A Study to Evaluate the Efficacy, Safety and Tolerability of MIV-711 in Osteoarthritis Patients

Study Overview
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Brief Summary
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This is a multicentre, randomised, placebo-controlled, double-blind, three-arm parallel, Phase IIa study to evaluate the efficacy, safety and tolerability of MIV-711 in patients with knee osteoarthritis (OA).

Official Title
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A Randomised, Double-blind Placebo-controlled Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of MIV-711 in Knee Joint Osteoarthritis

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: MIV-711
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current average knee pain, defined as pain in either knee, within 1 week before visit 1, for which the patient gives a severity score of ≥4, <10 on a 0-10 NRS (Numeric Rating Scale). Inclusive of 40-80 years old. Diagnosis of primary knee osteoarthritis Exclusion Criteria: The presence of any inflammatory arthritis Any generalized pain condition that may interfere with the evaluation of the target knee pain (e.g., fibromyalgia) as judged by the investigator. 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. Known or suspected intolerance or hypersensitivity to the investigational product, closely related compounds, or any of the stated ingredients.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIV-711:1<br>MIV-711 for a total of 26 w | Drug: MIV-711<br>* MIV-711 administered orally once daily<br>|
| Experimental: MIV-711:2<br>MIV-711 for a total of 26 w | Drug: MIV-711<br>* MIV-711 administered orally once daily<br>|
| Placebo Comparator: Placebo<br>Placebo for a total of 26 w | Drug: Placebo<br>* Placebo manufactured to mimic MIV-711 capsule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale (NRS) Average Target Knee Pain Score at Week 26 | Change from Visit 2 (Baseline) to Visit 8 (Week 26) in NRS average target knee pain score. NRS (Numeric rating scale) ranges from 0 indicating -no pain, to 10 indicating - pain as bad as it could be. | baseline and 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnetic Resonance Imaging (MRI) Bone Area of the Target Knee at Week 26 | Change from Visit 2 (Baseline) to Visit 8 (Week 26) in MRI (Magnetic Resonance Imaging;) bone area of the target knee in mm^2. | baseline and 26 weeks | 
| Magnetic Resonance Imaging (MRI) of Cartilage Thickness (Femur) at Week 26 | Change from Visit 2 (baseline) to Visit 8 (week 26) in MRI cartilage thickness in the Central Medial Femur Region of the target knee in mm. | baseline and 26 weeks | 
| Normalised Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) Pain Score | Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC pain score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 5 questions in the WOMAC pain scale which is summed up for the total WOMAC score, leading to a range of 0 to 50. The total WOMAC pain score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain): - Normalised WOMAC pain score = Total WOMAC pain score multiplicated with 2. | baseline and 26 weeks | 
| Normalised Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) Difficulty Score | Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC difficulty score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 17 questions in the WOMAC difficulty scale which is summed up for the total WOMAC difficulty score, leading to a range of 0 to 170. The total WOMAC difficulty score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain): - Normalised WOMAC difficulty score = Total WOMAC difficulty score divided with 1.7 | baseline and 26 weeks | 
| Normalised Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score | Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC stiffness score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 2 questions in the WOMAC stiffness scale which is summed up for the total WOMAC stiffness score, leading to a range of 0 to 20. The total WOMAC stiffness score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain): - Normalised WOMAC stiffness score = Total WOMAC stiffness score multiplicated with 5 | baseline and 26 weeks | 
| Serum C-terminal Telopeptide of Collagen Type I (CTX-I) at Week 26 | Change from Visit 2 (baseline) to Visit 8 (week 26) in serum CTX-I, a biomarker for bone resorption. | baseline and 26 weeks | 
| Creatinine Corrected Urine C-terminal Telopeptide of Collagen Type II (CTX-II) at Week 26 | Change from Visit 2 (baseline) to Visit 8 (week 26) in creatinine corrected urine CTX-II, a biomarker for cartilage degradation. | baseline and 26 weeks |