Evaluate the Efficacy and Safety of Fasinumab in Patients With Moderate-to-Severe Chronic Low Back Pain and Osteoarthritis of the Hip or Knee (FACT CLBP 1)

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

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.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis; Chronic Low Back Pain
• Intervention / Treatment: Drug: Fasinumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Regeneron Research Site
    • Tucson, Arizona, United States, 85704
      • Regeneron Research Site
    • Tucson, Arizona, United States, 85712
      • Regeneron Research Site
  • California
    • Anaheim, California, United States, 92801
      • Regeneron Research Site
    • Anaheim, California, United States, 92805
      • Regeneron Research Site
    • La Mesa, California, United States, 91942
      • Regeneron Research Site
    • North Hollywood, California, United States, 91606
      • Regeneron Research Site
    • San Diego, California, United States, 92103
      • Regeneron Research Site
    • San Marcos, California, United States, 92078
      • Regeneron Research Site
    • Santa Ana, California, United States, 92703
      • Regeneron Research Site
    • Spring Valley, California, United States, 91978
      • Regeneron Research Site
    • Whittier, California, United States, 90602
      • Regeneron Research Site
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Regeneron Research Site
    • Waterbury, Connecticut, United States, 06708
      • Regeneron Research Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • Regeneron Research Site
    • Hialeah, Florida, United States, 33012
      • Regeneron Research Site
    • Jacksonville, Florida, United States, 32256
      • Regeneron Research Site
    • Lauderdale Lakes, Florida, United States, 33319
      • Regeneron Research Site
    • Miami, Florida, United States, 33155
      • Regeneron Research Site
    • Ocoee, Florida, United States, 34761
      • Regeneron Research Site
    • Orlando, Florida, United States, 32801
      • Regeneron Research Site
    • Orlando, Florida, United States, 32806
      • Regeneron Research Site
    • Port Orange, Florida, United States, 32127
      • Regeneron Research Site
    • Sarasota, Florida, United States, 34232
      • Regeneron Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30189
      • Regeneron Research Site
    • Columbus, Georgia, United States, 31904
      • Regeneron Research Site
    • Marietta, Georgia, United States, 30060
      • Regeneron Research Site #1
    • Marietta, Georgia, United States, 30060
      • Regeneron Research Site #2
    • Newnan, Georgia, United States, 30265
      • Regeneron Research Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Regeneron Research Site
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Regeneron Research Site
    • Chicago, Illinois, United States, 60607
      • Regeneron Research Site
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Regeneron Research Site
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Regeneron Research Site
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Regeneron Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Regeneron Research Site
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Regeneron Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Regeneron Research Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Regeneron Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89144
      • Regeneron Research Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Regeneron Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Regeneron Research Site
  • New York
    • Hartsdale, New York, United States, 10530
      • Regeneron Research Site
    • New York, New York, United States, 10036
      • Regeneron Research Site
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Regeneron Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58105
      • Regeneron Research Site
  • Ohio
    • Beavercreek, Ohio, United States, 45431
      • Regeneron Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Regeneron Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Regeneron Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Regeneron Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Regeneron Research Site #1
    • Memphis, Tennessee, United States, 38119
      • Regeneron Research Site #2
  • Texas
    • Houston, Texas, United States, 77058
      • Regeneron Research Site
    • Katy, Texas, United States, 77498
      • Regeneron Research Site
    • Plano, Texas, United States, 75075
      • Regeneron Research Site
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fasinumab; Subcutaneous (SC) every 4 weeks (Q4W)	Drug: Fasinumab; Subcutaneous (SC) every 4 weeks (Q4W); Other Names: REGN475
EXPERIMENTAL: Placebo; SC every 4 weeks	Drug: Placebo; Subcutaneous (SC) every 4 weeks (Q4W)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Teva Pharmaceutical Industries, Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 30, 2017
• Primary Completion (ACTUAL): May 5, 2018
• Study Completion (ACTUAL): May 2, 2019

Study Registration Dates

• First Submitted: September 14, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (ACTUAL): September 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 9, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Knee; Hip
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Back Pain; Low Back Pain; Osteoarthritis, Hip; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Fasinumab
• Other Study ID Numbers: R475-PN-1612; 2017-001943-12 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No