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

Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03956550
• Other study ID #: R5069-OA-1849
• Status: Terminated
• Phase: Phase 2
• Start date: May 21, 2019
• Est. completion date: October 29, 2020

Study information

• Verified date: June 2021
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 259
• Est. completion date: October 29, 2020
• Est. primary completion date: May 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis of the Knee
• Osteoarthritis, Knee
• Pain

Intervention

Drug:
• REGN5069
Intravenous (IV) Dose every 4 weeks (Q4W)
• Matching Placebo
Intravenous (IV) Dose every 4 weeks (QW4)

Locations

Country	Name	City	State
Georgia	Regeneron Study Site	Tbilisi
Moldova, Republic of	Regeneron Study Site	Chisinau
Poland	Regeneron Study Site	Bialystok	Podlaskie
Poland	Regeneron Study Site	Lublin	Lubelskie
Poland	Regeneron Study Site	Warsaw	Mazowieckie
Poland	Regeneron Study Site	Zamosc	Lubelskie
Poland	Regeneron Study Site	Zgierz	Lodzkie
Ukraine	Regeneron Study Site	Kyiv
United States	Regeneron Study Site	Charleston	South Carolina
United States	Regeneron Study Site	DeLand	Florida
United States	Regeneron Study Site	Jupiter	Florida
United States	Regeneron Study Site	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Georgia,  Moldova, Republic of,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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