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

Phase 2

Terminated

Conditions: Pain
Osteoarthritis of the Knee

Interventions: Drug: REGN5069
Drug: Matching Placebo

Registration Number: NCT03956550

Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 259

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
REGN5069 High Dose	REGN5069	Randomized in a 1:1:1 ratio
Matching Placebo	Matching Placebo	Randomized in a 1:1:1 ratio
REGN5069 Low Dose	REGN5069	Randomized in a 1:1:1 ratio

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score	Baseline to Week 12	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.

Secondary Outcome Measures

Name	Time	Method
Number of Imaging Abnormalities Consistent With Adjudicated Arthropathies Through End of Study	Baseline to Week 36	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.
Change From Baseline to Week 12 in WOMAC Total Score	Week 12	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.
Change From Baseline to Week 12 in Patient Global Assessment (PGA) Score	Week 12	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).
Change From Baseline to Week 12 in WOMAC Physical Function Subscale Score	Week 12	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.
Change From Baseline to Week 12 in WOMAC Stiffness Subscale Score	Week 12	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.
Percentage of Participants With ≥30% Improvement in WOMAC Pain Subscale Score	Week 12	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.
Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study	Baseline to Week 36	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.
Number of Participants With Presence of Anti-REGN5049 Antibody Development Through End of Study	Baseline to Week 36	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.