Chronic Low Back Pain, Osteoarthritis
Conditions
Keywords
Knee, Hip
Brief summary
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.
Interventions
DRUGFasinumab
Subcutaneous (SC) every 4 weeks (Q4W)
DRUGPlacebo
Subcutaneous (SC) every 4 weeks (Q4W)
Sponsors
Teva Pharmaceutical Industries, Ltd.
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
The study consisted of a screening period of up to 30 days and a 7 (+3 day) day pre-randomization period during which all pain medication except study-provided rescue medication was discontinued.
Participants by arm
| Arm | Count |
|---|---|
| Fasinumab-matching Placebo Participants received fasinumab-matching placebo subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks. | 32 |
| Fasinumab 3 mg SC Q4W Participants received fasinumab 3 milligrams (mg) subcutaneously (SC) every 4 weeks (Q4W) from day 1 through week 12 of the 16 week treatment period. Participants were permitted to use only acetaminophen/paracetamol as rescue medication. The treatment period included both study visits and a phone contact on day 8 (±1 day) up to 16 weeks. | 31 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Investigator/Sponsor Decision | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 2 |
Baseline characteristics
| Characteristic | Fasinumab-matching Placebo | Fasinumab 3 mg SC Q4W | Total |
|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 9.88 | 60.0 years STANDARD_DEVIATION 10.52 | 58.8 years STANDARD_DEVIATION 10.18 |
| Average Daily Low Back Pain Intensity (LBPI) Numerical Rating Scale (NRS) Score | 6.66 Score on a Scale STANDARD_DEVIATION 1.475 | 6.81 Score on a Scale STANDARD_DEVIATION 1.338 | 6.73 Score on a Scale STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 28 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 15 Participants | 14 Participants | 29 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 17 Participants | 32 Participants |
| Sex: Female, Male Female | 21 Participants | 18 Participants | 39 Participants |
| Sex: Female, Male Male | 11 Participants | 13 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 31 |
| other Total, other adverse events | 14 / 32 | 4 / 31 |
| serious Total, serious adverse events | 1 / 32 | 2 / 31 |
Outcome results
Primary
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
Population: Number of Participants analyzed = Participants evaluable for this endpoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 2 | -0.98 Score on a Scale | Standard Deviation 1.588 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 1 | -0.73 Score on a Scale | Standard Deviation 1.424 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 4 | -1.28 Score on a Scale | Standard Deviation 1.878 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 8 | -1.21 Score on a Scale | Standard Deviation 1.568 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 12 | -2.12 Score on a Scale | Standard Deviation 1.582 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 16 | -0.77 Score on a Scale | Standard Deviation 1.943 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 4 | -2.64 Score on a Scale | Standard Deviation 2.038 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 16 | -2.32 Score on a Scale | Standard Deviation 1.367 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 12 | -3.18 Score on a Scale | Standard Deviation 2.046 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 1 | -1.62 Score on a Scale | Standard Deviation 2.037 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 2 | -2.15 Score on a Scale | Standard Deviation 2.067 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Intensity (LBPI) Numeric Rating Scale (NRS) Score | Change from Baseline to Week 8 | -2.82 Score on a Scale | Standard Deviation 1.963 |
Secondary
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
Population: Number of Participants Analyzed = Participants evaluable for this endpoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 4 | -0.60 Score on a Scale | Standard Deviation 0.957 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 12 | -0.57 Score on a Scale | Standard Deviation 1.134 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 8 | -0.55 Score on a Scale | Standard Deviation 0.945 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 16 | 0.00 Score on a Scale | — |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 2 | -0.44 Score on a Scale | Standard Deviation 0.751 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 16 | -0.75 Score on a Scale | Standard Deviation 0.5 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 2 | -0.76 Score on a Scale | Standard Deviation 0.786 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 4 | -1.04 Score on a Scale | Standard Deviation 0.676 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 8 | -1.10 Score on a Scale | Standard Deviation 1.021 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Change from Baseline to Week 12 | -1.00 Score on a Scale | Standard Deviation 1.333 |
Secondary
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
Population: Number of Participants Analyzed = Participants evaluable for this endpoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 4 | -1.49 Score on a Scale | Standard Deviation 2.39 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 8 | -1.31 Score on a Scale | Standard Deviation 2.119 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 12 | -1.63 Score on a Scale | Standard Deviation 2.096 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 16 | -1.14 Score on a Scale | — |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 2 | -1.55 Score on a Scale | Standard Deviation 2.306 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 16 | -1.29 Score on a Scale | Standard Deviation 3.017 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 4 | -2.15 Score on a Scale | Standard Deviation 2.157 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 8 | -2.70 Score on a Scale | Standard Deviation 2.774 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 12 | -1.84 Score on a Scale | Standard Deviation 1.978 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Brief Pain Inventory-Short Form (BPI-sf) Pain Interference Score | Change from Baseline to Week 2 | -1.94 Score on a Scale | Standard Deviation 2.255 |
Secondary
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
Population: Number of Participants Analyzed = Participants evaluable for this endpoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 2 | -2.70 Score on a Scale | Standard Deviation 5.12 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 4 | -1.92 Score on a Scale | Standard Deviation 4.529 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 8 | 0.37 Score on a Scale | Standard Deviation 4.487 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 12 | 0.83 Score on a Scale | Standard Deviation 3.061 |
| Fasinumab-matching Placebo | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 16 | -1.00 Score on a Scale | — |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 2 | -2.54 Score on a Scale | Standard Deviation 4.836 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 4 | -3.09 Score on a Scale | Standard Deviation 3.884 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 16 | -5.75 Score on a Scale | Standard Deviation 3.948 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 12 | -3.33 Score on a Scale | Standard Deviation 4.301 |
| Fasinumab 3 mg SC Q4W | Change From Baseline to Week 16 in the Roland Morris Disability Questionnaire (RMDQ) Total Score | Change from Baseline to Week 8 | -4.18 Score on a Scale | Standard Deviation 5.015 |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Adjudicated Arthropathy (AA) Events | 0 Adjudicated Arthropathy (AA) Events |
| Fasinumab 3 mg SC Q4W | Number of Adjudicated Arthropathy (AA) Events | 2 Adjudicated Arthropathy (AA) Events |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria | 0 Destructive Arthropathy (DA) Events |
| Fasinumab 3 mg SC Q4W | Number of Adjudicated Arthropathy (AA) Events Meeting Destructive Arthropathy (DA) Criteria | 0 Destructive Arthropathy (DA) Events |
Secondary
Number of All-Cause Joint Replacement (JR) Surgery Events
All joint replacement surgery events regardless of cause.
Time frame: Up to Week 36
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of All-Cause Joint Replacement (JR) Surgery Events | 2 Joint Replacement (JR) Surgery Events |
| Fasinumab 3 mg SC Q4W | Number of All-Cause Joint Replacement (JR) Surgery Events | 1 Joint Replacement (JR) Surgery Events |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug | 0 Joint Replacement (JR) Surgery Events |
| Fasinumab 3 mg SC Q4W | Number of Joint Replacement (JR) Surgery Events Reported at Telephone Survey After Last Dose of Study Drug | 0 Joint Replacement (JR) Surgery Events |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score | 12 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants Achieving ≥30% Reduction From Baseline to Week 16 in Average Daily LBPI NRS Score | 21 Participants |
Secondary
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
Population: Anti-Drug Antibody (ADA) analysis set: All treated participants who received any study drug or placebo (safety analysis set) and had at least one non-missing anti-drug antibody result following the first dose of study drug or placebo
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fasinumab-matching Placebo | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment Boosted | 0 Participants |
| Fasinumab-matching Placebo | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment-Emergent: Persistent | 0 Participants |
| Fasinumab-matching Placebo | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Negative/Pre-Existing | 31 Participants |
| Fasinumab-matching Placebo | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment-Emergent: Transient | 0 Participants |
| Fasinumab-matching Placebo | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment-Emergent: Indeterminate | 0 Participants |
| Fasinumab-matching Placebo | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment-Emergent | 0 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment-Emergent: Indeterminate | 0 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Negative/Pre-Existing | 31 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment Boosted | 0 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment-Emergent | 0 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment-Emergent: Persistent | 0 Participants |
| Fasinumab 3 mg SC Q4W | Number of Participants With at Least One Positive Anti-Drug Antibody (ADA) Assay | Treatment-Emergent: Transient | 0 Participants |
Secondary
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fasinumab-matching Placebo | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Paraesthesia events | 1 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab-matching Placebo | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Hypoaesthesia events | 1 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab 3 mg SC Q4W | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Hypoaesthesia events | 0 Peripheral Sensory Adverse Events (AEs) |
| Fasinumab 3 mg SC Q4W | Number of Peripheral Sensory Adverse Events (AEs) That Require a Neurology Consultation | Paraesthesia events | 0 Peripheral Sensory Adverse Events (AEs) |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Sympathetic Nervous System (SNS) Dysfunction Events | 0 Sympathetic NS Dysfunction Events |
| Fasinumab 3 mg SC Q4W | Number of Sympathetic Nervous System (SNS) Dysfunction Events | 0 Sympathetic NS Dysfunction Events |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fasinumab-matching Placebo | Number of Treatment-Emergent Adverse Events (TEAEs) | 33 Treatment-Emergent Adverse Events |
| Fasinumab 3 mg SC Q4W | Number of Treatment-Emergent Adverse Events (TEAEs) | 14 Treatment-Emergent Adverse Events |
Secondary
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
Population: Number of Participants Analyzed = Participants evaluable for this endpoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab Over Time | Baseline | 0 Milligram per Liter (mg/L) | Standard Deviation 0 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab Over Time | Week 2 | 0.262 Milligram per Liter (mg/L) | Standard Deviation 0.0992 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab Over Time | Week 4 | 0.176 Milligram per Liter (mg/L) | Standard Deviation 0.0679 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab Over Time | Week 8 | 0.247 Milligram per Liter (mg/L) | Standard Deviation 0.13 |
| Fasinumab-matching Placebo | Serum Concentration of Functional Fasinumab Over Time | Week 16 | 0.192 Milligram per Liter (mg/L) | Standard Deviation 0.0932 |