A Study to Determine the Efficacy and Safety of Fasinumab for the Treatment of Adults With Chronic Low Back Pain

Study Overview
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Brief Summary
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The main objective of the trial is to evaluate the efficacy of fasinumab compared to placebo as measured by the change from baseline in the average daily Low Back Pain Intensity (LBPI) Numerical Rating Scale (NRS). Secondary objectives of the study are to evaluate the efficacy of fasinumab compared to placebo as measured by: Change from baseline in the Roland Morris disability questionnaire (RMDQ) total score Change from baseline in the Patient Global Assessment (PGA) of Low Back Pain (LBP) score Change from baseline in the average daily LBPI NRS score

Official Title
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A Randomized, Double-blind, Multi-dose, Placebo-controlled Phase 2/3 Study to Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate to Severe Chronic Low Back Pain

Conditions
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Low Back Pain

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: Male or female ≥35 years of age at the screening visit Clinical diagnosis of chronic moderate to severe LBP (nonradiculopathic)for ≥3 months History of regular analgesic medication History of inadequate pain relief or intolerance to analgesics used for chronic LBP Willing to discontinue current pain medication Key Exclusion Criteria: History of lumbosacral radiculopathy within the past 2 years Evidence on baseline lumbar spine magnetic resonance imaging of potentially confounding conditions Recent use of longer acting pain medications Evidence of destructive arthropathy Other medical conditions that may interfere with participation or accurate assessments during the trial

Ages Eligible for Study
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Minimum Age: 35 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 6 mg SC Q4W and Placebo IV Q8W<br>Participants randomized to the fasinumab 6 mg SC Q4W arm received fasinumab 12 mg SC on Day 1 (loading dose) and then 6 mg SC (planned maintenance dose) at Weeks 4, 8, and 12 for a total of 4 doses. Matching placebo was received via intravenous (IV) infusion Q8W on Day 1 and at Week 8. | Drug: Fasinumab<br>* Participants received fasinumab SC or IV, Q4W or Q8W.<br>* Other names: REGN475;Drug: placebo<br>* Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.<br>|
| Experimental: Fasinumab 9 mg SC Q4W and Placebo IV Q8W<br>Participants randomized to the fasinumab 9 mg SC Q4W arm received 18 mg SC on day 1 (loading dose) and then 9 mg SC (planned maintenance dose) at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo IV Q8W was received on Day 1 and at Week 8. | Drug: Fasinumab<br>* Participants received fasinumab SC or IV, Q4W or Q8W.<br>* Other names: REGN475;Drug: placebo<br>* Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.<br>|
| Experimental: Fasinumab 9 mg IV Q8W and Placebo SC Q4W<br>Participants randomized to the fasinumab 9 mg IV Q8W arm received IV infusions of fasinumab 9 mg on Day 1 and Week 8, for a total of 2 doses. Matching placebo SC Q4W was received on day 1 and at weeks 4, 8, and 12. | Drug: Fasinumab<br>* Participants received fasinumab SC or IV, Q4W or Q8W.<br>* Other names: REGN475;Drug: placebo<br>* Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.<br>|
| Experimental: Placebo SC Q4W and Placebo IV Q8W<br>Participants randomized to the matching placebo subcutaneously (SC) every four weeks (Q4W) arm received SC placebo in a manner similar to the SC loading dose of the active groups (placebo loading dose) on Day 1 and then an SC injection of placebo at weeks 4, 8, and 12 for a total of 4 doses. Matching placebo intravenously (IV) every 8 weeks (Q8W) was received on Day 1 and at Week 8. | Drug: placebo<br>* Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.<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 Index Numeric Rating Scale (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. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | 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. | Baseline to Weeks 2, 4, 8, and 12 | 
| Change From Baseline to Week 16 in Roland Morris Disability Questionnaire (RMDQ) Total Score | The RMDQ is a self-administered, widely used 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 - that is from a minimum of 0 (no disability) to a maximum of 24 (maximum disability), where lower scores indicative of better function. | Baseline to Week 16 | 
| Change From Baseline to Week 16 in the 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 0-5 where 1=very well; 2=well; 3=fair; 4=poor; and 5=very poor. | Baseline to Week 16 |