Open-label Trial to Check the Safety and Tolerability of RTX-GRT7039 Injections for Pain Associated With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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An open-label, single-arm clinical trial to confirm the safety of monoarticular injections or bi-lateral intra-articular injections of RTX-GRT7039 in patients who have pain associated with osteoarthritis of the knee despite standard of care.

Detailed Description
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This trial comprises a total observation period of up to 78 weeks.

Official Title
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A Single-arm, Open-label, Phase III Trial to Evaluate the Safety and Tolerability of Intra-articular Injections of RTX-GRT7039 in Subjects With Moderate to Severe Pain Associated With Osteoarthritis of the Knee.

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: RTX-GRT7039


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has given written informed consent to participate. The participant is 18 years of age or older at the Screening Visit. The participant has a diagnosis of osteoarthritis of the knee based on American College of Rheumatology criteria and functional capacity class of I to III. There is a documented history indicating that participant has insufficient pain relief with previous Standard of Care. Exclusion Criteria: The participant has past joint replacement surgery of the index knee. The participant has a history of significant trauma or surgery (e.g., open or arthroscopic) to the index knee within 12 months of Screening. The participant has periarticular pain at the index knee from any cause other than osteoarthritis, including referred pain, bursitis, tendonitis. The participant has clinical hip osteoarthritis on the side of the index knee. The participant has a history of osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, rapidly progressing osteoarthritis (RPOA) Type I or Type II,pathologic fracture, primary or metastatic tumor, or joint infection in the index knee. The participant has significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus >10°, valgus >10°) by radiograph as assessed by independent Central Readers at Screening Visit. The participant has other conditions that could affect trial endpoint assessments of the index knee. The participant has current clinically significant disease(s) or condition(s) that may affect safety assessments, or any other reason which may preclude the participant's participation for the full duration of the trial. The participant has a history of hypersensitivity to resiniferatoxin (RTX) or any similar component (capsaicin, chili peppers). The participant is currently participating or was participating in another investigational drug trial within 3 months prior to the Screening Visit. The participant is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site or is a family member of the employees or the investigator. The non-index knee is not eligible for treatment in the trial, if any of the knee-related exclusion criteria applies to the non-index knee.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RTX-GRT7039<br>Participants will receive up to 5 intra-articular injections of RTX-GRT7039 into either the index knee (affected knee or in case of bilateral OA the knee with highest pain intensity), or each of both knees up to Week 52. | Drug: RTX-GRT7039<br>* RTX-GRT7039 monoarticular injections or bilateral intra-articular injections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) |  | From Baseline up to Week 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Representing Structural Changes as Assessed by Imaging Methods |  | From Baseline up to Week 78 | 
| Change from Baseline in WOMAC Pain Subscale Score | The WOMAC pain subscale will be assessed using an 11-point numerical rating scale (NRS), where 0= no pain and 10=worst pain. | From Baseline up to Week 12 | 
| Change from Baseline in WOMAC Physical Function Subscale Score | The WOMAC physical function subscale will be assessed using 11-point NRS, where 0= no difficulty and 10=extreme difficulty. | From Baseline up to Week 12 | 
| Change from Baseline in WOMAC Stiffness Subscale Score | The WOMAC stiffness subscale will be assessed using an 11-point NRS, where 0= no stiffness and 10= extreme stiffness. | From Baseline up to Week 12 | 
| Change from Baseline in WOMAC A1 (Walking Pain) Score | The WOMAC A1 score will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain. | From Baseline up to Week 12 | 
| Change from Baseline in WOMAC Total Score | The WOMAC total score will be calculated as the sum of pain subscale score, stiffness subscale score and physical function subscale score. It will be calculated by averaging all of the scores available for the questions and assessed using an 11-point NRS, where 0=best outcome and 10=worst outcome. | From Baseline up to Week 12 | 
| Percentage of Participants With at Least 30%, 50% and 70% Reduction From Baseline in WOMAC Pain Subscale Score | The WOMAC pain subscale will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain. | From Baseline up to Week 12 | 
| Percentage of Participants With at Least 30%, 50% and 70% Reduction From Baseline in WOMAC A1 (Walking Pain) Score | The WOMAC A1 score will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain. | From Baseline up to Week 12 | 
| Percentage of Participants Categorized by Each Patient Global Impression of Change (PGIC) Score | The 7-point PGIC is a complementary assessment of analgesic efficacy on a 7-point scale where 1 = Very much improved and 7 = Very much worse. | From Baseline up to Week 12 | 
| Change From Baseline in Patient-Specific Functional Scale (PSFS) | The PSFS scale will be assessed using an 11-point NRS, where 0= Unable to perform activity and 10=Able to perform activity at the same level as before your osteoarthritis of the knee started. | From Baseline up to Week 12 | 
| Change From Baseline in EuroQol-5 Dimension Health Questionnaire 5 Levels (EQ-5D-5L) Score | EQ-5D consists of EQ-5D descriptive system (Index score) and EQ visual analogue scale (VAS). EQ-5D-5L Index Score ranges from 0 to 1, with 0 representing death and 1 representing perfect health. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that range from 0 (worst imaginable) to 100 (best imaginable). | From Baseline up to Week 12 | 
| Change From Baseline in 36-Item Short-Form (SF-36) Domain Scores | The 8 SF-36 domain scores range from 0 (worst value) to 100 (best value), with higher scores reflecting better health status. | From Baseline up to Week 12 | 

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