Study to Evaluate the Safety and Efficacy of CNTX-4975 in Subjects With Chronic, Moderate to Severe Osteoarthritis Knee Pain

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and efficacy of a single injection of CNTX-4975 in subjects with chronic, moderate to severe osteoarthritis knee pain.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging 24-Week Study to Evaluate the Safety and Efficacy of a Single Injection of CNTX-4975 in Subjects With Chronic, Moderate to Severe Osteoarthritis Knee Pain

Conditions
-----------------
Osteoarthritis

Intervention / Treatment
-----------------
* Drug: CNTX-4975
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Radiography of both knees with a posterior-anterior, fixed flexion view taken during the Screening period. The index knee must show evidence of chronic OA. Moderate to severe pain in the index knee associated with OA must be stable for a minimum of 2 months prior to Screening, as assessed by the Investigator. A specified mean pain score in the index knee over the 7 days prior to dosing, based on question A1 of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC A1). Specified baseline and screening scores on the WOMAC A1 Body Mass Index ≤ 45 kg/m2. Subjects must have had a therapeutic failure (no relief, or inadequate relief), and/or AEs resulting in stopping treatment, and/or contraindication to the standard of care appropriate to the severity of the index knee OA pain they are experiencing. Exclusion Criteria: Joint replacement surgery of the index knee at any time, or open surgery of the index knee in the past 12 months. Prior arthroscopic surgery of the index knee within 3 months of Screening. Any painful conditions of the index knee due to joint disease other than OA. Mild pain in the non-index knee when walking. Other chronic pain anywhere in the body that requires the use of analgesic medications. Secondary OA of the index knee due to acute traumatic injury. Significant current or past instability (e.g., cruciate ligament tear or rupture or previous repair) or misalignment (> 10 degrees varus or valgus) of the index knee Has used topical capsaicin on the index knee within 90 days of Screening. Corticosteroid injection in the index knee within 90 days of Screening. Received IA viscosupplementation (e.g., Synvisc®, Hyalgan®) within 90 days of Screening. Prior participation in an ALGRX 4975 or CNTX-4975 study. Has any of the following characteristics: active or historic substance use disorder within the previous year as defined by the Diagnostic and Statistical Manual for Mental Health Disorders, fifth edition, or tests positive upon urine drug screen for a substance of abuse. Has moderate to severe depression or anxiety.

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects will receive a single injection of placebo into the index knee following local anesthesia and adjunct joint cooling. | Other: Placebo<br> <br> |
| Experimental: 0.5 mg CNTX-4975<br>Subjects will receive a single injection of 0.5 mg CNTX-4975 into the index knee following local anesthesia and adjunct joint cooling. | Drug: CNTX-4975<br> <br> |
| Experimental: 1.0 mg CNTX-4975<br>Subjects will receive a single injection of 1.0 mg CNTX-4975 into the index knee following local anesthesia and adjunct joint cooling. | Drug: CNTX-4975<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline through Week 12 in average knee index pain with walking over previous 24 hours using WOMAC A1 question in subjects treated with CNTX-4975 1.0 mg compared to placebo in subjects with osteoarthritis (OA) of the knee |  | At 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline through Week 12 in average index knee pain with walking using WOMAC A1 question in subjects treated with CNTX 0.5 mg compared to placebo |  | At 12 Weeks | 
| Change from Baseline to each study visit through Week 24 in average index knee pain with walking using WOMAC A1 in subjects treated with CNTX-4975 compared to placebo |  | Up to 24 weeks | 
| Change from Baseline through Week 4 in the average index knee pain with walking using the WOMAC A1 question |  | Up to 4 weeks |