Clinical trial NCT03304379: 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
Official title: Phase 3 Randomized, Double-Blind, Multi-Dose, Placebo And NSAID Controlled Study To Evaluate The Efficacy And Safety Of Fasinumab In Patients With Pain Due To Osteoarthritis Of The Knee Or Hip
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis, Knee
Osteoarthritis, Hip
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Teva Pharmaceutical Industries, Ltd.
First posted: 2017-10-09
Enrollment: 1650
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Key Inclusion Criteria (additional criteria may apply at screening):

1. A clinical diagnosis of osteoarthritis (OA) of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2 for the index joint) at the screening visit.
2. Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments (acetaminophen/paracetamol to be taken as needed with a maximum daily dose of 2500 mg \[countries where 500 mg strength tablets/capsules are available\] or 2600 mg \[countries where 325 mg strength tablets/capsules are available\])
3. A history of at least 12 weeks of inadequate pain relief or intolerance to analgesics used for pain due to OA of the knee or hip
4. Currently using a stable dose of NSAID
5. Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the 24 weeks of treatment

Key Exclusion Criteria (additional criteria may apply at screening):

1. Non-compliance with the numeric rating scale (NRS) recording during the pre-randomization period
2. History or presence at the screening visit of non-OA inflammatory joint disease, Paget's disease of the spine, pelvis or femur, neuropathic disorders, multiple sclerosis, fibromyalgia, tumors or infections of the spinal cord, or renal osteodystrophy
3. History or presence on imaging of arthropathy, hip or knee dislocation, extensive subchondral cysts, evidence of severe structural damage, bone collapse, or primary metastatic tumor with the exception of chondromas or pathologic fractures
4. Trauma to the index joint within 3 months prior to the screening visit
5. Signs or symptoms of carpal tunnel syndrome within 6 months of screening
6. Patient is not a candidate for magnetic resonance imaging (MRI)
7. Is scheduled for a JR surgery to be performed during the study period or who would be unwilling or unable to undergo JR surgery if needed
8. History or presence at the screening visit of autonomic or diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy
9. Evidence of autonomic neuropathy as defined in the schedule of assessments (SoAs)
10. History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy
11. Use of systemic 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
12. Exposure to an anti-NGF antibody prior to the screening visit or known sensitivity or intolerance to anti-NGF antibodies
13. Women of childbearing potential who are unwilling to practice highly effective contraception prior to the start of the first treatment, during the study, and for at least 20 weeks after the last dose

Primary outcomes:
measure: 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 Placebo
timeFrame: Baseline up to Week 24
measure: Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
timeFrame: Baseline up to Week 24
Secondary outcomes:
measure: 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 Placebo
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo
timeFrame: Baseline up to Week 24
measure: Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
timeFrame: Baseline up to Week 24
measure: Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
timeFrame: Baseline up to Week 24
measure: Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale
timeFrame: Baseline up to Week 24
measure: Number of Participants With Adjudicated Arthropathy (AA) Events
timeFrame: Baseline up to follow-up period (Week 44)
measure: Number of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria
timeFrame: Baseline up to follow-up period (Week 44)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to follow-up period (Week 44)
measure: Number of Participants With Sympathetic Nervous System (SNS) Dysfunction Events
timeFrame: Baseline up to follow-up period (Week 44)
measure: Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs)
timeFrame: Baseline up to Week 44
measure: Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24
timeFrame: Baseline up to Week 24
measure: Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44
timeFrame: Baseline up to Week 44
measure: Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (Week 72)
timeFrame: At Week 72
measure: Serum Concentrations of Functional Fasinumab
timeFrame: At Weeks 0, 4, 8, 16, 24 and 44
measure: Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development
timeFrame: Baseline up to Week 44
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, Llc
state: Alabama
city: Mobile
country: United States
facility: Horizon Research Partners
state: Alabama
city: Chandler
country: United States
facility: Clinical Research Advantage, Inc./Warner Family Practice, PC
state: Arizona
city: Phoenix
country: United States
facility: Synexus Central Phoenix Medical Clinic
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortium Arizona
state: Arizona
city: Anaheim
country: United States
facility: Advance Research Center
state: California
city: El Cajon
country: United States
facility: TriWest Research Associates, LLC
state: California
city: Garden Grove
country: United States
facility: Paragon Rx Clinical Research, Inc.
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Roseville
country: United States
facility: Sierra Clinical Research
state: California
city: Sacramento
country: United States
facility: UC Davis Center for Musculoskeletal Health
state: California
city: San Diego
country: United States
facility: Advanced Research Center, Inc
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: Santa Ana
country: United States
facility: Paragon Rx Clinical Research, Inc
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Thousand Oaks
country: United States
facility: Westlake Medical Research
state: California
city: Vista
country: United States
facility: Synexus Clinical Research US, Inc.
state: California
city: Denver
country: United States
facility: Mountain View Clinical Research
state: Colorado
city: Bridgeport
country: United States
facility: New England Research Associates, LLC
state: Connecticut
city: Hamden
country: United States
facility: CRM of Greater New Haven, LLC
state: Connecticut
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research, LLC
state: Florida
city: Miami
country: United States
facility: AMB Research Center, Inc
state: Florida
city: Miami
country: United States
facility: Allied Biomedical Research Institute
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Pensacola
country: United States
facility: Gulf Region Clinical Research institute
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology & Immunology Specialists (IRIS)
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Marietta
country: United States
facility: Drug Studies America
state: Georgia
city: Marietta
country: United States
facility: Georgia Institute For Clinical Research LLC
state: Georgia
city: Woodstock
country: United States
facility: North Georgia Clinical Research
state: Georgia
city: Chicago
country: United States
facility: Chicago Clinical Research Institute, Inc
state: Illinois
city: Oak Lawn
country: United States
facility: Affinity Clinical Research Institute
state: Illinois
city: Evansville
country: United States
facility: Clinical Research Advantage, Inc.
state: Indiana
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC
state: Indiana
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center, Inc.
state: Massachusetts
city: Bay City
country: United States
facility: Great Lakes Research Group, Inc.
state: Michigan
city: Caro
country: United States
facility: Onyx Clinical Research
state: Michigan
city: Richfield
country: United States
facility: Synexus Clinical Research US, Inc.
state: Minnesota
city: Elkhorn
country: United States
facility: Skyline Medical Center /Radiant Research, Inc.
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research Associates, LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Robert Kaplan, D.O.
state: Nevada
city: Raritan
country: United States
facility: Amici Clinical Research, LLC
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Brooklyn
country: United States
facility: Drug Trial Brooklyn
state: New York
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Hartsdale
country: United States
facility: Drug Trials America
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates, LLC
state: New York
city: Shelby
country: United States
facility: Carolina Research Center
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: The Center For Clinical Research
state: North Carolina
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Inc
state: Ohio
city: Dayton
country: United States
facility: DOC Clinical Research
state: Ohio
city: Indiana
country: United States
facility: Center for Orthopaedics and Sports Medicine
state: Pennsylvania
city: Anderson
country: United States
facility: Radiant Research, Inc.
state: South Carolina
city: Greenville
country: United States
facility: Piedmont Comprehensive Pain Management Group
state: South Carolina
city: Greer
country: United States
facility: Radiant Research, Inc.
state: South Carolina
city: Indian Land
country: United States
facility: Piedmont Research Partners, LLC
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center at LowCountry Orthopaedics
state: South Carolina
city: Orangeburg
country: United States
facility: ACME Research, LLC
state: South Carolina
city: Memphis
country: United States
facility: Office of Dr.Ramesh C. Gupta MD
state: Tennessee
city: Lubbock
country: United States
facility: West Texas Clinical Research
state: Texas
city: Plano
country: United States
facility: Clinical Investigations Of Texas
state: Texas
city: Plano
country: United States
facility: Synexus USA
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center LLC
state: Virginia
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc
state: Virginia
city: Spokane
country: United States
facility: Spokane Joint Replacement Center
state: Washington
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: