Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03956550
Recruitment Status : Terminated (Regeneron has discontinued further clinical development of REGN5069, an antibody to GFRα3, which was previously being studied in osteoarthritis pain of the knee)
First Posted : May 20, 2019
Results First Posted : July 1, 2021
Last Update Posted : July 1, 2021
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Osteoarthritis of the Knee Pain Drug: REGN5069 Drug: Matching Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 259 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : May 21, 2019
Actual Primary Completion Date : May 1, 2020
Actual Study Completion Date : October 29, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: REGN5069 Low Dose
Randomized in a 1:1:1 ratio
Drug: REGN5069
Intravenous (IV) Dose every 4 weeks (Q4W)

Experimental: REGN5069 High Dose
Randomized in a 1:1:1 ratio
Drug: REGN5069
Intravenous (IV) Dose every 4 weeks (Q4W)

Experimental: Matching Placebo
Randomized in a 1:1:1 ratio
Drug: Matching Placebo
Intravenous (IV) Dose every 4 weeks (QW4)




Primary Outcome Measures :
  1. Change From Baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score [ Time Frame: 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 :
  1. Change From Baseline to Week 12 in WOMAC Total Score [ Time Frame: 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.

  2. Change From Baseline to Week 12 in WOMAC Physical Function Subscale Score [ Time Frame: 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.

  3. Change From Baseline to Week 12 in Patient Global Assessment (PGA) Score [ Time Frame: 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).

  4. Change From Baseline to Week 12 in WOMAC Stiffness Subscale Score [ Time Frame: 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.

  5. Percentage of Participants With ≥30% Improvement in WOMAC Pain Subscale Score [ Time Frame: 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.

  6. Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study [ Time Frame: 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.

  7. Number of Imaging Abnormalities Consistent With Adjudicated Arthropathies Through End of Study [ Time Frame: 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.

  8. Number of Participants With Presence of Anti-REGN5049 Antibody Development Through End of Study [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03956550


Locations
Layout table for location information
United States, Florida
Regeneron Study Site
DeLand, Florida, United States, 32720
Regeneron Study Site
Jupiter, Florida, United States, 33458
Regeneron Study Site
Miami, Florida, United States, 33143
United States, South Carolina
Regeneron Study Site
Charleston, South Carolina, United States, 29406
Georgia
Regeneron Study Site
Tbilisi, Georgia, 112
Moldova, Republic of
Regeneron Study Site
Chisinau, Moldova, Republic of, MD2025
Poland
Regeneron Study Site
Zgierz, Lodzkie, Poland, 95-100
Regeneron Study Site
Lublin, Lubelskie, Poland, 20-412
Regeneron Study Site
Zamosc, Lubelskie, Poland, 22-400
Regeneron Study Site
Warsaw, Mazowieckie, Poland, 02 - 777
Regeneron Study Site
Bialystok, Podlaskie, Poland, 15-879
Ukraine
Regeneron Study Site
Kyiv, Ukraine, 1135
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:
Study Protocol  [PDF] September 4, 2019
Statistical Analysis Plan  [PDF] November 17, 2020

Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03956550    
Other Study ID Numbers: R5069-OA-1849
First Posted: May 20, 2019    Key Record Dates
Results First Posted: July 1, 2021
Last Update Posted: July 1, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, EMA, PMDA, etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
URL: https://vivli.org/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases