A Study to Evaluate the Analgesic Efficacy and Safety of VM902A in Subjects With Osteoarthritis (OA) of the Knee

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the analgesic efficacy, safety, and tolerability of VM902A twice daily compared to placebo in subjects with moderate to severe chronic pain due to OA of the knee.

Official Title
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A Phase 2a, Multicenter, Randomized, Double-blind, Placebo Controlled and Active-controlled, Parallel-group Study Evaluating the Analgesic Efficacy and Safety of VM902A in Subjects With Moderate to Severe Chronic Pain Due to Osteoarthritis of the Knee

Conditions
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Osteoarthritis Pain of the Knee

Intervention / Treatment
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* Drug: VM902A 200-mg Capsules
* Drug: VM902A 400-mg Capsules
* Drug: Naproxen 500-mg Capsules
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Include: Males and females ≥ 40 and ≤ 75 years of age with moderate to severe chronic OA pain of the knee (lasting several hours daily) as their predominant pain condition for at least 6 months prior to screening Diagnostic criteria for primary pain condition (American College of Rheumatology [ACR] clinical and radiographic criteria): At least 1 of the following in addition to knee pain: age > 50, stiffness < 30 min, crepitus on active motion, and Kellgren-Lawrence (K-L) grade 2 or 3 radiographic evidence at the screening visit as determined by a local radiologist or rheumatologist. Note that K-L grades 2 to 3 require the presence of osteophytes, which is required to meet ACR clinical and radiographic criteria for knee OA Subjects whose OA pain of the index knee is not adequately treated prior to the screening visit: • Subjects must have a self-reported average pain intensity rating of moderate or severe on a verbal rating scale (ie, none, mild, moderate, and severe) over the 7 days prior to the screening visit The subjects must have average pain over the last 24 hours scores ≥ 5 and ≤ 9 on an 11-point numerical rating scale (NRS) for the index knee on ≥ 3 consecutive days during the screening period and come in for randomization within 72 hours after qualification is met Subjects who are willing and able to stop taking any/all analgesic medications, including over-the-counter pain medications, opioids, marijuana, and topical analgesics for OA pain for the duration of the treatment period, with the exception of study-specific rescue medication. Key Exclusion Criteria Include: Subjects with radiographic evidence of OA with K-L grade 0, 1, or 4 Subjects at risk for destructive arthropathy, subjects with a history of osteonecrosis, osteoporotic fracture, rapidly progressive osteoarthritis (RPOA 1 and 2), subchondral insufficiency fracture, and hip/knee dislocations Subjects considered high risk for surgery based upon American Society of Anesthesiologists physical classification system for surgery grading, or subjects who would not be willing to undergo joint replacement surgery if required Subjects with chronic pain conditions other than OA of the knee as their predominant pain condition, including gout (except for subjects with gout that is controlled with diet and/or with stable suppressive treatment with uric acid reducing medication(s) and/or colchicine, and who have not had any attack within the past 2 years), pseudogout, psoriatic arthritis, active Lyme disease, rheumatoid arthritis or any other inflammatory arthritis, fibromyalgia, neuropathic pain conditions, bursitis, or acute injury or signs of active infection in the target pain area Subjects scheduled for surgical interventions of the disease site or any other major surgery during the study conduct period Subjects with a history of a prior joint replacement of the index knee Subjects who have had arthroscopy on either knee or hip within 6 months of entering the study, or open surgery on either knee or hip within 12 months of entering the study. Other protocol-specific inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VM902A 200 mg<br>VM902A 200-mg Capsules | Drug: VM902A 200-mg Capsules<br>* Taken orally with food twice daily<br>Drug: Placebo<br>* Capsules to match VM902A and/or naproxen taken orally with food twice daily<br>|
| Experimental: VM902A 400 mg<br>VM902A 400-mg Capsules (2 x 200-mg capsules) | Drug: VM902A 400-mg Capsules<br>* Taken orally with food twice daily<br>Drug: Placebo<br>* Capsules to match VM902A and/or naproxen taken orally with food twice daily<br>|
| Active Comparator: Naproxen<br>Naproxen 500-mg Capsules | Drug: Naproxen 500-mg Capsules<br>* Taken orally with food twice daily<br>Drug: Placebo<br>* Capsules to match VM902A and/or naproxen taken orally with food twice daily<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Capsules to match VM902A and/or naproxen taken orally with food twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Average Pain Over the Last 24 Hours Score at Week 4 |  | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Average Pain Over the Last 24 Hours at Week 4 |  | Week 4 | 
| Average Daily Pain Right Now Score at Week 4 |  | Week 4 | 
| Western Ontario and McMaster OA Index (WOMAC) - Total Scores |  | Week 4 | 
| Western Ontario and McMaster OA Index (WOMAC) Pain Severity Subscale Score |  | Week 4 | 
| Western Ontario and McMaster OA Index (WOMAC) Physical Function Subscale Score |  | Week 4 | 
| Western Ontario and McMaster OA Index (WOMAC) Stiffness Subscale Score |  | Week 4 | 
| Modified Brief Pain Inventory-Short Form (mBPI-SF) - Total Scores |  | Week 4 | 
| Modified Brief Pain Inventory-Short Form (mBPI-SF) Pain Severity Subscale Score |  | Week 4 | 
| Modified Brief Pain Inventory-Short Form (mBPI-SF) Pain Interference Subscale Score |  | Week 4 | 
| Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) |  | Week 4 | 
| EuroQol-5D (EQ-5D) to Measure Health Status |  | Week 4 | 
| Patient Global Impression of Change (PGIC) at the End of the Double-blind Period |  | Week 4 | 
| Supplemental Analgesic Medication Use | The average daily number of tablets of supplemental pain medication taken during the study. | Days 1 - 28 | 
| Responder to Treatment | The percentage reduction from the baseline mean average pain over the last 24 hours score to the week 4 mean pain score from the mBPI-SF pain severity subscale. | Week 4 | 
| Hospital Anxiety and Depression Scale (HADS) Score | Safety assessment to evaluate the impact of VM902A on mood (anxiety and depression) | Baseline to Week 4 | 
| Columbia-Suicide Severity Rating Score (C-SSRS) | Safety assessment to evaluate the occurrence of treatment-emergent suicidal ideation | Baseline to Week 4 | 
| Survey of Autonomic Symptoms (SAS) Score | Safety assessment to evaluate symptoms of autonomic dysfunction | Baseline to Week 4 | 
| Kellgren-Lawrence Classification (K-L) Score | Safety assessment to classify the severity of knee OA | Baseline to Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Pain, Osteoarthritis, knee