is expected 
to occur on the same calendar day as Visit 1 in Study MIV-711-202. For the biomarkers in 
Study Population B, the baseline will be Visit 2 in the present study (MIV-711-202).
9.5.3.2
Statistical Methodology for Exploratory Endpoints
The exploratory analysis of patient reported outcomes, bone and cartilage biomarkers, MRI 
imaging and PK assessments will be listed and summarised using descriptive statistics only or 
presented in separate reports. The pharmacokinetic measurements in this study will be 
performed using sparse sampling in which the date/time of sample collection as well as the 
date/time of the most recent dose will be collected in the eCRF to allow for a future 
population pharmacokinetic analysis of these data. For the purpose of this study, the plasma 
concentrations of parent and potential metabolites of MIV-711 will be an additional 
exploratory endpoint and will be reported as outlined above. In the analysis of biomarkers that 
are sampled at multiple visits, all sampled time points will be considered for change from 
Baseline in the respective cases. In applicable cases, PK and biomarker data may be analysed 
using area under the curve calculations.
9.5.4
Safety
The primary purpose and endpoint of the present study is safety and tolerability as described 
above. There will be no formal statistical hypothesis testing for safety data in this study,
therefore only summary statistics will be provided. Safety summaries will be presented by 
scheduled assessment for the SAF. Summary statistics (number of observations, mean, SD,
median, minimum and maximum values) will be presented for continuous variables, and 
number and percentages (n, %) will be presented for categorical variables. Where applicable, 
changes from Baseline will also be summarised over time.
Treatment-emergent adverse events will be summarised by preferred term and system organ 
class and classified according to the latest version of coded Medical Dictionary for Regulatory 
Activities (MedDRA). The number and percentage of TEAEs will be summarised by system 
organ class and preferred term in the SAF. Treatment-emergent adverse events will be further 
summarised with respect to severity and relationship to IMP. Treatment-emergent adverse 
events related to IMP, leading to withdrawal, serious TEAEs, and deaths will be summarised.


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Clinical laboratory tests (haematology, serum chemistry), ECG, and vital signs will be 
summarised for the SAF at each scheduled assessment. Potentially clinically important 
findings will also be summarised and listed.
The number of patients taking rescue medication (see definition in Section 6.6.1), the amount 
of rescue medication taken and the reason for use will be tabulated and summarised 
descriptively.
9.6
Interim Analyses
No interim analysis will be conducted for any efficacy endpoint.
An unblinded interim safety analysis may be conducted after the first 25 patients have 
completed Visit 4 and Visit 5. No formal statistical tests will be undertaken. Adverse events 
will be summarised descriptively and tabulated for all patients by treatment group (see 
Section 9.5.4). The DMEC will consider the results of the AE summaries when making 
decisions regarding dosing of subsequent cohorts (i.e. need for dose stoppages) or the need for 
formal interim analysis of non-safety data.


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10 ETHICAL, LEGAL, AND ADMINISTRATIVE ASPECTS
This study will be conducted according to the protocol, European Union clinical trial directive 
(2001/20/EC), ICH E6 (R1), GCP guidelines, and applicable local or regional regulatory 
requirements.
10.1
Data Quality Assurance
The Investigator is required to prepare and maintain adequate and accurate source documents
designed to record all observations and other data pertinent to the study for each study patient.
All information recorded on the eCRF for this study must be consistent with the patients’ 
source documentation (i.e., medical records).
10.1.1 Database!Management!and!Quality!Control
All data generated by the site personnel will be captured electronically at each study centre
using eCRFs. Data from external sources (such as laboratory data and eDiary data) will be 
imported into the database. Once the eCRF clinical data have been submitted to the central 
server at the independent data centre, corrections to the data fields will be captured in an audit 
trail. The reason for change, the name of the person who performed the change, together with 
the time and date will be logged to provide an audit trail. 
If additional corrections are needed, the responsible CRA or data manger will raise a query in 
the eCRF. The appropriate staff at the study site will answer queries sent to the Investigator.
The name of the staff member responding to the query, and time and date stamp will be 
captured to provide an audit trail.
The specific procedures to be used for data entry and query resolution using the eCRF will be 
provided to study sites in an eCRF completion guideline. In addition, site personnel will 
receive training on the eCRF.
10.2
Case Report Forms and Source Documentation
All data obtained during this study should be entered in the eCRF promptly. All source 
documents from which eCRF entries are derived should be placed in the patient’s medical 
records. Measurements for which source documents are usually available include laboratory 
assessments, ECG, MRI scans, and X-rays.
The original eCRF entries for each patient will be checked against source documents at the 
study site by the CRA.
10.2.1 Data!Collection
The Investigators (and appropriately authorised staff) will be given access to an online web/
based eCRF system called DataLabs which is 21 CFR Part 11 compliant. DataLabs is 
specifically designed for the collection of the clinical data in electronic format. Access rights
to the eCRF system will be carefully controlled and configured according to each individual’s 
role throughout the study. In general, only the Investigator and authorised staff will be able to 
enter data and make corrections in the eCRFs.
The eCRF should be completed for each patient included in the study and should reflect the 
latest observations on the patients participating in the study. Therefore, the eCRFs are to be
completed as soon as possible during or immediately after the patient’s visit or assessment. 
The Investigator must verify that all data entries in the eCRF are accurate and correct. If some 
assessments cannot be done, or if certain information is unavailable, not applicable or 
unknown, the Investigator should indicate this in the eCRF.
Computerised data-check programs and manual checks will identify any clinical data 
discrepancies for resolution. Corresponding queries will be loaded into the system and the site 


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will be informed about new issues to be resolved on-line. All discrepancies will be solved on-
line directly by the Investigator or by authorised staff. Off-line edit checks will be done to 
examine relationships over time and across panels to facilitate quality data.
After completion, the Investigator will be required to electronically sign off the clinical data
entered into the eCRF.
10.3
Access to Source Data
During the study, a CRA will make site visits to review protocol compliance, compare eCRF
entries and individual patient’s medical records, assess drug accountability, and ensure that 
the study is being conducted according to pertinent regulatory requirements. eCRF entries 
will be verified with source documentation. The review of medical records will be performed 
in a manner to ensure that patient confidentiality is maintained.
Checking of the eCRF entries for completeness and clarity, and cross-checking with source 
documents, will be required to monitor the progress of the study. Moreover, Regulatory
Authorities of certain countries, IECs, and/or the Sponsor’s Clinical Quality Assurance Group 
may wish to carry out such source data checks and/or on-site audits or inspections. Direct 
access to source data will be required for these inspections and audits; they will be carried out 
giving due consideration to data protection and medical confidentiality. The Investigator
assures PAREXEL and the Sponsor of the necessary support at all times.
10.4
Data Processing
All data will be entered by site personnel into the eCRF (as detailed in Section 10.2.1).
Previous and concomitant medications will be coded using the World Health Organization 
(WHO) Drug Reference List (DRL), which employs the Anatomical Therapeutic Chemical 
(ATC) classification system. Medical history/current medical conditions and adverse events 
will be coded using the MedDRA terminology.
The versions of the coding dictionaries will be provided in the Clinical Study Report.
10.5
Data Monitoring
A Trial Steering Committee (TSC) will be established and will be blinded and responsible for 
providing overall supervision for the study in accordance with pre-agreed terms of reference, 
in particular to the progress of the study, adherence to the protocol and patient safety. 
Operationally this will include consultation regarding the study design, subsequent 
amendments and emerging data and research relevant to the study, including open DMEC 
reports and the results of other research that may have a direct bearing on the future conduct 
of the study. They will also ensure that any action taken protects the rights, safety and 
wellbeing of patients and the study is conducted to the rigorous standards of GCP. It is 
anticipated that the TSC will meet at approximately 6-12 monthly intervals and after each 
independent DMEC review as required. Any SAE will be reported to the DMEC who may 
recommend stopping the study for safety reasons. Interim safety analyses (i.e. no efficacy 
analyses) will be undertaken after the first 25 patients have completed Visit 4 and Visit 5.
The independent DMEC will be set up to monitor study safety which will be specified in a 
DMEC charter. The independent DMEC will be unblinded and will include three members:
an independent chair having specialist osteoarthritis expertise and experience of studies in this 
area, an independent statistician and a second physician. Specifically they will monitor AEs 
and serious SAEs related to the treatments received in accordance with the recommendations 
of performing a clinical study of an IMP. In addition the independent DMEC will make 
recommendations on continuation of the study based on interim safety analyses.


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10.6
Safety Monitoring Plan
A change in the value of a clinical laboratory investigation can represent an AE if the change 
is clinically relevant or if, during treatment with the investigational product, a shift of a 
parameter is observed from a normal value to an abnormal value, or a further worsening of an 
already abnormal value.  When evaluating such changes, the extent of deviation from the 
reference range, the duration until return to the reference range, either while continuing 
treatment or after the EOT with the investigational product, and the range of variation of the 
respective parameter within its reference range, must be taken into consideration.
If, at the end of the treatment phase, there are abnormal clinical laboratory values which were 
not present at Baseline, further clinical or laboratory investigations should be performed until 
the values return to within the reference range or until a plausible explanation (e.g.,
concomitant disease) is found for the abnormal clinical laboratory values.
The Investigator should decide, based on the above criteria and the clinical condition of a 
patient, whether a change in a clinical laboratory parameter is clinically significant and 
therefore represents an AE.
10.7
Archiving Study Records
According to ICH guidelines, essential documents should be retained for a minimum of 
2 years after the last approval of a marketing application in an ICH region and until there are 
no pending or contemplated marketing applications in an ICH region or at least 10 years have 
elapsed since the formal discontinuation of clinical development of the investigational 
product. However, these documents should be retained for a longer period if required by the 
applicable legal requirements.
No essential documents may be destroyed without prior written approval from the Sponsor.
10.8
Good Clinical Practice
The procedures set out in this study protocol are designed to ensure that the Sponsor and 
Investigator abide by the principles of the GCP guidelines of the ICH, and of the Declaration 
of Helsinki (1996). The study also will be carried out in accordance with local legal 
requirements. 
10.9
Informed Consent
Before each patient is admitted to the study, informed consent will be obtained from the 
patient according to the regulatory and legal requirements of the participating country. This 
consent form must be dated and retained by the Investigator as part of the study records. The 
Investigator will not undertake any investigation specifically required only for the clinical 
study until valid consent has been obtained. The terms of the consent and when it was 
obtained must also be documented in the eCRF system.
If a protocol amendment is required, the ICF may need to be revised to reflect the changes to 
the protocol. If the consent form is revised, it must be reviewed and approved by the 
appropriate IEC, and signed by all patients subsequently enrolled in the study as well as those 
currently enrolled in the study.
10.10
Protocol Approval and Amendment
Before the start of the study, the study protocol and/or other relevant documents will be 
approved by the IEC/Regulatory Authorities, in accordance with local legal requirements. The 
Sponsor must ensure that all ethical and legal requirements have been met before the first 
patient is enrolled in the study.


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This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
receive approval from the appropriate personnel, and receive IEC/Regulatory Authority 
approval prior to implementation (if appropriate). Administrative changes (not affecting the 
patient benefit/risk ratio) may be made without the need for a formal amendment. All 
amendments will be distributed to all protocol recipients, with appropriate instructions.
10.11
Duration of the Study
The study will be conducted from September 2016 to August 2017.
10.12
Confidentiality
All study findings and documents will be regarded as confidential. The Investigator and 
members of his/her research team must not disclose such information without prior written 
approval from the Sponsor.
The anonymity of participating patients must be maintained. Patients will be identified in the
eCRF system and other documents submitted to PAREXEL by their patient number and date
of birth, not by name. Documents that identify the patient (e.g., the signed informed consent) 
must be maintained in confidence by the Investigator and should never be submitted to 
PAREXEL or the Sponsor.
10.13
Other Ethical and Regulatory Issues
If a significant safety issue is identified, either from an individual case report or review of 
aggregate data, then the Sponsor will issue prompt notification to all parties – Regulatory 
Authorities, Investigators, and Institutional Review Boards/IECs.
A significant safety issue is one that has a significant impact on the course of the clinical 
study or program (including the potential for suspension of the development program or 
amendments to protocols) or warrants immediate update of informed consent.
10.14
Liability and Insurance
The Sponsor will take out reasonable third-party liability insurance cover in accordance with 
all local legal requirements. The civil liability of the Investigator, the persons instructed by 
him or her and the hospital, practice, or institute in which they are employed and the liability 
of the Sponsor with respect to financial loss due to personal injury and other damage that may 
arise as a result of the carrying out of this study are governed by the applicable law.
The Sponsor will arrange for patients participating in this study to be insured against financial 
loss due to personal injury caused by the pharmaceutical products being tested or by medical 
steps taken in the course of the study.
10.15
Publication Policy
By signing the study protocol, the Investigator agrees with the use of results of the study for 
the purposes of national and international registration, publication and information for 
medical and pharmaceutical professionals. If necessary, Regulatory Authorities will be 
notified of the Investigator's name, address, qualifications and extent of involvement.
An Investigator shall not publish any data (poster, abstract, paper, etc.) without having 
consulted with the sponsor in advance.


Sponsor Name
Clinical Study Protocol
MIV-711-202
CONFIDENTIAL
Final
65 of 69
01 July 2016
11 REFERENCE LIST
1
World Medical Association Declaration of Helsinki. Recommendations guiding physicians in biomedical 
research involving human subjects. Adopted by the 18th WMA General Assembly, Helsinki, Finland, 
June 1964, and amended by the 29th WMA General Assembly, Tokyo, Japan, October 1975 35th WMA 
General Assembly, Venice, Italy, October 1983 41st WMA General Assembly, Hong Kong, September 
1989 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996
2
Murray, C. J., et al. (2012). "Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 
regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010." Lancet 
380(9859): 2197-2223.
3
Vos, T., et al. (2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 
1990-2010: a systematic analysis for the Global Burden of Disease Study 2010." Lancet 380(9859): 
2163-2196.
4
Peat, G., et al. (2001). "Knee pain and osteoarthritis in older adults: a review of community burden and 
current use of primary health care." Ann Rheum Dis 60(2): 91-97.
5
Conaghan, P. G., et al. (2008). "Care and management of osteoarthritis in adults: summary of NICE 
guidance." BMJ 336(7642): 502-503.
6
Hochberg, M. C., et al. (2012). "American College of Rheumatology 2012 recommendations for the use 
of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee." Arthritis 
care & research 64(4): 455-474.
7
Zhang, W., et al. (2010). "OARSI recommendations for the management of hip and knee osteoarthritis: 
part III: Changes in evidence following systematic cumulative update of research published through 
January 2009." Osteoarthritis Cartilage 18(4): 476-499.
8
Pendleton, A., et al. (2000). "EULAR recommendations for the management of knee osteoarthritis: report 
of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials 
(ESCISIT)." Ann Rheum Dis 59(12): 936-944.
9
Conaghan, P. G., et al. (2012). "The personal impact of osteoarthritis on individuals and how they use 
therapies: the arthritis care OA Nation 2012 Survey." Ann Rheum Dis 71(Suppl3): 584.
10
Conaghan, P. G., et al. (2014). "Impact and therapy of osteoarthritis: the Arthritis Care OA Nation 2012 
survey." Clinical Rheumatology.
11
Herrero-Beaumont, G. and J. A. Roman-Blas (2013). "Osteoarthritis: Osteoporotic OA: a reasonable 
target for bone-acting agents." Nat Rev Rheumatol 9(8): 448-450.
12
Karsdal, M. A., et al. (2014). "The coupling of bone and cartilage turnover in osteoarthritis: opportunities 
for bone antiresorptives and anabolics as potential treatments?" Annals of the Rheumatic Diseases 73(2): 
336-348.
13
Ringe, J. D., et al. (2005). "Effective and rapid treatment of painful localized transient osteoporosis (bone 
marrow edema) with intravenous ibandronate." Osteoporosis International 16(12): 2063-2068.
14
Laslett, L. L., et al. (2012). "Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a 
randomised controlled trial." Ann Rheum Dis 71(8): 1322-1328.
15
Cauley, J. A., et al. (2011). "Once-yearly zoledronic acid and days of disability, bed rest, and back pain: 
randomized, controlled HORIZON Pivotal Fracture Trial." Journal of Bone and Mineral Research 26(5): 
984-992.
16
Reginster, J. Y., et al. (2013). "Strontium ranelate in the treatment of knee osteoarthritis: new insights and 
emerging clinical evidence." Therapeutic advances in musculoskeletaldisease 5(5): 268-276.
17
Reginster, J. Y. (2014). "Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: 
results of a double-blind randomised, placebo-controlled trial." Annals of the Rheumatic Diseases 73(2): 
e8.
18
Reginster, J. Y., et al. (2012). "Efficacy and safety of strontium ranelate in the treatment of knee 
osteoarthritis: results of a double-blind, randomised placebo-controlled trial." Annals of the Rheumatic 
Diseases 72(2): 179-186.
19
Tan, Y. K. and P. G. Conaghan (2012). "Insights into osteoarthritis from MRI." International journal of 
rheumatic diseases 15(1): 1-7.


Sponsor Name
Clinical Study Protocol
MIV-711-202
CONFIDENTIAL
Final
66 of 69
01 July 2016
20
Guermazi, A., et al. (2013). "MRI-based semiquantitative scoring of joint pathology in osteoarthritis." Nat 
Rev Rheumatol 9(4): 236-251.
21
Roemer, F. W., et al. (2009). "Magnetic resonance imaging-based semiquantitative and quantitative 
assessment in osteoarthritis." Rheumatic Diseases Clinics of North America 35(3): 521-555.
22
Conaghan, P. G., et al. (2011). "Summary and recommendations of the OARSI FDA osteoarthritis 
Assessment of Structural Change Working Group." Osteoarthritis and cartilage / OARS, Osteoarthritis 
Research Society 19(5): 606-610.
23
Bowes, M. A., et al. (2015). "A novel method for bone area measurement provides new insights into 
osteoarthritis and its progression." Annals of the Rheumatic Diseases. 74(3): 519-525.
24
Neogi, T., et al. (2013). "Magnetic resonance imaging-based three-dimensional bone shape of the knee 
predicts onset of knee osteoarthritis: data from the osteoarthritis initiative." Arthritis and Rheumatism 
65(8): 2048-2058.
25
Bowes, M. A. and P. G. Conaghan ( 2014). "Bone area demonstrates change in 3 months in a very small 
OA cohort." Osteoarthritis and Cartilage 22(suppl 1): 488.
26
Morko, J., et al. (2005). "Spontaneous development of synovitis and cartilage degeneration in transgenic 
mice overexpressing cathepsin K." Arthritis and Rheumatism 52(12): 3713-3717.
27
Schaller, S., et al. (2005). "In vitro, ex vivo, and in vivo methodological approaches for studying 
therapeutic targets of osteoporosis and degenerative joint diseases: how biomarkers can assist?" Assay 
Drug Dev Technol 3(5): 553-580.
28
Kraus, V. B., et al. (2011). "Application of biomarkers in the development of drugs intended for the 
treatment ofosteoarthritis." Osteoarthritis and Cartilage 19(5): 515-542.
29
Van Spil, W. E., et al. (2010). "Serum and urinary biochemical markers for knee and hip-osteoarthritis: a 
systematic review applying the consensus BIPED criteria." Osteoarthritis and Cartilage 18(5): 605-612.
30
Pelletier, J. P., et al. (2015). "Disease-modifying effect of strontium ranelate in a subset of patients from 
the Phase III knee osteoarthritis study SEKOIA using quantitative MRI: reduction in bone marrow lesions 
protects against cartilage loss." Annals of the Rheumatic Diseases74(2): 422-429.
31
Reginster, J. Y., et al. (2013). "Efficacy and safety of strontium ranelate in the treatment of knee 
osteoarthritis: results of a double-blind, randomised placebo-controlled trial." Annals of the Rheumatic 
Diseases 72(2): 179-186.
32
Hayami, T., et al. (2012). "Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate 
ligament transection rabbit and murine models of osteoarthritis." Bone 50(6): 1250-1259.
33
Connor, J. R., et al. (2009). "Protective effects of a cathepsin K inhibitor, SB-553484, in the canine partial 
medial meniscectomy model of osteoarthritis." Osteoarthritis and Cartilage 17(9): 1236-1243.
34
McDougall, J. J., et al. (2010). "Cathepsin K inhibition reduces CTXII levels and joint pain in the guinea 
pig model of spontaneous osteoarthritis." Osteoarthritis and Cartilage 18(10): 1355-1357.
35
Hunter, D. J., et al. (2010). "Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3-6 
months' observation using advanced image analysis of 3T MRI?" Osteoarthritis and cartilage /OARS, 
Osteoarthritis Research Society 18(5): 677-683.
36
Hunter, D. J., et al. "Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI 
Osteoarthritis Knee Score).[Erratum appears in Osteoarthritis Cartilage. 2011 Sep;19(9):1168]." 
Osteoarthritis & Cartilage 19(8): 990-1002.
37
Heimann, T. and H. P. Meinzer (2009). "Statistical shape models for 3D medical image segmentation: a 
review." Medical Image Analysis 13(4): 543-563
38
Heimann, T., et al. (2007). "Automatic generation of 3D statistical shape models with optimal landmark 
distributions." Methods of Information in Medicine 46(3): 275-281. 
39
Hunter, D. J., et al. (2010). "Can cartilage loss be detected in knee osteoarthritis (OA) patients with 3-
6 months' observation using advanced image analysis of 3T MRI?" Osteoarthritis and cartilage /OARS, 
Osteoarthritis Research Society 18(5): 677-683.
40
Murphy, L. B., et al. (2010). "Estimating medical costs attributable to osteoarthritis in the US population:
comment on the article by Kotlarz et al." Arthritis and Rheumatism 62(8): 2566-2567; author reply 
2567-2568.
41
Hawker, G. A., et al. (2008). "Development and preliminary psychometric testing of a new OA pain 
measure-an OARSI/OMERACT initiative." Osteoarthritis Cartilage 16(4): 409-414. 


Sponsor Name
Clinical Study Protocol
MIV-711-202
CONFIDENTIAL
Final
67 of 69
01 July 2016
42
Dougados, M., et al. (2000). "Response criteria for clinical trials on osteoarthritis of the knee and hip: a 
report of the Osteoarthritis Research Society International Standing Committee for Clinical Trials 
response criteria initiative." Osteoarthritis Cartilage 8(6): 395-403. 
43
(2007). "User’s Guide for the Measure of Intermittent and Constant Osteoarthritis Pain: ICOAP. Version 
3. December 2007." from http://www.osteoarthritisresearch.ca/pdf/ICOAP-user-guide.pdf. 
44
Hurst, N. P., et al. (1994). "Validity of Euroqol--a generic health status instrument--in patients with 
rheumatoid arthritis. Economic and Health Outcomes Research Group." Br J Rheumatol 33(7): 655-662.
45
Brooks, R. (1996). "EuroQol: the current state of play." Health Policy 37(1): 53-72. 
46
Harrison, M. J., et al. (2010). "Exploring the validity of estimating EQ-5D and SF-6D utility values from 
the health assessment questionnaire in patients with inflammatory arthritis." Health Qual Life Outcomes 
8: 21. 
47
Svarstad, B. L., et al. (1999). "The Brief Medication Questionnaire: a tool for screening patient adherence 
and barriers to adherence." Patient Educ Couns 37(2): 113-124.


Sponsor Name
Clinical Study Protocol
MIV-711-202
CONFIDENTIAL
Final
68 of 69
01 July 2016
12 APPENDICES


Sponsor Name
Clinical Study Protocol
MIV-711-202
CONFIDENTIAL
Final
69 of 69
01 July 2016
12.1
APPENDIX 1: Total Blood Volumes
The total volume of blood that will be drawn from each patient in this study is as follows:
Assessment
Sample 
Volume 
(mL)
No of 
samples
Total 
Volume 
(mL)
Safety 
•
Clinical chemistry
9.5
6
57
•
Haematology
2
6
12
Pharmacokinetic samples
5
3
15
Blood samples for pharmacogenomics, 
proteomics, genomics, metabolomics and 
lipidomics
19
1
19
Biomarker analysis
15
4
60
Additional unforeseeable samples
37
Total
200

SAP_001.pdf: 
PAREXEL International 
Statistical Analysis Plan 
Medivir 
Protocol: MIV-711-202 
Final 1.0 
16 January 2018 
Page 1 of 183
STATISTICAL ANALYSIS PLAN  
Medivir AB
Protocol MIV-711-202 
An Open-Label, One-Arm Phase II Extension Study to Evaluate Safety 
and Tolerability of MIV-711 in Patients with Knee Joint Osteoarthritis 
PAREXEL Study Number: 230610 
Final 1.0 
Date:  16 January 2018 


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PAREXEL International 
Statistical Analysis Plan 
Medivir 
Protocol: MIV-711-202 
Final 1.0 
16 January 2018 
Page 4 of 183
TABLE OF CONTENTS 
SIGNATURE PAGE - MEDIVIR .................................................................................................. 2
SIGNATURE PAGE - PAREXEL ................................................................................................. 3
TABLE OF CONTENTS ................................................................................................................ 4
1.
STATISTICAL ANALYSIS PLAN .................................................................................. 9
2.
STUDY OBJECTIVES AND HYPOTHESES ................................................................. 9
2.1
PRIMARY OBJECTIVE STUDY GROUP A .................................................................. 9
2.2
SECONDARY OBJECTIVES STUDY GROUP A ......................................................... 9
2.3
SECONDARY OBJECTIVES STUDY GROUP B ........................................................ 10
2.4
EXPLORATORY OBJECTIVES STUDY GROUP A ................................................... 10
2.5
EXPLORATORY OBJECTIVES STUDY GROUP B ................................................... 11
3.
STUDY DESIGN ............................................................................................................ 11
3.1
STUDY POPULATION .................................................................................................. 14
3.2
RECRUITMENT, PLANNED SAMPLE SIZE AND NUMBER OF STUDY 
CENTRES ....................................................................................................................... 14
3.3
PATIENT WITHDRAWAL AND REPLACEMENT .................................................... 14
3.4
PATIENT IDENTIFICATION ........................................................................................ 14
3.4.1
PATIENT IDENTIFICATION ........................................................................................ 14
3.4.2
ALLOCATION OF PATIENTS TO TREATMENT ...................................................... 15
3.5
STUDY DRUG ADMINISTRATION ............................................................................ 15
3.6
INTERIM ANALYSIS .................................................................................................... 15
4.
STUDY ANALYSIS VARIABLES ................................................................................ 15
4.1
STUDY SCHEDULE MIV-711-201 ............................................................................... 16
4.2
STUDY SCHEDULE MIV-711-202 ............................................................................... 20
4.3
DEMOGRAPHIC AND BACKGROUND VARIABLES .............................................. 24
4.4
SAFETY VARIABLES ................................................................................................... 24
4.4.1
ADVERSE EVENTS ...................................................................................................... 24
4.4.2
CLINICAL LABORATORY TESTS ............................................................................. 24
4.4.3
OTHER LABORATORY TESTS ................................................................................... 25
4.4.4
VITAL SIGNS ................................................................................................................. 25
4.4.5
ELECTROCARDIOGRAMS .......................................................................................... 25
4.4.6
PHYSICAL EXAMINATION ........................................................................................ 25


PAREXEL International 
Statistical Analysis Plan 
Medivir 
Protocol: MIV-711-202 
Final 1.0 
16 January 2018 
Page 5 of 183
4.4.7
PRIOR AND CONCOMITANT MEDICATIONS ......................................................... 26
4.4.8
PHONE CALL TO ASSESS SAFETY AND TOLERABILITY ................................... 26
4.5
EFFICACY VARIABLES .............................................................................................. 26
4.5.1
MRI BONE SHAPE MODELLING BY IMORPHICS .................................................. 26
4.5.2
MRI MOAKS .................................................................................................................. 27
4.5.3
PATIENT REPORTED OUTCOMES (PROS) .............................................................. 28
4.5.3.1 NRS SCORE DESCRIPTIONS ...................................................................................... 29
4.5.3.2 ICOAP SCORE DESCRIPTIONS .................................................................................. 30
4.5.3.3 WOMAC SCORE DESCRIPTIONS .............................................................................. 30
4.5.3.4 OARSI OMERACT SCORE DESCRIPTIONS .............................................................. 31
4.5.3.5 GLOBAL IMPROVEMENT SCORE DESCRIPTIONS ................................................ 32
4.5.3.6 QUALITY OF LIFE ........................................................................................................ 32
4.5.3.7 BRIEF MEDICATION QUESTIONNAIRE .................................................................. 32
4.5.3.8 E-DIARY ASSESSMENT OF NRS AND ANALGESIC USE ..................................... 32
4.5.4
OTHER EFFICACY PARAMETERS – BIOMARKERS, IMAGING, 
PHARMACOKINETICS ................................................................................................ 33
4.6
ANALYSIS POPULATIONS ......................................................................................... 33
4.6.1
INTENT-TO-TREAT POPULATION (ITT) .................................................................. 34
4.6.2
PER PROTOCOL POPULATION (PPS) ....................................................................... 34
4.6.3
SAFETY ANALYSIS POPULATION (SAF) ................................................................ 34
5.
PROTOCOL DEVIATIONS ........................................................................................... 34
6.
GENERAL CONSIDERATIONS FOR DATA PRESENTATIONS ............................. 34
6.1
SOFTWARE .................................................................................................................... 36
7.
PATIENT AND TREATMENT INFORMATION ......................................................... 36
7.1
PATIENT DISPOSITION ............................................................................................... 36
7.2
PATIENTS EXCLUDED FROM ANALYSIS POPULATIONS .................................. 36
7.3
ELIGIBILITY CRITERIA .............................................................................................. 36
7.4
EXCLUSION TESTS ...................................................................................................... 36
7.5
PROTOCOL DEVIATIONS ........................................................................................... 36
7.6
DEMOGRAPHIC DATA ................................................................................................ 37
7.7
MEDICAL HISTORY ..................................................................................................... 37
7.8
PRIOR AND CONCOMITANT MEDICATION ........................................................... 37
7.9
DOSE ADMINISTRATION ........................................................................................... 38


PAREXEL International 
Statistical Analysis Plan 
Medivir 
Protocol: MIV-711-202 
Final 1.0 
16 January 2018 
Page 6 of 183
8.
PHARMACODYNAMIC ANALYSIS – EFFICACY ................................................... 38
8.1
IMORPHICS MRI ASSESSMENTS .............................................................................. 39
8.1.1
STATISTICAL ANALYSIS – IMORPHICS MRI ASSESSMENTS ............................ 39
8.2
MOAKS MRI ASSESSMENTS ..................................................................................... 42
8.3
ANALYSIS OF PATIENT REPORTED OUTCOMES (PROS) ................................... 43
8.3.1
NRS PAIN DATA ........................................................................................................... 43
8.3.1.1 STATISTICAL ANALYSIS OF THE NRS PAIN DATA ............................................. 43
8.3.2
INTERMITTENT AND CONSTANT OSTEOARTHRITIS PAIN (ICOAP) 
KNEE VERSION ............................................................................................................ 43
8.3.3
ANALYSIS OF WOMAC ............................................................................................... 44
8.3.3.1 STATISTICAL ANALYSIS OF WOMAC .................................................................... 44
8.3.4
(OARSI)-OMERACT RESPONDER CRITERIA .......................................................... 45
8.3.5
GLOBAL IMPROVEMENTS ........................................................................................ 46
8.3.6
QUALITY OF LIFE PRO – EQ-5D-5L .......................................................................... 46
8.3.7
E-DIARY FOR PATIENT PAIN .................................................................................... 47
8.3.7.1 DERIVED E-DIARY VARIABLES ............................................................................... 47
8.3.7.2 STATISTICAL ANALYSIS OF E-DIARY SCORES ................................................... 48
8.3.8
BIOMARKERS FROM SERUM AND URINE SAMPLES .......................................... 48
8.3.8.1 STATISTICAL ANALYSIS BIOMARKERS FROM SERUM AND URINE 
SAMPLES ....................................................................................................................... 49
8.3.9
BRIEF MEDICATION QUESTIONNAIRE .................................................................. 49
9.
SAFETY ANALYSIS ..................................................................................................... 49
9.1
ADVERSE EVENTS ...................................................................................................... 50
9.2
CLINICAL 
SAFETY 
LABORATORY 
TESTS 
(HEMATOLOGY, 
CHEMISTRY, URINALYSIS) ....................................................................................... 51
9.2.1
HEMATOLOGY AND CHEMISTRY ........................................................................... 51
9.2.2
URINALYSIS ................................................................................................................. 52
9.3
VITAL SIGNS ................................................................................................................. 52
9.4
12-LEAD SAFETY ECG ................................................................................................ 53
9.5
PHYSICAL EXAMINATION AND WEIGHT .............................................................. 53
9.6
PHONE CALL TO ASSESS SAFETY ........................................................................... 54
10.
REPORTING OUTPUT .................................................................................................. 55
11.
SUMMARY TABLES .................................................................................................... 56
12.
FIGURES ......................................................................................................................... 59


PAREXEL International 
Statistical Analysis Plan 
Medivir 
Protocol: MIV-711-202 
Final 1.0 
16 January 2018 
Page 7 of 183
13.
LISTINGS........................................................................................................................ 61
14.
TABLE SHELLS ............................................................................................................. 63
15.
LISTING SHELLS ........................................................................................................ 121


PAREXEL International 
Statistical Analysis Plan 
Medivir 
Protocol: MIV-711-202 
Final 1.0 
16 January 2018 
Page 8 of 183
Abbreviations and definitions 
AE 
Adverse event 
BLQ 
Below the lower limit of quantification 
BMI 
Body Mass Index 
BML 
Bone Marrow Lesions
CI 
Confidence interval 
CS 
Clinically significant 
CV 
Coefficient of variation 
DMC 
Data monitoring committe 
ECG 
Electrocardiogram 
FAS 
Full analysis set
h 
Hour 
IMP 
Investigational Medicinal Product 
LLOQ 
Lower limit of quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOAKS 
MRI Osteoarthritis Knee Score
NCS 
Not clinically significant 
NRS 
Numeric Rating Scale 
NK 
Not known 
OA 
Osteoarthritis
PK 
Pharmacokinetic 
PPS 
Per Protocol Set 
q.d. 
Once a day
QOL 
Quality of Life 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation  
SOC 
System Organ Class 
TEAE 
Treatment-emergent adverse event 
TIC 
Time Integrated Concentrations 
WHO-DD 
World Health Organisation - Drug Dictionary 


PAREXEL International 
Statistical Analysis Plan 
Medivir 
Protocol: MIV-711-202 
Final 1.0 
16 January 2018 
Page 9 of 183
1.
Statistical Analysis Plan 
This Statistical Analysis Plan (SAP) provides a detailed and technical description of the 
planned statistical evaluation of the Medivir study MIV-711-202: “An Open-Label, One-
Arm Phase II Extension Study to Evaluate Safety and Tolerability of MIV-711 in Patients 
with Knee Joint Osteoarthritis”. The SAP also outlines the statistical programming 
specifications for the tables, listings and figures. 
Full description of the investigational plan, selection criteria, assessments, etc. are given in 
the Clinical Study Protocol (CSP): MIV-711-202, dated 01 July 2016.  
The planned analyses will be conducted by PAREXEL.  
2.
Study Objectives and Hypotheses 
2.1
Primary Objective Study Group A 
To assess the safety and tolerability of 200 mg MIV-711 q.d. over 52 (26+26) weeks in 
patients with symptomatic and radiographic knee osteoarthritis. 
-
Study Group A will be recruited from patients treated with 200 mg MIV-711 q.d. in Study 
MIV-711-201 and whose symptoms did not clinically significantly deteriorate as defined by 
an increase in NRS of ≤2 compared to Baseline.
2.2
Secondary Objectives Study Group A 
To assess, in patients with symptomatic and radiographic knee OA, over 52 (26+26) 
weeks: 
• The effect of MIV-711 on MRI cartilage thickness loss 
• The effect of MIV-711 on MRI bone marrow lesion volume 
• The effect of MIV-711 in the semi quantitative MRI Osteoarthritis Knee 
Score (MOAKS) parameters 
• To assess the effect of MIV-711 on MRI knee joint bone area.  
Note: all MRI assessments refer to the target knee unless stated otherwise. 
Target knee is identified by knee pain on a numeric rating scale and Kellgren and Lawrence 
classification grade. If patients have knee pain in both sides with equal regard to these two criteria, the 
right knee should always be prioritized. The target knee in Study MIV-711-202 must be the same as in 
Study MIV-711-201. 


PAREXEL International 
Statistical Analysis Plan 
Medivir 
Protocol: MIV-711-202 
Final 1.0 
16 January 2018 
Page 10 of 183
2.3
Secondary Objectives Study Group B 
To assess the effect of 200 mg MIV-711 q.d. on safety and tolerability over 26 weeks in 
patients with symptomatic and radiographic knee osteoarthritis. 
-
Study Group B will be recruited from patients receiving placebo in Study MIV-711-201 
having experienced a clinical worsening as defined by an increase in NRS of ≥2 versus 
Baseline. 
-
Data from both MIV-711-201 and MIV-711-202 studies will be used for Group B assessment 
2.4
Exploratory Objectives Study Group A 
Data from both MIV-711-201 and MIV-711-202 study will be used for Group A 
assessment. 
In addition, the study will investigate the following exploratory parameters. 
• The effect of MIV-711 on worst target knee pain (1 week recall) 
• The effect of MIV-711 on average contralateral knee pain (1 week recall) 
• The effect of MIV-711 on constant and intermittent OA pain 
• The effect of MIV-711 on global improvements in knee problem, knee pain and 
knee function 
• The effect of MIV-711 on knee joint OA symptoms (function, pain, stiffness) 
• The effect of MIV-711 on global disease activity 
• The effect of MIV-711 on quality of life (QoL) 
• The effect of MIV-711 on patient reported e-diary daily recall knee joint pain 
• The effect of MIV-711 on patient reported e-diary daily recall analgesics use 
• Assessment of the effect of MIV-711 on exploratory serum and urinary biomarkers 
of relevance for OA including but not limited to procollagen type I N-terminal 
propeptide (PINP), bone specific alkaline phosphatase (BSAP ), N-terminal 
telopeptide of collagen type I (NTX-I), CTX-I, aCTX-I, CTX-II and tartrate-
resistant acid phosphatases (TRAP5b). 
• Baseline and steady state treatment blood and urinary samples will be stored for 
patients who sign a separate voluntary Informed Consent Form (ICF) for potential 
future pharmacogenomics and disease-related proteomics, genomics, 
metabolomics and lipidomics analyses. 
• The effect of MIV-711 on a compound index of MRI bone area and cartilage 
thickness 
• The pharmacokinetics of MIV-711 and the relationship to patient actors 
and concomitant medications 


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2.5
Exploratory Objectives Study Group B 
All of the above noted secondary and exploratory parameters described in Section 2.2 and 
Section 2.4 for study group A, are considered as exploratory objectives in study group B 
and will be evaluated over 26 weeks on 200 mg MIV-711 succeeding 26 weeks on 
Placebo.  
3.
Study Design 
This study is a 6-month open-label one-arm extension study evaluating safety and 
tolerability as well as the efficacy of 200 mg MIV-711 q.d. in two separate patient 
populations denoted as study Group A and Group B. 
Study Group A patients will be recruited from Study MIV-711-201 who were treated 
with 200 mg MIV-711 q.d. and whose symptoms did not clinically significantly 
deteriorate as defined by an increase in the numeric rating scale (NRS) of ≤2 compared to 
Baseline. Patients eligible for Study Group A will be offered 6 months’ extended 
treatment, primarily evaluating longer term safety and tolerability. The total treatment 
duration of 52 weeks also allows a more suitable treatment length for the exploratory 
study of any structural effects of MIV-711 on joint cartilage thickness. 
A further rationale of this study is to explore the treatment effect in a group of OA 
patients that have confirmed symptom progression over the last 6 months (Study Group 
B). Study Group B will be recruited from patients receiving placebo in Study MIV-711-
201 who experienced a clinical worsening as defined by an increase in NRS of ≥2 versus 
Baseline. Patients eligible for Study Group B will be offered 200 mg MIV-711 q.d. for 
the next 26 weeks. In addition to offering the treatment to appropriate patients, this also 
enables the assessment of the effects of MIV-711 based on MRI imaging, symptoms and 
biomarkers in patients with progressing symptoms and, as such, has the potential to 
provide valuable information for future patient selection in OA trials. Similar to Study 
MIV-711-201, the joint structural endpoint of choice over 6 months treatment constitutes 
MRI joint bone surface measurement. All analyses, with the exception of safety and 
tolerability, will be conducted as exploratory with regards to Study Group B. 
The analysis of data from this study will not be based on a formal statistical analysis 
since the primary endpoint constitutes safety and tolerability.  


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The study consists of a Screening period of approximately 2 weeks (Visit 1), eligibility at 
Visit 2, an open-label treatment period of 26 weeks from Visit 2 through Visit 5, and a 
follow-up period of 4 weeks (Visit 6) after the last dose of study treatment is 
administered. Telephone calls will be made 5-9 days after all dosing visits for safety and 
tolerability. There will be additional phone calls at Week 10 and Week 20 for safety and 
tolerability. 
A Data Monitoring Committee (DMC) will meet to review the safety and tolerability data 
after the first 25 patients complete Visit 4 and Visit 5. 
The study design is summarized in the figure below. 


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3.1
Study Population 
The study population will consist of patients with symptomatic and radiographic knee 
joint OA who have participated in Study MIV-711-201. Patients must be able to 
provide written consent and meet all the inclusion criteria and none of the exclusion 
criteria. 
3.2
Recruitment, Planned Sample Size and Number of Study Centres 
The roll-over of individual patients to Study MIV-711-202 is based on the criteria for 
study Groups A and B detailed above and is executed by a central person independent 
from the study with access to the randomisation list and eCRF for Study MIV-711-201. 
Based on a selection criteria for study Group A and B described earlier in this section, it 
is anticipated that 50-80 patients will be eligible for participation. Recruitment may be 
terminated if considered appropriate or necessary by the sponsor. 
3.3
Patient Withdrawal and Replacement 
In order to perform the intent to treat (ITT) analysis, and to enable safety analyses, all 
patients who discontinue their randomised medication will be asked to still complete their 
follow-up visit (visit 6) as outlined in the study schedule. An MRI scan should be 
completed if withdrawal is after Visit 4. This MRI is only done as a safety parameter and 
is not to be included in any endpoint analysis. 
Patients who withdraw from the study will not be replaced.
Other reasons a patient maybe removed from the study are outlined in Section 5.3 in the 
protocol. 
3.4
Patient Identification 
3.4.1 Patient Identification 
The Principal Investigator or qualified designee will obtain signed, informed consent 
from the potential study patient before any study-specific procedures are performed. 
After written informed consent has been obtained, each patient will receive a unique 
patient number. 


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The patient number allocated to any patient will not be reallocated to other patients if 
he/she terminates the study participation for any reason, regardless of whether IMP was 
taken or not. 
3.4.2 Allocation of Patients to Treatment 
This is an open label study and all patients will receive 200 mg q.d. The first dose of IMP 
will be administered at Visit 2 (Enrolment) after the patient has signed the informed 
consent form and the Investigator has confirmed the patient’s eligibility based on 
screening procedures performed. 
3.5
Study Drug Administration 
In Study MIV-711-202, all patients will receive 200 mg q.d. oral dose of MIV-711 for 26 
weeks. The IMP should be taken q.d. in the morning approximately 24 hours apart. The 
first dose in Study MIV-711-202 is administered at the site during Visit 2 (Enrolment). 
All patients must stay at the site 2 hours after administration of the first dose. 
IMP should be dispensed during the Visits 2 and 4 and returned by the patients for drug 
accountability at Visit 4 and Visit 5. 
On days when the patient is visiting the site the IMP must be taken at the site under 
fasting conditions (and not at home) and the time of the intake must be recorded in the 
source documents. 
3.6
Interim Analysis 
No interim analysis will be conducted for any efficacy endpoint. Interim safety data will 
be reviewed during DMC meetings after the first 25 patients have completed Visit 4 and 
Visit 5. No formal statistical tests will be undertaken. Adverse events will be summarised 
descriptively and tabulated for all patients by treatment group. The DMC will consider 
the results of the AE summaries when making decisions regarding dosing of subsequent 
cohorts (i.e. need for dose stoppages) or the need for formal interim analysis of non-safety 
data. 
4.
Study Analysis Variables 
The study variables are collected for the two studies MIV-711-201 and MIV-711-202 
according to the study schedules displayed in section 4.1 and section 4.2, respectively.


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4.1
Study Schedule MIV-711-201 
Study Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
Weeks
-4
1
2
4
8
14
20
26
30
Day
up to 
30 days
Day 1
day 15
±2 days
day 29
±2 days
day 57
±2 days
±7 days
±7 days
±7 days
± 7 days
Visit Description
Screening Randomisation/
Baseline
Treatment period
Safety
follow- up
Signed informed consent
X
Randomisation
X
Inclusion/exclusion criteria
X
X
Target knee identificationA
X
Demographics
X
Weight
X
X
Height
X
Medical & Surgical history
X
Physical examination
X
X
XB
XB
X
X
XB
X
Vital signs, including 
body temperature
X
X
X
X
X
X
X
X
X
12-Lead ECGC
X
X
X
X
X
X
X
X
X


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Study Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
Weeks
-4
1
2
4
8
14
20
26
30
Day
up to 
30 days
Day 1
day 15
±2 days
day 29
±2 days
day 57
±2 days
±7 days
±7 days
±7 days
± 7 days
Visit Description
Screening Randomisation/
Baseline
Treatment period
Safety
follow- up
Clinical chemistry/
Haematology
X
X
X
X
X
X
X
X
X
UrinalysisD
X
X
X
X
X
X
X
X
X
Urine drug screen
X
X
Post-menopausal assessment
(females only)
X
HBsAg, anti-HBc, anti-HBs,
HCV, and HIV test
X
e-diary dispensing and
training
X
Patient Emergency Card
dispense
X
MRI of target kneeE
X
X
e-diary for pain and
analgesicF
X
X
X
Duration and onset of knee
pain
X
NRS, ICOAP, WOMAC
XG
X
X
X
X
XG


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Study Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
Weeks
-4
1
2
4
8
14
20
26
30
Day
up to 
30 days
Day 1
day 15
±2 days
day 29
±2 days
day 57
±2 days
±7 days
±7 days
±7 days
± 7 days
Visit Description
Screening Randomisation/
Baseline
Treatment period
Safety
follow- up
Global improvement
(6-point Likert scale)
X
X
X
EuroQoL EQ-5D-5L
X
X
Brief Medication
Questionnaire
X
X
X
Dispense IMPI
XH
X
X
Drug accountability
X
X
X
X
PK sampling (blood)
X
X
Biomarker samplesJ
X
X
X
X
X
AEs/SAEs monitoring
X
X
X
X
X
X
X
X
X
Concomitant Medication
X
X
X
X
X
X
X
X
Phone call to assess safety
and tolerabilityK
X
X
X
X
X
X
Blood sample for
pharmacogenomics, proteomics, 
genomics, metabolomics and
lipidomics and urine sample for 
proteomics and metabolomicsL
X
X


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Abbreviations: AE=Adverse event; anti-HBc=Total Hepatitis B core antibody; anti-HBs= Antibody to Hepatitis B surface antigen; ECG=Electrocardiogram; 
eCRF=Electronic case report form; EQ-5D-5L=EQ-5D is a standard measure of health status developed by the EuroQol Group in order to 
provide a simple, generic measure of health for clinical and economic appraisal; HBsAg=Hepatitis B surface antigen; HCV=Hepatitis C virus; 
HIV=Human immunodeficiency virus; ICOAP=Intermittent and constant osteoarthritis pain; IMP=Investigation medicinal product; 
K-L=Kellgren and Lawrence; MRI=Magnetic resonance imaging; NRS=Numeric rating scale; PK=pharmacokinetic(s); PRO=Patient reported 
outcomes; SAE=Serious adverse event; WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index. 
A. Selection of target knee was to be primarily based on pain, secondarily on K-L Grade, and if both sides were equal with regard to these two criteria, the 
right knee was always to be prioritised. 
B.
Targeted physical examination. Full physical examination at all other visits. 
C.
At Visit 2 at pre-dosing, 0.5, 1 and 2 hours post-dosing (± 10 minutes). At all other visits 30 minutes post-dose (± 10 minutes). 
D. If urinalysis was positive for blood, nitrites, leukocyte esterase, and/or protein, additional microscopic analysis was to be performed. 
E.
MRI was to be performed at Visit 2 (-7 days) and at Visit 8 (± 5 days). 
F.
To be completed at home during the 2 weeks prior to the marked visit. 
G. Only NRS for average overall knee pain severity (1-week recall) for both knees. 
H. The first dose of IMP was to be dispensed to the patient at the site. Date and time was to be recorded in the eCRF. The first dose was to be given to the 
patient after all baseline assessments had been performed including completion of Patient Reported Outcomes (PROs).  Patients were to take the IMP in 
the clinic in a fasting state and were required to stay at the clinic for 2 hours after intake of the IMP. 
I.
Patients were to take the IMP in the clinic in a fasting state.  Breakfast was to be eaten 1 hour after IMP intake.  The last dose of the IMP was to be taken 
at the site during Visit 8. 
J.
Both blood and urine samples were to be collected for biomarker.  The first void of morning urine must have occurred before the urine sample was taken 
from a later void.  The patients were to be fasting when all biomarker samples were taken. 
K.
The phone call was to be made 5-9 days after all dosing visits.
L.
Blood was to be collected for pharmacogenomics, proteomics, genomics, metabolomics and lipidomics and urine was to be collected for proteomics and 
metabolomics pre-dose at Visit 2 (baseline) and Visit 8 from patients who provided additional written.


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4.2
Study Schedule MIV-711-202 
Study Visit 
V1 
V2 
V3 
V4 
V5 
V6 
Weeks 
-2 
1 
4 ±2 days 
14 ±7 days 
26 ± 7 days 
30 ± 7 days
Day 
-10 ± 5 days 
Day 1 
28 ±2 days 
98 ±7 days 
182 ± 7 days 
210 ± 7 days 
Visit Description 
ScreeningA
Enrolment 
Safety 
Safety and Treatment 
Safety follow-up 
Signed informed consent 
X 
XB
Inclusion/exclusion criteria 
X 
X 
Demographics 
X 
Weight 
X 
Medical & Surgical history 
X 
Physical examination 
XC
X 
X 
X 
X 
Vital signs, including body 
temperature 
XC
X 
X 
X 
X 
X 
12-Lead ECGD 
XC
XE
X 
X 
X 
X 
Clinical chemistry/Haematology 
XC
X 
X 
X 
X 
X 
UrinalysisF
XC
X 
X 
X 
X 
X 
Urine drug screen 
X 
Post-menopausal assessment 
(females only) 
X 
e-diary dispensing and training 
X 


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Study Visit 
V1 
V2 
V3 
V4 
V5 
V6 
Weeks 
-2 
1 
4 ±2 days 
14 ±7 days 
26 ± 7 days 
30 ± 7 days
Day 
-10 ± 5 days 
Day 1 
28 ±2 days 
98 ±7 days 
182 ± 7 days 
210 ± 7 days 
Visit Description 
ScreeningA
Enrolment 
Safety 
Safety and Treatment 
Safety follow-up 
e-diary for pain and analgesicG
X 
X 
Patient Emergency Card 
Dispensing 
X 
MRI of the bone area 
XH
Registration in the IWRS 
X 
NRS, ICOAP, WOMAC 
X 
X 
Global improvement (6-point 
Likert scale) 
X 
X 
EuroQoL EQ-5D-5L
X 
Brief Medication Questionnaire 
X 
X 
Dispense IMPI
XJ
X 
Drug accountability 
X 
X 
e-diary return 
X 
PK sampling (blood) 
X 
Biomarker samplesK
X 
X 
X 
X 
AEs/SAEs monitoring 
X 
X 
X 
X 
X 
X 


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Study Visit 
V1 
V2 
V3 
V4 
V5 
V6 
Weeks 
-2 
1 
4 ±2 days 
14 ±7 days 
26 ± 7 days 
30 ± 7 days
Day 
-10 ± 5 days 
Day 1 
28 ±2 days 
98 ±7 days 
182 ± 7 days 
210 ± 7 days 
Visit Description 
ScreeningA
Enrolment 
Safety 
Safety and Treatment 
Safety follow-up 
Concomitant Medication 
X 
X 
X 
X 
X 
Phone call to assess safety and 
tolerabilityL
X 
X 
X 
X 
Blood sample for 
pharmacogenomics, proteomics, 
genomics, metabolomics and 
lipidomics and urine sample for 
proteomics and metabolomics 
XM
Abbreviations: AE=adverse event; ECG=electrocardiogram; eCRF=electronic case report form; DNA=deoxyribose nucleic acid;  EuroQoL EQ-5D-5L= a standard measure of 
health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal; FSH=follicle stimulating hormone; 
ICF=informed consent form; ICOAP=intermittent and constant osteoarthritis pain; IMP=investigational medicinal product; IWRS= Interactive Web Response System; 
MRI=magnetic resonance imaging; NRS=numeric rating scale; PK=pharmacokinetic; PRO=patient-reported outcomes; RNA=ribonucleic acid; SAE=serious adverse event; 
WOMAC= Western Ontario and McMaster Universities Osteoarthritis Index 
A) The Screening visit (Visit 1) will coincide with 26-week End of Treatment visit of Study MIV-711-201 (Visit 8).  
B) Optional ICF to be provided and signed at Visit 2. 
C) Assessed at Visit 8 in Study MIV-711-201. Only need to be re-assessed if Visit 8 does not occur on the same day as Visit 1 in Study MIV-711-202 
D) 30 minutes post-dose (± 10 minutes). 
E) 12-lead serial ECGs will be recorded at Visit 2 (Enrolment) pre-dosing and after 30 minutes, 1 hour and 2 hours post-dosing (± 10 minutes). 
F) If urinalysis is positive for blood, nitrites, leukocyte esterase, and/or protein, additional microscopic analysis may be performed. 
G) To be completed at home during the 2 weeks leading up to the marked visit with final recording the day before. 
H) ± 5 days 
I) Patients take IMP in the clinic in a fasting state. Breakfast can be eaten 1 hour after IMP intake. The last dose of the IMP will be taken at the site during Visit 5. 
J) The first dose of IMP will be dispensed to the patient at the site and the patient must stay at the clinic for 2 hours after intake of IMP. Date and time should be recorded in the 


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Study Visit 
V1 
V2 
V3 
V4 
V5 
V6 
Weeks 
-2 
1 
4 ±2 days 
14 ±7 days 
26 ± 7 days 
30 ± 7 days
Day 
-10 ± 5 days 
Day 1 
28 ±2 days 
98 ±7 days 
182 ± 7 days 
210 ± 7 days 
Visit Description 
ScreeningA
Enrolment 
Safety 
Safety and Treatment 
Safety follow-up 
eCRF. The first dose should be given to the patient after all assessments at Enrolment have been performed.  
K) Both blood and urine sample will be collected for biomarkers. The first void of morning urine should have occurred before the urine sample is taken from a later void. The 
patients must be fasting when all biomarker samples are taken. 
L) The phone call should be made 5-9 days after all dosing visits. There will be additional phone calls at Week 10 and Week 20.  
M) Blood will be collected for pharmacogenomics, proteomics, genomics, metabolomics and lipidomics and urine will be collected for proteomics and metabolomics pre-dose at 
Visit 5 from patients who provide additional written consent. 


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4.3
Demographic and Background Variables 
The following demographic and anthropometric information will be recorded at 
screening: 
•
Date of informed consent 
•
Medical and surgical history (including previous and current medical conditions and 
medications) 
•
Age calculated as (date of informed consent – date of birth)/365.25 
•
Gender 
•
Ethnic origin 
•
Race 
•
Height (cm) 
•
Body weight (kg) 
•
Body mass index (BMI) (kg/m2) 
Adverse Events from MIV-711-201 will be recorded as Medical history in MIV-711-202. 
Concomitant medication in MIV-711-201 will be recorded as prior medication in MIV- 
711-202. 
4.4
Safety Variables 
4.4.1 Adverse Events 
All AEs and SAEs will be recorded in the eCRF system from the date the informed 
consent form is signed (visit 1) until the safety follow up visit (visit 6) is completed.
4.4.2 Clinical Laboratory Tests 
Blood samples for hematology and clinical chemistry, and urinalysis assessments will be 
collected during all study visits: Visit 1 (screening), Visit 2 (Week 1), Visit 3 (Week 4), 
Visit 4 (Week 14), Visit 5 (Week 26), Visit 6 (Week 30, follow-up). 
The following safety laboratory parameters will be measured: 
Hematology: WBC and differential, % and absolute for: neutrophils, lymphocytes, 
monocytes, eosinophils, basophils; hemoglobin, hematocrit, RBC, RBC indices (MCV, 
MCH and MCHC) and morphology, platelet count 


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Chemistry: urea nitrogen, creatinine, calcium, sodium, potassium, bicarbonate, chloride, 
total protein, fasting glucose, total bilirubin, direct bilirubin and indirect bilirubin, ALT, 
AST, alkaline phosphatase, GGT, CPK, CRP.  
Urinalysis: with microscopic: specific gravity, pH, protein, glucose, ketones, nitrites, 
blood and leukocyte esterase  
4.4.3 Other Laboratory Tests 
•
Post-menopausal determination at Visit 1 (screening): Follicle stimulation 
hormone (FSH) in female patients. 
•
Urine Drug Screen measured at screening and Visit 1 (Screening): Amphetamine, 
Benzodiazepines, THC, Cocaine, Oxycodone and Opiate.  
•
PTH (parathyroid hormone) 
4.4.4 Vital Signs 
Vital signs (body temperature, heart rate, blood pressure, oxygen saturation) will be 
performed at all clinic visits prior to IMP dosing: Visit 1 (screening), Visit 2 (Week 1), 
Visit 3 (Week 4), Visit 4 (Week 14), Visit 5 (Week 26), Visit 6 (Week 30), safety follow 
up. All assessments will be collected in the supine position. 
Weight will be measured at visit 1 (screening).  
4.4.5 Electrocardiograms 
A 12-lead ECG will be performed at all clinic visits.  12-lead serial ECGs will be 
recorded at visit 2 (enrolment) pre-dosing and after 30 minutes, 1 hour and 2 hours post-
dosing (± 10 minutes).  
The clinical significance of ECG results will be determined by the investigator after 
review of the ECG report in relation to the patient‘s medical history, physical 
examination findings, and concomitant medications.  
4.4.6 Physical Examination 
A standard complete physical examination will be performed at Visit 1 (Screening), Visit 
2 (Enrolment), Visit 3, Visit 4 and Visit 5. 


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4.4.7 Prior and Concomitant Medications 
All prior and concomitant medications taken during the MIV-711-202 study will be 
recorded with generic name, indication, daily dose, and start and stop dates of 
administration at each visit. For this study, prescription medicines, other than those 
prohibited by the study protocol are permitted as concomitant medications to manage 
ongoing or chronic, stable medical conditions. Concomitant medications from the MIV-
711-201 study that were taken prior to visit 2 in the MIV-711-202 study are captured as 
prior medications in the current study. Any change in prior medications past visit 2 IMP 
administration in MIV-711-202, or any new medications, are documented as concomitant 
medication. All patients will be asked about concomitant medication use and any changes 
to use of concomitant medications at all study visits. Patients will be permitted to 
reinstate prohibited concomitant medications on completion of their follow up study visit. 
The Brief Medication Questionnaire self-reported measure for the use of concomitant 
medication will be included at visit 4 and visit 5. 
4.4.8 Phone Call to Assess Safety and Tolerability 
Follow-up telephone calls to assess safety and tolerability will occur 5 to 9 days after 
visit 2, visit 3 and visit 4. There will be additional phone calls at Week 10 and Week 20 
for safety and tolerability.  
4.5
Efficacy Variables 
4.5.1 MRI Bone Shape Modelling by Imorphics 
MRIs will be analysed quantitatively using statistical shape modelling (SSM, Imorphics 
Ltd). 
Bone shape modelling of MRI by Imorphics will be used to assess: 
•
Mean cartilage thickness (mm) for each of the anterior, posterior and central 
regions, with areas denuded of cartilage included as having zero thickness
•
Bone marrow lesion volume (mm3) by anatomical region: medial and lateral 
femorotibial region of femur, medial and lateral pate llofemoral region of femur, 
medial and lateral tibia, and patella
•
Bone area (mm2) for anatomical regions: lateral and medial femur 
(patellofemoral); lateral and medial femur (femorotibial); lateral and medial 
patella, lateral and medial tibial condyle
•
Bone shape by distance along an OA shape vector for femur, tibia and patella
•
Index bone area/cartilage thickness


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Below are the denominations of the data items provided by Imorphics that will provide 
the basis for bone area and cartilage thickness and bone marrow lesion volume.
•
MF_TAB: Area of bone in the medial femur region, MF 
•
CM_FEMUR_THCTAB: Average thickness of cartilage in the central medial 
femur region  
•
CM_TIBIA_THCTAB: Average thickness of cartilage in the central medial tibia 
region 
•
TOTAL_BML_VOLUME: Combined volume of all BML regions 
4.5.2 MRI MOAKS 
MRIs will be analysed semi-quantitatively by a central musculoskeletal radiologist using 
the MOAKS. 
MOAKS scoring will be used to assess the following features: 
•
Bone marrow lesions (BMLs) and cysts 
•
Articular cartilage 
•
Osteophytes  
MRI assessment using MOAKS scoring will be used to assess the following features, as 
provided by PAREXEL MRI:  
•
Bone Marrow Lesions (BMLs) and cysts. This involves 15 subregions graded for 
BML size (including ill-defined lesion and cysts) measuring the total volume of 
the subregion occupied by BML(s). Grade 0= none, grade 1 < 33% of subregional 
volume, grade 2 = 33 to 66% of subregional volume and grade 3 > 66% of 
subregional volume.  
•
Articular Cartilage: This involves 14 articular cartilage regions graded for size of 
any cartilage loss (including partial and full thickness loss) as a percentage of 
surface area as related to the size of each individual region surface and percentage 
of loss in this subregion that is full-thickness loss.  
•
Osteophytes: This involves 12 sites scored for presence and size of osteophytes. 
Grade 0=none, Grade 1= small, Grade 2 = medium, Grade 3 = large.  
The specific subregions associated with the above three groups of MOAKS scoring are 
outlined in the table below: 
Bone Marrow Lesions (BMLs) and cysts 
Articular Cartilage 
Osteophytes 
Medial Patella  
Lateral Patella  
Medial Femur Trochlea 
Medial Patella 
Lateral Patella 
Medial Femur Trochlea 
Superior Patella 
Inferior Patella 
Medial Patella  


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Medial Femur Central 
Medial Femur Posterior 
Lateral Femur Trochlea 
Lateral Femur Central 
Lateral Femur Posterior 
Medial Tibia Anterior 
Medial Tibia Central 
Medial Tibia Posterior 
Subspinous 
Lateral Tibia Anterior 
Lateral Tibia Central 
Lateral Tibia Posterior  
Medial Femur Central 
Medial Femur Posterior 
Lateral Femur Trochlea 
Lateral Femur Central 
Lateral Femur Posterior 
Medial Tibia Anterior 
Medial Tibia Central 
Medial Tibia Posterior 
Lateral Tibia Anterior 
Lateral Tibia Central 
Lateral Tibia Posterior 
Lateral Patella  
Medial Femur Trochlea 
Medial Femur Central 
Medial Femur Posterior 
Lateral Femur Trochlea 
Lateral Femur Central 
Lateral Femur Posterior 
Tibia Medial 
Tibia Lateral 
Bone Marrow Lesions (BMLs) and cysts: The 15 subregions will be assessed for: 
•
Size of BML 
•
Number of BMLs 
•
Percentage that is BML  
Articular Cartilage: The 14 subregions will be assessed for: 
•
Size of any cartilage loss 
•
Percentage of Full Thickness Loss 
4.5.3 Patient Reported Outcomes (PROs) 
At Visit 4 and 5 the following PROs will be recorded using questionnaires as 
specified in the schedule of assments (see Protocol Table 2). 
• Average overall knee pain severity in the target knee over the past 1 week (0-10 
NRS) 
• Worst knee pain severity in the target knee over the past 1 week (0-10 NRS) 
• Global disease activity over the past 1 week (0-10 NRS) 
• Average overall knee pain severity in the contralateral knee over the past 1 week 
(0-10 NRS) 
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 
Higher scores indicate worse pain, stiffness and physical function. The subscale 
scores are derived by summing the assigned values on component items. The 
study joint referred in the WOMAC questionnaire corresponds to the target knee 
(as referenced elsewhere in this protocol). 
• Osteoarthritis Research Society International (OARSI)-OMERACT Responder 
index will be calculated using the WOMAC pain and function subscales and the 
patient’s global assessment score.  


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• Intermittent and constant osteoarthritis pain (ICOAP) - an 11-item tool designed to 
assess constant and intermittent OA pain. The tool will be self-reported. (The tool 
was designed for telephone or interview administration but self-reporting is 
allowed.) The questions will be scored according to a user manual into a constant 
pain subscale, intermittent pain subscale and total pain score. These scores will be 
transformed to a 0-100 scale for analysis. 
• Global improvements in knee problem, knee pain and knee function recorded 
on a 6-point Likert scale: completely better, much better, better, no change, 
worse, much worse. 
•
EuroQol-5 Dimensions (EQ-5D-5L) (Visit 5 only) - a generic measure of self-
reported health status that defines health status in terms of five dimensions – 
mobility; self-care; usual activity; pain or discomfort; and anxiety or depression  
•
In an e-diary format, a patient knee pain diary (NRS) and analgesia questionnaire 
will be completed daily during two 2-week periods prior to Visit 4 and Visit 5. 
Baseline (Visit 8 of Study MIV-711-201) will be defined as the last observation 
prior to the first dose of investigational product. The assessments in the e-diary 
comprise: 
1)
Average overall knee pain severity in the target knee over the past 12 
hours (0-10 NRS) 
2)
Adherence to usual analgesics regimen 
•
Intake of IMP (only included with an attempt to improve compliance, no data to 
be reported) 
4.5.3.1
NRS Score Descriptions  
For the purposes of the questions below, the target knee is defined as the knee studied in 
this trial. Pain in the knee relates to any knee symptom the patient may experience for 
example pain or aching. 
The scale ranges for NRS pain scores range from 0 indicating —“no pain“, to 10 
indicating —“pain as bad as it could be“. The NRS scales will be used to assess for: 
1) NRS question 1: NRSPTO. On average, how would you rate the overall pain severity 
in your target knee over the last week (7 days)? 
2) NRS question 2: NRSPAINW. How would you rate your worst pain severity in your 
target knee over the last week (7 days)? 


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3) NRS question 3: NRSPAINS. On average, how would you rate the overall pain 
severity in your other knee over the last week (7 days)? 
4) NRS question 4: NRSACT. Over the last week (7 days), how active do you think 
your target knee arthritis has been? 
5) NRS question 5: NRSSAT. Over the last week (7 days), how satisfied have you been 
with your target knee function? 
For purposes of this SAP NRS question 4 refers to the patients “Global Assessment 
Score”. 
4.5.3.2
ICOAP Score Descriptions 
Intermittent and constant osteoarthritis pain (ICOAP): an 11-item tool designed to assess 
constant and intermittent pain. Higher scores indicate worse constant and intermittent 
pain. The items assessed include: 
•
IP1- How intense has constant knee pain been  
•
IP2-Constant knee pain affecting sleep 
•
IP3-Constant knee pain - quality of life 
•
IP4-Frustrated by your constant knee pain 
•
IP5-Upset by your constant knee pain 
•
IP6-Intensity of pain that comes and goes 
•
IP7-Frequency pain that comes and goes 
•
IP8-Pain comes and goes affecting sleep 
•
IP9-Pain comes and goes quality of life 
•
IP10-Frustration pain that comes and goes 
•
IP11-Upset pain that comes and goes 
4.5.3.3
WOMAC Score Descriptions 
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 3.1: a 24-
item OA - specific, tri-dimensional self-administered questionnaire, for assessing health 
status and health outcomes in OA of the knee. Using an 11-box NRS scale, higher scores 
indicate worse pain, stiffness and physical function. Items assessed include: 
•
WOMAC1-Pain - walking on a flat surface 
•
WOMAC2-Pain - going up or down stairs 
•
WOMAC3-Pain - at night while in bed 


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•
WOMAC4-Pain - sitting or lying down 
•
WOMAC5-Pain - while standing 
•
WOMAC6-Stiffness after first woke up in morning 
•
WOMAC7-Stiffness sitting or lying down 
•
WOMAC8-Difficulty - When going down the stairs 
•
WOMAC9-Difficulty - When going up the stairs 
•
WOMAC10-Difficulty - Getting up from a sitting 
•
WOMAC11-Difficulty - While standing 
•
WOMAC12-Difficulty - When bending to the floor 
•
WOMAC13-Difficulty - Walking on a flat surface 
•
WOMAC14-Difficulty - Getting in or out of a car 
•
WOMAC15-Difficulty - While going shopping 
•
WOMAC16-Difficulty - When putting on your socks 
•
WOMAC17-Difficulty - When getting out of bed 
•
WOMAC18-Difficulty - When taking off your socks 
•
WOMAC19-Difficulty - While lying in bed 
•
WOMAC20-Difficulty - Getting in or out of bath 
•
WOMAC21-Difficulty - While sitting 
•
WOMAC22-Difficulty - Getting on or off toilet 
•
WOMAC23-Difficulty - Performing heavy duties 
•
WOMAC24-Difficulty - Performing light duties 
4.5.3.4
OARSI OMERACT Score Descriptions 
OARSI-OMERACT Responder index [2, 3] will be calculated using the WOMAC pain 
and function subscales and the patient‘s global assessment score as described in sections 
4.5.3.1 and 4.5.3.3. A responder will be defined as any subject that satisfies one of the 
following two overall conditions:  
CASE 1.  Improvement in pain or function ≥50% and absolute change ≥20 
CASE 2. Improvement in at least two of the following conditions:
1. pain ≥20% and absolute change ≥10
2. function ≥20% and absolute change ≥10
3. patients‘ global assessment ≥20% and absolute change ≥10  
Higher scores indicate worse pain, stiffness and physical function so that an 
“improvement” is only concerned with negative changes (or decreases) from baseline. 
Positive increases in scores relative to baseline suggest a worsening of pain (scores 
increasing over time suggests pain is increasing in severity over time).  


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4.5.3.5
Global Improvement Score Descriptions 
Global improvements in knee problem, knee pain and knee function (Ability to use knee), 
recorded on a 6-point Likert scale at visit 4 and visit 5: (completely better, much better, 
better, no change, worse, much worse).   
4.5.3.6
Quality of Life 
At visit 5:  EuroQol -5 Dimensions (EQ-5D-5L) - a generic measure of self-reported 
health status.  Items assessed include: 
•
Usual Activities 
•
Anxiety/Depression 
•
Self-Care 
•
Pain/Discomfort 
•
Mobility 
•
Health Rating 
4.5.3.7
Brief Medication Questionnaire  
The Brief Medication Questionnaire is a self-reported measure for the use of concomitant 
medication and will be administered at visit 4 and visit 5. Items assessed include: 
•
How much did you take each time 
•
How many days did you take it 
•
The dosage times are inconvenient 
•
How many times per day did you take it 
•
It is hard to get my refill on time 
•
How many times did you miss taking it 
•
It is hard to open the container 
•
Hard to read the print on the container 
•
For what reason were you taking it 
•
It is hard to remember all doses 
•
Stop taking meds since the start of the study or since the previous visit 
•
Medication Name 
4.5.3.8
E-Diary Assessment of NRS and Analgesic Use 
In an e-diary format, a patient knee pain diary (NRS) and analgesia questionnaire will be 
completed daily every 12 hours (AM, PM) during two 2-week periods prior to visit 4 and 
visit 5. The assessments in the e-diary comprise:  


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•
Average overall knee pain severity in the target knee over the past 12 h (0 -10 
NRS)  
•
Adherence to usual analgesics regimen:  
o
Has patient taken any pain medication over last 12 hours? (Yes, No). 
o
Classify your pain medication usage over the last 12 hours: (More than 
normal, Normal, Less than normal)  
•
Intake of IMP (note: the e-diary device is kept by the patients for the  
full duration of the study, intake of IMP will be registered daily throughout the  
study)  
4.5.4 Other Efficacy Parameters – Biomarkers, Imaging, Pharmacokinetics 
Biomarkers 
Blood and urine samples will be taken at Visits 2, 4, 5 and 6, for analysis of exploratory 
bone and cartilage markers of relevance for OA disease, such as CTX-I, PINP, BSAP 
and TRAP5b in serum and NTX-I, CTX-I, alphaCTX-I and CTX-II in urine. 
Imaging 
The imaging assessment will be derived in the source as change from baseline to Visit 5 
in the current study as a calculated compound index of MRI bone area and cartilage 
thickness. 
Pharmacokinetics 
The analysis of the pharmacokinetics and metabolism of MIV-711 and the relationship to 
patient factors and concomitant medications will be conducted by the sponsor and 
described in a separate report. The PK analysis will not be considered in this SAP.  
4.6
Analysis Populations 
The analysis populations that will be used in the analyses are defined in Section 4.6.1, 
Section 4.6.2 and Section 4.6.3 below. Note that the analysis populations Population A 
and Population B as defined in the CSP are not considered statistical analysis populations 
but defined to indicate the two different treatment groups. No amendment to the CSP will 
be done, but the discrepancy between the CSP and the SAP regarding the analysis 
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4.6.1 Intent-to-Treat Population (ITT) 
All patients enrolled to the study MIV-711-202 and recieves at least one dose of the IMP. 
4.6.2 Per Protocol Population (PPS) 
The patients in the ITT population without any major protocol deviations as described in 
section 5. A patient that discontinuates from the study will typically be part of the ITT 
population but will not be included in the PPS population.   
4.6.3 Safety Analysis Population (SAF) 
The safety analysis population will be the same as the ITT population. 
5.
Protocol Deviations 
Deviations from the protocol including violations of inclusion/exclusion criteria will 
be assessed as “minor” or “major” in cooperation with the sponsor. Major deviations 
from the protocol will lead to the exclusion of a patient from the Per Protocol Set 
(PPS). Deviations will be defined prior to data base hard lock. 
The following criteria will be used to exclude a patient from an analysis set:  
•
Incorrect diagnosis  
•
Any of the prohibited interventions/injuries for the target knee 
•
Missing more than 7 doses of MIV-711 
•
Discontinuation from the study 
Note: this is not an exhaustive list of deviations, these are only the deviations specified 
per protocol. The discussion during the data review meeting post data base soft lock will 
review all deviations collected at each site and it will be decided to which analysis set 
each patient belongs.  
6.
General Considerations for Data Presentations 
In this study IMP refers to any amount of the treatments defined in section 3.5, regardless 
of the time or period of administration. 
Data for all patients enrolled in study MIV-711-202 who receives at least one dose of 
IMP will be presented in the data listings.  


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A patient who is enrolled in study MIV-711-202 but does not receive IMP will be 
included in those data listings for which they have data but will be excluded from all data 
summaries. Data summaries will only include those patients that receive IMP.  
For those listings or data summaries where baseline and change from baseline 
measurements will be presented, unless stated otherwise, the baseline assessment to be 
used for calculating change from baseline will be the last valid assessment prior to first 
dose of 200 mg MIV-711. Note that the change from baseline will be calculated also for 
visits prior to the baseline visit, not only for visits succeeding the baseline visit. 
Data from both studies for patients enrolled in study MIV-711-202 will be included in the 
data listings, tables and figures, as appropriate. 
All pre- and post-dose assessments including unscheduled assessments will be included 
in the data listings. For unscheduled assessments collected pre-dose, the last assessment 
taken for a time point will be used in the data summaries (summary tables, figures, and 
statistical analysis); for all post-dose time points, the original assessment for any given 
time point will be used in the data summaries (summary tables, figures, and statistical 
analysis). 
Descriptive statistics for observed values and derived change from baseline values will be 
tabulated by visit and study group. Continuous variables will be summarized by study 
group and visit, as appropriate, using descriptive statistics including: number of 
observations (n), mean (arithmetic), median, standard deviation (SD), minimum, and 
maximum. Frequencies and percentages will be used for summarizing discrete 
(categorical) data by study group and visit, as appropriate. The denominator used when 
calculating percentages will be the number of patients assessed at a particular 
combination of study group and study visit, as appropriate 
Safety and efficacy data that are reported as missing will be excluded from all descriptive 
and non-descriptive data analysis. There will be no imputation of any data.  Observations 
that might be considered spurious (extreme relative to the majority of the data) will not 
be altered or removed from any presentation of the data, including the calculation of 
summary statistics (means, medians, etc.), unless approved by the sponsor.  
For data listings, all raw data will be reported/displayed exactly as provided. For 
summaries of quantitative safety data, the minimum and maximum value will be reported 
exactly as the raw data are reported; measures of central tendency (means, medians) will 
be reported to one more decimal place than the raw data; measures of variance (SD) will 
be reported to two more decimal places than the raw data.   
Unless stated otherwise there will be no adjustment for multiple comparisons. 


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In all data presentations ‘Treatment’ will be defined as 200 mg MIV-711. Listings will 
include all patients and will be sorted by patient number and time point (where 
applicable). All derived data used in a data summary or statistical analysis will be listed.  
6.1
Software  
All statistical analyses will be performed using Statistical Analysis Software (SAS®)
(SAS® Institute Inc., Cary, North Carolina, United States of America [USA]) Version 9.2 
or higher. 
7.
Patient and Treatment Information 
7.1
Patient Disposition 
The completion status, date of completion or discontinuation, the reason for 
discontinuation, and the study day of withdrawal will be listed. The number of patients 
enrolled and the frequency and percentage of patients completing the study, patients 
withdrawing early, and primary reason for withdrawal will be summarized. Also included 
in this summary will be the numbers of patients in each of the analysis populations: ITT, 
PPS, SAF. 
7.2
Patients Excluded from Analysis Populations 
Each patient excluded from one of the analysis populations will be listed along with the 
reason for their exclusion. 
7.3
Eligibility Criteria 
All enrolled patients who did not meet an inclusion criterion and all enrolled patients who 
met an exclusion criterion will be listed. 
7.4
Exclusion Tests
Results of the exclusion tests will be listed. These will include laboratory tests performed 
prior to dosing for: FSH testing, and urine drug screen. 
7.5
Protocol Deviations 
All reported protocol deviations will be listed.    


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7.6
Demographic Data
Demographic and baseline characteristics will be evaluated for Group A and Group B. 
Demographic information will be listed.  Descriptive statistics will be obtained for the 
continuous variables: height, age, BMI, and body weight and presented overall.  
Frequencies and percentage of patients will be tabulated for the categorical variables 
ethnicity, race, and gender.   
Patient height will be obtained from MIV-711-201 study. 
7.7
Medical History 
Medical and surgical history data recorded prior to dosing will be listed for each patient. 
Medical history will be coded using the MedDRA (Version 18.1).  
Only those body systems where a condition or abnormality has been reported will be 
listed. 
Any medical history data with start date after visit 2 in the MIV-711-201 study will be 
flagged in the medical history data listing. This data was collected as adverse event data 
during the MIV-711-201 study.  
AEs from the MIV-711-201 study are recorded as medical history in the MIV-711-202 
study. Any medical history data with start date after visit 2 in the MIV-711-201 study (i.e 
AEs) and which were ongoing at visit 1 in the MIV-711-202 study will be flagged in the 
medical history data listing.  
Flagged medical history items will be summarized by system organ class, preferred term, 
and treatment. 
7.8
Prior and Concomitant Medication
Prior and concomitant medications will be coded using WHO Drug (September 2015 
version). These medications will be classified by Anatomical Therapeutic Chemical 
(ATC) categories.  
Prior and Concomitant Medications will be listed by patient. 
Summary tables of the number of patients and percentage of patients by group and ATC 
classification will be provided for prior and concomitant medications. ATC level 1 and 
ATC level 3 will be used.  


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Relevant prior and concomitant medication from MIV-711-201 will be recorded as prior 
medication in the MIV-711-202 study. Two indicative variables/flags will be added to the 
data listings/database:  
1. Prior medications with start date after visit 2 in the MIV-711-201 study will be flagged 
in the data listing. 
2. Prior medications ongoing after visit 1 in the MIV-711-202 study will be flagged in the 
data listing.  
Flagged prior medications will be summarized by ATC level 1 and ATC level 3, and 
treatment group. 
7.9
Dose Administration 
Information collected per the dose administration CRF will be listed including patient 
number, visit, date and time of administration, number of capsules dispensed and number 
of capsules returned.  
The number and percentage of patients who received IMP will be summarized for each 
on site visit. Descriptive statistics will be used to summarize drug accountability as the 
number of capsules returned for each on site study visit by treatment. 
Compliance will be derived as the number of days patient were exposed to IMP. 100% 
compliance will be considered for dosing during the period Visit 2 to Visit 5.  
The number of capsules used will be derived as the number of capsules dispensed minus 
the number of capsules returned. Subjects with less than 100% compliance will be 
identified among those who have results for “Reason not all unused Capsules returned”. 
The compliance will not be calculated for withdrawn patients, as the date of the last IMP 
dose taken is not captured in the database. 
8.
Pharmacodynamic Analysis – Efficacy 
The baseline will be the last valid assessment prior to first dose of 200 mg MIV-711, 
i.e. the baseline visit is defined as  
•
Visit 2 in study MIV-711-201 for study group A
•
Visit 8 in study MIV-711-201 for study group B
The exception is for the biomarkers in study group B, where the baseline visit is defined 
as visit 2 in the present study (MIV-711-202).  
The change from baseline for visit X will be calculated as the (visit X – baseline visit) 
difference in observed values. Note that the change from baseline will be calculated for 
all visits in study MIV-711-201 and study MIV-711-202 where the actual endpoint has 


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been observed, i.e. not only for visits in study MIV-711-202 succeeding the baseline 
visit.  
All efficacy analyses will be made on the ITT population if not stated otherwise. 
8.1
Imorphics MRI Assessments 
The analyses of the imporphics MRI will be made on the ITT group and on the PPS 
population.  
The observed values and the derived change from baseline values will be listed and 
summarized descriptively for the following MRI variables: 
•
MRI of the bone area of the medial femur for the target knee. 
•
MRI of the cartilage thickness for the target knee.  
o
CM_FEMUR_THCTAB: Average thickness of cartilage in the central 
medial femur region 
o
CM_TIBIA_THCTAB: Average thickness of cartilage in the central 
medial tibia region 
•
MRI of the total bone marrow lesion volume for the target knee 
8.1.1 Statistical Analysis – Imorphics MRI Assessments 
A linear mixed effects model will be used to assess the behaviour of the MRI response 
over the entire period of the two studies, i.e. from visit 2 in study MIV-711-201 to visit 5 
in study MIV-711-202. The model will include fixed factors for study group (A or B), 
visit, group*visit interaction, baseline analgesic user (Yes/No), and random effect for site 
and patient.   
Patients considered analgesic users at baseline will be identified via concomitant 
medication analgesic usage. A patient exposed to a prescribed analgesic and ongoing 
medication at time of the first 200 mg MIV-711 intake (visit 2 study MIV-711-201 for 
patients in group A and visit 2 study MIV-711-202 for group B) will be considered as a 
baseline analgesic user.  
The dependent variable in the linear mixed model is the observed MRI score. Separate 
mixed model analyses will be considered for each of the MRI endpoints noted in section 
8.1. The following SAS code will be used as default, but a reduced model may be used in 
case of convergence issues:  
PROC MIXED data=; 
  CLASS patient visit group baseline_conmed_pain_use; 


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  MODEL MRI_score = group visit group*visit baseline_conmed_pain_use/ DDFM=KR ; 
  RANDOM site; 
  REPEATED visit / SUBJECT=patient TYPE=UN; 
  LSMEAN group*visit  / diff CL ALPHA=0.1  ; 
RUN;   
In case of convergence issues, a reduced model will be used to achieve convergence. The 
first two model reductions that will be considered are the following: 
1. Simplify the covariance structure by using a compound symmetry covariance 
structure instead of unstructured.
2. Omitt the random effect of site
The mean level and the change from visit 2 in study MIV-711-201 will be estimated for 
each population*visit combination in the model above together with the corresponding 
90% confidence interval. The estimates and confidence intervals will be tabulated and 
visualized over visits with the two groups in the same table/figure (see example figures 
and example table below). In this example table and example figures (Figure 1, Figure 2 
and Table 1), ‘Population A’ and ‘Population B’ refer to Group A and Group B. 


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Figure 1  Example figure of estimated mean levels 
Figure 2  Example figure of estimated change from visit 2 (MIV-711-201)


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Table 1 Example table of statistical analysis corresponding to Figure 1 and Figure 2. 
8.2
MOAKS MRI Assessments 
The MOAKS variables below will be listed for each patient. 
MOAKS Variables 
•
Bone Marrow Lesions (BMLs) and cysts (15 regions) 
o
Number of BML cyst 
o
Size of BML 
o
% that is BML 
•
Cartilage Assessment (14 regions) 
o
Size of any Cartilage Loss: 0=’Normal’, 1=’<10% Area’, 2=’10-75% 
Area’, 3=’>75% Area’, 9=’Not Evaluable’ 
o
Percentage Full Thickness Loss: 0=’Normal’, 1=’<10% Region’, 2=’10-
75% Region’, 3=’>75% Region’, 9=’Not Evaluable’ 
•
Osteophytes (12 regions): 0=’None’, 1=’Small’,  2=’Medium’, 3=’Large’, 9=’Not 
Evaluable’ 
•
Hoffa-Synovitis: 0=’None’, 1=’Mild’,  2=’Moderate’, 3=’Severe’ 
•
Effusion-Synovitis: 0 = ‘Physiologic Amount’, 1 = ‘Small’, 2 = ‘Medium’, 3 = 
‘Large’ 
For each patient and visit, the number of subregions/locations impacted by a MOAKS 
MRI feature will be calculated for the following variables: 
•
Number of BMLs and cysts. 
•
Size of any Cartilage Loss. 
•
Osteophytes
A subregion/location is considered to be by the MRI feature if it has score =1 or higher.  
Shift tables by group will be tabulated for the shift from baseline to visit 5 for the number 
of subregions impacted by the MRI feature for the three MOAKS variables above.  


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8.3
Analysis of Patient Reported Outcomes (PROs) 
8.3.1 NRS Pain Data 
The observed values and the derived change from baseline values will be listed and 
summarized descriptively for the following NRS knee pain variables:  
•
Overall of pain severity in the target knee last week (SDTM: Overall pain severity 
in target knee 
•
Worst pain severity in target knee (SDTM: Worst pain severity in target knee) 
•
Overall pain severity in other knee (SDTM: Overall pain severity in other knee) 
•
Global Disease Activity (SDTM: How active was target knee arthritis) 
•
Satisfaction with target knee function (SDTM: How satisfied are you with target 
knee function) 
8.3.1.1
Statistical Analysis of the NRS Pain Data 
The statistical analysis of NRS Pain data will be performed using the same statistical 
analysis as for the Imorphics MRI described in in section 8.1.1. The output of the 
statistical analysis will be similar (see example figures and table section 8.1.1.) but will 
be based on the visits when the NRS assessments were conducted.  
8.3.2 Intermittent and Constant Osteoarthritis Pain (ICOAP) Knee Version
The observed values and the derived change from baseline values will be listed for the 
three transformed ICOAP scores (Constant Pain, Intermittent Pain, and Total Pain). The 
transformed ICOAP will take values between 0 and 100 and will be calculated as follows: 
Constant pain subscale   
To calculate the Total constant pain subscale, sum the scores within each time point for 
items IP1 through IP5.  Maximum constant pain score ranges from 0 to 20.  
This score can be transformed to a score out of 100 using the following formula:    
(Total constant pain score / 20) x 100   
Intermittent pain subscale 
To calculate the total intermittent pain subscale, sum the scores within each time point for 
items IP6 through IP11. Maximum intermittent pain subscale ranges from 0 to 24.   
This score can be transformed to a score out of 100 using the following formula:    
(Total intermittent pain score / 24) x 100   


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Total pain score 
To calculate the total ICOAP score, sum the constant and intermittent pain subscales 
within each time point.  Maximum total pain score ranges from 0 to 44.    
This score can be transformed to a score out of 100 using the following formula:    
(Total pain score / 44) x 100   
8.3.3 Analysis of WOMAC
Normalized WOMAC scores, taking scores between 0 and 100, will be derived for each 
of the three WOMAC domains: WOMAC pain, WOMAC function, and WOMAC 
stiffness as follows:  
For each subject and each scheduled time point derive the total WOMAC score for each 
of the three domains: 
•
Total WOMAC Pain Score (Total_WOMAC_Pain_50) = Sum of the five 
WOMAC pain item scores. Denote this new variable in the data set as 
‘WOMAC_Pain_50’. 
•
Total WOMAC Function Score (Total_WOMAC_Func_170) = Sum of all 17 
WOMAC difficulty item scores. Denote this new variable in the data set as 
‘WOMAC_Func_170’ 
•
Total WOMAC Stiffness Score (Total_WOMAC_Stiff_20) = Sum of the 2 
WOMAC stiffness item scores. Denote this new variable in the data set as 
‘WOMAC_Stiff_20’. 
Each of the total WOMAC scores will be normalized using the following multipliers:
•
Normalized WOMAC PAIN Score = Total_WOMAC_Pain_50 x 2. 
•
Normalized WOMAC Function Score = Total_WOMAC_Func_170 ÷ 1.7. 
•
Normalized WOMAC stiffness Score = Total_WOMAC_Stiff_20 x 5. 
8.3.3.1
Statistical analysis of WOMAC
The statistical analysis of the three normalized WOMAC scores will be performed using 
the same statistical analysis as for the Imorphics MRI described in section 8.1.1. An 
additional linear model will be included for the individual WOMAC Pain score 
WOMAC1-Pain - walking on a flat surface. The output from these statistical analysis will 
be similar to that for the imorphics and NRS data (see example figures and table section 
8.1.1.), except the analysis will be based on the visits when the WOMAC assessments 
were conducted. 


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8.3.4  (OARSI)-OMERACT Responder Criteria
The OARSI-OMERACT response (Yes, No) will be derived from the PROs from the 
WOMAC scores (the Normalized WOMAC PAIN Score and the Normalized WOMAC 
Function Score as defined in section 8.3.3 and the Patient Global Assessment (NRS 
question 4: Over the past week, how active do you think your knee arthritis has been?).  
The OARSI-OMERACT response (Yes, No) will be calcuted for visit 5 MIV-711-202 for 
each patient by the following steps: 
Step 1. Normalize the Patient Global Assessment score so it takes values between 0 and 
100 in the same way as the Normalized WOMAC PAIN Score and th Normalized 
WOMAC Function Score described in section 8.3.3: 
a) Normalized Global Assessment Score:  
NRSACT_100 = (Global Assessment Score ) ⌧ 10. 
Step 2. Use the normalized scores to derive change from baseline and percentage change 
from baseline for visit 5 MIV-711-202: 
Denote the change from baseline scores as: 
•
CHG_WOMAC_PAIN_100 
•
CHG_WOMAC_FUNC_100 
•
CHG_NRSACT_100 
Denote the percentage change from baseline scores as: 
•
PCHG_WOMAC_PAIN_100 
•
PCHG_WOMAC_FUNC_100 
•
PCHG_NRSACT_100 
Percentage change from baseline will be calculated as: 
((Visit 5 Score –baseline Score) ÷ aseline Score) ⌧ 100 
.  
Step 3. Derive Responder OARSI-OMERACT (Yes, No): In assessing for a positive 
OMERACT response, patient improvement (Response = Yes) is associated with 
decreases (negative changes) from baseline and (negative) percentage (changes) 
decreases from baseline. The different criteria are quantified in the tables below. 
Case 1: using the change from baseline and percentage change from baseline scores  
for WOMAC pain and WOMAC function (from step 2), an OMERACT responder will 
be flagged as ‘Yes’ if either of the following 2 criteria are satisfied: 


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Criteria 
Decrease from 
Baseline 
       
Percentage 
Decrease from 
Baseline 
OMERACT 
Responder 
1 
WOMAC Pain 
 ≥ 20 
and 
≥ 50% 
Yes 
2 
WOMAC Function 
 ≥ 20 
and 
≥ 50% 
Yes 
Case 2: using the change from baseline and percentage change from baseline scores  
for WOMAC pain, WOMAC function, and global assessment score (from step 2), an 
OMERACT responder will be flagged as ‘Yes’ if at least 2 of the following 3 criteria are 
satisfied: 
Criteria 
Decrease 
from 
Baseline 
       
Percentage 
Decrease from 
Baseline 
OMERACT 
Responder 
3 
WOMAC Pain 
 ≥ 10 
and 
≥ 20% 
Yes 
4 
WOMAC Function 
 ≥ 10 
and 
≥ 20% 
Yes 
5 
Global Assessment NRS 
 ≥ 10 
and 
≥ 20% 
Yes 
A subject is a ‘Yes’ responder if either of criteria 1 or 2 are satisfied. If neither criteria 1 
or 2 are satisfied, criteria 3, 4 and 5 will be checked. 
A listing will be created that presents each patient’s responder status by visit. Included in 
this listing will be the associated change from baseline and percent change from baseline 
values. 
8.3.5 Global Improvements
Global improvements in knee problem, knee pain and knee function that were recorded 
on a 6-point Likert scale: completely better, much better, better, no change, worse, much 
worse.  All data will be listed for each patient.  
8.3.6 Quality of Life PRO – EQ-5D-5L
The observed values and the derived change from baseline values for the six items of 
Quality of Life PRO – EQ-5D-5L described in section 4.5.3.6 will be listed and 
summarized descriptively.  


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8.3.7 E-diary for Patient Pain
All data collected in e-diary fomat will be listed for each patient. 
The observed values and the change from baseline values for the derived e-diary 
summary scores described in section 8.3.7.1 below will be listed and summarized 
descriptively. 
8.3.7.1
Derived e-diary variables  
Three e-diary variables will be derived: 
•
NRS score  
•
Percentage score for analgesic usage last 12 hours 
•
Severity and extent of their pain medication usage
For each e-diary endpoint and visit, a patient’s summary value will be calculated by using 
the e-diary assessments recorded at the study days asscociated with that study visit. The 
study days asscociated with study Visit ‘x’ will be identified as follows: beginning at the 
last date of assessment associated with Visit ‘x’ and including up to 14 days prior to the 
visit recorded within 19 calendar days prior to the date of Visit ‘x’. If there are less than 
10 days of recorded e-diary assessment within those 19 calendar days, the summary value 
will not be calculated for that visit.  
NRS score 
The derived summary scores for e-diary NRS scores associated with each visit will be 
obtained as the arithmetic mean (the average) of all e-diary NRS scores observed during 
the study days  associated with that visit (as defined above). Separate e-diary NRS 
summary scores will be provided for AM and PM response. In addition, the overall 24 
hour summary score will be calculated as the mean of the AM and PM summary scores 
for each visit. The overall 24 hour summary score will only be calculated if both mean 
AM and mean PM scores are available.  
Percentage score for analgesic usage last 12 hours 
Each patient’s ‘pain medication usage over the last 12 hours (Yes/No)’ will be calculated 
as the percentages of days with a YES-response of the study days associated with that 
visit (as defined above). This will provide each patient with a percentage score for 
analgesic use for each study visit and for each of AM, PM. The denominator for AM and 
PM percentage calculations will be the actual number of days assessed, such that the 
number of days is at least 10 days and less than or equal to 14 days. The overall 
percentage, combining AM and PM measures, will be calculated as the mean of the AM 
and PM percentages: 
•
Overall percentage = (xx/AM denominator + yy/PM denominator)/2 
where ‘xx’ is the count of AM ‘Yes’ responses, ‘yy’ is the count of PM ‘Yes’ responses.  


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Severity and extent of their pain medication usage 
Each patient’s summary score for severity and extent of their pain medication usage 
(‘More than Normal’, ‘Normal’, ‘Less than normal’) will be the worst (most severe) 
response recorded during the study days associated with each visit (as defined above). 
The summary score will only be calculated if the patient responded ‘YES’ to ‘Pain 
medication Usage’ within the study days associated with the actual visit (as defined 
above). Summaries will be provided by visit, with separate summary score for AM and 
PM. The overall 24 hour summary score will be the worst (most severe) of the AM and 
the PM summary score and will be calculated if the AM and the PM summary score are 
available.  
8.3.7.2
Statistical analysis of e-diary scores
The derived e-diary NRS score will be analysed using the same statistical analysis as for 
the Imorphics MRI described in detail in section 8.1.1. Outputs from these statistical 
analysis will be similar to that as presented for the MRI data (see example figures and 
table section 8.1.1.) however outputs and analysis of the e-diary scores will be based on 
the visits when the e-diary assessments were recorded.
8.3.8 Biomarkers from Serum and Urine Samples
The observed values and the change from baseline values for the serum CTX-I and 
urinary CTX-II biomarkers will be listed and summarized descriptively. Note the baseline 
visit is defined as visit 2 in study MIV-711-202 for study Group B. 
Time-Integrated-Concentrations (TIC) will be derived for each serum CTX-I and urinary 
CTX-II biomarkers. For each biomarker the mean TIC value and the standard deviation 
(SD) of the TIC regarding the time period on drug will be derived. Thus, for group A the 
time period will include 26 + 26 weeks whereas the time period for group B will be the 
26 weeks in study MIV-711-202. For each biomarker a Z-score will be derived by 
subtracting the mean and dividing by SD. TIC results and associated Z-scores will be 
listed and summarized for each subject. 
Box plots will be used to visualize the distribution of TIC response and biomarker Z-
score. 


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8.3.8.1
Statistical analysis biomarkers from serum and urine samples
The statistical analysis of the serum CTX-I and urinary CTX-II biomarkers will be 
performed using the same statistical analysis as for the Imorphics MRI described in in 
section 8.1.1. Outputs from these statistical analysis will be similar to that as presented 
for the MRI data (see example figures and table section 8.1.1.) however outputs and 
analysis of the biomarker scores will be based on the visits when the biomarker 
assessments were recorded. 
8.3.9 Brief Medication Questionnaire
Brief medication questionnaire results will be summarized for the number and percentage 
of patients reporting: 
-
each medication taken 
-
each indication 
-
combination of medication taken per indication 
-
compliance for each medication taken 
Descriptive summary tables will be presented separately for Group A and Group B. 
Summary tables and listings for brief medication questionnaire will only be based on data 
from MIV-711-202 study. 
9.
Safety Analysis 
For the safety outcomes, for study Group A, changes from baseline will be assessed 
using the Visit 2 baseline data from MIV-711-201. For study Group B, changes from 
baseline will be assessed using the Visit 2 data from Study MIV-711-202.  
The change from baseline for visit X will be calculated as the (visit X – baseline visit)-
difference in observed values. Note that the change from baseline will be calculated for 
all visits in study MIV-711-201 and study MIV-711-202 where the actual endpoint has 
been observed, i.e. not only for visits in study MIV-711-202 succeeding the baseline 
visit.  
All safety summary tables will be based on the SAF population.  
Descriptive summaries for safety will be presented by study group and visit, as 
appropriate. 


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9.1
Adverse Events 
All AEs reported will be coded and classified according to MedDRA version 18.1.   
A treatment-emergent AE (TEAE) will be defined as an AE that begins or that worsens in  
severity after IMP has been administered. 
Non-treatment emergent adverse events (NTEAE): AEs that occurred before the 
administration of IMP and did not worsen in severity or relationship after exposure to 
IMP. 
All AE data as captured on the CRF for MIV-711-202 study will be listed by patient. All 
AEs from MIV-711-201 study for those patients admitted into the MIV-711-202 study 
will also be listed. All serious AEs (SAEs) will be listed. A listing of all AEs leading to 
treatment discontinuation will be presented.  
Unless specified otherwise, all adverse event summaries will include the TEAEs only and 
adverse event summary counts of AEs will be the number of patients reporting adverse 
events and not the number of events reported. The number and percentage of patients 
with adverse events will be tabulated by body system (SOC) and preferred term (PT) for 
each group (A, B) and study (MIV-711-201, MIV-711-202). A patient with multiple 
adverse events within a body system is only counted once towards the total of that body 
system.  If the same AE (preferred term) is reported several times for the same patient, it 
will only appear once for that specified treatment in the summary tables. 
For patients with multiple adverse events of the same preferred term and of different 
severities, the AE with the highest assessment of severity will be used in the summaries 
presented by severity.   
A general summary of all treatment-emergent adverse events will show the number and 
percentage of patients, as well as the number of events, according to the following 
categories: 
•
All treatment emergent adverse events  
•
‘Related’ treatment emergent adverse events 
•
Mild treatment emergent adverse events 
•
Moderate treatment emergent adverse events 
•
Severe treatment emergent adverse events 
•
Serious treatment emergent adverse events 
•
Treatment emergent adverse events leading to early termination 
•
Deaths 
Other summary tables for adverse events will include: 


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•
Number and Percentage of Patients with Treatment Emergent Adverse Events by 
System Organ Class, and Preferred Term  
•
Number and Percentage of Patients with Treatment Emergent Adverse Events 
‘Related to IMP’ by System Organ Class, Preferred Term, and Severity.  
•
Number and Percentage of Patients with Serious Treatment Emergent Adverse Events 
by System Organ Class, and Preferred Term 
•
Number and Percentage of Patients with Treatment Emergent Adverse Events 
Leading to Discontinuation by System Organ Class, and Preferred Term 
•
Number and Percentage of Patients with Treatment Emergent Adverse Events by  
Preferred Term per Frequency of Occurrence 
All AE summary tables will display the AEs that occurred in both MIV-711-201 and 
MIV-711-202 studies for patients that were dosed in MIV-711-202. For tabulations of 
AEs by study group, any AE that starts on or after administration of the first dose 
received in MIV-711-201 and before the first dose received in MIV-711-202, will be 
assigned to the the 201 study group.  Any AE occurring after the first dose administered 
in MIV-711-202 will be assigned to the 202 study group.  
If a subject has multiple AEs with the same preferred term but occurring after each dose 
administration (MIV-711-201 and MIV-711-202), then one AE will be counted for each 
treatment administration.  Adverse events that emerge in the first treatment period (201) 
and carry over into the next period (202) will be attributed to only the period in which the 
AE emerged (201). Such AEs that carry over into MIV-711-202 will be recorded as part 
of MIV-711-202 medical history.   
9.2
Clinical Safety Laboratory Tests (Hematology, Chemistry, Urinalysis) 
9.2.1 Hematology and Chemistry 
A by-patient listing of all observed chemistry and hematology laboratory data will be 
provided.  Laboratory results outside the normal range will be flagged.  The abnormal 
values will be flagged with ‘L’ (low) for values below the lower limit of the laboratory’s 
normal range or ‘H’ (high) for values above the upper limit of the laboratory’s normal 
range. Abnormal values will be graded as not clinically significant (NCS) or clinically 
significant (CS). Clinically significant laboratory results will be included in the AE 
listings.   
The observed values of all safety laboratory assessments for clinical chemistry and 
hematology will be summarized using descriptive statistics showing the number of 


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observations (n), mean, median, SD, minimum, and maximum value. Table summaries 
will be presented by time point. 
Baseline values for all clinical chemistry and hematology parameters will be categorized 
as being below the normal range (Low), within the normal range (Normal), and above the 
normal range (High).  In addition, the minimum and maximum score over visits post 
baseline will be calculated and categorized into Low, Normal and High. Note that the 
minimum/maximum are taken over visits post the baseline visit, i.e. visits when the 
patients are on 200 mg MIV-711. Shift from baseline tables of the minimum category 
score and the maximum category score will be tabulated displaying frequency counts and 
percentage of patients in each (low, normal, high)-matrix by study group. 
All hematology, chemistry, and coagulation, laboratory parameters noted in Section 4.4.2 
of this SAP will be tabulated.   
9.2.2 Urinalysis 
Urinalysis test results will be listed. All positive findings in the microscopic examination 
will be listed.  
Observations outside the normal range will be flagged.  The abnormal quantitative values 
will be flagged with ‘L’ for values below the lower limit of the laboratory’s normal range, 
‘H’ for values above the upper limit of the laboratory’s normal range, or ‘Ab’ for 
abnormal qualitative test results.  All original and unscheduled assessments will be listed. 
9.3
Vital Signs 
The observed data for blood pressure (systolic and diastolic), heart rate (pulse), pulse 
oximetry, and body temperature will be listed by patient, and time point. Change from 
baseline values for blood pressure (systolic and diastolic), and heart rate (pulse) will be 
derived and listed. The overall qualitative assessment for vital signs will be listed. 
For systolic and diastolic blood pressure and heart rate, the observed values and change 
from baseline data will be summarized by group and time point. Table summaries will 
include descriptive statistics showing the number of observations (n), mean, SD, median, 
minimum, and maximum value. 
Figures of the observed mean response will be used to visualize blood pressure and heart 
rate response by time point. The two study groups will be shown in the same figure. 


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9.4
12-Lead Safety ECG 
Observed quantitative results for RR, PR, QRS, QT, QTcB (corrected QT according to 
Bazett), QTcF (corrected QT according to Fridericia) and heart rate will be listed for each 
patient.  Change from baseline for QT, QTcB, QTcF will be derived and listed. 
The overall qualitative ECG assessment Abnormal NCS, Abnormal CS, and any 
comments will be listed for each patient. 
For QT, QTcB, QTcF the observed and change from baseline data will be summarized by 
study group and time point. Summaries will include tables of descriptive statistics 
showing the number of observations (n), mean, SD, median, minimum, and maximum 
value.  
Figures of the observed mean response will be used to visualize QTcB and QTcF 
response by time point. The two stdy groups will be shown in the same figure.  
The number and percentage of patients having observed QT, QTcB, QTcF values that 
satisfy the following conditions will be summarized by time point and and study group: 
•
≤ 450 msec 
•
450 < to ≤ 480 msec 
•
480 < to ≤ 500 msec 
•
> 500 msec 
The number and percentage of patients having change from baseline QT, QTcB, QTcF 
values that satisfy the following conditions will be presented by time point and study 
group: 
•
≤ 0 msec 
•
> 0 to ≤ 30 msec 
•
> 30 to ≤ 60 msec 
•
> 60 msec 
9.5
Physical Examination and Weight 
All abnormal physical exam findings (pre and post-dose assessments) will be listed. 
Patient weight will be collected and listed. Patient weight data wil be obtained from the 
MIV-711-201 study as weight was not collected in MIV-711-202. 


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9.6
Phone Call to Assess Safety  
Results of this assessment will be listed for each patient and each visit. 


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10.
Reporting Output 
The following details the requirements and specifications for the presentation of the 
tables, figures and listings (TFLs) as set out in the TFL shells. 
The tables, listings, figures and any non-descriptive statistical analysis will be produced 
using Unix SAS Software (Version 9.2 or higher).  The REPORT procedure will be 
used to produce all tables and listings; SAS/GRAPH will be used to produce all figures.   
Tables, listings, and figures will be produced in the order that they appear in the textual 
sections of the plan.  
All tables, listings, and graphs will be produced to landscape orientation using Courier 
New 8pt font and will be incorporated into a MS Word document as a (RTF) rich text file 
(margins: top, left, right, and bottom: 1 inch).  Details are provided below. 
•
A separate RTF document will be created for each table, figure and listing 
individually. 
•
All TFLs will be produced in a landscape format, as far as is feasible. 
•
The standard font size and font type are "8 point", "Courier New" for all TFLs. 
•
Every page of each output will contain a footer indicating the date and time when 
the output was produced. 
•
Page numbering of tables and listings will use the format "Page X of Y". Page 
numbering for figures will be consecutive integers.  
•
The ordering of visits will be chronological  
•
Footnotes are left justified. 


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11.
Summary Tables 
TLF Number
Title
Table 14.1.1 
Patient Disposition – All Enrolled Patients 
Table 14.1.2 
Demographics - Continuous Variables, ITT Population  
Table 14.1.3 
Demographics - Categorical Variables, ITT Population  
Table 14.1.4 
Prior Medications, ITT Population  
Table 14.1.5 
Concomitant Medications, ITT Population  
Table 14.1.6 
Flagged Prior Medications, ITT Population  
Table 14.1.7 
Flagged Medical History, ITT Population  
Table 14.1.8 
Dose Administration - Number and Percentage of Patients Who Received IMP by 
Visit, PPS Population 
Table 14.1.9 
Dose Administration – Summary of Drug Compliance, PPS Population  
Pharmacodynamics 
Table 14.2.1.1 
Imaging variables - MRI of Bone Area for the Target Knee Observed and Change 
from Baseline Summary, ITT Population  
Table 14.2.1.2 
Imaging variables - MRI of Cartilage Thickness for the Target Knee Observed and 
Change from Baseline Summary, ITT Population  
Table 14.2.1.3 
Imaging variables - MRI of Total BML Volume for the Target Knee Observed and 
Change from Baseline Summary, ITT Population  
Table 14.2.1.4 
Imaging variables - MRI of Bone Area for the Target Knee Observed and Change 
from Baseline Summary, PPS Population  
Table 14.2.1.5 
Imaging variables - MRI of Cartilage Thickness for the Target Knee Observed and 
Change from Baseline Summary, PPS Population  
Table 14.2.1.6 
Imaging variables - MRI of Total BML Volume for the Target Knee Observed and 
Change from Baseline Summary, PPS Population  
Table 14.2.1.7 
Statistical Analysis – MRI of Bone Area for the Target Knee in Patients with 
Moderate Osteoarthritis, ITT Population 
Table 14.2.1.8 
Statistical Analysis - MRI of Cartilage Thickness for the Target Knee in Patients 
with Moderate Osteoarthritis, ITT Population 
Table 14.2.1.9 
Statistical Analysis - MRI of Total BML Volume for the Target Knee in Patients 
with Moderate Osteoarthritis, ITT Population 
Table 14.2.2.1 
Imaging variables - MOAKS Bone Marrow Lesion (BML) and Cyst 
Shift from Baseline to Visit 5 Number of Subregions Impacted by MRI Feature, 
ITT Population 
Table 14.2.2.2 
Imaging variables - MOAKS Cartilage Assessments Size of any Cartilage  
Loss Shift from Baseline to Visit 5 Number of Subregions Impacted by MRI 
Feature, ITT Population 
Table 14.2.2.3 
Imaging variables - MOAKS Cartilage Assessments Percentage of Full Thickness 
Loss Shift from Baseline to Visit 5 Number of Subregions Impacted by MRI 
Feature, ITT Population 
Table 14.2.2.4 
Imaging variables - MOAKS Osteophyte Size Shift from Baseline to Visit 5 
Number of Subregions Impacted by MRI Feature, ITT Population 


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Table 14.2.3.1 
NRS Scores Observed and Change from Baseline Summary, ITT Population 
Table 14.2.3.2 
Statistical Analysis of NRS Scores, ITT Population 
Table 14.2.4.1 
Normalized WOMAC Scores Observed and Change from Baseline Summary - 
ITT Population
Table 14.2.4.2 
Individual WOMAC Scores Observed and Change from Baseline Summary, ITT 
Population 
Table 14.2.4.3 
Statistical Analysis – Normalized WOMAC Scores, ITT Population
Table 14.2.4.4 
Statistical Analysis – WOMAC Pain Score (walking on a flat surface), ITT 
Population 
Table 14.2.5 
EQ-5D-5L Health Rating Score Response Observed and Change from Baseline 
Summary, ITT Population 
Table 14.2.6.1 
E-Diary NRS Scores Observed and Change from Baseline Summary, ITT 
Population 
Table 14.2.6.2 
Statistical Analysis of e-diary NRS Assessment, ITT Population  
Table 14.2.6.3 
E-Diary Observed and Change from Baseline Summary of the Percentage of 
‘Yes’ Scores for Analgesic Useage, ITT Population 
Table 14.2.6.4 
E-Diary Pain Medication Usage Over Last 12 Hours Number and Percentage of 
Patients with each Reported Severity Category, ITT Population 
Table 14.2.7.1 
Efficacy Biomarkers from Serum and Urine Samples - Summary of Observed 
and Change from Baseline Values, ITT Population
Table 14.2.7.2 
Time-Integrated Concentrations (TIC) and Their Z-scores for Efficacy  
Biomarkers from Serum and Urine Samples Summary of Observed Values 
ITT Population 
Table 14.2.7.3 
Statistical Analysis – Efficacy Biomarkers from Serum CIX-I and Urine CIX-II
Samples, ITT Population 
Table 14.2.8.1 
Brief Medication Questionnaire - Number and Percentage of Patients with each 
Medication Used by Visit and Group, ITT Population 
Table 14.2.8.2 
Brief Medication Questionnaire - Number and Percentage of Patients with each 
Indication by Visit and Group, ITT Population  
Table 14.2.8.3 
Brief Medication Questionnaire - Number and Percentage of Patients with each 
Medication by Indication, Visit and Group, ITT Population 
Table 14.2.8.4 
Brief Medication Questionnaire Compliance - Number and Percentage of Patients 
Who Missed Taking their Medication by Visit, ITT Population 
Safety  
Table 14.3.1.1 
Summary of Treatment Emergent Adverse Events , SAF Population  
Table 14.3.1.2 
Number and Percentage of  Patients with Treatment Emergent Adverse Events by 
System Organ Class, Preferred Term, and Group, SAF Population  
Table 14.3.1.3 
Number and Percentage of Patients with Treatment Emergent  
Adverse Events ‘Related to IMP’ by System Organ Class,  
Preferred Term, Severity, and Group, SAF Population 
Table 14.3.1.4 
Number and Percentage of  Patients with Serious Treatment Emergent  
Adverse Events by System Organ Class, Preferred Term, and Group, SAF 
Population 
Table 14.3.1.5 
Number and Percentage of Patients with Treatment Emergent Adverse Events 
Leading to Discontinuation by System Organ Class, Preferred Term, and Group, 
SAF Population 


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Table 14.3.1.6 
Number and Percentage of Patients with Treatment Emergent Adverse Events by 
Frequency, Preferred Term, and Group 
Table 14.3.2.1 
Clinical Laboratory Chemistry Summary of Observed Values, SAF Population 
Table 14.3.2.2 
Clinical Laboratory Hematology Summary of Observed Values, SAF Population 
Table 14.3.2.3 
Clinical Laboratory Chemistry – Shift From Baseline to Maximum Value, SAF 
Population  
Table 14.3.2.4 
Clinical Laboratory Chemistry – Shift From Baseline to Minimum Value, SAF 
Population 
Table 14.3.2.5 
Clinical Laboratory Hematology – Shift From Baseline to Maximum Value, SAF 
Population 
Table 14.3.2.6 
Clinical Laboratory Hematology – Shift From Baseline to Minimum Value, SAF 
Population 
Table 14.3.3 
Vital Signs Blood Pressure and Heart Rate Summary of Observed and Change 
from Baseline Values, SAF Population 
Table 14.3.4.1 
12 Lead ECG – Summary of Observed and Change from Baseline Values SAF 
Population 
Table 14.3.4.2 
12-Lead ECG – Categorical Summary of Observed Values, SAF Population  
Table 14.3.4.3 
12-Lead ECG – Categorical Summary of Change From Baseline, SAF Population  


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12.
Figures 
TLF Number 
Title 
Figure 14.2.1.1 
Estimated Mean ± 95% CI for MRI of Bone Area by Week and Group, ITT 
Population  
Figure 14.2.1.2 
Estimated Mean ± 95% CI for MRI of Cartilage Thickness by Week and 
Group, ITT Population 
Figure 14.2.1.3 
Estimated Mean ± 95% CI for MRI of Total BML Volume by Week and 
Group, ITT Population 
Figure 14.2.1.4 
Estimated change from Visit 2 MIV-711-201 ± 95% for MRI of Bone Area 
by Week and Group, ITT Population 
Figure 14.2.1.5 
Estimated change from Visit 2 MIV-711-201 ± 95% for Cartilage Thickness 
by by Week and Group, ITT Population 
Figure 14.2.1.6 
Estimated change from Visit 2 MIV-711-201 ± 95% for MRI of Total BML 
Volume by Week and Group, ITT Population 
Figure 14.2.1.7 
Estimated change from Visit 2 MIV-711-201 ± 95% for MRI of Bone Area 
by Week and Group, PPS Population 
Figure 14.2.1.8 
Estimated change from Visit 2 MIV-711-201 ± 95% for Cartilage Thickness 
by Week and Group, PPS Population 
Figure 14.2.1.9 
Estimated change from Visit 2 MIV-711-201 ± 95% for MRI of Total BML 
Volume by Week and Group, PPS Population  
Figure 14.2.3.1 
Estimated Mean ± 95% CI for NRS Items by Week and Group,  ITT 
Population 
Figure 14.2.3.2 
Estimated change from visit 2 MIV-711-201 ± 95% CI for NRS Items by 
Week and Group, ITT Population 
Figure 14.2.4.1 
Estimated Mean ± 95% CI for WOMAC Items by Week and Group, ITT 
Population 
Figure 14.2.4.2 
Estimated change from visit 2 MIV-711-201 ± 95% CI for WOMAC Items 
by Week and Group, ITT Population 
Figure 14.2.4.3 
Estimated Mean ± 95% CI for Normalized WOMAC Scores by Week and 
Group, ITT Population 
Figure 14.2.4.4 
Estimated change from visit 2 MIV-711-201 ± 95% CI for Normalized 
WOMAC Scores by Week and Group, ITT Population 
Figure 14.2.5.1 
Estimated Mean ± 95% CI for NRS E-Diary by Week and Group, ITT 
Population 
Figure 14.2.5.2 
Estimated change from visit 2 MIV-711-201 ± 95% CI for NRS e-diary by 
Week and Group, ITT Population 
Figure 14.2.5.3 
Estimated Mean ± 95% CI for Percentage Score E-Diary Analgesic Usage 
by Week and Group, ITT Population 
Figure 14.2.5.4 
Estimated change from visit 2 MIV-711-201 ± 95% CI for Percentage 
Scores of E-Diary Analgesic Usage by Week and Group, ITT Population 
Figure 14.2.6.1 
Estimated Mean ± 95% CI for Efficacy Biomarkers by Week and Group, 
ITT Population 
Figure 14.2.6.2 
Box Plots of Time Integrated Concentrations and their Z-Scores for Efficacy 
Biomarkers from Serum and Urine Samples by Group, ITT Population  


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Figure 14.2.7.1 
Mean ± 95% CI Profiles of  Observed Systolic Blood Pressure by Week and 
Group, SAF Population 
Figure 14.2.7.2 
Mean ± 95% CI Profiles of  Observed Heart Rate by Week and Group, SAF 
Population 
Figure 14.2.8.1 
Mean (95% CI) Profiles of  Observed QTcB Interval by Week and Group, 
SAF Population 
Figure 14.2.8.2 
Mean (95% CI) Profiles of  Observed QTcF Interval by Week and Group, 
SAF Population 


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13.
Listings 
TLF Number 
Title 
Listing 16.2.1.1 
Patient Disposition 
Listing 16.2.1.2 
Patients Excluded from Analysis Populations 
 Listing 16.2.1.3 
 Enrolled Patients Who Did Not Meet All Eligibility Criteria 
Listing 16.2.1.4 
Exclusion Tests  
 Listing 16.2.2.1 
 Protocol Deviations  
Listing 16.2.4.1 
Demographics 
Listing 16.2.4.2 
Medical History  
Listing 16.2.5.1 
Prior and Concomitant Medications 
Listing 16.2.5.2 
Dose Administration at Clinic Visits 
Listing 16.2.5.3 
Dose Administration Compliance, ITT Population 
Listing 16.2.5.4 
Dose Administration Overall Compliance at Visit 5, ITT Population 
Listing 16.2.6.1 
Numerical Rating Scale of Knee Pain 
Listing 16.2.6.2 
Numerical Rating Scale of Knee Pain Change From Baseline 
Listing 16.2.6.3 
Imaging Results Imorphics - MRI of Bone Area for the Target Knee, 
Observed and Change from Baseline 
Listing 16.2.6.4 
Imaging Results Imorphics - MRI of Cartilage Thickness for the Target 
Knee, Observed and Change from Baseline 
Listing 16.2.6.5 
Imaging Results Imorphics – Total BML Volume 
Observed and Change from Baseline 
Listing 16.2.6.7.1 
Other Imaging variables - Imorphics Bone Area 
Listing 16.2.6.7.2 
Other Imaging variables - Imorphics Bone 3D Shape 
Listing 16.2.6.7.3
Other Imaging variables - Imorphics Cartilage Thickness 
Listing 16.2.6.7.4
Other Imaging variables - Imorphics Cartilage Denudation 
Listing 16.2.6.7.5
Other Imaging variables - Imorphics Cartilage Reference Bone Area 
Listing 16.2.6.7.6
Other Imaging variables - Imorphics BML volume 
Listing 16.2.6.7.7
Other Imaging variables - Imorphics Combined 
Listing 16.2.6.8.1 
Other Imaging variables - MOAKS Bone Marrow Lesion (BML) and Cyst  
Listing 16.2.6.8.2 
Other Imaging variables - MOAKS Cartilage Assessments  
Listing 16.2.6.8.3 
Other Imaging variables - MOAKS Hoffa-Synovitis/Effusion-Synovitis  
Listing 16.2.6.8.4 
Other Imaging variables - MOAKS Ligament Assessments  
Listing 16.2.6.8.5 
Other Imaging variables - MOAKS Meniscus  
Listing 16.2.6.8.6 
Other Imaging variables - MOAKS Osteophytes Assessments  
Listing 16.2.6.8.7 
Other Imaging variables - MOAKS Periarticular Features  
Listing 16.2.6.9 
Observed Raw ICOAP Scores 
Listing 16.2.6.10 
Transformed ICOAP Scores
Listing 16.2.6.11 
Western Ontario and McMaster Index (WOMAC)  - Pain Questions  
Listing 16.2.6.12 
Western Ontario and McMaster Index (WOMAC) -  Stiffness Questions 
Listing 16.2.6.13 
Western Ontario and McMaster Index (WOMAC) - Difficulty Questions 
Listing 16.2.6.14 
Western Ontario and McMaster Index (WOMAC) Derived Scores and 
Change from Baseline
Listing 16.2.6.15 
OARSI-OMERACT Responder Index  


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Listing 16.2.6.16 
OARSI-OMERACT Responder Index  
Change from Baseline and Percentage Change from Baseline Scores 
Listing 16.2.6.17 
Global Improvements
Listing 16.2.6.18 
Quality of Life Patient Reported Outcomes - EQ-5D-5L  
Listing 16.2.6.19 
Quality of Life Patient Reported Outcomes Change from Baseline Scores - 
EQ-5D-5L  
Listing 16.2.6.20 
Brief Medication Questionnaire 
Listing 16.2.6.21 
E-Diary Assessments over the Last 12 Hours 
Listing 16.2.6.22 
E-Diary Assessments – Derived Results for each Study Visit 
Listing 16.2.6.23 
Efficacy Biomarkers from Serum and Urine Samples 
Listing 16.2.6.24 
Time-Integrated Concentrations (TIC) and Their Z-scores  
for Efficacy Biomarkers from Serum and Urine Samples 
Listing 16.2.7.1 
Adverse Events 
Listing 16.2.7.2 
Serious Adverse Events 
Listing 16.2.7.3 
Adverse Events Leading to Discontinuation 
Listing 16.2.8.1 
Clinical Laboratory Chemistry – Observed Values 
Listing 16.2.8.2 
Clinical Laboratory Hematology – Observed Values 
Listing 16.2.8.3 
Clinical Laboratory Urinalysis – Observed Values 
Listing 16.2.8.4 
Clinical Laboratory Urinalysis – Positive Microscopic Findings 
Listing 16.2.8.5 
Vital Signs Observed Values 
Listing 16.2.8.6 
Vital Signs Change from Baseline 
Listing 16.2.8.7 
Vital Signs Overall Qualitative Results Abnormal Assessments 
Listing 16.2.8.8 
12 Lead ECG Quantitative Findings 
Listing 16.2.8.9 
12 Lead ECG Change From Baseline 
Listing 16.2.8.10 
12 Lead ECG Overall Qualitative Assessment 
Listing 16.2.8.11 
Physical Examination Abnormal Findings 
Listing 16.2.8.12 
Phone Call to Assess Safety 


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14.
Table Shells 


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Protocol Number: MIV-711-202 
Table 14.1.1 
Patient Disposition  
All Enrolled Patients 
Group A 
N = x 
Group B 
N = x 
Number Patients Enrolled 
nn (nn.n%) 
nn (nn.n%) 
Completed Study 
nn (nn.n%) 
nn (nn.n%) 
Discontinued from Study 
nn (nn.n%) 
nn (nn.n%) 
Number Patients in ITT 
nn (nn.n%) 
nn (nn.n%) 
Number Patients in PPS 
nn (nn.n%) 
nn (nn.n%) 
Number Patients in SAF 
nn (nn.n%) 
nn (nn.n%) 
Reason for Discontinuation 
Adverse Event  
nn (nn.n%) 
nn (nn.n%) 
Protocol Deviation 
nn (nn.n%) 
nn (nn.n%) 
Consent Withdrawn  
nn (nn.n%) 
nn (nn.n%) 
Lost to Follow-Up 
nn (nn.n%) 
nn (nn.n%) 
Death 
nn (nn.n%) 
nn (nn.n%) 
Other 
nn (nn.n%) 
nn (nn.n%) 


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Table 14.1.2 
Demographics – Continuous Variables 
ITT Population 
Statistic 
Group A 
N = x 
Group B 
N = x 
Age 
(years) 
n 
nn 
nn 
Mean 
xx.x
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
Height 
(cm) 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
Weight 
(kg) 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
BMI 
(kg/m^2) 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 


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Table 14.1.3 
Demographics – Categorical Variables 
ITT Population 
Group A 
N = x 
Group B 
N = x 
Ethnicity 
Hispanic/Latino 
nn (nn.n%) 
nn (nn.n%) 
   Non-Hispanic/Latino 
nn (nn.n%) 
nn (nn.n%) 
Race 
White  
nn (nn.n%) 
nn (nn.n%) 
American Indian/Alaska Native 
nn (nn.n%) 
nn (nn.n%) 
Asian 
nn (nn.n%) 
nn (nn.n%) 
Native Hawaiian or other Pacific Islander 
nn (nn.n%) 
nn (nn.n%) 
Black/African American 
nn (nn.n%) 
nn (nn.n%) 
Other 
nn (nn.n%) 
nn (nn.n%) 
Gender 
Female 
nn (nn.n%) 
nn (nn.n%) 
Male 
nn (nn.n%) 
nn (nn.n%) 


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Table 14.1.4 
Prior Medications  
ITT Population 
ATC Level 1  
     ACT Level 3 
Group A 
N = x 
Group B 
N = x 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


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Table 14.1.5 
Concomitant Medications  
ITT Population 
ATC Level 1  
     ACT Level 3 
Group A 
N = x 
Group B 
N = x 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


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Table 14.1.6 
Flagged Prior Medications  
ITT Population 
Prior Medications starting after Visit 2 in MIV-711-201 
ATC Level 1  
     ACT Level 3 
Group A 
N = x 
Group B 
N = x 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Programming note: table will be expanded to include flagging for: Prior Medications ongoing after Visit 1 in MIV-711-202  


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Table 14.1.7 
Flagged Medical History  
ITT Population 
AEs ongoing during the rollover from MIV-711-201 
System Organ Class  
     Preferred Term 
Group A 
N = x 
Group B 
N = x 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


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Table 14.1.8 
Dose Administration - Number and Percentage of Patients Who Received IMP by Visit 
PPS Population 
Visit 
Group A 
N = x 
Group B 
N = x 
VISIT 2 BASELINE DAY 1 
nn (nn.n%) 
nn (nn.n%) 
VISIT 4 WEEK 14 
nn (nn.n%) 
nn (nn.n%) 
Etc… 
Summary table will include dose administration data only for MIV-711-202 assessment times. 


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Table 14.1.9 
Dose Administration - Summary of Drug Compliance  
PPS Population 
Withdrawn patients are not included in the summary 
Summary table will include dose administration data only for MIV-711-202 assessment times. 
Statistic 
Group A 
N = x 
Group B 
N = x 
Total 
Planned 
Number of 
Days IMP 
exposure 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
Total 
Actual 
Number of 
Capsules  
used 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
Overall 
IMP  
SD 
xx.xx 
xx.xx 
Compliance Median 
xx.x 
xx.x 
(%) 
Min 
xx 
xx 
Max 
xx 
xx 


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Table 14.2.1.1 
Imaging variables - MRI of Bone Area for the Target Knee Observed and Change from Baseline Summary  
ITT Population 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2 
MIV-711-201 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
Visit 8 
MIV-711-201 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
Visit 5 
MIV-711-202 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
Programming note: source data obtained from MF_TAB: Area of bone in the medial femur region, MF 
Similar table will be provided for PPS population: 
Table 14.2.1.4 Imaging variables - MRI of Bone Area for the Target Knee Observed and Change from Baseline Summary, PPS Population 


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Table 14.2.1.2 
Imaging variables – MRI of Cartilage Thickness for the Target Knee Observed and Change from Baseline Summary  
ITT Population 
Parameter = Femur Region 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2 
MIV-711-201 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
Visit 8 
MIV-711-201 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
Visit 5 
MIV-711-202 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
Programming note: source data obtained from: 
•
CM_FEMUR_THCTAB: Average thickness of cartilage in the central medial femur region 
•
CM_TIBIA_THCTAB: Average thickness of cartilage in the central medial tibia region 
Similar table will be created for PPS population: 
Table 14.2.1.5 Imaging variables – MRI of Cartilage Thickness for the Target Knee Observed and Change from Baseline Summary  
PPS Population 


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Table 14.2.1.3 
Imaging variables – MRI of Total BML Volume for the Target Knee Observed and Change from Baseline Summary  
ITT Population 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2 
MIV-711-201 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
Visit 8 
MIV-711-201 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
Visit 5 
MIV-711-202 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
Programming note: source data obtained from: TOTAL_BML_VOLUME 
Similar table will be created for PPS population: 
Table 14.2.1.6 Imaging variables – MRI of Total BML Volume for the Target Knee Observed and Change from Baseline Summary  
PPS Population 


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Table 14.2.1.7 
Statistical Analysis – MRI of Bone Area for the Target Knee in Patients with Moderate Osteoarthritis
ITT Population  
Endpoint 
Group 
Week 
N 
Estimated Mean Level 
Estimated Change from Visit 2 
Study MIV-711-201 
LS  
Mean 
95% CI 
LS Mean 
Difference from V2 
MIV-711-201 
95% CI 
xxxxx 
A 
1 (V2: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
1 (V2: 201) 
nn  
xx.xx 
(x.xx, x.xx) 
B 
26 (V8: 201) nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
LS Mean = least squares mean, N denotes the number of Patients for each level of treatment used to estimate the LS means. 
Programming note: source data obtained from MF_TAB: Area of bone in the medial femur region, MF 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 77 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.1.8 
Statistical Analysis - MRI of Cartilage Thickness for the Target Knee in Patients with Moderate Osteoarthritis
ITT Population 
                                    Parameter = Average thickness of cartilage in the central medial femur region 
Endpoint 
Group 
Week 
N 
Estimated Mean Level 
Estimated Change from Visit 2 
Study MIV-711-201 
LS  
Mean 
95% CI 
LS Mean 
Difference from V2 
MIV-711-201 
95% CI 
xxxxx 
A 
1 (V2: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
1 (V2: 201) 
nn  
xx.xx 
(x.xx, x.xx) 
B 
26 (V8: 201) nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
LS Mean = least squares mean, N denotes the number of Patients for each level of treatment used to estimate the LS means. 
Programming note: source data obtained from: 
•
CM_FEMUR_THCTAB: Average thickness of cartilage in the central medial femur region 
•
CM_TIBIA_THCTAB: Average thickness of cartilage in the central medial tibia region 
Table will include results for both femur region and tibia region


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 78 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.1.9 
Statistical Analysis - MRI of Total BML Volume for the Target Knee in Patients with Moderate Osteoarthritis
ITT Population 
Endpoint 
Group 
Week 
N 
Estimated Mean Level 
Estimated Change from Visit 2 
Study MIV-711-201 
LS  
Mean 
95% CI 
LS Mean 
Difference from V2 
MIV-711-201 
95% CI 
xxxxx 
A 
1 (V2: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
1 (V2: 201) 
nn  
xx.xx 
(x.xx, x.xx) 
B 
26 (V8: 201) nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
LS Mean = least squares mean, N denotes the number of Patients for each level of treatment used to estimate the LS means. 
Programming note: source data obtained from: TOTAL_BML_VOLUME 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 79 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.2.1 
Imaging variables - MOAKS Bone Marrow Lesion (BML) and Cyst 
Shift from Baseline to Visit 5 Number of Subregions Impacted by MRI Feature, ITT Population 
MOAKS Test/Examination Name = Number of BMLs 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
[1] for each examination test, the summary will consider all possible subregions associated with BML and Cyst. Maximum number of subregions is 
15. In this analysis a subregion is said to be affected by a BML if the MRI score > 0. A subregion is not affected by any BML if that subregion 
is scored as 0. 
Programming note: table will include summaries for each MOAKS test: Number of BMLs, Size of BML, % that is BML.  
Follow-up data will be excluded from all MOAKs table summaries. 
Group 
Number of 
subregions 
affected 
Baseline 
0 
1 
2 
3 
4 
5+ 
  A 
N = x 
   0 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
   1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
   2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
4 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
5+ 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  B 
N = x  
     0 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
     1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  4 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  5+ 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 80 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.2.2 
Imaging variables - MOAKS Cartilage Assessments Size of any cartilage loss
Shift from Baseline to Visit 5 Number of Subregions Impacted by MRI Feature, ITT Population 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
[1] for each examination test, the summary will consider all possible subregions associated with Cartilage Assessment. Maximum number of 
subregions is 14. In this analysis a subregion is said to be affected by cartilage if the MRI score > 0. A subregion is not affected by cartilage 
if that subregion is scored as 0. 
Group 
Number of 
subregions 
affected 
[1] 
Baseline 
0 
1 
2 
3 
4 
5 
6 
7 
8+ 
  A 
N = x 
0 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
4 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
5 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
6 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
7 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
8+ 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  B 
N = x 
0 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
4 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
5 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
6 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
7 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
8+ 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 81 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Programming note: Similar table will be created:  
Table 14.2.2.3 Imaging variables - MOAKS Cartilage Assessments Percentage of Full Thickness Loss Shift from Baseline to Visit 5 Number of 
Subregions Impacted by MRI Feature, ITT Population 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 82 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.2.4 
Imaging variables - MOAKS Osteophyte Size 
Shift from Baseline to Visit 5 Number of Subregions Impacted by MRI Feature, ITT Population 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
[1] the summary will consider all possible subregions associated with osteophyte assessment. Maximum number of subregions is 12. In this analysis 
a subregion is said to be affected by an osteophyte if the MRI score > 0. A subregion is not affected by an osteophyte if that subregion is 
scored as 0. 
Group 
Number of 
subregions 
affected 
[1] 
Baseline 
0 
1-3 
4-5 
6 
7 
8 
9 
10 
11 
12 
A 
0 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
1-3 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
4-5 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
6 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
7 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
8 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
9 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
10 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
11 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
12 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
B 
0 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
1-3 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
4-5 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
6 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
7 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
8 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
9 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
10 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
11 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
12 
nn (nn.n%) nn (nn.n%) nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 83 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.3.1 
NRS Scores Observed and Change from Baseline Summary 
ITT Population 
Parameter = How Active the target knee arthritis has been 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2  
MIV-711-
201  
DAY 1 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
VISIT 5  
MIV-711-
201 
WEEK 8 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 6  
MIV-711-
201  
WEEK 14 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 8 
MIV-711-
201 
WEEK 26  
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 84 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.3.1 
NRS Scores Observed and Change from Baseline Summary 
ITT Population 
Parameter = How Active the target knee arthritis has been 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
VISIT 4 
MIV-711-
202 
WEEK 40  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 5  
MIV-711-
202 
WEEK 52 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
Programming note: table will include summaries for following other NRS scores: 
•
Amount of pain severity in the target knee last week (SDTM: Overall pain severity in target knee 
•
Global Assessment Score: How active has the target knee arthritis has been in the past week (SDTM: How active was target knee arthritis) 
•
Satisfaction with target knee function (SDTM:How satisfied are you with target knee function) 
•
Worst pain severity in target knee (SDTM: Worst pain severity in target knee) 
•
Overall pain severity in other knee (SDTM: Overall pain severity in other knee) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 85 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.3.2 
Statistical Analysis of NRS Scores, ITT Population  
Endpoint 
Group 
Week 
N 
Estimated Mean Level 
Estimated Change from Visit 2 
Study MIV-711-201 
LS  
Mean 
95% CI 
LS Mean 
Difference from V2 
MIV-711-201 
95% CI 
xxxxx 
A 
1 (V2: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
8 (V5: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
B 
1 (V2: 201) 
nn  
xx.xx 
(x.xx, x.xx) 
8 (V5: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
LS Mean = least squares mean, N denotes the number of Patients for each level of treatment used to estimate the LS means. 
Programming notes: 
Low pain scores are associated with a positive outcome (effect of drug).  
For positive study expect large (negative changes) decreases from baseline by the time treatment reaches week 52.    
Table will be expanded to include the analysis of the following NRS scores:  
•
Amount of Pain severity in the Target Knee Last Week 
•
Global Assessment Score: How active has the target knee arthritis has been in the past week (SDTM: How active was target knee arthritis) 
•
Satisfaction with target knee function (SDTM:How satisfied are you with target knee function) 
•
Worst pain severity in target knee (SDTM: Worst pain severity in target knee) 
•
Overall pain severity in other knee (SDTM: Overall pain severity in other knee) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 86 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.4.1 
Normalized WOMAC Scores Observed and Change from Baseline Summary  
ITT Population 
Parameter = Normalized WOMAC Pain Score
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2  
MIV-711-
201  
DAY 1 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
VISIT 5  
MIV-711-
201 
WEEK 8 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 6  
MIV-711-
201  
WEEK 14 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 8 
MIV-711-
201 
WEEK 26  
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 


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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 87 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.4.1 
Normalized WOMAC Scores Observed and Change from Baseline Summary  
ITT Population 
Parameter = Normalized WOMAC Pain Score
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
VISIT 4 
MIV-711-
202 
WEEK 40  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 5  
MIV-711-
202 
WEEK 52 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
Normalized WOMAC PAIN Score = Total_WOMAC_Pain_50 x 2. 
Normalized WOMAC Function Score = Total_WOMAC_Func_170 ÷ 1.7. 
Normalized WOMAC stiffness Score = Total_WOMAC_stiff_20 x5. 
Programming note: table will be expanded to include all Normalized WOMAC Pain scores, Normalized WOMAC Function score, Normalized WOMAC Stiffness 
scores 


PAREXEL International 
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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 88 of 183 
Medivir 
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Protocol Number: MIV-711-202 
Programming note: similar table will be provided for the individual WOMAC scores 
Table 14.2.4.2 Individual WOMAC Scores Observed and Change from Baseline Summary, ITT Population 


PAREXEL International 
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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 89 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.4.3 
Statistical Analysis – Normalized WOMAC Scores, ITT Population 
Parameter 
Group 
Week 
N 
Estimated Mean Level 
Estimated Change from Visit 2 
Study MIV-711-201 
LS  
Mean 
95% CI 
LS Mean 
Difference from V2 
MIV-711-201 
95% CI 
A 
1 (V2: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
8 (V5: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
Pain Scores 
B 
1 (V2: 201) 
nn  
xx.xx 
(x.xx, x.xx) 
8 (V5: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
LS Mean = least squares mean, N denotes the number of Patients for each level of treatment used to estimate the LS means. 
Progrmming note: table will be expanded to include Normalized WOMAC stiffness score and normalized WOMAC Difficulty score 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 90 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.4.4 
Statistical Analysis – WOMAC Pain Score (walking on a flat surface), ITT Population 
Endpoint 
Group 
Week 
N 
Estimated Mean Level 
Estimated Change from Visit 2 
Study MIV-711-201 
LS  
Mean 
95% CI 
LS Mean 
Difference from V2 
MIV-711-201 
95% CI 
xxxxx 
A 
1 (V2: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
8 (V5: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
B 
1 (V2: 201) 
nn  
xx.xx 
(x.xx, x.xx) 
8 (V5: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
LS Mean = least squares mean, N denotes the number of Patients for each level of treatment used to estimate the LS means. 


PAREXEL International 
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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 91 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.5 
EQ-5D-5L Health Rating Score Response Observed and Change from Baseline Summary 
ITT Population 
Parameter = Mobility
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2 
MIV-711-201 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
Visit 8 
MIV-711-201 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
Visit 5 
MIV-711-202 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
Programming note: table will be expanded to include all QOL variables:  
Mobility, self-care, usual activity, pain or discomfort, and anxiety or depression, health rating score. 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 92 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.6.1 
E-Diary NRS Scores Observed and Change from Baseline Summary 
ITT Population 
Parameter = How would you rate overall pain severity over last 12 Hours? 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Endpoint 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2  
MIV-711-
201  
DAY 1 
n 
nn 
nn 
nn 
AM Response 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
VISIT 6  
MIV-711-
201  
WEEK 14 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 8 
MIV-711-
201 
WEEK 26 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 93 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.6.1 
E-Diary NRS Scores Observed and Change from Baseline Summary 
ITT Population 
Parameter = How would you rate overall pain severity over last 12 Hours? 
Endpoint 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
VISIT 4 
MIV-711-
202 
WEEK 40  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
AM Response 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 5  
MIV-711-
202 
WEEK 52 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
Programming note: 
Table will be expanded to include the analysis of the following e-diary assessments:  
•
AM assessment 
•
PM assessment 
•
24 Hour Overall Assessment 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 94 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.6.2 
Statistical Analysis of e-diary NRS Assessment, ITT Population 
Endpoint 
Group 
Week 
N 
Estimated Mean Level 
Estimated Change from Visit 2 
Study MIV-711-201 
LS  
Mean 
95% CI 
LS Mean 
Difference from V2 
MIV-711-201 
95% CI 
AM 
Assessment 
A 
1 (V2: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
8 (V5: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
B 
1 (V2: 201) 
nn  
xx.xx 
(x.xx, x.xx) 
8 (V5: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
LS Mean = least squares mean, N denotes the number of Patients for each level of treatment used to estimate the LS means. 
Programming note: 
Table will be expanded to include the PM assessment and 24 Hour Overall Assessment 


PAREXEL International 
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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 95 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.6.3 
E-Diary Observed and Change from Baseline Summary of the Percentage of ‘Yes’ Scores for Analgesic Useage 
ITT Population 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Endpoint 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2  
MIV-711-
201  
DAY 1 
n 
nn 
nn 
nn 
AM Response 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
VISIT 6  
MIV-711-
201  
WEEK 14 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 8 
MIV-711-
201 
WEEK 26 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 96 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.6.4 
E-Diary Observed and Change from Baseline Summary of the Percentage of ‘Yes’ Scores for Analgesic Useage 
ITT Population 
Endpoint 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
VISIT 4 
MIV-711-
202 
WEEK 40  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
AM Response 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 5  
MIV-711-
202 
WEEK 52 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 study for Group A and Group B 
Table summarizes for those patients who responded Yes to the question: “Have you taken any pain medication over the last 12 hours since you last 
answered your OA Daily Diary?“ 
Programming note: 
Table will be expanded to include the analysis of the following e-diary assessments:  
•
AM assessment 
•
PM assessment 
•
24 Hour Overall Assessment 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 97 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.6.65 
E-Diary Pain Medication Usage Over Last 12 Hours  
Number and Percentage of Patients with each Reported Severity Category 
ITT Population 
Endpoint 
Visit 
 Category 
Group A 
N = x 
Group B 
N = x 
Number of Patients [1] 
nn 
nn 
AM Assessment 
Visit 2  
MIV-711-201  
DAY 1 
Less than Normal
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
More than Normal
nn (nn.n%) 
nn (nn.n%) 
Number of Patients [1]
nn 
nn 
VISIT 6  
MIV-711-201  
WEEK 14 
Less than Normal
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
More than Normal
nn (nn.n%) 
nn (nn.n%) 
Number of Patients [1]
nn 
nn 
VISIT 8 
MIV-711-201 
WEEK 26 
Less than Normal
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
More than Normal
nn (nn.n%) 
nn (nn.n%) 
Number of Patients [1]
nn 
nn 
VISIT 4 
MIV-711-202 
WEEK 40 
Less than Normal
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
More than Normal
nn (nn.n%) 
nn (nn.n%) 
Number of Patients [1]
nn 
nn 
VISIT 5  
MIV-711-202 
WEEK 52 
Less than Normal
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
More than Normal
nn (nn.n%) 
nn (nn.n%) 
 [1] indicates the number of patients with a YES response for each combination of visit and group 
Programming note: 
Table will be expanded to include the analysis of the following e-diary assessments:  
•
AM assessment 
•
PM assessment 
•
24 Hour Overall Assessment 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 


PAREXEL International 
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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 98 of 183 
Table 14.2.7.1 
Efficacy Biomarkers from Serum and Urine Samples - Summary of Observed and Change from Baseline Values 
ITT Population 
Parameter = Serum CTX-I 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
AM/PM 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
Visit 2  
MIV-711-
201  
DAY 1 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
VISIT 4  
MIV-711-
201  
WEEK 4 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 6  
MIV-711-
201  
WEEK 14 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Etc.... 
 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group, Visit 2 in the MIV-711-202 for Group B 
Programming note: table will include parameters Serum CTX-I and urine CIX-II


PAREXEL International 
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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 99 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.7.1 
Efficacy Biomarkers from Serum and Urine Samples - Summary of Observed and Change from Baseline Values 
ITT Population 
Parameter = Serum CTX-I 
AM/PM 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x 
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
VISIT 8 
MIV-711-
201 
WEEK 26  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
AM Response 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 2  
MIV-711-
202  
WEEK 27 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
n 
nn 
nn 
nn 
nn 
VISIT 4  
MIV-711-
202  
WEEK 40 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 5  
MIV-711-
202  
WEEK 52 
n 
nn 
nn 
nn 
Nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B 
Programming note: table will include parameters Serum CTX-I and urine CIX-II 


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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 100 of 183 
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Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.7.2 
Time-Integrated Concentrations (TIC) and Their Z-scores for Efficacy Biomarkers from Serum and Urine Samples 
Summary of Observed Values 
ITT Population 
Parameter = TIC Serum CTX-I 
Statistic 
Group A 
N = x 
Group B 
N = x  
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
Programming note: table will include parameters TIC Serum CTX-I, TIC urine CIX-II, Z-Score Serum CTX-I, Z-Score urine CIX-II  


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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
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                                                                                                                                                                                                                Page 101 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.7.3 
Statistical Analysis – Efficacy Biomarkers from Serum CIX-I and Urine CIX-II Samples, ITT Population 
Parameter 
Group 
Week 
N 
Estimated Mean Level 
Estimated Change from Visit 2 
Study MIV-711-201 
LS  
Mean 
95% CI 
LS Mean 
Difference from V2 
MIV-711-201 
95% CI 
A 
1 (V2: 201) 
nn 
xx.xx 
(x.xx, x.xx) 
4 (V4: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
Serum CIX-I
26 (V2: 202) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) 
nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
B 
1 (V2: 201) 
nn  
xx.xx 
(x.xx, x.xx) 
4 (V4: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
14 (V6: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V8: 201 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
26 (V2: 202) 
nn  
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
40 (V4: 202) nn 
xx.xx 
(x.xx, x.xx) 
xx.xx 
(x.xx, x.xx) 
52 (V5: 202) 
nn 
xx.xx 
(xx.x, xx.x) 
xx.xx 
(x.xx, x.xx) 
Etc… 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B 
LS Mean = least squares mean, N denotes the number of Patients for each level of treatment used to estimate the LS means. 
Programming note: table will be expanded to include urine CIX-II 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 102 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.8.1 
Brief Medication Questionnaire - Number and Percentage of Patients with each Medication Used by Visit  
ITT Population 
Table is sorted by descending frequency count of medication. 
Medication 
Visit 
Group A 
N = x 
Group B 
N = x  
Medication 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Medication 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Etc.. 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 103 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.8.2 
Brief Medication Questionnaire - Number and Percentage of Patients with each Indication by Visit   
ITT Population 
Table is sorted by descending frequency count of indication 
Indication 
Visit 
Group A 
N = x 
Group B 
N = x  
Indication 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Indication 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Etc.. 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 104 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.8.3 
Brief Medication Questionnaire - Number and Percentage of Patients with each Medication by Indication and Visit  
PPS Population 
Medication 
Visit 
Group A 
N = x 
Group B 
N = x  
Indication 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
 Indication 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Etc.. 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 105 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.2.8.4 
Brief Medication Questionnaire – Compliance 
Number and Percentage of Patients Who Missed Taking their Medication by Visit  
ITT Population 
Medication Name 
How many times did you 
miss taking it? 
Visit 
Group A 
N = x 
Group B 
N = x  
0 
1 
2 
3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Etc.. 


PAREXEL International 
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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 106 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.1.1 
Summary of Treatment Emergent Adverse Events   
SAF Population 
MIV-711-201 
MIV-711-202 
Group A 
26 weeks 
N = x 
Group B 
26 weeks 
N = x 
Overall 
N = x  
Group A 
26 weeks 
N = x 
Group B  
26 weeks  
N = x  
Overall 
N = x 
All AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
‘Related’ AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Mild AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Moderate AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Severe AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Deaths 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
Serious AEs 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
AEs Leading to early discontinuation from study 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
nn (nn.n%) E 
TEAE = Treatment Emergent Adverse Event  
nn = Number of Patientswith TEAEs 
N  = Number of PatientsExposed  
(nn.n%) = nn/N x 100 
E = Number of AEs 


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Protocol: MIV-711-202 
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                                                16 January 2018 
                                                                                                                                                                                                                Page 107 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.1.2 
Number and Percentage of Patients with Treatment Emergent Adverse Events 
by System Organ Class, Preferred Term, and Group  
SAF Population 
System Organ Class 
   Preferred Term 
MIV-711-201 
MIV-711-202 
Group A 
26 weeks 
N = x 
Group B 
26 weeks 
N = x 
Overall 
N = x  
Group A 
26 weeks 
N = x 
Group B  
26 weeks  
N = x  
Overall 
N = x 
System Organ Class 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
System Organ Class 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 108 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.1.3 
Number and Percentage of Patients with Treatment Emergent Adverse Events ‘Related to IMP’ 
by System Organ Class, Preferred Term, Severity, and Group  
SAF Population 
For patients with multiple adverse events of the same preferred term and different severities, the AE with the highest assessment of severity was 
used in the summary table. 
System Organ Class 
   Preferred Term 
Severity 
MIV-711-201 
MIV-711-202 
Group A 
26 weeks 
N = x 
Group B 
26 weeks 
N = x 
Overall 
N = x  
Group A 
26 weeks 
N = x 
Group B  
26 weeks  
N = x  
Overall 
N = x 
System Organ Class 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
System Organ Class 2 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
Mild 
Moderate 
Severe 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 109 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.1.4 
Number and Percentage of Patients with Serious Treatment Emergent Adverse Events 
by System Organ Class, Preferred Term, and Group  
SAF Population 
System Organ Class 
   Preferred Term 
MIV-711-201 
MIV-711-202 
Group A 
26 weeks 
N = x 
Group B 
26 weeks 
N = x 
Overall 
N = x  
Group A 
26 weeks 
N = x 
Group B  
26 weeks  
N = x  
Overall 
N = x 
System Organ Class 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
System Organ Class 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 110 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.1.5 
Number and Percentage of Patients with Treatment Emergent Adverse Events Leading to Discontinuation 
by System Organ Class, Preferred Term, and Group  
SAF Population 
System Organ Class 
   Preferred Term 
MIV-711-201 
MIV-711-202 
Group A 
26 weeks 
N = x 
Group B 
26 weeks 
N = x 
Overall 
N = x  
Group A 
26 weeks 
N = x 
Group B  
26 weeks  
N = x  
Overall 
N = x 
System Organ Class 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
System Organ Class 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 111 of 183 
Medivir 
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.1.6 
Number and Percentage of Patients with Treatment Emergent Adverse Events by Frequency, Preferred Term, and Group  
SAF Population 
   Preferred Term 
MIV-711-201 
MIV-711-202 
Group A 
26 weeks 
N = x 
Group B 
26 weeks 
N = x 
Overall 
N = x  
Group A 
26 weeks 
N = x 
Group B  
26 weeks  
N = x  
Overall 
N = x 
  Preferred Term 1 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 2 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term 3 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
  Preferred Term xx 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 112 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.2.1 
Clinical Laboratory Chemistry - Summary of Observed Values  
SAF Population 
Lab Parameter = Lab Parameter (unit) 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x  
VISIT 1  
MIV-711-
201 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
VISIT 2 
MIV-711-
201 
DAY 1  
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
VISIT 3 
MIV-711-
201 
WEEK 2  
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
Etc… 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B 


PAREXEL International 
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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 113 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.2.2 
Clinical Laboratory Hematology - Summary of Observed Values  
SAF Population 
Lab Parameter = Lab Parameter (unit) 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x  
VISIT 1  
MIV-711-
201 
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
VISIT 2 
MIV-711-
201 
DAY 1  
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
VISIT 3 
MIV-711-
201 
WEEK 2  
n 
nn 
nn 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min 
xx 
xx 
Max 
xx 
xx 
Etc… 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 114 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Table 14.3.2.3 
Clinical Laboratory Chemistry – Shift From Baseline to Maximum Value 
SAF Population 
Lab Parameter = Lab Parameter (unit)
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B 
Note that the maximum is taken over the visits post first MIV-711 dose. Thus, the number of vists the maximum is taken over will not be the same 
for Group A and Group B. 
Group 
Maximum 
Value 
Baseline  
Low 
Normal 
High 
 A 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
B 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


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Table 14.3.2.4 
Clinical Laboratory Chemistry – Shift From Baseline to Minimum Value 
SAF Population 
Lab Parameter = Lab Parameter (unit)
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B 
Note that the minimum is taken over the visits post first MIV-711 dose. 
Thus, the number of vists the minimum is taken over will not be the same for Group A and Group B. 
Group 
Minimum 
Value 
Baseline  
Low 
Normal 
High 
 A 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
B 
Low 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
Normal 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 
High 
nn (nn.n%) 
nn (nn.n%) 
nn (nn.n%) 


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Programming Note: Similar tables will be created for hematology parameters: 
Table 14.3.2.5 Clinical Laboratory Hematology – Shift From Baseline to Maximum Value, SAF Population 
Table 14.3.2.6 Clinical Laboratory Hematology – Shift From Baseline to Minimum Value, SAF Population 


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Table 14.3.3 
Vital Signs Blood Pressure and Heart Rate Summary of Observed and Change from Baseline Values  
SAF Population 
Parameter = Systolic Blood Pressure (mmHg) 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x  
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
VISIT 1  
MIV-711-
201 
SCREENING 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 2 
MIV-711-
201 
DAY 1 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
VISIT 3 
MIV-711-
201 
WEEK 2  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Visit 4 
MIV- 711-
201 
WEEK 3  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Etc… 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B. 
Programming Notes: Table will be expanded to include diastolic blood pressure and heart rate, subject weight. 


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Table 14.3.4.1 
12 Lead ECG – Summary of Observed and Change from Baseline Values 
SAF Population 
Parameter = QT Interval (msec) 
Visit 
Statistic 
Group A 
N = x 
Group B 
N = x  
Observed 
N = x 
Change 
N = x 
Observed 
N = x 
Change 
N = x 
VISIT 1  
MIV-711-
201 
SCREENING 
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
VISIT 2 
MIV-711-
201 
DAY 1 
n 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
VISIT 3 
MIV-711-
201 
WEEK 2  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Visit 4 
MIV- 711-
201 
WEEK 3  
n 
nn 
nn 
nn 
nn 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
Min 
xx 
xx 
xx 
xx 
Max 
xx 
xx 
xx 
xx 
Etc… 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 


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Table 14.3.4.2 
12 Lead ECG – Categorical Summary of Observed Values   
SAF Population 
Parameter = QT (msec) 
Visit 
Category (unit) 
Group A 
N = x 
Group B 
N = x  
VISIT 1  
MIV-711-201 
SCREENING 
≤ 450  
nn (nn.n%) 
nn (nn.n%) 
450 < to ≤ 480 
nn (nn.n%) 
nn (nn.n%) 
480 < to ≤ 500 
nn (nn.n%) 
nn (nn.n%) 
>500 
nn (nn.n%) 
nn (nn.n%) 
VISIT 2 
MIV-711-201 
DAY 1 
≤ 450  
nn (nn.n%) 
nn (nn.n%) 
450 < to ≤ 480 
nn (nn.n%) 
nn (nn.n%) 
480 < to ≤ 500 
nn (nn.n%) 
nn (nn.n%) 
>500 
nn (nn.n%) 
nn (nn.n%) 
VISIT 3 
MIV-711-201 
WEEK 2 
≤ 450  
nn (nn.n%) 
nn (nn.n%) 
450 < to ≤ 480 
nn (nn.n%) 
nn (nn.n%) 
480 < to ≤ 500 
nn (nn.n%) 
nn (nn.n%) 
>500 
nn (nn.n%) 
nn (nn.n%) 
Etc…  
Baseline is defined as: Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 2 in the MIV-711-202 for Group B 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 
Programming note: Table will include: QTcB interval and QTcF interval


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Protocol Number: MIV-711-202 
Table 14.3.4.3 
12 Lead ECG – Categorical Summary of Change from Baseline   
SAF Population 
 Parameter = QT (msec) 
Visit 
Category (unit) 
Group A 
N = x 
Group B 
N = x  
VISIT 1  
MIV-711-201 
SCREENING 
<= 0 
nn (nn.n%) 
nn (nn.n%) 
>0 to ≤ 30  
nn (nn.n%) 
nn (nn.n%) 
>30 to ≤ 60 
nn (nn.n%) 
nn (nn.n%) 
>60 
nn (nn.n%) 
nn (nn.n%) 
VISIT 2 
MIV-711-201 
DAY 1 
<= 0 
nn (nn.n%) 
nn (nn.n%) 
>0 to ≤ 30  
nn (nn.n%) 
nn (nn.n%) 
>30 to ≤ 60 
nn (nn.n%) 
nn (nn.n%) 
>60 
nn (nn.n%) 
nn (nn.n%) 
Etc… 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 
Programming note: Table will include: QTcB interval and QTcF interval


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15.
Listing Shells 


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Listing 16.2.1.1 
Patient Disposition   
     Study Group = Group A 
Patient 
MIV-711-202 
Patient 
MIV-711-201 
Completion Status 
If Discontinued,
Day of 
Withdrawal 
If Discontinued,
Date of 
Withdrawal 
Reason For 
Discontinuation 
Completed  
Discontinued  


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Listing 16.2.1.2 
Patients Excluded from the Analysis Populations 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-711-201 
Population 
Reason for Exclusion 
PPS 
ITT 


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Listing 16.2.1.3 
Enrolled Patients Who Did Not Meet All Eligibility Criteria 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-711-201 
Criteria Category 
Criteria Description 
Response 
Inclusion 
No  
Exclusion 
Yes 


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Listing 16.2.1.4 
Exclusion Tests   
FSH test, Serology, Urine Drug Screen 
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
MIV-711-
201 
Visit 
Collection 
Date 
 Collection 
Time 
Exclusion Test 
Result 
Units 
FSH test 
Etc... 


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Listing 16.2.2.1 
Protocol Deviations  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-711-
201 
Study 
Day 
Time Point 
Date Deviation 
Occurred 
Category 
Explanation 
Classification 
Time Window  
Minor  
Dosing  
Major 
Exclusion Tests 
Major 
Etc… 


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Listing 16.2.4.1  
Demographics  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-711-201 
Gender 
Ethnicity 
Race 
Age 
(yrs) 
Height 
(cm) 
Weight
(kg) 
BMI 
(kg/m^2) 


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Listing 16.2.4.2 
 Medical History   
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
MIV-711-201 
Reported Term 
>MedDRA Preferred 
Term 
>>System Organ 
Class 
Onset 
Date 
Status 
Recovered 
Date 
Currently 
Treated with 
Medication? 
Ongoing 
Yes/No 


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Listing 16.2.5.1 
Prior and Concomitant Medications   
Study Group = Group A 
Patient 
MIV-
711-202 
Patient 
MIV-711-201 
Medication 
Name 
>WHO Drug Name 
>>ATC 
Classification 
>>>ATC Code 
>>>>ATC 
Dictionary 
Text 
Category 
Start 
Date 
Stop
Date 
Ongoing? 
Dose/ 
Unit 
Frequency Route Indication 
Was 
There
an AE 
Pain 
Medication 
Prior  
 
Yes/No 
 
Yes/No 
CM 
Programming note: Pain Medication = ‘Yes’ if ATC = ‘ANALGESICS’


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Listing 16.2.5.2 
Dose Administration at Clinic Visits  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-711-
201 
Visit 
Date of 
Dose 
Time of 
Dose 
Dose Form / 
Route 


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Listing 16.2.5.3 
Dose Administration Compliance, ITT Population 
Study Group = Group A 
Patient 
MIV-
711-202 
Patient 
MIV-
711-201 
Visit 
Date 
of 
Dose 
Dispensed
Amount 
(Capsules) 
Returned 
Amount 
(Capsules) 
Actual 
Number of 
Capsules 
Used 
Were all 
unused 
Capsules 
returned? 
Reason 
not all 
unused 
Capsules 
returned 
Medication 
error 
Number 
of 
Actual 
Days 
exposed 
to IMP 
The ‘actual number of capsules used’ was derived as the ‘number of capsules dispensed’ minus the ‘number of capsules returned’.  
‘Number of actual days exposed to IMP’ is the number of days of actual dose exposure from V2 (first dose) to V5 (last dose), since each patient 
is to receive 1 capsule of dosing per day of dose administration.  
Withdrawn patients are not included in this listing. 


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Listing 16.2.5.4 
Dose Administration Overall Compliance at Visit 5, ITT Population 
Study Group = Group A 
Patient 
MIV-
711-202 
Patient 
MIV-
711-201 
Visit 
Date 
of 
Dose 
Total 
Dispensed
Amount 
(Capsules) 
[1] 
Total 
Returned 
Amount 
(Capsules) 
[2] 
Total 
Actual 
Number 
of 
Capsules 
Used 
Total 
Number 
of Days 
exposed 
to IMP 
Overall 
IMP 
Compliance 
[1] obtained as the total number over visits 2, 4. 
[2] obtained as the total number over visits 4, 5. 
The ‘Total actual number of capsules used’ was derived as the ‘Total number of capsules dispensed’ minus the ‘Total number of capsules returned’.  
Overall IMP compliance: (Total actual number of capsules used / Total number of days exposed to IMP) x 100% 
Withdrawn patients are not included in this listing. 


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Protocol Number: MIV-711-202 
Listing 16.2.6.1 
Numerical Rating Scale of Knee Pain (One Week Recall) 
Study Group = Group A 
Patient 
MIV-
711-202 
Patient 
MIV-711-201 
Visit 
Date of 
Assessment 
Target 
Knee 
Used 
for NRS 
Overall
Pain 
Severity
in 
Target 
Knee 
Worst 
Pain 
Severity 
Target 
Knee 
Overall 
Pain 
Severity
in 
Other 
Knee 
Global 
Disease 
Activity 
Satisfied
with 
Target 
Knee 
Function 


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Listing 16.2.6.2 
Numerical Rating Scale of Knee Pain Change From Baseline (One Week Recall) 
Study Group = Group A 
Patient 
MIV-
711-202 
Patient 
MIV-711-201 
Visit 
Date of 
Assessment 
Target 
Knee 
Used 
for NRS 
Overall 
Pain 
Severity 
in 
Target 
Knee 
Worst 
Pain 
Severity
Target 
Knee 
Overall 
Pain 
Severity
in 
Other 
Knee 
Global 
Disease 
Activity 
Satisfied
with 
Target 
Knee 
Function 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 


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Protocol Number: MIV-711-202 
Listing 16.2.6.3 
Imaging Results Imorphics - MRI of Bone Area for the Target Knee  
Observed and Change from Baseline 
Study Group = Group A 
Patient 
MIV-
711-202 
Visit 
Date of 
Assessment 
Area of bone in the 
medial femur region, MF 
Patient 
MIV-711-201 
Score 
Change 
Score 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: source data obtained from Imorphics: Area of bone in the medial femur region, MF (MF_TAB) 


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Listing 16.2.6.4 
Imaging Results Imorphics - MRI of Cartilage Thickness for the Target Knee  
Observed and Change from Baseline 
Study Group = Group A 
Patient 
MIV-
711-202 
Visit 
Date of 
Assessment 
Average thickness of 
cartilage in the 
central medial femur 
region 
Average thickness of 
cartilage in the central 
medial tibia region 
Patient 
MIV-711-201 
Score 
Change 
Score 
Score 
Change 
Score 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: source data obtained from Imorphics variables: 
Average thickness of cartilage in the central medial femur region (CM_FEMUR_THCTAB) 
Average thickness of cartilage in the central medial tibia region (CM_TIBIA_THCTAB) 


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Protocol Number: MIV-711-202 
Listing 16.2.6.5 
Imaging Results Imorphics – Total BML Volume 
Observed and Change from Baseline 
Study Group = Group A 
Patient 
MIV-
711-202 
Visit 
Date of 
Assessment 
Combined volume of all 
BML regions 
Patient 
MIV-711-201 
Score 
Change 
Score 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: source data obtained from Imorphics:  
Combined volume of all BML regions (TOTAL_BML_VOLUME) 


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Listing 16.2.6.7.1 
Other Imaging variables - Imorphics Bone Area 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Imorphics 1 
Imorphics 2 
Imorphics 3 
Imorphics 4 
Score 
Change Score  
Score 
Change 
Score  
Score 
Change 
Score  
Score 
Change 
Score  
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: Imorphics tests will include:  
Area of bone in the lateral femur region, LF (LF_TAB) 
Area of bone in the medial tibia region, MT (MT_TAB) 
Area of bone in the lateral femur region, LT (LT_TAB) 
Area of bone in the medial patella region, MP (MP_TAB) 
Area of bone in the lateral patella region, LP (LP_TAB) 


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Listing 16.2.6.7.2 
Other Imaging variables - Imorphics Bone 3D Shape 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Imorphics 1 
Imorphics 2 
Imorphics 3 
Imorphics 4 
Score 
Change Score  
Score 
Change 
Score  
Score 
Change 
Score  
Score 
Change 
Score  
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: Imorphics tests will include:  
Distance along the femur 3D OA bone shape vector 0 is defined as the mean shape of a population of knees without osteoarthritis, units are 1 
Standard Deviation of population of healthy knees.  Likely range -2 to +8 (FEMUR_3D_VECTOR) 
Distance along the tibia 3D OA bone shape vector (TIBIA_3D_VECTOR) 
Distance along the patella 3D OA bone shape vector (PATELLA_3D_VECTOR) 


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Protocol Number: MIV-711-202 
Listing 16.2.6.7.3 
Other Imaging variables - Imorphics Cartilage Thickness 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Collection 
Date  
Imorphics 1 
Imorphics 2 
Imorphics 3 
Imorphics 4 
Score 
Change Score  
Score 
Change 
Score  
Score 
Change 
Score  
Score 
Change 
Score  
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: Imorphics tests will include:  
Average thickness of cartilage in the central lateral femur region (CL_FEMUR_THCTAB) 
Average thickness of cartilage in the central lateral tibia region (CL_TIBIA_THCTAB) 
Average thickness of cartilage in the trochlear femur region (TR_FEMUR_THCTAB) 
Average thickness of cartilage in the patella region (PATELLA_THCTAB) 


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Listing 16.2.6.7.4 
Other Imaging variables - Imorphics Cartilage Denudation 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Imorphics 1 
Imorphics 2 
Imorphics 3 
Imorphics 4 
Score 
Change Score  
Score 
Change 
Score  
Score 
Change 
Score  
Score 
Change 
Score  
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: Imorphics tests will include:  
Denuded area of cartilage in the central medial femur region (CM_FEMUR_DAB) 
Denuded area of cartilage in the central medial tibia region (CM_TIBIA_DAB) 
Denuded area of cartilage in the central lateral femur region (CL_FEMUR_DAB) 
Denuded area of cartilage in the central lateral tibia region (CL_TIBIA_DAB) 
Denuded area of cartilage in the trochlear femur region (TR_FEMUR_DAB) 
Denuded area of cartilage in the patella (PATELLA_DAB) 


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Protocol Number: MIV-711-202 
Listing 16.2.6.7.5 
Other Imaging variables - Imorphics Cartilage Reference Bone Area 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Collection 
Date  
Imorphics 1 
Imorphics 2 
Imorphics 3 
Imorphics 4 
Score 
Change Score  
Score 
Change 
Score  
Score 
Change 
Score  
Score 
Change 
Score  
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: Imorphics tests will include:  
Total area of the central medial femur region (CM_FEMUR_TAB) 
Total area of the central medial tibial region (CM_TIBIA_TAB) 
Denuded area of cartilage in the central lateral femur region (CL_FEMUR_TAB) 
Total area of the central lateral tibial region (CL_TIBIA_TAB) 
Denuded area of cartilage in the trochlear femur region (TR_FEMUR_TAB) 
Denuded area of cartilage in the patella (PATELLA_TAB) 


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Listing 16.2.6.7.6 
Other Imaging variables - Imorphics BML volume 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Collection 
Date  
Imorphics 1 
Imorphics 2 
Imorphics 3 
Imorphics 4 
Score 
Change Score  
Score 
Change 
Score  
Score 
Change 
Score  
Score 
Change 
Score  
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
Programming note: Imorphics tests will include:  
BML volume in medial femur, MF region (Figure 3) (MF_BML_VOLUME) 
BML volume in lateral femur, LF region (LF_BML_VOLUME) 
BML volume in trochlear femur, TrF region (TRF_BML_VOLUME) 
BML volume in medial tibia, MT region (MT_BML_VOLUME) 
BML volume in lateral tibia, LT region (LT_BML_VOLUME) 
BML volume in patella, P region (P_BML_VOLUME) 


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Listing 16.2.6.7.7 
Other Imaging variables - Imorphics Combined 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Collection 
Date  
Overall Knee Change, 
Compose of 3D Bone 
and Cartilage Thickness 
 Score  
Programming note: Imorphics tests will include:  
Exploratory endpoint representing overall knee change, compose of 3D bone and cartilage thickness (INDEX_BONE_CARTILAGE)


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Protocol Number: MIV-711-202 
Listing 16.2.6.8.1 
Other Imaging variables - MOAKS Bone Marrow Lesion (BML) and Cyst 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Laterality 
of Patient 
Subcategory 
MOAKS Test 1 
MOAKS Test 2 
MOAKS Test 3 
Score 
Score Text 
Score 
Score Text 
Score 
Score Text 
Programming note: MOAKS tests will include:  
Number of BMLs  
% that is BML 
Size of BML


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Protocol Number: MIV-711-202 
Listing 16.2.6.8.2 
Other Imaging variables - MOAKS Cartilage Assessments 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Laterality 
of Patient 
Subcategory 
MOAKS Test 1 
MOAKS Test 2 
Score 
Score Text 
Score 
Score Text 
Programming note: MOAKS tests will include:  
% Full Thickness Loss  
Size of any cartilage loss 


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Protocol Number: MIV-711-202 
Listing 16.2.6.8.3 
Other Imaging variables - MOAKS Hoffa-Synovitis/Effusion-Synovitis 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Collection 
Date  
Laterality 
of Patient 
Subcategory 
MOAKS Test 1 
MOAKS Test 2 
Score 
Score Text 
Score 
Score Text 
Programming note: MOAKS tests will include: Effusion-Synovitis, Hoffa-Synovitis 


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Protocol Number: MIV-711-202 
Listing 16.2.6.8.4 
Other Imaging variables - MOAKS Ligament Assessments 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Laterality 
of Patient 
Subcategory 
MOAKS Test 1 
MOAKS Test 2 
MOAKS Test 3 
Score 
Score Text 
Score 
Score Text 
Score 
Score Text 
Programming note: MOAKS tests will include: ACL Repair, ACL Tears, Assoc wth BML/Cysts at site of insertion, PCL Tears, Patellar Tendon Signal 


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Protocol Number: MIV-711-202 
Listing 16.2.6.8.5 
Other Imaging variables - MOAKS Meniscus 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Laterality 
of Patient 
Subcategory 
MOAKS Test 1 
MOAKS Test 2 
MOAKS Test 3 
Score 
Score Text 
Score 
Score Text 
Score 
Score Text 
Programming note: MOAKS tests will include: Lateral Meniscus: Anterior Extrusion, Lateral Meniscus: Lateral Extrusion, Medial Meniscus: Anterior 
Extrusion, Medial Meniscus: Medial Extrusion, Lateral Meniscus Anterior, Lateral Meniscus Body, Lateral Meniscus Posterior 


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Protocol Number: MIV-711-202 
Listing 16.2.6.8.6 
Other Imaging variables - MOAKS Osteophytes Assessments 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Laterality 
of Patient 
Subcategory 
MOAKS Test 1 
Score 
Score Text 
Programming note: MOAKS tests will include: Osteophyte Size 


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Protocol Number: MIV-711-202 
Listing 16.2.6.8.7 
Other Imaging variables - MOAKS Periarticular Features 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Laterality 
of Patient 
Subcategory 
MOAKS Test 1 
MOAKS Test 2 
MOAKS Test 3 
Score 
Score Text 
Score 
Score Text 
Score 
Score Text 
Programming note: MOAKS tests will include: Ganglion Cysts, Infrapatellar Bursae Signal, Pes Anserine bursitis, Prepatellar Bursae Signal,
Iliotibial Band Signal, Loose Bodies,Popliteal Cyst 


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Protocol Number: MIV-711-202 
Listing 16.2.6.9 
Observed Raw ICOAP Scores 
Study Group = Group A 
Patient 
MIV-
711-202 
Patient 
MIV-711-201 
Visit 
Date of 
Assessment 
Time of 
Assessment IP1 
IP2 
IP3 
IP4 
IP5 
IP6 
IP7 IP8 
IP9 
IP10 IP11 
VISIT 2 BASELINE DAY 
VISIT 5 WEEK 8 
VISIT 6 WEEK 14 
Etc… 


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Protocol Number: MIV-711-202 
Listing 16.2.6.10 
Transformed ICOAP Scores 
Study Group = Group A 
Patient 
MIV-
711-202 
Patient 
MIV-711-201 
Visit 
Date of 
Assessment 
Time of 
Assessment 
Constant Pain Subscale
Intermittent pain 
subscale 
Total pain score 
Observed 
Change 
Observed 
Change Observed Change 
VISIT 2 BASELINE 
DAY  
VISIT 5 WEEK 8 
VISIT 6 WEEK 14 
Etc… 


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Protocol Number: MIV-711-202 
Listing 16.2.6.11 
Western Ontario and McMaster Index (WOMAC) – Pain Questions 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Of 
Assessment 
Walking 
on 
a Flat 
Surface 
Going 
Up or 
Down 
Stairs 
at Night 
While 
in Bed 
Sitting 
or 
Lying 
Down 
While 
Standing 


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Protocol Number: MIV-711-202 
Listing 16.2.6.12 
Western Ontario and McMaster Index (WOMAC) – Stiffness Questions 
                                    Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Of 
Assessment 
Stiffness 
after 
First 
Woke Up 
in 
Morning 
Stiffness 
Sitting 
or Lying 
Down 


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Protocol Number: MIV-711-202 
Listing 16.2.6.13 
Western Ontario and McMaster Index (WOMAC) – Difficulty Questions 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Of 
Assessment 
When 
going 
Down 
the 
Stairs 
When 
Going 
Up the 
Stairs 
Getting 
Up 
from a 
sitting 
While 
Standing 
When 
Bending 
to the 
Floor 
Walking 
on 
a Flat 
Surface 
Programming note: listing will be expanded to show all 17 difficulty questions  


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Protocol Number: MIV-711-202 
Listing 16.2.6.14 
Western Ontario and McMaster Index (WOMAC) 
Derived Scores and Change from Baseline 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Total 
WOMAC 
Pain 
Score 
[1] 
Total 
WOMAC 
Function 
Score 
[2] 
Total WOMAC
Stiffness 
Score 
[3] 
Normalized
WOMAC 
Pain 
Score 
Change from 
Baseline 
Normalized 
WOMAC 
Pain 
Score 
Normalized 
WOMAC 
Function 
Score 
Change 
from 
Baseline 
Normalized
WOMAC 
Function 
Score 
Normalized
WOMAC 
Stiffness 
Score 
Change from 
Baseline 
Normalized
WOMAC 
Stiffness 
Score 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
[1] Total WOMAC Pain Score (Total_WOMAC_Pain_50): sum of the 5 WOMAC pain responses 
[2] Total WOMAC Function Score (Total_WOMAC_Func_170): sum of the 17 WOMAC function responses 
[3] Total WOMAC Stiffness Score (Total_WOMAC_stiff_2): sum of the 2 WOMAC stiffness responses 
WOMAC PAIN Score 100 = Total_WOMAC_Pain_50 x 2.  
WOMAC Function Score 100 = Total_WOMAC_Func_170 ÷ 1.7. 
WOMAC stiffness Score 100 = Total_WOMAC_stiff_2 ÷ 0.2. 


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Protocol Number: MIV-711-202 
Listing 16.2.6.15 
OARSI-OMERACT Responder Index 
                        Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-711-
201 
Visit 
Total 
WOMAC 
Pain 
Score 
[1] 
Total 
WOMAC 
Function 
Score 
[2] 
Normalized 
WOMAC 
Pain 
Score 
Normalized 
WOMAC 
Function 
Score 
Normalized 
Global 
Assessment 
NRS 
Visit 2 
 
Visit 8 
 
[1] Total WOMAC Pain Score (Total_WOMAC_Pain_50): sum of the 5 WOMAC pain responses 
[2] Total WOMAC Function Score (Total_WOMAC_Func_170): sum of the 17 WOMAC function responses 
Global Assessment NRS = “How Active Target Knee Arthritis Has Been”, from Listing 16.2.6.1 
Normalized WOMAC PAIN Score = Total_WOMAC_Pain_50 x 2. 
Normalized WOMAC Function Score = Total_WOMAC_Func_170 ÷ 1.7. 
Normalized Global Assessment NRS = (Global Assessment NRS) x 10. 


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Protocol Number: MIV-711-202 
Listing 16.2.6.16 
OARSI-OMERACT Responder Index 
Change from Baseline and Percentage Change from Baseline Scores 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-711-201 
Score 
Change 
from 
Baseline 
Percent 
Change 
from 
Baseline 
Criteria 
(1, 2) 
Response 
Criteria 
(1, 2) 
Criteria 
(3,4,5) 
Response 
Criteria 
(3,4,5) 
Responder 
101 
xx 
yy 
1 
Yes 
3 
NA  
No 
101 
xx 
yy 
2 
No 
4 
NA  
101 
xx 
yy 
5 
NA  
102 
xx 
yy 
1 
No 
3 
Yes 
Yes 
102 
xx 
yy 
2 
No 
4 
Yes 
102 
xx 
yy 
5 
No 
103 
xx 
yy 
1 
Yes 
103 
xx 
yy 
2 
103 
xx 
yy 
5 
104 
xx 
yy 
3 
104 
xx 
yy 
4 
104 
xx 
yy 
105 
xx 
yy 
105 
xx 
yy 
4 
105 
xx 
yy 
Percent Change from Baseline: ((Visit 5 Score – Baseline Score) ÷ Baseline Score) x 100 
Criteria 1: WOMAC Pain: decrease from baseline >=20 and Percentage Decrease from Baseline >=50%
Criteria 2: WOMAC Function: decrease from baseline >=20 and Percentage Decrease from Baseline >=50%
Criteria 3: WOMAC Pain: decrease from baseline >=10 and Percentage Decrease from Baseline >=20%
Criteria 4: WOMAC Function: decrease from baseline >=10 and Percentage Decrease from Baseline >=20%
Criteria 5: Global Assessment: decrease from baseline >=10 and Percentage Decrease from Baseline >=20%
A subject is a ‘Yes’ responder if either of criteria 1 or 2 are satisfied. If neither criteria 1 or 2 are satisfied, criteria 3, 4 and 5 will be 
checked. A subject is a ‘Yes’ responder if at least 2 of these 3 criteria (3, 4, 5) are satisfied. 
Programming notes: Criteria column will be flagged with the number 1, 2, 3, 4, 5 only if the conditions for that criteria are satisfied. 
Criteria 3, 4, 5 will be shown only if Criteria 1 and 2 have been checked and neither of these initial two conditions are satisfied. 


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Protocol Number: MIV-711-202 
Listing 16.2.6.17 
Global Improvements
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Of 
Assessment 
Knee 
problem 
Knee Pain 
 Knee 
Function  


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Protocol Number: MIV-711-202 
Listing 16.2.6.18 
Quality of Life Patient Reported Outcomes - EQ-5D-5L  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Of 
Assessment 
Mobility
Self-care
Usual 
activity
Pain or 
Discomfort
Anxiety or 
depression
Health rating 
score 
For questions on Mobility, Self-care, Usual Activity, Pain or discomfort, and Anxiety or Depression higher scores indicate 
worse quality of life. 
The Health Rating Score is a VAS score ranging from 0 to 100 such that higher scores are associated with improved health and better 
quality of life. 


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Protocol Number: MIV-711-202 
Listing 16.2.6.19 
Quality of Life Patient Reported Outcomes Change from Baseline Scores - EQ-5D-5L  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Of 
Assessment 
Mobility
Self-care
Usual 
activity
Pain or 
Discomfort
Anxiety or 
depression
Health rating 
score 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
For questions on Mobility, Self-care, Usual Activity, Pain or discomfort, and Anxiety or Depression higher scores indicate 
worse quality of life. 
The Health Rating Score is a VAS score ranging from 0 to 100 such that higher scores are associated with improved health and better 
quality of life. 


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Protocol Number: MIV-711-202 
Listing 16.2.6.20 
Brief Medication Questionnaire 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Of 
Assessment 
Question 
Response 
How much did you take each time 
How many days did you take it 
The dosage times are inconvenient 
Etc… 


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Protocol Number: MIV-711-202 
Listing 16.2.6.21 
E-Diary Assessments over the Last 12 Hours 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Study 
Day  
Date 
Of 
Assessment 
Time 
Point 
Pain 
Medication
Use 
Over Last
12 Hours? 
Severity 
Pain 
Medication 
Usage 
Over last 
12 Hours 
NRS: 
Overall Pain
Severity in 
Target Knee 
Over Last 
12 Hours 
AM  
PM 
YES 
NO 
Less than Normal 
Normal 
More than normal 


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Protocol Number: MIV-711-202 
Listing 16.2.6.22 
E-Diary Assessments – Derived Results for each Study Visit 
                  Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-711-201 
Visit 
Time 
Point 
Percentage 
of 
Patients 
who used 
Pain 
medication 
use over 
last 12 
hours? 
Change from Baseline 
percentage of ‘Yes’ 
scores for analgesic 
use
Severity Pain 
medication usage over 
last 12 hours 
[2] 
NRS: Overall 
pain 
severity in 
target knee 
over last 12 
hours 
[3] 
Change from 
Baseline NRS 
xxxxxx 
 
Baseline 
AM 
xx.x 
Visit 4  
Visit 5  
Baseline 
Visit 4  
Visit 5  
Baseline 
Visit 4  
Visit 5  
AM 
AM 
PM 
PM 
PM 
Overall 
Overall 
Overall 
xx.x 
xx.x 
xx.x 
xx.x 
Less than Normal 
Normal 
More than normal 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
[1] Denominator for AM, PM calculations is the actual number of days assessed, where the number of days >=10 days and <= 14 days. The overall 
percentage combining AM and PM measures: 
Overall percentage = (xx/AM denominator + yy/PM denominator)/2,  where ‘xx’ = count of AM ‘Yes’, ‘yy’ = count of PM ‘Yes’.  
[2] Derived results were considered only for YES responses in [1]. For those cases the worst response over the interval of all responses for each 
visit was interpreted as the derived response for that Visit. 
[3] the derived NRS score for each Visit was obtained as the arithmetic mean (the average) of all scores recorded within the identified interval 
for that Visit. 


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Protocol Number: MIV-711-202 
Listing 16.2.6.23 
Efficacy Biomarkers from Serum and Urine Samples 
                                 Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Of 
Assessment 
Serum 
CTX-I 
(ug/L) 
Serum 
CTX-I 
Change 
from 
Baseline 
(ug/L) 
Urine 
CTX-II 
(ug/L) 
Urine 
Creatinine
(mmol/L) 
Urine 
CTX-II 
/Creat 
(ng/mmoL) 
Urine 
CTX-II 
/Creat 
Change 
from 
Baseline 
(ng/mmoL) 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 


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Protocol Number: MIV-711-202 
Listing 16.2.6.24 
Time-Integrated Concentrations (TIC) and Their Z-scores  
for Efficacy Biomarkers from Serum and Urine Samples 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
TIC 
Serum 
CTX-I 
(ug/L) 
TIC Urine
CTX-II 
/Creat 
(ng/mmoL) 
Z-Score 
Serum 
CTX-I 
Z-Score 
Urine 
CTX-
II/Creat 


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Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
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Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.7.1 
Adverse Events 
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
        MIV-711-201 
Adverse Event 
>MedDRA Preferred Term 
>>System Organ Class  
Start 
Date 
Time 
Stop 
Date 
Time 
Seri- 
ous 
Outcome 
Severity 
Action 
Taken 
Study 
Medica- 
tion 
[1] 
Relation- 
ship to 
Study 
Medica- 
tion 
AE 
Start 
Time 
from 
First 
Dose 
(day) 
[1] Action taken results that state ‘MEDICATION’ indicate a concomitant medication was administered. No action was taken with respect to study 
medication unless specifically stated otherwise 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 169 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.7.2 
Serious Adverse Events 
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
       MIV-711-201 
Adverse Event 
>MedDRA Preferred Term 
>>System Organ Class  
Start 
Date 
Time 
Stop 
Date 
Time 
Outcome 
Severity 
Action 
Taken 
Study 
Medica- 
tion 
[1] 
Relation- 
ship to 
Study 
Medica- 
tion 
AE 
Start 
Time 
from 
First 
Dose 
(day) 
[1] Action taken results that state ‘MEDICATION’ indicate a concomitant medication was administered. No action was taken with respect to study 
medication unless specifically stated otherwise 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 170 of 183 
Medivir  
           
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.7.3 
Adverse Events Leading To Discontinuation  
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
      MIV-711-201 
Adverse Event 
>MedDRA Preferred Term 
>>System Organ Class  
Start 
Date 
Time 
Stop 
Date 
Time 
Seri- 
ous 
Outcome 
Severity 
Action 
Taken 
Study 
Medica- 
tion 
[1] 
Relation- 
ship to 
Study 
Medica- 
tion 
AE 
Start 
Time 
from 
First 
Dose 
(day) 
[1] Action taken results that state ‘MEDICATION’ indicate a concomitant medication was administered. No action was taken with respect to study 
medication unless specifically stated otherwise 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 171 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.1 
Clinical Laboratory Chemistry - Observed Values  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Collection 
Time 
Lab 
Parameter 1 
(unit) 
Lab  
parameter 2 
(unit) 
Lab 
parameter 3 
(unit) 
Lab 
parameter 4 
(unit) 
Result/Flag 
Result/Flag 
Result/Flag 
Result/Flag
H=High, L=Low, CS=Clinically Significant, NCS=Not Clinically Significant 
Programming Note: If Flag is present (H or L), clinical significance will be identified by one of ‘NCS’ or ‘CS’. 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 172 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.2 
Clinical Laboratory Hematology - Observed Values  
                     Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Collection 
Time 
Lab 
Parameter 1 
(unit) 
Lab  
parameter 2 
(unit) 
Lab 
parameter 3 
(unit) 
Lab 
parameter 4 
(unit) 
Result/Flag 
Result/Flag 
Result/Flag 
Result/Flag
H=High, L=Low, CS=Clinically Significant, NCS=Not Clinically Significant 
Programming Note: If Flag is present (H or L), clinical significance will be identified by one of ‘NCS’ or ‘CS’. 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 173 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.3 
Clinical Laboratory Urinalysis - Observed Values  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 Visit 
Collection 
Date  
Collection 
Time 
Lab 
Parameter 1 
(unit) 
Lab  
parameter 2 
(unit) 
Lab 
parameter 3 
(unit) 
Lab 
parameter 4 
(unit) 
Result/Flag 
Result/Flag 
Result/Flag 
Result/Flag
H=High, L=Low, AB=Abnormal, CS=Clinically Significant, NCS=Not Clinically Significant 
Programming Note: If Flag is present (H, L, or AB), clinical significance will be identified by one of ‘NCS’ or ‘CS’. 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 174 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.4 
Clinical Laboratory Urinalysis – Positive Microscopic Findings  
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
MIV-711-
201 
Visit 
Collection
Date 
Collection 
Time 
Test Name 
Result 
Unit 
Flag 
Clinical 
Significance 
*H=High, L=Low, AB=Abnormal, CS=Clinically Significant, NCS=Not Clinically Significant 
Programming Note: If Flag is present (H, L, or AB), clinical significance will be identified by one of ‘NCS’ or ‘CS’. 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 175 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.5 
Vital Signs – Observed Values  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Collection 
Date 
Collection 
Time 
Supine 
Heart Rate
(beats/min) 
Supine 
Systolic 
Blood 
Pressure 
(mmHg) 
Supine 
Diastolic 
Blood 
Pressure 
(mmHg) 
Pulse 
Oximetry 
(%) 
Body 
Temperature 
(°C) 


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Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 176 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.6 
Vital Signs Change from Baseline   
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Collection 
Date 
Collection 
Time 
Supine 
Heart Rate 
(beats/min) 
Supine 
Systolic 
Blood 
Pressure 
(mmHg) 
Supine 
Diastolic 
Blood 
Pressure 
(mmHg) 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 177 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.7 
Vital Signs Overall Qualitative Results Abnormal Assessments  
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
MIV-711-
201 
Visit 
Collection 
Date 
Collection 
Time 
Assessment 
Interpretation 
ABNORMAL, NCS 
ABNORMAL, CS 
NCS = Not Clinically Significant, CS = Clinically Significant 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 178 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.8 
12 Lead ECG Quantitative Findings 
Study Group = Group A 
Patient 
MIV-711-
202 
Patie
nt 
MIV-
711-
201 
Visit 
Timepoint 
Collect-
ion 
Date 
Collec- 
tion 
Time 
Heart 
Rate 
(beats 
/min) 
PR 
(msec) 
RR 
(msec) 
QRS 
(msec) 
QT 
(msec) 
QTcB 
(msec) 
QTcF 
(msec) 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 179 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.9 
12 Lead ECG Change From Baseline  
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
MIV-711-
201 
Visit 
Timepoint 
Collection 
Date 
Collection 
Time 
QT  
(msec) 
QTcB 
 (msec) 
QTcF 
 (msec) 
Baseline is defined as: Visit 2 in the MIV-711-201 for Group A, Visit 8 in the MIV-711-201 for Group B 
QTcB = QT corrected according to Bazett, QTcF = QT corrected according to Fridericia. 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 180 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.10 
12 Lead ECG Overall Qualitative Assessment  
Study Group = Group A 
Patient 
MIV-711-202 
Patient 
MIV-711-
201 
Visit 
Timepoint 
Collection
Date 
Collection 
Time 
Assess- 
ment 
Interpretation 
Comment 
NCS = Not Clinically Significant, CS = Clinically Significant 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 181 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.11 
Physical Examination Abnormal Findings  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Exam 
Date 
Exam 
Time 
Body System 
Abnormality 
Clinical 
Significance 
NCS 
CS 
NCS = Not Clinically Significant, CS = Clinically Significant 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 182 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.12 
Patient Weight 
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
Date 
Time 
Weight (kg) 


PAREXEL International 
SAP Amendment Shells 
Medivir 
Protocol: MIV-711-202 
                                                                                                          Final 1.0  
                                                16 January 2018 
                                                                                                                                                                                                                Page 183 of 183 
Medivir  
Page X of Y 
Protocol Number: MIV-711-202 
Listing 16.2.8.13 
Phone Call to Assess Safety  
Study Group = Group A 
Patient 
MIV-711-
202 
Patient 
MIV-
711-201 
Visit 
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