Back to resultsA Study to Examine the Efficacy and Safety of REGN5069 in Patients With Pain Due to Osteoarthritis of the Knee
Primary Purpose
Osteoarthritis of the Knee, Pain
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
REGN5069
Matching Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis of the Knee
Eligibility 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.
Sites / Locations
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
- Regeneron Study Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
REGN5069 Low Dose
REGN5069 High Dose
Matching Placebo
Arm Description
Randomized in a 1:1:1 ratio
Randomized in a 1:1:1 ratio
Randomized in a 1:1:1 ratio
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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).
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03956550
Brief Title
A Study to Examine the Efficacy and Safety of REGN5069 in Patients With Pain Due to Osteoarthritis of the Knee
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Terminated
Why Stopped
Regeneron has discontinued further clinical development of REGN5069, an antibody to GFRα3, which was previously being studied in osteoarthritis pain of the knee
Study Start Date
May 21, 2019 (Actual)
Primary Completion Date
May 1, 2020 (Actual)
Study Completion Date
October 29, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis of the Knee, Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
259 (Actual)
8. Arms, Groups, and Interventions
Arm Title
REGN5069 Low Dose
Arm Type
Experimental
Arm Description
Randomized in a 1:1:1 ratio
Arm Title
REGN5069 High Dose
Arm Type
Experimental
Arm Description
Randomized in a 1:1:1 ratio
Arm Title
Matching Placebo
Arm Type
Experimental
Arm Description
Randomized in a 1:1:1 ratio
Intervention Type
Drug
Intervention Name(s)
REGN5069
Intervention Description
Intravenous (IV) Dose every 4 weeks (Q4W)
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Intravenous (IV) Dose every 4 weeks (QW4)
Primary Outcome Measure Information:
Title
Change From Baseline to Week 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
Description
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.
Time Frame
Baseline to Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 12 in WOMAC Total Score
Description
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.
Time Frame
Week 12
Title
Change From Baseline to Week 12 in WOMAC Physical Function Subscale Score
Description
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.
Time Frame
Week 12
Title
Change From Baseline to Week 12 in Patient Global Assessment (PGA) Score
Description
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).
Time Frame
Week 12
Title
Change From Baseline to Week 12 in WOMAC Stiffness Subscale Score
Description
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.
Time Frame
Week 12
Title
Percentage of Participants With ≥30% Improvement in WOMAC Pain Subscale Score
Description
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.
Time Frame
Week 12
Title
Number of Non-Serious and Serious Treatment-Emergent Adverse Events (TEAEs) Through End of Study
Description
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.
Time Frame
Baseline to Week 36
Title
Number of Imaging Abnormalities Consistent With Adjudicated Arthropathies Through End of Study
Description
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.
Time Frame
Baseline to Week 36
Title
Number of Participants With Presence of Anti-REGN5049 Antibody Development Through End of Study
Description
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.
Time Frame
Baseline to Week 36
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Regeneron Study Site
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Regeneron Study Site
City
Jupiter
State/Province
Florida
ZIP/Postal Code
33458
Country
United States
Facility Name
Regeneron Study Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Regeneron Study Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Regeneron Study Site
City
Tbilisi
ZIP/Postal Code
112
Country
Georgia
Facility Name
Regeneron Study Site
City
Chisinau
ZIP/Postal Code
MD2025
Country
Moldova, Republic of
Facility Name
Regeneron Study Site
City
Zgierz
State/Province
Lodzkie
ZIP/Postal Code
95-100
Country
Poland
Facility Name
Regeneron Study Site
City
Lublin
State/Province
Lubelskie
ZIP/Postal Code
20-412
Country
Poland
Facility Name
Regeneron Study Site
City
Zamosc
State/Province
Lubelskie
ZIP/Postal Code
22-400
Country
Poland
Facility Name
Regeneron Study Site
City
Warsaw
State/Province
Mazowieckie
ZIP/Postal Code
02 - 777
Country
Poland
Facility Name
Regeneron Study Site
City
Bialystok
State/Province
Podlaskie
ZIP/Postal Code
15-879
Country
Poland
Facility Name
Regeneron Study Site
City
Kyiv
ZIP/Postal Code
1135
Country
Ukraine
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All IPD that underlie publicly available results will be considered for sharing
IPD Sharing 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.
IPD Sharing 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).
IPD Sharing URL
https://vivli.org/
Learn more about this trial
A Study to Examine the Efficacy and Safety of REGN5069 in Patients With Pain Due to Osteoarthritis of the Knee
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