Low Back Pain
Conditions
Brief summary
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
Interventions
DRUGFasinumab
Participants received fasinumab SC or IV, Q4W or Q8W.
DRUGplacebo
Participants received placebo matching to fasinumab SC or IV, Q4W or Q8W.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male or female ≥35 years of age at the screening visit 2. Clinical diagnosis of chronic moderate to severe LBP (nonradiculopathic)for ≥3 months 3. History of regular analgesic medication 4. History of inadequate pain relief or intolerance to analgesics used for chronic LBP 5. Willing to discontinue current pain medication Key
Exclusion criteria
1. History of lumbosacral radiculopathy within the past 2 years 2. Evidence on baseline lumbar spine magnetic resonance imaging of potentially confounding conditions 3. Recent use of longer acting pain medications 4. Evidence of destructive arthropathy 5. Other medical conditions that may interfere with participation or accurate assessments during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 16 in the Average Daily Low Back Pain Index Numeric Rating Scale (LBPI NRS) Score | Baseline to 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 Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Baseline to Weeks 2, 4, 8, and 12 | 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 Roland Morris Disability Questionnaire (RMDQ) Total Score | Baseline to Week 16 | 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. |
| Change From Baseline to Week 16 in the Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | Baseline to Week 16 | 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. |
Countries
Canada, Czechia, Denmark, Estonia, Hungary, Poland, United States
Participant flow
Recruitment details
The study was conducted at 105 sites in US, CA & EU from 26Jan2016 - 13Sep2017. Of 1,783 participants screened, 563 randomized to 1 of 4 groups stratified by baseline low back pain numerical rating scale (LBP NRS) score (\<7, ≥7), duration of chronic LBP (\<5, ≥5yrs) & max. Kellgren-Lawrence (K-L) score (≤2, \>2) at any knee/ hip joint at screening.
Pre-assignment details
The study consisted of a screening period of up to 30 days & a 7-day pre-randomization period during which pain medication, except study-provided rescue medication, was discontinued. Confirmation of no exclusionary findings on joint on which imaging was performed during screening must have been received before a participant could be randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo SC Q4W and Placebo IV Q8W 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. | 141 |
| Fasinumab 6 mg SC Q4W and Placebo IV Q8W 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. | 141 |
| Fasinumab 9 mg SC Q4W and Placebo IV Q8W 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. | 140 |
| Fasinumab 9 mg IV Q8W and Placebo SC Q4W 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. | 141 |
| Total | 563 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 4 | 3 | 5 |
| Overall Study | Death | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 8 | 1 | 4 |
| Overall Study | Physician Decision | 7 | 4 | 3 | 4 |
| Overall Study | Protocol Violation | 5 | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 20 | 16 | 17 | 12 |
Baseline characteristics
| Characteristic | Placebo SC Q4W and Placebo IV Q8W | Fasinumab 6 mg SC Q4W and Placebo IV Q8W | Fasinumab 9 mg SC Q4W and Placebo IV Q8W | Fasinumab 9 mg IV Q8W and Placebo SC Q4W | Total |
|---|---|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 12.54 | 58.2 years STANDARD_DEVIATION 11.29 | 56.6 years STANDARD_DEVIATION 10.99 | 55.4 years STANDARD_DEVIATION 10.49 | 57.1 years STANDARD_DEVIATION 11.38 |
| Age, Customized < 65 years | 93 Participants | 95 Participants | 109 Participants | 117 Participants | 414 Participants |
| Age, Customized ≥ 65 years | 48 Participants | 46 Participants | 31 Participants | 24 Participants | 149 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 4 Participants | 4 Participants | 10 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 134 Participants | 135 Participants | 135 Participants | 131 Participants | 535 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Low Back Pain Intensity Numerical Rating Scale (LBPI NRS) Baseline Score | 6.50 Scores on a scale STANDARD_DEVIATION 1.297 | 6.49 Scores on a scale STANDARD_DEVIATION 1.2481 | 6.66 Scores on a scale STANDARD_DEVIATION 1.3 | 6.45 Scores on a scale STANDARD_DEVIATION 1.191 | 6.53 Scores on a scale STANDARD_DEVIATION 1.267 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 13 Participants | 19 Participants | 19 Participants | 21 Participants | 72 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 127 Participants | 119 Participants | 118 Participants | 116 Participants | 480 Participants |
| Sex: Female, Male Female | 83 Participants | 85 Participants | 84 Participants | 81 Participants | 333 Participants |
| Sex: Female, Male Male | 58 Participants | 56 Participants | 56 Participants | 60 Participants | 230 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 140 | 1 / 139 | 0 / 139 | 0 / 140 |
| other Total, other adverse events | 44 / 140 | 35 / 139 | 52 / 139 | 49 / 140 |
| serious Total, serious adverse events | 4 / 140 | 2 / 139 | 3 / 139 | 5 / 140 |
Outcome results
Primary
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.
Time frame: Baseline to Week 16
Population: Analysis performed on modified intent to treat set (mITT) included all randomized participants who received at least one dose of study drug based on the treatment allocated (as randomized) including data up to 5 weeks after the last dose of study drug. Number of participants analyzed = participants with available data for specified time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Index Numeric Rating Scale (LBPI NRS) Score | -1.7 Scores on a scale | Standard Error 0.23 |
| Fasinumab 6 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Index Numeric Rating Scale (LBPI NRS) Score | -2.0 Scores on a scale | Standard Error 0.23 |
| Fasinumab 9 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Index Numeric Rating Scale (LBPI NRS) Score | -2.5 Scores on a scale | Standard Error 0.22 |
| Fasinumab 9 mg IV Q8W and Placebo SC Q4W | Change From Baseline to Week 16 in the Average Daily Low Back Pain Index Numeric Rating Scale (LBPI NRS) Score | -2.4 Scores on a scale | Standard Error 0.22 |
p-value: 0.387695% CI: [-0.88, 0.34]Mixed Models Analysis
p-value: 0.01895% CI: [-1.32, -0.12]Mixed Models Analysis
p-value: 0.028895% CI: [-1.26, -0.07]Mixed Models Analysis
Secondary
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.
Time frame: Baseline to Week 16
Population: Analysis was performed on mITT population. Here, number of participants analyzed = participants with available data for specified time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in Roland Morris Disability Questionnaire (RMDQ) Total Score | -3.8 Units on a scale | Standard Error 0.54 |
| Fasinumab 6 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in Roland Morris Disability Questionnaire (RMDQ) Total Score | -6.0 Units on a scale | Standard Error 0.54 |
| Fasinumab 9 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in Roland Morris Disability Questionnaire (RMDQ) Total Score | -5.8 Units on a scale | Standard Error 0.51 |
| Fasinumab 9 mg IV Q8W and Placebo SC Q4W | Change From Baseline to Week 16 in Roland Morris Disability Questionnaire (RMDQ) Total Score | -6.3 Units on a scale | Standard Error 0.51 |
p-value: 0.002895% CI: [-3.65, -0.77]Mixed Models Analysis
p-value: 0.006895% CI: [-3.36, -0.54]Mixed Models Analysis
p-value: 0.000695% CI: [-3.88, -1.06]Mixed Models Analysis
Secondary
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.
Time frame: Baseline to Week 16
Population: Analysis was performed on mITT population. Here, number of participants analyzed=participants with available data for specified time point.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in the Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | -0.7 Units on a scale | Standard Error 0.1 |
| Fasinumab 6 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in the Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | -0.9 Units on a scale | Standard Error 0.1 |
| Fasinumab 9 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Week 16 in the Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | -0.8 Units on a scale | Standard Error 0.1 |
| Fasinumab 9 mg IV Q8W and Placebo SC Q4W | Change From Baseline to Week 16 in the Patient Global Assessment (PGA) of Low Back Pain (LBP) Score | -1.0 Units on a scale | Standard Error 0.09 |
p-value: 0.150195% CI: [-0.46, 0.07]Mixed Models Analysis
p-value: 0.260395% CI: [-0.41, 0.11]Mixed Models Analysis
p-value: 0.013595% CI: [-0.59, -0.07]Mixed Models Analysis
Secondary
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.
Time frame: Baseline to Weeks 2, 4, 8, and 12
Population: Analysis performed on modified intent to treat set (mITT) included all randomized participants who received at least one dose of study drug based on the treatment allocated (as randomized) including data up to 5 weeks after the last dose of study drug. Number of participants analyzed = participants with available data for specified time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 2 | -0.9 Scores on a scale | Standard Error 0.17 |
| Placebo SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 4 | -0.9 Scores on a scale | Standard Error 0.17 |
| Placebo SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 8 | -1.2 Scores on a scale | Standard Error 0.19 |
| Placebo SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 12 | -1.5 Scores on a scale | Standard Error 0.21 |
| Fasinumab 6 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 4 | -1.5 Scores on a scale | Standard Error 0.17 |
| Fasinumab 6 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 8 | -1.8 Scores on a scale | Standard Error 0.19 |
| Fasinumab 6 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 12 | -2.0 Scores on a scale | Standard Error 0.21 |
| Fasinumab 6 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 2 | -1.3 Scores on a scale | Standard Error 0.17 |
| Fasinumab 9 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 8 | -2.3 Scores on a scale | Standard Error 0.19 |
| Fasinumab 9 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 4 | -2.0 Scores on a scale | Standard Error 0.17 |
| Fasinumab 9 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 12 | -2.6 Scores on a scale | Standard Error 0.21 |
| Fasinumab 9 mg SC Q4W and Placebo IV Q8W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 2 | -1.6 Scores on a scale | Standard Error 0.17 |
| Fasinumab 9 mg IV Q8W and Placebo SC Q4W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 12 | -2.5 Scores on a scale | Standard Error 0.21 |
| Fasinumab 9 mg IV Q8W and Placebo SC Q4W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 4 | -1.9 Scores on a scale | Standard Error 0.16 |
| Fasinumab 9 mg IV Q8W and Placebo SC Q4W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 2 | -1.6 Scores on a scale | Standard Error 0.16 |
| Fasinumab 9 mg IV Q8W and Placebo SC Q4W | Change From Baseline to Weeks 2, 4, 8, and 12 in the Average Low Back Pain Index Numeric Rating Scale Score (LBPI NRS) | Change from Baseline to Week 8 | -2.2 Scores on a scale | Standard Error 0.19 |