FACT OA2: 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

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03304379

Collaborator

Teva Pharmaceutical Industries, Ltd. (Industry)

1,650

Enrollment

Locations

Arms

36.5

Actual Duration (Months)

23.2

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee Osteoarthritis, Hip	Drug: Fasinumab Other: Diclofenac Other: Celecoxib Drug: Matching placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1650 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 26, 2017

Actual Primary Completion Date :

Dec 13, 2019

Actual Study Completion Date :

Nov 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dosing regimen 1	Drug: Fasinumab Solution for injection in pre-filled syringe Other Names: REGN475 MT-5547 Drug: Matching placebo Fasinumab-matching placebo (solution for injection in pre-filled syringe); NSAID-matching placebo (capsule)
Experimental: Dosing regimen 2	Other: Diclofenac NSAID active comparator (capsule) Other Names: ZORVOLEX Drug: Matching placebo Fasinumab-matching placebo (solution for injection in pre-filled syringe); NSAID-matching placebo (capsule)
Experimental: Dosing regimen 3	Other: Celecoxib NSAID active comparator (capsule) Other Names: CELEBREX Drug: Matching placebo Fasinumab-matching placebo (solution for injection in pre-filled syringe); NSAID-matching placebo (capsule)
Experimental: Dosing regimen 4	Drug: Matching placebo Fasinumab-matching placebo (solution for injection in pre-filled syringe); NSAID-matching placebo (capsule)

Outcome Measures

Primary Outcome Measures

Change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores from baseline to week 24 in patients treated with fasinumab compared to patients treated with placebo. [Baseline to week 24]
Change in the WOMAC physical function subscale scores from baseline to week 24 in patients treated with fasinumab compared to patients treated with placebo. [Baseline to week 24]

Secondary Outcome Measures

Change from baseline to week 24 in Patient Global Assessment (PGA) in patients treated with fasinumab compared to patients treated with placebo [Baseline to week 24]
Percentage of patients treated with fasinumab, compared to patients treated with placebo, who had a response at week 24, with response defined as an improvement by ≥30% in WOMAC pain sub scale score [Baseline, Week 24]
Change from baseline to week 24 in WOMAC pain subscale scores in patients treated with fasinumab compared to patients treated with NSAIDs (pooled celecoxib and diclofenac arms) [Baseline to week 24]
Change from baseline to week 24 in WOMAC physical function subscale scores in patients treated with fasinumab compared to patients treated with NSAIDs (pooled celecoxib and diclofenac arms) [Baseline to week 24]
Change from baseline to week 24 in PGA score in patients treated with fasinumab compared to patients treated with NSAIDs (pooled celecoxib and diclofenac arms) [Baseline to week 24]
Incidence of adjudicated arthropathy (AA) (as confirmed by independent adjudication) [Baseline through the follow-up period (week 44)]
Incidence of destructive arthropathy (DA) (as confirmed by independent adjudication) [Baseline through the follow-up period (week 44)]
Incidence of Treatment Emergent Adverse Events (TEAEs) [Baseline through the follow-up period (week 44)]
Incidence of sympathetic nervous system dysfunction (as diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist) [Baseline through the follow-up period (week 44)]
Incidence of peripheral sensory Adverse Events (AEs) that require a neurology consultation [Baseline through the follow-up period (week 44)]
Incidence of all-cause joint replacements (JRs) through week 24 [Baseline through week 24]
Incidence of all-cause JRs through week 44 [Baseline through the follow-up period (week 44)]
Incidence of JR at telephone survey [Week 72]
Telephone survey to occur at week 72 ([Week 20 (completion of study drug) plus 52 weeks])

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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.
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])
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
Currently using a stable dose of NSAID
Willing to discontinue glucosamine sulfate and chondroitin sulfate treatments during the 24 weeks of treatment

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

Non-compliance with the numeric rating scale (NRS) recording during the pre-randomization period
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
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
Trauma to the index joint within 3 months prior to the screening visit
Signs or symptoms of carpal tunnel syndrome within 6 months of screening
Patient is not a candidate for magnetic resonance imaging (MRI)
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
History or presence at the screening visit of autonomic or diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy
Evidence of autonomic neuropathy as defined in the schedule of assessments (SoAs)
History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy
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
Exposure to an anti-NGF antibody prior to the screening visit or known sensitivity or intolerance to anti-NGF antibodies
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Research Group, Llc	Anniston	Alabama	United States	36207
2	Horizon Research Partners	Mobile	Alabama	United States	36608
3	Clinical Research Advantage, Inc./Warner Family Practice, PC	Chandler	Arizona	United States	85224
4	Synexus Central Phoenix Medical Clinic	Phoenix	Arizona	United States	85020
5	Clinical Research Consortium Arizona	Tempe	Arizona	United States	85283
6	Advance Research Center	Anaheim	California	United States	92805
7	TriWest Research Associates, LLC	El Cajon	California	United States	92020
8	Paragon Rx Clinical Research, Inc.	Garden Grove	California	United States	92840
9	Catalina Research Institute, LLC	Montclair	California	United States	91763
10	Sierra Clinical Research	Roseville	California	United States	95661
11	UC Davis Center for Musculoskeletal Health	Sacramento	California	United States	95817
12	Advanced Research Center, Inc	San Diego	California	United States	92103
13	California Research Foundation	San Diego	California	United States	92123
14	Paragon Rx Clinical Research, Inc	Santa Ana	California	United States	92703
15	Encompass Clinical Research	Spring Valley	California	United States	91978
16	Westlake Medical Research	Thousand Oaks	California	United States	91360
17	Synexus Clinical Research US, Inc.	Vista	California	United States	92083
18	Mountain View Clinical Research	Denver	Colorado	United States	80209
19	New England Research Associates, LLC	Bridgeport	Connecticut	United States	06606
20	CRM of Greater New Haven, LLC	Hamden	Connecticut	United States	06157
21	Stamford Therapeutics Consortium	Stamford	Connecticut	United States	06905
22	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
23	Lakes Research, LLC	Miami Lakes	Florida	United States	33014
24	AMB Research Center, Inc	Miami	Florida	United States	33144
25	Allied Biomedical Research Institute	Miami	Florida	United States	33155
26	Bioclinica Research	Orlando	Florida	United States	32806
27	Gulf Region Clinical Research institute	Pensacola	Florida	United States	32514
28	Integral Rheumatology & Immunology Specialists (IRIS)	Plantation	Florida	United States	33324
29	Progressive Medical Research	Port Orange	Florida	United States	32127
30	Drug Studies America	Marietta	Georgia	United States	30060
31	Georgia Institute For Clinical Research LLC	Marietta	Georgia	United States	30060
32	North Georgia Clinical Research	Woodstock	Georgia	United States	30189
33	Chicago Clinical Research Institute, Inc	Chicago	Illinois	United States	60607
34	Affinity Clinical Research Institute	Oak Lawn	Illinois	United States	60453
35	Clinical Research Advantage, Inc.	Evansville	Indiana	United States	47714
36	MediSphere Medical Research Center, LLC	Evansville	Indiana	United States	47714
37	L-MARC Research Center	Louisville	Kentucky	United States	40213
38	Tandem Clinical Research	Marrero	Louisiana	United States	70072
39	Tufts Medical Center, Inc.	Boston	Massachusetts	United States	02111
40	Great Lakes Research Group, Inc.	Bay City	Michigan	United States	48706
41	Onyx Clinical Research	Caro	Michigan	United States	48723
42	Synexus Clinical Research US, Inc.	Richfield	Minnesota	United States	55423
43	Skyline Medical Center /Radiant Research, Inc.	Elkhorn	Nebraska	United States	68022
44	Meridian Clinical Research Associates, LLC	Omaha	Nebraska	United States	68134
45	Robert Kaplan, D.O.	Las Vegas	Nevada	United States	89144
46	Amici Clinical Research, LLC	Raritan	New Jersey	United States	08869
47	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico	United States	87102
48	Drug Trial Brooklyn	Brooklyn	New York	United States	11230
49	Northwell Health	Great Neck	New York	United States	11021
50	Drug Trials America	Hartsdale	New York	United States	10530
51	Upstate Clinical Research Associates, LLC	Williamsville	New York	United States	14221
52	Carolina Research Center	Shelby	North Carolina	United States	28150
53	PMG Research of Wilmington LLC	Wilmington	North Carolina	United States	28401
54	The Center For Clinical Research	Winston-Salem	North Carolina	United States	27103
55	New Horizons Clinical Research	Cincinnati	Ohio	United States	45242
56	Aventiv Research Inc	Columbus	Ohio	United States	43213
57	DOC Clinical Research	Dayton	Ohio	United States	45432
58	Center for Orthopaedics and Sports Medicine	Indiana	Pennsylvania	United States	15701
59	Radiant Research, Inc.	Anderson	South Carolina	United States	29621
60	Piedmont Comprehensive Pain Management Group	Greenville	South Carolina	United States	29601
61	Radiant Research, Inc.	Greer	South Carolina	United States	29651
62	Piedmont Research Partners, LLC	Indian Land	South Carolina	United States	29707
63	Coastal Carolina Research Center at LowCountry Orthopaedics	North Charleston	South Carolina	United States	29406
64	ACME Research, LLC	Orangeburg	South Carolina	United States	29118
65	Office of Dr.Ramesh C. Gupta MD	Memphis	Tennessee	United States	38119
66	West Texas Clinical Research	Lubbock	Texas	United States	79410
67	Clinical Investigations Of Texas	Plano	Texas	United States	75075
68	Synexus USA	Plano	Texas	United States	75093
69	Charlottesville Medical Research Center LLC	Charlottesville	Virginia	United States	22911
70	Health Research of Hampton Roads, Inc	Newport News	Virginia	United States	23606
71	Spokane Joint Replacement Center	Spokane	Washington	United States	99218