A Phase 3 interventional study of Fasinumab and Placebo in Chronic Low Back Pain and Osteoarthritis, sponsored by Regeneron Pharmaceuticals. Terminated at 56 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-30.
Sponsored by Regeneron Pharmaceuticals · Phase 3, Interventional, and Treatment
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.
Key Inclusion Criteria:
Key Exclusion Criteria:
Note: Other protocol defined Inclusion/ Exclusion criteria apply.
Subcutaneous (SC) every 4 weeks (Q4W)
Drug: Fasinumab
SC every 4 weeks
Drug: Placebo
Subcutaneous (SC) every 4 weeks (Q4W)
Also known as: REGN475
Subcutaneous (SC) every 4 weeks (Q4W)
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.
Time frame: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to Week 36
Number of All-Cause Joint Replacement (JR) Surgery Events
All joint replacement surgery events regardless of cause.
Time frame: 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.
Time frame: 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.
Time frame: 16 Weeks
Serum Concentration of Functional Fasinumab Over Time
Summary of mean concentration of functional fasinumab are presented by nominal time point.
Time frame: Baseline, Week 2, Week 4, Week 8, Week 16
Participants were screened for study eligibility across the US. Of the 377 participants screened, 63 met eligibility criteria. The most frequently reported reason for non-randomization was inclusion criteria not met and/or exclusion criteria met (224 participants):139 did not meet inclusion criteria, 86 participants met exclusion criteria.
| Milestone | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Started | 32 | 31 |
| Completed | 19 | 27 |
| Not completed | 13 | 4 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Withdrawal by subject | 10 | 2 |
| Withdrew: Lost to follow-up | 2 | 1 |
| Withdrew: Investigator/sponsor decision | 0 | 1 |
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.
| Score on a Scale | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Change from Baseline to Week 1 | -0.73 ± 1.424 | -1.62 ± 2.037 |
| Change from Baseline to Week 2 | -0.98 ± 1.588 | -2.15 ± 2.067 |
| Change from Baseline to Week 4 | -1.28 ± 1.878 | -2.64 ± 2.038 |
| Change from Baseline to Week 8 | -1.21 ± 1.568 | -2.82 ± 1.963 |
| Change from Baseline to Week 12 | -2.12 ± 1.582 | -3.18 ± 2.046 |
| Change from Baseline to Week 16 | -0.77 ± 1.943 | -2.32 ± 1.367 |
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.
| Score on a Scale | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Change from Baseline to Week 2 | -2.70 ± 5.120 | -2.54 ± 4.836 |
| Change from Baseline to Week 4 | -1.92 ± 4.529 | -3.09 ± 3.884 |
| Change from Baseline to Week 8 | 0.37 ± 4.487 | -4.18 ± 5.015 |
| Change from Baseline to Week 12 | 0.83 ± 3.061 | -3.33 ± 4.301 |
| Change from Baseline to Week 16 | -1.00 ± NA | -5.75 ± 3.948 |
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.
| Score on a Scale | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Change from Baseline to Week 2 | -0.44 ± 0.751 | -0.76 ± 0.786 |
| Change from Baseline to Week 4 | -0.60 ± 0.957 | -1.04 ± 0.676 |
| Change from Baseline to Week 8 | -0.55 ± 0.945 | -1.10 ± 1.021 |
| Change from Baseline to Week 12 | -0.57 ± 1.134 | -1.00 ± 1.333 |
| Change from Baseline to Week 16 | 0.00 ± NA | -0.75 ± 0.500 |
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.
| Participants | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score | 12 | 21 |
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.
| Score on a Scale | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Change from Baseline to Week 2 | -1.55 ± 2.306 | -1.94 ± 2.255 |
| Change from Baseline to Week 4 | -1.49 ± 2.390 | -2.15 ± 2.157 |
| Change from Baseline to Week 8 | -1.31 ± 2.119 | -2.70 ± 2.774 |
| Change from Baseline to Week 12 | -1.63 ± 2.096 | -1.84 ± 1.978 |
| Change from Baseline to Week 16 | -1.14 ± NA | -1.29 ± 3.017 |
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.
| Adjudicated Arthropathy (AA) Events | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Number of Adjudicated Arthropathy (AA) Events | 0 | 2 |
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.
| Destructive Arthropathy (DA) Events | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria | 0 | 0 |
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.
| Treatment-Emergent Adverse Events | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Number of Treatment-Emergent Adverse Events (TEAEs) | 33 | 14 |
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.
| Sympathetic NS Dysfunction Events | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Number of Sympathetic Nervous System (SNS) Dysfunction Events | 0 | 0 |
Any peripheral sensory AE (eg, paraesthesia and hypoaesthesia) that required a neurology consultation.
| Peripheral Sensory Adverse Events (AEs) | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Hypoaesthesia events | 1 | 0 |
| Paraesthesia events | 1 | 0 |
All joint replacement surgery events regardless of cause.
| Joint Replacement (JR) Surgery Events | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Number of All-Cause Joint Replacement (JR) Surgery Events | 2 | 1 |
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.
| Joint Replacement (JR) Surgery Events | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug | 0 | 0 |
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.
| Participants | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Negative/Pre-Existing | 31 | 31 |
| Treatment Boosted | 0 | 0 |
| Treatment-Emergent | 0 | 0 |
| Treatment-Emergent: Persistent | 0 | 0 |
| Treatment-Emergent: Transient | 0 | 0 |
| Treatment-Emergent: Indeterminate | 0 | 0 |
Summary of mean concentration of functional fasinumab are presented by nominal time point.
| Milligram per Liter (mg/L) | Fasinumab 3 mg SC Q4W |
|---|---|
| Baseline | 0 ± 0 |
| Week 2 | 0.262 ± 0.0992 |
| Week 4 | 0.176 ± 0.0679 |
| Week 8 | 0.247 ± 0.130 |
| Week 16 | 0.192 ± 0.0932 |
Collected over From the first dose of study drug up to 24 weeks post the last dose of study drug (up to week 36). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fasinumab-matching Placebo | 0/32 (0%) | 1/32 (3.1%) | 14/32 (43.8%) |
| Fasinumab 3 mg SC Q4W | 0/31 (0%) | 2/31 (6.5%) | 4/31 (12.9%) |
| Event | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Breast cancer stage IVNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/32 | 1/31 |
| DizzinessNervous system disorders | 0/32 | 1/31 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/32 | 1/31 |
| OsteoarthritisMusculoskeletal and connective tissue disorders | 1/32 | 0/31 |
| Event | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W |
|---|---|---|
| Back painMusculoskeletal and connective tissue disorders | 5/32 | 0/31 |
| Upper respiratory tract infectionInfections and infestations | 4/32 | 1/31 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 4/32 | 3/31 |
| Blood creatine phosphokinase increasedInvestigations | 3/32 | 1/31 |
| Neck PainMusculoskeletal and connective tissue disorders | 2/32 | 1/31 |
| Peripheral swellingGeneral disorders | 2/32 | 0/31 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/32 | 0/31 |
| Age, Continuous(years) | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W | Total |
|---|---|---|---|
| Mean | 57.7 ± 9.88 | 60.0 ± 10.52 | 58.8 ± 10.18 |
| Sex: Female, Male(Participants) | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W | Total |
|---|---|---|---|
| Female | 21 | 18 | 39 |
| Male | 11 | 13 | 24 |
| Ethnicity (NIH/OMB)(Participants) | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 3 | 4 |
| Not Hispanic or Latino | 31 | 28 | 59 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W | Total |
|---|---|---|---|
| White | 15 | 17 | 32 |
| Black or African American | 15 | 14 | 29 |
| American Indian or Alaska Native | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 |
| Average Daily Low Back Pain Intensity (LBPI) Numerical Rating Scale (NRS) Score(Score on a Scale) | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W | Total |
|---|---|---|---|
| Mean | 6.66 ± 1.475 | 6.81 ± 1.338 | 6.73 ± 1.400 |
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Regeneron Pharmaceuticals