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

Osteoarthritis, Knee Clinical Trial

— FACT OA2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03304379
• Other study ID #: R475-OA-1688
• Secondary ID: 2017-001702-15
• Status: Completed
• Phase: Phase 3
• Start date: October 26, 2017
• Est. completion date: November 9, 2020

Study information

• Verified date: January 2023
• 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 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1650
• Est. completion date: November 9, 2020
• Est. primary completion date: December 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Hip
• Osteoarthritis, Knee

Intervention

Drug:
• Fasinumab
Solution for injection in pre-filled syringe

Other:
• Diclofenac
NSAID active comparator (capsule)
• Celecoxib
NSAID active comparator (capsule)

Drug:
• Matching placebo
Fasinumab-matching placebo (solution for injection in pre-filled syringe); NSAID-matching placebo (capsule)

Locations

Country	Name	City	State
United States	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico
United States	Advance Research Center	Anaheim	California
United States	Radiant Research, Inc.	Anderson	South Carolina
United States	Pinnacle Research Group, Llc	Anniston	Alabama
United States	Great Lakes Research Group, Inc.	Bay City	Michigan
United States	Tufts Medical Center, Inc.	Boston	Massachusetts
United States	New England Research Associates, LLC	Bridgeport	Connecticut
United States	Drug Trial Brooklyn	Brooklyn	New York
United States	Onyx Clinical Research	Caro	Michigan
United States	Clinical Research Advantage, Inc./Warner Family Practice, PC	Chandler	Arizona
United States	Charlottesville Medical Research Center LLC	Charlottesville	Virginia
United States	Chicago Clinical Research Institute, Inc	Chicago	Illinois
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Aventiv Research Inc	Columbus	Ohio
United States	DOC Clinical Research	Dayton	Ohio
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Mountain View Clinical Research	Denver	Colorado
United States	TriWest Research Associates, LLC	El Cajon	California
United States	Skyline Medical Center /Radiant Research, Inc.	Elkhorn	Nebraska
United States	Clinical Research Advantage, Inc.	Evansville	Indiana
United States	MediSphere Medical Research Center, LLC	Evansville	Indiana
United States	Paragon Rx Clinical Research, Inc.	Garden Grove	California
United States	Northwell Health	Great Neck	New York
United States	Piedmont Comprehensive Pain Management Group	Greenville	South Carolina
United States	Radiant Research, Inc.	Greer	South Carolina
United States	CRM of Greater New Haven, LLC	Hamden	Connecticut
United States	Drug Trials America	Hartsdale	New York
United States	Piedmont Research Partners, LLC	Indian Land	South Carolina
United States	Center for Orthopaedics and Sports Medicine	Indiana	Pennsylvania
United States	Robert Kaplan, D.O.	Las Vegas	Nevada
United States	L-MARC Research Center	Louisville	Kentucky
United States	West Texas Clinical Research	Lubbock	Texas
United States	Drug Studies America	Marietta	Georgia
United States	Georgia Institute For Clinical Research LLC	Marietta	Georgia
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Office of Dr.Ramesh C. Gupta MD	Memphis	Tennessee
United States	Allied Biomedical Research Institute	Miami	Florida
United States	AMB Research Center, Inc	Miami	Florida
United States	Lakes Research, LLC	Miami Lakes	Florida
United States	Horizon Research Partners	Mobile	Alabama
United States	Catalina Research Institute, LLC	Montclair	California
United States	Health Research of Hampton Roads, Inc	Newport News	Virginia
United States	Coastal Carolina Research Center at LowCountry Orthopaedics	North Charleston	South Carolina
United States	Affinity Clinical Research Institute	Oak Lawn	Illinois
United States	Meridian Clinical Research Associates, LLC	Omaha	Nebraska
United States	ACME Research, LLC	Orangeburg	South Carolina
United States	Bioclinica Research	Orlando	Florida
United States	Gulf Region Clinical Research institute	Pensacola	Florida
United States	Synexus Central Phoenix Medical Clinic	Phoenix	Arizona
United States	Clinical Investigations Of Texas	Plano	Texas
United States	Synexus USA	Plano	Texas
United States	Integral Rheumatology & Immunology Specialists (IRIS)	Plantation	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Amici Clinical Research, LLC	Raritan	New Jersey
United States	Synexus Clinical Research US, Inc.	Richfield	Minnesota
United States	Sierra Clinical Research	Roseville	California
United States	UC Davis Center for Musculoskeletal Health	Sacramento	California
United States	Advanced Research Center, Inc	San Diego	California
United States	California Research Foundation	San Diego	California
United States	Paragon Rx Clinical Research, Inc	Santa Ana	California
United States	Carolina Research Center	Shelby	North Carolina
United States	Spokane Joint Replacement Center	Spokane	Washington
United States	Encompass Clinical Research	Spring Valley	California
United States	Stamford Therapeutics Consortium	Stamford	Connecticut
United States	Clinical Research Consortium Arizona	Tempe	Arizona
United States	Westlake Medical Research	Thousand Oaks	California
United States	Synexus Clinical Research US, Inc.	Vista	California
United States	Upstate Clinical Research Associates, LLC	Williamsville	New York
United States	PMG Research of Wilmington LLC	Wilmington	North Carolina
United States	The Center For Clinical Research	Winston-Salem	North Carolina
United States	North Georgia Clinical Research	Woodstock	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Teva Pharmaceutical Industries, Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline up to Week 24
Primary	Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo	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.	Baseline up to Week 24
Secondary	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	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.	Baseline up to Week 24
Secondary	Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Participants Treated With Fasinumab Compared to Placebo	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.	Baseline up to Week 24
Secondary	Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs	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.	Baseline up to Week 24
Secondary	Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs	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.	Baseline up to Week 24
Secondary	Change From Baseline in PGA Score up to Week 24 in Participants Treated With Fasinumab Compared to Participants Treated With NSAIDs	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.	Baseline up to Week 24
Secondary	Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale	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.	Baseline up to Week 24
Secondary	Number of Participants With Adjudicated Arthropathy (AA) Events	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.	Baseline up to follow-up period (Week 44)
Secondary	Number of Participants With AA Events Meeting Destructive Arthropathy (DA) Criteria	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.	Baseline up to follow-up period (Week 44)
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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.	Baseline up to follow-up period (Week 44)
Secondary	Number of Participants With Sympathetic Nervous System (SNS) Dysfunction Events	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.	Baseline up to follow-up period (Week 44)
Secondary	Number of Participants With At-least One Peripheral Sensory Adverse Events (AEs)	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).	Baseline up to Week 44
Secondary	Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 24	Number of participants who underwent a JR surgery from baseline up to Week 24 were reported.	Baseline up to Week 24
Secondary	Number of Participants Who Underwent a Joint Replacements (JR) Surgery From Baseline up to Week 44	Number of participants who underwent a JR surgery from baseline up to follow-up period (Week 44) were reported.	Baseline up to Week 44
Secondary	Number of Participants With Joint Replacement (JR) Surgery Reported at End of Study (EOS) (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.	At Week 72
Secondary	Serum Concentrations of Functional Fasinumab		At Weeks 0, 4, 8, 16, 24 and 44
Secondary	Number of Participants With At-least One Positive Anti-Drug Antibody (ADA) Development	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.	Baseline up to Week 44