A Study to Examine the Efficacy and Safety of REGN5069 in Patients With Pain Due to Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the efficacy of REGN5069 compared to placebo in patients with pain due to radiographically-confirmed OA of the knee who have a history of inadequate joint pain relief or intolerance to current analgesic therapy. The secondary objectives of the study are: To characterize the concentrations of functional REGN5069 in serum over time when patients are treated for up to 12 weeks To assess the safety and tolerability of REGN5069 compared with placebo when patients are treated for up to 12 weeks To measure levels of anti-drug antibodies (ADAs) against REGN5069 following multiple IV administrations

Official Title
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A Randomized, Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Efficacy and Safety of REGN5069 in Patients With Pain Due to Osteoarthritis of the Knee

Conditions
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Pain, Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: REGN5069
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Generally in good health at the screening visit Body mass index (BMI) ≤39 kg/m2 at the screening visit Clinical diagnosis of OA of the knee on the American College of Rheumatology criteria (Altman, 1986) with radiologic evidence of OA (K-L score ≥2) at the index joint at the screening visit Moderate-to-severe pain in the index joint A history of inadequate pain relief from or intolerance to analgesics used for OA Key Exclusion Criteria: Diagnosis of systemic diseases that may affect joints History or presence of osteonecrosis, destructive arthropathy, neuropathic joint arthropathy, pathologic fractures in any shoulder, hip, or knee joint(s), hip dislocation (prosthetic hip dislocation is eligible), or knee dislocation (patella dislocation is eligible) at the screening visit. Presence of subchondral insufficiency fracture on screening films or MRI as assessed by the central imaging reader. Is scheduled for a joint replacement surgery to be performed during the study period Received an intra-articular injection of hyaluronic acid in any joint within 90 days prior to the screening visit Systemic (ie, IV, oral, or intramuscular) corticosteroids within 30 days prior to the screening visit. Intra-articular corticosteroids in the index joint within 12 weeks prior to the screening visit, or to any other joint within 30 days prior to the screening visit (topical, intranasal, or inhaled corticosteroids are permitted). History or presence at the screening visit of multiple sclerosis, autonomic neuropathy, diabetic neuropathy, or other peripheral neuropathy Significant concomitant illness including, but not limited to, psychiatric, cardiac, renal, hepatic, neurological, endocrinological, metabolic, or lymphatic disease that, in the opinion of the investigator, would adversely affect the patient's participation in the study History of myocardial infarction, acute coronary syndromes, transient ischemic attack, or cerebrovascular accident within 12 months prior to the screening visit Note: Other protocol defined inclusion/exclusion criteria apply.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN5069 Low Dose<br>Randomized in a 1:1:1 ratio | Drug: REGN5069<br>* Intravenous (IV) Dose every 4 weeks (Q4W)<br>|
| Experimental: REGN5069 High Dose<br>Randomized in a 1:1:1 ratio | Drug: REGN5069<br>* Intravenous (IV) Dose every 4 weeks (Q4W)<br>|
| Experimental: Matching Placebo<br>Randomized in a 1:1:1 ratio | Drug: Matching Placebo<br>* Intravenous (IV) Dose every 4 weeks (QW4)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in WOMAC Total Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Week 12 | 
| Change From Baseline to Week 12 in WOMAC Physical Function Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Week 12 | 
| Change From Baseline to Week 12 in Patient Global Assessment (PGA) Score | The Patient Global Assessment of OA (PGA) is a patient-rated assessment of current disease state on a 5-point Likert scale (1 = very good; 2 = good; 3 = fair; 4 = poor; and 5 = very poor). | Week 12 | 
| Change From Baseline to Week 12 in WOMAC Stiffness Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Week 12 | 
| Percentage of Participants With ≥30% Improvement in WOMAC Pain Subscale Score | The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations. | Week 12 | 
| Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study | An adverse event (AE) is any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug. Treatment-emergent AEs (TEAEs) are AEs that developed or worsened during the treatment period. | Baseline to Week 36 | 
| Number of Imaging Abnormalities Consistent With Adjudicated Arthropathies Through End of Study | Adjudicated arthropathy is an umbrella term referring to Rapidly Progressive Osteoarthritis Type 1 (RPOA-1), Rapidly Progressive Osteoarthritis Type 2 (RPOA-2), subchondral insufficiency fractures (SIF) and osteonecrosis (ON) confirmed by an arthropathy adjudication committee. | Baseline to Week 36 | 
| Number of Participants With Presence of Anti-REGN5049 Antibody Development Through End of Study | Immunogenicity will be characterized by ADA responses & titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses < 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, ≥ 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the REG5069 ADA assay post first dose when baseline results = negative or missing. | Baseline to Week 36 |