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Study to Evaluate the Effects of Fasinumab on Peripheral Nerve Function in Patients With Pain Due to Osteoarthritis of the Hip or Knee

Primary Purpose

Osteoarthritis, Knee, Osteoarthritis, Hip

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Fasinumab

Placebo

About this trial

This is an interventional treatment trial for Osteoarthritis, Knee

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

A clinical diagnosis of 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
Moderate-to-severe pain in the index joint defined as a WOMAC average pain subscale score of ≥4 at both the screening and randomization visits
Willing to discontinue current pain medications and to adhere to study requirements for rescue treatments
A history of regular use of analgesic medications for OA pain (defined as an average of 4 days per week over the 4 weeks prior to the screening visit), including oral nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase 2 inhibitors, opioids, paracetamol/acetaminophen, or combinations thereof
Consent to allow all radiographs and medical/surgical/hospitalization records of care received elsewhere prior to and during the study period to be shared with the investigator

Key Exclusion Criteria:

History or presence at the screening visit of non-OA inflammatory joint disease (eg, rheumatoid arthritis, lupus erythematosus, psoriatic arthritis, pseudo-gout, gout, spondyloarthropathy, polymyalgia rheumatica, joint infections within the past 5 years), 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 (osteonecrosis, subchondral insufficiency fracture, rapidly progressive OA type 1 or type 2), stress fracture, recent stress fracture, neuropathic joint arthropathy, hip dislocation (prosthetic hip dislocation is eligible), knee dislocation (patella dislocation is eligible), congenital hip dysplasia with degenerative joint disease, extensive subchondral cysts, evidence of bone fragmentation or collapse, or primary metastatic tumor with the exception of chondromas or pathologic fractures during the screening period
Trauma to the index joint within 3 months prior to the screening visit
History or presence of signs or symptoms of compression neuropathy, including carpal tunnel syndrome or sciatica
Participant is not a candidate for Magnetic Resonance Imaging (MRI)
Poorly controlled diabetes
Known history of human immunodeficiency virus (HIV) infection
Known history of ocular herpes simplex virus, herpes simplex virus pneumonia, or herpes simplex virus encephalitis
History of poorly controlled hypertension
Known history of infection with hepatitis B or C virus

Note: Other protocol defined Inclusion/Exclusion apply

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Fasinumab

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Peroneal Motor Nerve Conduction Velocity at Week 16

Peroneal motor nerve conduction velocity was evaluated by electrical stimulation of the nerve and recorded the compound muscle action potential from surface electrodes overlying a muscle supplied by the nerve. Change from baseline in peroneal motor nerve conduction velocity at Week 16 was reported.

Change From Baseline in Peroneal Motor Nerve Action Potential Amplitude at Week 16

Peroneal motor nerve action potential amplitude was evaluated at ankle by electrical stimulation of the nerve and recorded the compound muscle action potential from surface electrodes overlying a muscle supplied by the nerve. Change from baseline in peroneal motor nerve action potential amplitude at Week 16 was reported.

Change From Baseline in Sural Sensory Nerve Conduction Velocity at Week 16

Sural sensory nerve conduction velocity was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in sural sensory nerve conduction velocity at Week 16 was reported.

Change From Baseline in Sural Sensory Nerve Action Potential Amplitude at Week 16

Sural sensory nerve action potential amplitude was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in sural sensory nerve action potential amplitude at Week 16 was reported.

Change From Baseline in Ulnar Sensory Nerve Conduction Velocity at Week 16

Ulnar sensory nerve conduction velocity was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline in ulnar sensory nerve conduction velocity at Week 16 was reported.

Change From Baseline in Ulnar Sensory Nerve Action Potential Amplitude at Week 16

Ulnar sensory nerve action potential amplitude was evaluated by electrically stimulating sensory fibers and recorded the nerve action potential at a point further along that nerve. Change from baseline ulnar sensory nerve action potential amplitude at Week 16 was reported.

Secondary Outcome Measures

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16

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. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicate higher pain. A negative change from baseline indicated improvement. Change from baseline in WOMAC Pain subscale score at Week 16 was reported.

Change From Baseline in WOMAC Physical Function Subscale Score at Week 16

Physical function referred to subject'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 (no difficulty) to 10 (extreme difficulty), where higher scores indicated worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. A negative change from baseline indicated improvement. Change from baseline in WOMAC physical function subscale score at Week 16 was reported.

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. 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. TEAE was defined as an AE with an onset that occurs after receiving study drug. Any TEAE included participants with both serious and non-serious TEAEs. Number of participants with TEAEs were reported.

Number of 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. Number of confirmed AA events from baseline up to follow-up (Week 36) were reported.

Number of AA Events Meeting Destructive Arthropathy (DA) Criteria

AAs were evaluated to determine if they met 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. Number of confirmed AA events meeting DA criteria from baseline up to follow-up (Week 36) were reported.

Number of 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. Number of SNS dysfunction events from baseline up to follow-up (Week 36) were reported.

Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation

Any peripheral sensory AE (for example [e.g.], paraesthesia and hypoaesthesia) that required a neurology consultation. Number of peripheral sensory adverse events from baseline up to follow-up (Week 36) were reported.

Number of All-Cause Joint Replacement (JR) Surgery Events

All joint replacement surgery events regardless of cause.

Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug

An end of study phone contact was conducted approximately 52 weeks following the last dose of study drug (Week 64) to evaluate the number of participants who had undergone or were scheduled for JR surgery.

Serum Concentration of Functional Fasinumab

Serum concentrations of functional Fasinumab were reported.

Number of Participants With At-least One Positive Anti-Drug Antibody (ADA)

Samples for ADA evaluation were collected at baseline and at subsequent study visits. ADA variables included ADA status (+/-) and titer as follows: Total participants negative in ADA assay at all time points analyzed. Pre-existing immunoreactivity- positive response at baseline with all post-dose results negative/positive response at baseline with all post-dose responses less than 9-fold over baseline titer levels. Treatment emergent - post-dose positive result when baseline results were negative. Persistent - A positive result detected in at least/ more 2 consecutive post baseline samples separated by at least a 16-week post baseline period, with no negative results in-between. Indeterminate - A positive result at the last collection time point analyzed only. Transient - Not persistent or indeterminate regardless of any missing samples. Treatment boosted- positive response in ADA assay post first dose that is greater than/equal 9-fold over baseline level when baseline is positive.

Full Information

NCT ID

NCT03691974

First Posted

September 12, 2018

Last Updated

February 27, 2023

Sponsor

Regeneron Pharmaceuticals

Collaborators

Teva Pharmaceutical Industries, Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03691974

Brief Title

Study to Evaluate the Effects of Fasinumab on Peripheral Nerve Function in Patients With Pain Due to Osteoarthritis of the Hip or Knee

Official Title

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Effects of Fasinumab on Peripheral Nerve Function in Patients With Pain Due to Osteoarthritis of the Hip or Knee

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

October 15, 2018 (Actual)

Primary Completion Date

January 30, 2020 (Actual)

Study Completion Date

January 7, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneron Pharmaceuticals

Collaborators

Teva Pharmaceutical Industries, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objective of the study is to evaluate the effect of fasinumab compared to placebo on peripheral nerves in participants with pain due to Osteoarthritis (OA) of the hip or knee. The secondary objectives of the study are to: Evaluate the efficacy of fasinumab compared to placebo in participants with pain due to OA of the hip or knee Evaluate the safety and tolerability of fasinumab compared to placebo in participants with pain due to OA of the hip or knee Characterize the concentrations of fasinumab in serum in participants with pain due to OA of the hip or knee Evaluate the immunogenicity of fasinumab in participants with pain due to OA of the hip or knee.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoarthritis, Knee, Osteoarthritis, Hip

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

180 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fasinumab

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Fasinumab

Other Intervention Name(s)

REGN475

Intervention Description

Subcutaneous (SC) every four weeks (Q4W)

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Subcutaneous (SC) every four weeks (Q4W)

Primary Outcome Measure Information:

Title

Change From Baseline in Peroneal Motor Nerve Conduction Velocity at Week 16

Description

Time Frame

Baseline, Week 16

Title

Change From Baseline in Peroneal Motor Nerve Action Potential Amplitude at Week 16

Description

Time Frame

Baseline, Week 16

Title

Change From Baseline in Sural Sensory Nerve Conduction Velocity at Week 16

Description

Time Frame

Baseline, Week 16

Title

Change From Baseline in Sural Sensory Nerve Action Potential Amplitude at Week 16

Description

Time Frame

Baseline, Week 16

Title

Change From Baseline in Ulnar Sensory Nerve Conduction Velocity at Week 16

Description

Time Frame

Baseline, Week 16

Title

Change From Baseline in Ulnar Sensory Nerve Action Potential Amplitude at Week 16

Description

Time Frame

Baseline, Week 16

Secondary Outcome Measure Information:

Title

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16

Description

Time Frame

Baseline, Week 16

Title

Change From Baseline in WOMAC Physical Function Subscale Score at Week 16

Description

Time Frame

Baseline, Week 16

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Description

Time Frame

Baseline up to Week 16

Title

Number of Adjudicated Arthropathy (AA) Events

Description

Time Frame