NCT03691974

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

Completed Phase 2 Results posted Last updated 1 March 2023

What this trial tests

Phase 2 trial testing Fasinumab in Osteoarthritis, Knee in 180 participants. Completed in 7 January 2021.

Timeline

15 October 2018

Primary endpoint
30 January 2020

7 January 2021

Quick facts

Lead sponsor	Regeneron Pharmaceuticals
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	180
Start date	15 October 2018
Primary completion	30 January 2020
Estimated completion	7 January 2021
Sites	47 locations across United Kingdom, United States, Poland

Drugs / interventions tested

• Fasinumab — full drug profile →
• Placebo

Conditions studied

• Osteoarthritis, Knee — all drugs for Osteoarthritis, Knee →
• Osteoarthritis, Hip — all drugs for Osteoarthritis, Hip →

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Osteoarthritis, Knee or Osteoarthritis, Hip. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Peroneal Motor Nerve Conduction Velocity at Week 16 Primary · Baseline, 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.

Group	Value	95% CI
Fasinumab-matching Placebo	-0.2	± 0.46
Fasinumab 1 mg SC Q4W	0.2	± 0.42

Change From Baseline in Peroneal Motor Nerve Action Potential Amplitude at Week 16 Primary · Baseline, 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.

Group	Value	95% CI
Fasinumab-matching Placebo	-0.2	± 0.20
Fasinumab 1 mg SC Q4W	0.2	± 0.19

Change From Baseline in Sural Sensory Nerve Conduction Velocity at Week 16 Primary · Baseline, 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.

Group	Value	95% CI
Fasinumab-matching Placebo	-2.9	± 0.90
Fasinumab 1 mg SC Q4W	-1.6	± 0.83

Change From Baseline in Sural Sensory Nerve Action Potential Amplitude at Week 16 Primary · Baseline, 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.

Group	Value	95% CI
Fasinumab-matching Placebo	0.5	± 0.69
Fasinumab 1 mg SC Q4W	0.3	± 0.64

Change From Baseline in Ulnar Sensory Nerve Conduction Velocity at Week 16 Primary · Baseline, 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.

Group	Value	95% CI
Fasinumab-matching Placebo	-0.7	± 0.74
Fasinumab 1 mg SC Q4W	-1.1	± 0.68

Change From Baseline in Ulnar Sensory Nerve Action Potential Amplitude at Week 16 Primary · Baseline, 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.

Group	Value	95% CI
Fasinumab-matching Placebo	2.4	± 1.21
Fasinumab 1 mg SC Q4W	1.4	± 1.12

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

Group	Value	95% CI
Fasinumab-matching Placebo	-1.19	± 0.359
Fasinumab 1 mg SC Q4W	-2.52	± 0.335

Change From Baseline in WOMAC Physical Function Subscale Score at Week 16 Secondary · Baseline, 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 highe

Group	Value	95% CI
Fasinumab-matching Placebo	-0.83	± 0.366
Fasinumab 1 mg SC Q4W	-2.24	± 0.341

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Secondary · Baseline up to Week 16

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 T

Group	Value	95% CI
Fasinumab-matching Placebo	57
Fasinumab 1 mg SC Q4W	63

Number of Adjudicated Arthropathy (AA) Events Secondary · Baseline up to follow-up (Week 36)

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.

Group	Value	95% CI
Fasinumab-matching Placebo	0
Fasinumab 1 mg SC Q4W	4

Number of AA Events Meeting Destructive Arthropathy (DA) Criteria Secondary · Baseline up to follow-up (Week 36)

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.

Group	Value	95% CI
Fasinumab 1 mg SC Q4W	0

Number of Sympathetic Nervous System (SNS) Dysfunction Events Secondary · Baseline up to follow-up (Week 36)

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.

Group	Value	95% CI
Fasinumab-matching Placebo	0
Fasinumab 1 mg SC Q4W	0

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug up to 24 weeks post the last dose of study drug (up to Week 36). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fasinumab-matching Placebo

Serious: 6/88 (7%)

Deaths: 0/88

Fasinumab 1 mg SC Q4W

Serious: 3/91 (3%)

Deaths: 0/91

Serious adverse events (9 terms)

Reaction	System	Fasinumab-matching Placebo	Fasinumab 1 mg SC Q4W
Supraventricular tachycardia	Cardiac disorders	—	—
Multiple injuries	Injury, poisoning and procedural complications	—	—
Humerus fracture	Injury, poisoning and procedural complications	—	—
Limb traumatic amputation	Injury, poisoning and procedural complications	—	—
Patella fracture	Injury, poisoning and procedural complications	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Rapidly progressive osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Lung squamous cell carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Knee arthroplasty	Surgical and medical procedures	—	—

Other adverse events (12 terms — click to expand)

Reaction	System	Fasinumab-matching Placebo	Fasinumab 1 mg SC Q4W
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Nerve conduction studies abnormal	Investigations	—	—
Headache	Nervous system disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—

Most-reported serious reactions: Supraventricular tachycardia, Multiple injuries, Humerus fracture, Limb traumatic amputation, Patella fracture, Arthralgia, Rapidly progressive osteoarthritis, Lung squamous cell carcinoma metastatic.

Data from ClinicalTrials.gov NCT03691974 adverse events section.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Challenges and opportunities of pharmacological interventions for osteoarthritis: A review of current clinical trials and developments.
   Vrouwe JPM, Burggraaf J, Kloppenburg M, Stuurman FE. · · 2021 · cited 16× · PMID 36474768 · DOI 10.1016/j.ocarto.2021.100212
2. An update on targets for treating osteoarthritis pain: NGF and TRPV1.
   Obeidat AM, Donner A, Miller RE. · · 2020 · cited 14× · PMID 34178580 · DOI 10.1007/s40674-020-00146-x
3. Identification of alkaline phosphatase as a putative biomarker of anti-NGF treatment-associated arthropathies: Machine learning-assisted analyses of clinical trial data.
   Wipperman MF, Ehmann PJ, McIntyre DAG, Wang CG, et al · · 2026 · PMID 41540988 · DOI 10.1016/j.ocarto.2025.100735
4. The Effects of Fasinumab on Peripheral Nerve Function and Ganglion Anatomy: Results From a Randomized, Double-Blind, Placebo-Controlled Study in Patients With Pain Due to Osteoarthritis of the Knee or Hip, and a Series of Nonclinical Studies.
   Eng S, Fetell M, Gao H, Mei J, et al · · 2025 · PMID 41323020 · DOI 10.1016/j.curtheres.2025.100813