Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate-to-Severe Chronic Low Back Pain and Osteoarthritis of the Hip or Knee

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the efficacy of fasinumab in relieving Chronic low back pain (CLBP) as compared to placebo in participants with a clinical diagnosis of moderate-to-severe non-radicular CLBP and Osteoarthritis (OA) of the knee or hip when treated for up to 16 weeks. The secondary objectives of the study are: To evaluate the safety and tolerability of fasinumab compared to placebo when participants with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip are treated for up to 16 weeks; To characterize the concentrations of fasinumab in serum over time when participants with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip are treated for up to 16 weeks; To evaluate the immunogenicity of fasinumab when treated for up to 16 weeks in participants with a clinical diagnosis of moderate-to-severe non-radicular CLBP and OA of the knee or hip.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate-to-Severe Chronic Low Back Pain and Osteoarthritis of the Hip or Knee

Conditions
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Chronic Low Back Pain, Osteoarthritis

Intervention / Treatment
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* Drug: Fasinumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Clinical diagnosis of non-radicular moderate-to-severe CLBP for ≥3 months (prior to screening visit) Clinical diagnosis of OA in at least 1 hip or knee joint based on the American College of Rheumatology Criteria with radiographic evidence of OA (K-L ≥2) at screening History of inadequate relief of CLBP from non-pharmacologic therapy Willing to undergo joint replacement (JR) surgery, if necessary History of regular analgesic medication use History of inadequate pain relief or intolerance to analgesics used for chronic LBP Key Exclusion Criteria: Patient is not a candidate for MRI History of major trauma or back surgery in the past 6 months prior to the screening visit History or presence of pyriformis syndrome Evidence on baseline lumbar spine magnetic resonance imaging of potentially confounding conditions History or evidence on joint imaging of conditions that may confound joint safety evaluation Evidence or symptoms consistent with autonomic dysfunction (e.g., orthostatic hypotension and/or autonomic symptoms) as defined in the protocol Recent use of longer acting pain medications Other medical conditions that may interfere with participation or accurate assessments during the trial Note: Other protocol defined Inclusion/ Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fasinumab<br>Subcutaneous (SC) every 4 weeks (Q4W) | Drug: Fasinumab<br>* Subcutaneous (SC) every 4 weeks (Q4W)<br>* Other names: REGN475;|
| Experimental: Placebo<br>SC every 4 weeks | Drug: Placebo<br>* Subcutaneous (SC) every 4 weeks (Q4W)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Average daily low back pain (LBP) was assessed on an 11-point numeric rating scale (NRS) and was defined as the average of the non-missing daily LBPI NRS scores for the 7 days before and including nominal visit. Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain. | Week 1, Week 2, Week 4, Week 8, Week 12, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | The RMDQ is a self-administered, health status measure for lower back pain (LBP). It measures pain and function using 24 items describing limitations to everyday life that can be caused by LBP. The score of the RMDQ is the total number of items checked from a minimum of 0 (no disability) to a maximum of 24 (maximum disability), where lower scores are indicative of better function. | Week 2, Week 4, Week 8, Week 12, Week 16 | 
| Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | The PGA of LBP is a participant assessed 5 point Likert scale of LBP ranging from 1-5 where 1 = very well; 2 = well; 3 = fair; 4 = poor; and 5 = very poor. | Week 2, Week 4, Week 8, Week 12, Week 16 | 
| Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score | Average daily low back pain (LBP) was assessed on an 11-point numeric rating scale (NRS) and was defined as the average of the non-missing daily LBPI NRS scores for the 7 days before and including nominal visit. Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain. | Week 16 | 
| Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | The BPI-sf is a self-administered questionnaire for participants to rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function. With a recall period of 24 hours, the questionnaire contains the front and back body diagrams, the 4 pain severity items and 7 pain interference items rated on 0-10 scale; total interference score ranges from 0-10 (0, does not interfere; 10 completely interferes), and the question about percentage of pain relief by analgesics. The BPI pain interference is typically scored as the mean of the 7 interference items. | Week 2, Week 4, Week 8, Week 12, Week 16 | 
| Number of Adjudicated Arthropathy (AA) Events | Adjudicated arthropathy (AA) is a composite term that encompasses the following conditions: Rapidly progressive OA type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis. AAs were also evaluated to determine if they met Destructive Arthropathy criteria. | Up to Week 36 | 
| Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria | Destructive arthropathy (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 Osteoarthritis type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis. | Up to Week 36 | 
| Number of Treatment-Emergent Adverse Events (TEAEs) | Treatment-emergent adverse events (TEAEs) are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. | Up to Week 16 | 
| Number of Sympathetic Nervous System (SNS) Dysfunction Events | Potential events of sympathetic nervous system (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. | Up to Week 36 | 
| Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Any peripheral sensory AE (eg, paraesthesia and hypoaesthesia) that required a neurology consultation. | Up to Week 36 | 
| Number of All-Cause Joint Replacement (JR) Surgery Events | All joint replacement surgery events regardless of cause. | Up to Week 36 | 
| 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 12) to evaluate the number of participants who had undergone or were scheduled for JR surgery. | Up to Week 64 | 
| Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Samples for Anti-Drug Antibody (ADA) evaluation were collected at baseline and at subsequent study visits. ADA variables include ADA status (+ or -) and titer as follows: Total participants negative in the ADA assay at all time points analyzed. Pre-existing immunoreactivity - positive response at baseline with all post-dose results negative, or a 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 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 - any post-dose positive result at least 9-fold over the baseline level when baseline is positive. | 16 Weeks | 
| Serum Concentration of Functional Fasinumab Over Time | Summary of mean concentration of functional fasinumab are presented by nominal time point. | Baseline, Week 2, Week 4, Week 8, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee, Hip