An Open-label, 8-week Safety, Efficacy, and Assessment of Cooling Methods for Administration of CNTX-4975-05 for Knee OA

Study Overview
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Brief Summary
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An Open-label, 8-Week Study to Compare the Comfort and Ease of Use of Five Different Treatment Regimens for CNTX 4975-05 Intra-articular Injection in Subjects with Chronic, Moderate-to-Severe Osteoarthritis Knee Pain.

Detailed Description
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This is an open-label, single injection (per knee), 8-week study to evaluate the comfort and ease of use of 5 different treatment regimens, and to evaluate the efficacy and safety of a single intra-articular (IA) injection, in one or both knees, of CNTX-4975-05 in subjects with chronic, moderate-to-severe knee OA pain. Procedural pain associated with IA injection of the investigational product, CNTX-4975-05, will be controlled primarily through adjunct controlled joint cooling and secondarily by pre-medication with IA lidocaine.

Official Title
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An Open-label, 8-Week Study to Compare the Comfort and Ease of Use of Five Different Treatment Regimens for CNTX-4975-05 Intra-articular Injection in Subjects With Chronic, Moderate-to-Severe Osteoarthritis Knee Pain

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: CNTX-4975-05
* Drug: Lidocaine without epinephrine
* Device: ElastoGel
* Device: Breg Ice Water Pump


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female subjects between 40 and 95 years of age (inclusive) Confirmation of osteoarthritis (OA) of the knee: radiography of both knees using standard standing films (scored by the investigator) or using the fixed flexion method, taken during the Screening Visit of CNTX-4975i-OA-301 or CNTX-4975i-OA-304. Confirmation of OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria For subjects for monoarticular knee injection, the index knee must have moderate to severe pain at screening associated with OA, which must be stable for a minimum of 6 months prior to Screening, as assessed by the investigator. These subjects may have: unilateral or bilateral OA, with the index knee having moderate to severe pain, and the contralateral knee having none to mild pain, OR unilateral or bilateral OA, with the index knee having moderate to severe pain and the other knee having had a PJR or TJR within 5 years of the Screening Visit. The knee with the PJR/TJR is not to be injected with CNTX-4975-05. For subjects for bilateral knee injection, the index knee must have moderate to severe pain at screening associated with OA, and greater pain in the index knee than in the contralateral knee. Their pain must be stable for a minimum of 6 months prior to Screening, as assessed by the investigator. The index knee in these subjects is the one with the worst pain with walking. Where both knees have equal pain with walking, then the knee on the subject's dominant side will be designated the index knee. For qualifying knee pain with walking, subjects will use an NPRS (0-10; 0=no pain, 10=worst possible pain) to rate their knee pain with walking (both knees, except knees with PJR/TJR). The PJR/TJR pain should be rated using the NPRS scale, but will not be a qualifying pain score. Body mass index ≤45 kg/m^2. Key Exclusion Criteria: Joint replacement surgery of the index knee at any time, or open surgery of the index knee in the past 24 months. Joint replacement of the contralateral knee is permitted for subjects who will not receive an injection in the contralateral (natural) knee. Prior arthroscopic surgery of the index knee within 6 months of Screening. Any painful conditions of the index knee due to joint disease other than OA. Radicular or referred pain involving the index knee or from joint disease other than OA involving the index knee, such as, but not restricted to chondromalacia patellae, inflammatory disease, metabolic diseases, gout/pseudogout, hemochromatosis, acromegaly, etc. Periarticular pain from any cause, including referred pain, bursitis, tendonitis, soft tissue tenderness, or subacute/acute pain from injury. Other chronic pain anywhere in the body that requires the use of chronic analgesic medications, including, but not limited to, local painful areas, myofascial pain syndromes, fibromyalgia, genetic, metabolic abnormalities, hematologic, or neuropathic pain.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 95 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Breg Cooling Control Group<br>Subject receives 2% lidocaine and CNTX-4975-05 with cooling device Breg ice water pump. | Drug: CNTX-4975-05<br>* Osteoarthritis (OA) intra-articular injection of CNTX-4975-05<br>* Other names: capsaicin;Drug: Lidocaine without epinephrine<br>* 15 mL lidocaine intra-articular injection<br>* Other names: Lidocaine;Device: Breg Ice Water Pump<br>* Cooling Device<br>|
| Experimental: Gel Pack Cooling Group<br>Subject receives 2% lidocaine and CNTX-4975-05 with cooling device Elasto-Gel. | Drug: CNTX-4975-05<br>* Osteoarthritis (OA) intra-articular injection of CNTX-4975-05<br>* Other names: capsaicin;Drug: Lidocaine without epinephrine<br>* 15 mL lidocaine intra-articular injection<br>* Other names: Lidocaine;Device: ElastoGel<br>* Cooling Device<br>|
| Experimental: Shortened Gel Pack Cooling Group<br>Subject receives 2% lidocaine and CNTX-4975-05 with cooling device Elasto-Gel. | Drug: CNTX-4975-05<br>* Osteoarthritis (OA) intra-articular injection of CNTX-4975-05<br>* Other names: capsaicin;Drug: Lidocaine without epinephrine<br>* 15 mL lidocaine intra-articular injection<br>* Other names: Lidocaine;Device: ElastoGel<br>* Cooling Device<br>|
| Experimental: Single Needle Injection Gel Pack Cooling Group - 2% Lidocaine<br>Subject receives 2% lidocaine and CNTX-4975-05 with cooling device Elasto-Gel. | Drug: CNTX-4975-05<br>* Osteoarthritis (OA) intra-articular injection of CNTX-4975-05<br>* Other names: capsaicin;Drug: Lidocaine without epinephrine<br>* 15 mL lidocaine intra-articular injection<br>* Other names: Lidocaine;Device: ElastoGel<br>* Cooling Device<br>|
| Experimental: Single Needle Injection Gel Pack Cooling Group - 1% Lidocaine<br>Subject receives 1% lidocaine and CNTX-4975-05 with cooling device Elasto-Gel. | Drug: CNTX-4975-05<br>* Osteoarthritis (OA) intra-articular injection of CNTX-4975-05<br>* Other names: capsaicin;Drug: Lidocaine without epinephrine<br>* 15 mL lidocaine intra-articular injection<br>* Other names: Lidocaine;Device: ElastoGel<br>* Cooling Device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Optimal Procedure for Administering CNTX-4975-05 With Regards to Pain, Participant Satisfaction, and Investigator's Satisfaction | A composite score was calculated for each of the 5 treatment regimens by summing the scores of three assessments: (1) procedure pain 30 minutes after injection of CNTX-4975-05 on a 0-4 scale, 0 was best indicating no procedure pain, 4 was worst indicating severe procedure pain; (2) assessment of subjects' satisfaction with the regimen on a scale of 1 (completely dissatisfied) to 7 (completely satisfied), 1 was worst and 7 was best; and (3) assessment of investigators' satisfaction with the regimen on a scale of 1 (completely dissatisfied) to 7 (completely satisfied), 1 was worst and 7 was best. The procedure pain at 30 minutes was reversed to a 1-7 scale so 7 was best indicating no procedure pain and 1 was worst indicating severe procedure pain. The three assessments were summed for a total score from 3-21, 3 being the worst outcome and 21 being the best outcome. The geometric mean of the scores was derived for each group. All assessments were administered on Day 1 (Baseline). | Day 1 assessments | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in KOOS Symptoms Subscale Score by Subject Type | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. | Baseline, Week 8 | 
| Mean Change From Baseline in KOOS Pain Subscale Score by Subject Type | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. | Baseline, Week 8 | 
| Mean Change From Baseline in KOOS Pain With Walking Single Question Score by Subject Type | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS Pain with Walking is a single question from the KOOS Pain subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. | Baseline, Week 8 | 
| Mean Change From Baseline in KOOS Function (Daily Living) Subscale Score by Subject Type | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. | Baseline, Week 8 | 
| Mean Change From Baseline in KOOS Function (Sport and Recreational Activities) Subscale Score by Subject Type | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. | Baseline, Week 8 | 
| Mean Change From Baseline in KOOS Knee-Related Quality of Life Subscale Score by Subject Type | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. | Baseline, Week 8 | 
| Mean Change From Baseline in Average Daily Pain With Walking NPRS (0-10) Score by Subject Type | The pain with walking Numerical Pain Rating Scale (NPRS) (0-10, 0 being no pain, 10 being greatest pain) collected subjects' average pain with walking over the past 24 hours. Subjects recorded the pain in their target knee, either the index knee or additionally the non-index knee in the case of bilateral subjects. The NPRS was collected at Day 1 (Baseline) and Week 8. Lower scores (or negative change from baseline) indicate improvement | Baseline, Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, knee pain, non opioid, analgesic, capsaicin, pain, intra-articular