Efficacy and Safety of G001 in Patients With Osteoarthritis (OA) of the Knee

Study Overview
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Brief Summary
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Phase 2 multicenter, double-blind, randomized, parallel-group, vehicle-controlled study to evaluate the efficacy, safety, and local tolerability of G001 topical gel compared to matching Vehicle topical gel in patients with symptomatic OA of the knee. Each patient's participation is approximately 7 weeks ( 1 week screening, 4 weeks of treatment, and 2 weeks of post-treatment follow-up). Eligible patients with adequate OA pain in the index knee are randomized (1:1 allocation ratio) at the Baseline/Flare Visit 1. Following screening, prior NSAID and/or acetaminophen use is discontinued to allow for washout and symptom flare. Patients are instructed to rate their worst daily and nightly pain in their daily diary, as well as to document all study drug applications and any rescue medication (acetaminophen) use for breakthrough pain. Acetaminophen may be used as rescue medication only, except within 12 hours prior to the Baseline Visit and within 12 hours prior to any post-baseline efficacy assessments (Weeks 2, 4, and 5). Patients are instructed to return to the clinic 3 to 7 days after the last study drug application for Flare Visit 2, and within approximately 2 weeks after the last study drug application for end-of-study evaluations.

Official Title
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Phase 2 Multicenter, Double-blind, Randomized, Parallel-Group, Vehicle-Controlled Study to Evaluate the Efficacy, Safety, and Local Tolerability of G001 in Patients With Osteoarthritis (OA) of the Knee

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: G001 Topical Gel
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of OA of the knee, meeting American College of Rheumatology (ACR) criteria for classification of idiopathic (primary) OA for at least 6 months prior to Screening Radiologic evidence of OA of the knee of grade 2 (mild) or grade 3 (moderate) according to Kellgren and Lawrence Radiographic Grading Worst daily pain (within 24 hours prior to Screening and Baseline) in the index knee between 4 and 8 on the 11-point pain NRS On stable analgesic therapy At Baseline: - Development of a flare of pain following washout of stable analgesic (NSAID and/or acetaminophen) therapy Exclusion Criteria: Radiologic evidence of severe OA of the knee (Kellgren and Lawrence grade 4) Secondary OA of the index knee Any other arthritis, included but not limited to rheumatoid arthritis, psoriatic arthritis, etc. History of pseudo-gout or inflammatory flare-ups History of severe neurological conditions Any other chronic pain conditions (e.g., back pain) or disabling conditions affecting the joints Patients who are non-ambulatory or require the use of crutches or a walker, or started using a cane within 30 days prior to Screening Any history of major surgery to the index knee, minor knee surgery, or injury to the index knee within 1 year prior to Screening Knee arthroscopy (index knee) within 3 months prior to Screening Planned or candidate for knee replacement or knee reconstruction surgery Received intra-articular viscosupplementation/hyaluronate, joint lavage, or other invasive therapies to the index knee in the past 90 days Treatment with or need for any of the following: (1) oral or intramuscular corticosteroids within the past 90 days; (2) intra-articular corticosteroid injection into the index knee within the past 90 days, or into any other joint within the past 30 days; (3) current use of topical corticosteroids on the index knee Prior stable therapy with an opioid analgesic, or anticipated need for opioid analgesic use during the study Use of sedative hypnotic medication, antidepressants with known analgesic effect, antipsychotics, antiepileptics, and anti-Parkinson drugs within the past 14 days Regular use of medication for headaches Anticipated use of any oral or topical NSAID (apart from the study drug) during the study Known sensitivity to the study drug (or any of its ingredients), or NSAIDs, or presence of contraindications, warnings, or precautions At Baseline: Worst daily pain (within the past 24 hours) in the contralateral knee assessed as >2 on the 11-point pain NRS scale Non-compliance with the daily diary requirement during the Screening period.

Ages Eligible for Study
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Minimum Age: 40 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G001 Topical Gel<br>G001 Topical Gel, 4 grams applied to the index knee four times a day over 4 weeks. | Drug: G001 Topical Gel<br>* Non-steroidal anti-inflammatory drug for topical administration<br>|
| Placebo Comparator: Vehicle Topical Gel<br>Vehicle Topical Gel, 4 grams applied to the index knee four times a day over 4 weeks. | Drug: Vehicle<br>* Vehicle Gel for topical administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in WOMAC Pain Subscale Score | 0-20 scale, with higher scores indicating worse outcome | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in WOMAC Physical Function Subscale score | 0-68 scale, with higher scores indicating worse outcome | Week 4 | 
| Change from Baseline in WOMAC Total score | 0-96 scale, with higher scores indicating worse outcome | Week 4 | 
| Change from Baseline in WOMAC Stiffness Subscale score | 0-8 scale, with higher scores indicating worse outcome | Week 4 | 
| Change from Baseline in WOMAC Total and Subscale Scores |  | Week 2 | 
| Change from Week 4 to Week 5 in WOMAC Total and Subscale Scores |  | Week 4 to Week 5 | 
| Worst daily and nightly pain severity scores (11-point pain NRS) from patient diary | 0-10 scale, with higher scores indicating worse outcome | Weeks 4 and 5 | 
| Change from Baseline in Patient Global Assessment (PGA) of disease activity over time | 0-4 scale, with higher scores indicating worse outcome | Weeks 2, 4 and 5 | 
| Change from Baseline in Investigator Global Assessment (IGA) of disease activity over time | 0-4 scale, with higher scores indicating worse outcome | Weeks 2, 4 and 5 | 
| PGA of overall treatment benefit | 0-4 scale, with higher scores indicating worse outcome | Weeks 2 and 4 | 
| IGA of overall treatment benefit | 0-4 scale, with higher scores indicating worse outcome | Weeks 2 and 4 | 
| Rescue medication use |  | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, knee, topical therapy, pain