Comparison of a Single RTX-GRT7039 and Placebo Intra-articular Injection for Pain Associated With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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A double-blind, randomized, placebo-controlled, parallel-group, multi-site, clinical trial to confirm the efficacy and safety of single injection of RTX-GRT7039 versus placebo 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 52 weeks.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase III Trial, to Evaluate the Efficacy and Safety of a Single Intra-articular Injection of RTX-GRT7039 in Adult Subjects With Pain Associated With Osteoarthritis of the Knee

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: RTX-GRT7039
* Drug: Placebo


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 from any cause other than osteoarthritis, including referred pain, bursitis, or tendonitis. The participant has clinical hip osteoarthritis on the side of the index knee. The participant has pre-existing osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, severe bone on bone osteoarthritis, knee pain attributable to disease other than osteoarthritis, or the participant has rapidly progressing osteoarthritis (RPOA) Type I or Type II. 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 X-ray 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 efficacy or safety assessments, or any other reason which, in the investigator's opinion, may preclude the participant's participation in 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.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RTX-GRT7039<br>Participants will receive a single intra-articular injection of RTX-GRT7039 during the 52-week double-blind treatment period. | Drug: RTX-GRT7039<br>* RTX-GRT7039 intra-articular injection.<br>|
| Placebo Comparator: Placebo<br>Participants will receive a single intra-articular injection of placebo matching RTX-GRT7039 during the 52-week double-blind treatment period. | Drug: Placebo<br>* Placebo matching RTX-GRT7039 intra-articular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score | The WOMAC pain subscale will be assessed using an 11-point numeric rating scale (NRS), where 0= no pain and 10=worst pain imaginable. | From Baseline up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change 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 imaginable. | From Baseline up to Week 52 | 
| 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 52 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) |  | From Baseline up to Week 52 | 
| 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 52 | 
| 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=better outcome and 10=worst outcome. | From Baseline up to Week 52 | 
| Change from Baseline in WOMAC A1 (Walking Pain) Subscale Score | The WOMAC A1 subscale will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable. | From Baseline up to Week 52 | 
| 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 imaginable. | From Baseline up to Week 52 | 
| Percentage of Participants With at Least 30%, 50% and 70% Reduction From Baseline in WOMAC A1 (Walking Pain) Subscale Score | The WOMAC A1 subscale will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable. | From Baseline up to Week 52 | 
| Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response | OMERACT-OARSI response: A high improvement of >=50% (percentage change) and >=2 (absolute change) in either the WOMAC pain subscale score or WOMAC physical function subscale score, OR an improvement in at least 2 of the following 3: Improvement of >=20% (percentage change) and >=1 (absolute change) in the WOMAC pain subscale score. Improvement of >=20% (percentage change) and >=1 (absolute change) in the WOMAC physical function subscale score. Improvement of >=20% (percentage change) and >=10 (absolute change) in Patient Global Assessment (PGA) of osteoarthritis. Absolute values will be normalized to the 0 (no pain) to 100 scale (higher pain/difficulty). | From Baseline up to Week 52 | 
| 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 52 | 
| 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 1.0 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 52 | 
| Change From Baseline in 36-Item Short-Form (SF-36) Domain Scores | The 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 52 | 
| Number of Participants Reporting Durability of Effect | Durability of effect is defined as time from an improvement in WOMAC pain subscale to pain recurrence. Pain recurrence is defined as no reduction of >=30% from baseline in the WOMAC Pain subscale score (assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable). | From Baseline up to Week 52 | 

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