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Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip

Phase 3
Completed
Conditions
Osteoarthritis, Knee
Osteoarthritis, Hip
Interventions
Other: Diclofenac
Other: Celecoxib
Drug: Fasinumab
Drug: Matching placebo
Registration Number
NCT03304379
Lead Sponsor
Regeneron Pharmaceuticals
Brief Summary

The primary objective of the study is to evaluate the efficacy of fasinumab compared to placebo, when administered for up to 24 weeks in patients with pain due to osteoarthritis (OA) of the knee or hip.

The secondary objectives of the study are:

* To evaluate the efficacy of fasinumab compared to non-steroidal anti-inflammatory drugs (NSAID)s, when administered for up to 24 weeks in patients with pain due to OA of the knee or hip

* To assess the safety and tolerability of fasinumab compared to placebo and compared to NSAIDs, when administered for up to 24 weeks in patients with pain due to OA of the knee or hip

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1650
Inclusion Criteria

Not provided

Read More
Exclusion Criteria

Not provided

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Dosing regimen 2Diclofenac-
Dosing regimen 2Matching placebo-
Dosing regimen 3Celecoxib-
Dosing regimen 3Matching placebo-
Dosing regimen 4Matching placebo-
Dosing regimen 1Matching placebo-
Dosing regimen 1Fasinumab-
Primary Outcome Measures
NameTimeMethod
Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to PlaceboBaseline up to Week 24

WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.

Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to PlaceboBaseline up to Week 24

Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Participants Treated With Fasinumab Compared to PlaceboBaseline up to Week 24

WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a NRS of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.

Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to PlaceboBaseline up to Week 24

The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition.

Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDsBaseline up to Week 24

WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.

Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDsBaseline up to Week 24

Physical function referred to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.

Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDsBaseline up to Week 24

The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition.

Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain ScaleBaseline up to Week 24

Participants reported weekly average walking index joint pain based on NRS. The NRS was nationally recognized numeric scale from 0 to 10, where 0 would demonstrate no pain, 1 to 3 would demonstrate mild pain, 4 to 6 would be moderate pain, 7 to 9 would be severe pain and 10 would be the worst pain possible. Higher score indicated greater pain.

Number of Participants With Adjudicated Arthropathy (AA) EventsBaseline up to follow-up period (Week 44)

AA was a composite term that encompasses the following conditions: Rapidly progressive Osteoarthritis (OA) type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee. AAs were also evaluated to determine if they met Destructive Arthropathy criteria.

Number of Participants With AA Events Meeting Destructive Arthropathy (DA) CriteriaBaseline up to follow-up period (Week 44)

DA is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee.

Number of Participants With Treatment Emergent Adverse Events (TEAEs)Baseline up to follow-up period (Week 44)

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a study drug which may or may not have a causal relationship with the study drug. TEAE was defined as an AE with an onset that occurs after receiving study drug. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs.

Number of Participants With Sympathetic Nervous System (SNS) Dysfunction EventsBaseline up to follow-up period (Week 44)

Potential events of SNS dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist.

Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs)Baseline up to Week 44

Any participants with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an Adverse Events of Special Interest (AESI).

Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24Baseline up to Week 24

Number of participants who underwent a JR surgery from baseline up to Week 24 were reported.

Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44Baseline up to Week 44

Number of participants who underwent a JR surgery from baseline up to follow-up period (Week 44) were reported.

Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72)At Week 72

An EOS phone contact was conducted at Week 72 following the last dose of study drug (Week 24) to evaluate the number of participants who had undergone or were scheduled for JR surgery.

Serum Concentrations of Functional FasinumabAt Weeks 0, 4, 8, 16, 24 and 44
Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) DevelopmentBaseline up to Week 44

Immunogenicity was characterized by ADA responses \& titers. Responses categories: 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 post first dose when baseline results = negative or missing.

Trial Locations

Locations (69)

Advance Research Center

🇺🇸

Anaheim, California, United States

Catalina Research Institute, LLC

🇺🇸

Montclair, California, United States

Clinical Research Advantage, Inc./Warner Family Practice, PC

🇺🇸

Chandler, Arizona, United States

Synexus Central Phoenix Medical Clinic

🇺🇸

Phoenix, Arizona, United States

Affinity Clinical Research Institute

🇺🇸

Oak Lawn, Illinois, United States

California Research Foundation

🇺🇸

San Diego, California, United States

Westlake Medical Research

🇺🇸

Thousand Oaks, California, United States

Georgia Institute For Clinical Research LLC

🇺🇸

Marietta, Georgia, United States

Lakes Research, LLC

🇺🇸

Miami Lakes, Florida, United States

Center for Orthopaedics and Sports Medicine

🇺🇸

Indiana, Pennsylvania, United States

Great Lakes Research Group, Inc.

🇺🇸

Bay City, Michigan, United States

Meridian Clinical Research Associates, LLC

🇺🇸

Omaha, Nebraska, United States

Tandem Clinical Research

🇺🇸

Marrero, Louisiana, United States

Robert Kaplan, D.O.

🇺🇸

Las Vegas, Nevada, United States

Albuquerque Clinical Trials, Inc.

🇺🇸

Albuquerque, New Mexico, United States

DOC Clinical Research

🇺🇸

Dayton, Ohio, United States

Drug Trials America

🇺🇸

Hartsdale, New York, United States

Piedmont Research Partners, LLC

🇺🇸

Indian Land, South Carolina, United States

Synexus USA

🇺🇸

Plano, Texas, United States

Coastal Carolina Research Center at LowCountry Orthopaedics

🇺🇸

North Charleston, South Carolina, United States

Clinical Investigations Of Texas

🇺🇸

Plano, Texas, United States

ACME Research, LLC

🇺🇸

Orangeburg, South Carolina, United States

West Texas Clinical Research

🇺🇸

Lubbock, Texas, United States

Health Research of Hampton Roads, Inc

🇺🇸

Newport News, Virginia, United States

Clinical Research Advantage, Inc.

🇺🇸

Evansville, Indiana, United States

MediSphere Medical Research Center, LLC

🇺🇸

Evansville, Indiana, United States

L-MARC Research Center

🇺🇸

Louisville, Kentucky, United States

Pinnacle Research Group, Llc

🇺🇸

Anniston, Alabama, United States

Horizon Research Partners

🇺🇸

Mobile, Alabama, United States

TriWest Research Associates, LLC

🇺🇸

El Cajon, California, United States

Clinical Research Consortium Arizona

🇺🇸

Tempe, Arizona, United States

UC Davis Center for Musculoskeletal Health

🇺🇸

Sacramento, California, United States

Advanced Research Center, Inc

🇺🇸

San Diego, California, United States

Paragon Rx Clinical Research, Inc

🇺🇸

Santa Ana, California, United States

Encompass Clinical Research

🇺🇸

Spring Valley, California, United States

New England Research Associates, LLC

🇺🇸

Bridgeport, Connecticut, United States

Stamford Therapeutics Consortium

🇺🇸

Stamford, Connecticut, United States

CRM of Greater New Haven, LLC

🇺🇸

Hamden, Connecticut, United States

Avail Clinical Research, LLC

🇺🇸

DeLand, Florida, United States

Bioclinica Research

🇺🇸

Orlando, Florida, United States

Integral Rheumatology & Immunology Specialists (IRIS)

🇺🇸

Plantation, Florida, United States

Progressive Medical Research

🇺🇸

Port Orange, Florida, United States

Drug Studies America

🇺🇸

Marietta, Georgia, United States

Allied Biomedical Research Institute

🇺🇸

Miami, Florida, United States

Chicago Clinical Research Institute, Inc

🇺🇸

Chicago, Illinois, United States

North Georgia Clinical Research

🇺🇸

Woodstock, Georgia, United States

Tufts Medical Center, Inc.

🇺🇸

Boston, Massachusetts, United States

Skyline Medical Center /Radiant Research, Inc.

🇺🇸

Elkhorn, Nebraska, United States

Northwell Health

🇺🇸

Great Neck, New York, United States

Upstate Clinical Research Associates, LLC

🇺🇸

Williamsville, New York, United States

Carolina Research Center

🇺🇸

Shelby, North Carolina, United States

PMG Research of Wilmington LLC

🇺🇸

Wilmington, North Carolina, United States

The Center For Clinical Research

🇺🇸

Winston-Salem, North Carolina, United States

New Horizons Clinical Research

🇺🇸

Cincinnati, Ohio, United States

Office of Dr.Ramesh C. Gupta MD

🇺🇸

Memphis, Tennessee, United States

Charlottesville Medical Research Center LLC

🇺🇸

Charlottesville, Virginia, United States

AMB Research Center, Inc

🇺🇸

Miami, Florida, United States

Synexus Clinical Research US, Inc.

🇺🇸

Richfield, Minnesota, United States

Paragon Rx Clinical Research, Inc.

🇺🇸

Garden Grove, California, United States

Aventiv Research Inc

🇺🇸

Columbus, Ohio, United States

Mountain View Clinical Research

🇺🇸

Denver, Colorado, United States

Radiant Research, Inc.

🇺🇸

Greer, South Carolina, United States

Gulf Region Clinical Research institute

🇺🇸

Pensacola, Florida, United States

Amici Clinical Research, LLC

🇺🇸

Raritan, New Jersey, United States

Piedmont Comprehensive Pain Management Group

🇺🇸

Greenville, South Carolina, United States

Drug Trial Brooklyn

🇺🇸

Brooklyn, New York, United States

Spokane Joint Replacement Center

🇺🇸

Spokane, Washington, United States

Onyx Clinical Research

🇺🇸

Caro, Michigan, United States

Sierra Clinical Research

🇺🇸

Roseville, California, United States

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