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

• Fasinumab (Drug), also known as REGN475: Subcutaneous (SC) every 4 weeks (Q4W)
• Placebo (Drug): Subcutaneous (SC) every 4 weeks (Q4W)

Primary outcomes

• Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score [Week 1, Week 2, Week 4, Week 8, Week 12, Week 16]: 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.

Secondary outcomes

• Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score [Week 2, Week 4, Week 8, Week 12, Week 16]: 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.
• Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score [Week 2, Week 4, Week 8, Week 12, Week 16]: 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.
• Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score [Week 16]: 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.
• Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score [Week 2, Week 4, Week 8, Week 12, Week 16]: 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.
• Number of Adjudicated Arthropathy (AA) Events [Up to Week 36]: 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.
• Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria [Up to Week 36]: 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.
• Number of Treatment-Emergent Adverse Events (TEAEs) [Up to Week 16]: 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.
• Number of Sympathetic Nervous System (SNS) Dysfunction Events [Up to Week 36]: 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.
• Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation [Up to Week 36]: Any peripheral sensory AE (eg, paraesthesia and hypoaesthesia) that required a neurology consultation.
• Number of All-Cause Joint Replacement (JR) Surgery Events [Up to Week 36]: 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 [Up to Week 64]: 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.
• Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay [16 Weeks]: 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.
• Serum Concentration of Functional Fasinumab Over Time [Baseline, Week 2, Week 4, Week 8, Week 16]: Summary of mean concentration of functional fasinumab are presented by nominal time point.

Sex: All, ages: 18 Years to any

Key Inclusion Criteria:

1. Clinical diagnosis of non-radicular moderate-to-severe CLBP for ≥3 months (prior to screening visit)
2. 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
3. History of inadequate relief of CLBP from non-pharmacologic therapy
4. Willing to undergo joint replacement (JR) surgery, if necessary
5. History of regular analgesic medication use
6. History of inadequate pain relief or intolerance to analgesics used for chronic LBP

Key Exclusion Criteria:

1. Patient is not a candidate for MRI
2. History of major trauma or back surgery in the past 6 months prior to the screening visit
3. History or presence of pyriformis syndrome
4. Evidence on baseline lumbar spine magnetic resonance imaging of potentially confounding conditions
5. History or evidence on joint imaging of conditions that may confound joint safety evaluation
6. Evidence or symptoms consistent with autonomic dysfunction (e.g., orthostatic hypotension and/or autonomic symptoms) as defined in the protocol
7. Recent use of longer acting pain medications
8. Other medical conditions that may interfere with participation or accurate assessments during the trial

Note: Other protocol defined Inclusion/ Exclusion criteria apply.

Participant flow

Outcome results

• Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score (Primary), Mean, Score on a Scale: Fasinumab-matching Placebo -0.73 +/- 1.424; Fasinumab 3 mg SC Q4W -1.62 +/- 2.037
• Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score (Secondary), Mean, Score on a Scale: Fasinumab-matching Placebo -2.70 +/- 5.120; Fasinumab 3 mg SC Q4W -2.54 +/- 4.836
• Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score (Secondary), Mean, Score on a Scale: Fasinumab-matching Placebo -0.44 +/- 0.751; Fasinumab 3 mg SC Q4W -0.76 +/- 0.786
• Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score (Secondary), Count of participants, Participants: Fasinumab-matching Placebo 12; Fasinumab 3 mg SC Q4W 21
• Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score (Secondary), Mean, Score on a Scale: Fasinumab-matching Placebo -1.55 +/- 2.306; Fasinumab 3 mg SC Q4W -1.94 +/- 2.255
• Number of Adjudicated Arthropathy (AA) Events (Secondary), Number, Adjudicated Arthropathy (AA) Events: Fasinumab-matching Placebo 0; Fasinumab 3 mg SC Q4W 2
• Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria (Secondary), Number, Destructive Arthropathy (DA) Events: Fasinumab-matching Placebo 0; Fasinumab 3 mg SC Q4W 0
• Number of Treatment-Emergent Adverse Events (TEAEs) (Secondary), Number, Treatment-Emergent Adverse Events: Fasinumab-matching Placebo 33; Fasinumab 3 mg SC Q4W 14
• Number of Sympathetic Nervous System (SNS) Dysfunction Events (Secondary), Number, Sympathetic NS Dysfunction Events: Fasinumab-matching Placebo 0; Fasinumab 3 mg SC Q4W 0
• Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation (Secondary), Number, Peripheral Sensory Adverse Events (AEs): Fasinumab-matching Placebo 1; Fasinumab 3 mg SC Q4W 0
• Number of All-Cause Joint Replacement (JR) Surgery Events (Secondary), Number, Joint Replacement (JR) Surgery Events: Fasinumab-matching Placebo 2; Fasinumab 3 mg SC Q4W 1
• Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug (Secondary), Number, Joint Replacement (JR) Surgery Events: Fasinumab-matching Placebo 0; Fasinumab 3 mg SC Q4W 0
• Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay (Secondary), Count of participants, Participants: Fasinumab-matching Placebo 31; Fasinumab 3 mg SC Q4W 31
• Serum Concentration of Functional Fasinumab Over Time (Secondary), Mean, Milligram per Liter (mg/L): Fasinumab 3 mg SC Q4W 0 +/- 0

Adverse events

Time frame: From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36)

Serious adverse events by term

Other adverse events by term

Limitations and caveats: Enrollment and study drug administration was stopped due to an urgent safety measure. As a result the small number of participants enrolled in this study limited the interpretability of the efficacy results.

• Study Protocol (PDF, 2017-07-25)
• Statistical Analysis Plan (PDF, 2018-12-10)

• Clinical Trial Management, Study director, Regeneron Pharmaceuticals

NIH grants: 2017