Chronic Low-back Pain
Conditions
Brief summary
This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of chronic low back pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.
Interventions
DRUGLY3016859
Administered IV
DRUGPlacebo
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a visual analog scale (VAS) pain value ≥40 and \<95 during screening. * Have a history of daily pain for at least 12 weeks based on participant report or medical history. * Have a value of ≤30 on the pain catastrophizing scale. * Have a body mass index \<40 kilograms per meter squared (kg/m²) (inclusive). * Are willing to maintain a consistent regimen of any ongoing nonpharmacologic pain-relieving therapies (for example, physical therapy) and will not start any new nonpharmacologic pain-relieving therapies during study participation. * Are willing to discontinue all medications taken for chronic pain conditions for the duration of the study. * Have a history of low back pain for at least 3 months located between the 12th thoracic vertebra and the lower gluteal folds, with or without radiation. * Have a history of low back pain as classified by the Quebec Task Force Category 1 through 3. * Have stable glycemic control as indicated by a glycated hemoglobin (HbA1c) less than or equal to 10 at time of screening. * Are men, or women able to abide by reproductive and contraceptive requirements.
Exclusion criteria
* Have second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia. * Have had a procedure within the past 6 months intended to produce permanent sensory loss in the target area of interest (for example, ablation techniques). * Have surgery planned during the study for any reason, related or not to the disease state under evaluation. * Have, in the judgment of the investigator, an acute, serious, or unstable medical condition or a history or presence of any other medical illness that would preclude study participation. * There is an inability to rule out other causative or confounding sources of pain in the primary condition under study. * Have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision. * Have a substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association). * Have congenital QT prolongation or QT interval corrected for heart rate using Fridericia's formula (QTcF) interval measurement \>450 milliseconds (msec) for male participants, \>470 msec for female participants, or \>480 msec for participants with bundle branch block. * Have any clinically important abnormality at screening, as determined by investigator, in physical or neurological examination, vital signs, electrocardiogram (ECG), or clinical laboratory test results that could be detrimental to the participant or could compromise the study. * Have a positive human immunodeficiency virus (HIV) test result at screening. * Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide. * Have an intolerance to acetaminophen or paracetamol or any of its excipients. * Have a history of alcohol, illicit drug, analgesic or narcotic use disorder within 2 years prior to screening. * Have used a therapeutic injection (botulinum toxin or corticosteroids) in the 3 months prior to starting the washout period. * Have history of or current compression fracture. * Have had a recent major trauma (within 6 months of baseline). * Have a history of low back pain as classified by the Quebec Task Force Categories 4 through 11. * Are using spinal cord stimulator or dorsal root ganglion stimulator. * Have fibromyalgia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for Average Pain Intensity as Measured by the NRS | Baseline, up to Week 8 | The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI) | Baseline, up to Week 8 | Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals. |
| Change From Baseline for Worst Pain Intensity as Measured by NRS | Baseline, up to Week 8 | The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals. |
| Change From Baseline on the Visual Analog Scale (VAS) for Pain | Baseline, up to Week 8 | VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals. |
| Change From Baseline on the Roland Morris Disability Questionnaire (RMDQ) | Baseline, up to Week 8 | The RMDQ is a simple, sensitive, and reliable method to measure disability in patients with back pain that consists of 24 statements relating to the person's perceptions of back pain and associated disability based on physical ability/activity, sleep/rest, psychosocial, household management, eating, and pain frequency. Participants are asked if they feel the statement is descriptive of their own circumstance on that day. The total score is obtained by counting the number of ''Yes'' responses, ranging from: 0 = no disability to 24 = maximal disability. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals. |
| Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week | Baseline up to Week 8 | Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence interval. |
| Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States) | Baseline, up to Week 8 | The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than dead) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals. |
| Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) | Baseline, up to Week 8 | The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1=all of the time to 6=none of the time. MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes. Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 750 Mg-500 mg LY3016859 Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses. | 100 |
| Placebo Participants received placebo every 2 weeks by IV infusion for a total of 4 doses. | 49 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Non-Compliance With Study Drug | 0 | 1 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | 750 Mg-500 mg LY3016859 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 16 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 80 Participants | 33 Participants | 113 Participants |
| Age, Continuous | 53.2 years STANDARD_DEVIATION 13.4 | 57.2 years STANDARD_DEVIATION 12.3 | 54.5 years STANDARD_DEVIATION 13.2 |
| Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) | 5.68 score on a scale STANDARD_DEVIATION 1.46 | 5.58 score on a scale STANDARD_DEVIATION 1.89 | 5.65 score on a scale STANDARD_DEVIATION 1.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 8 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 79 Participants | 40 Participants | 119 Participants |
| Region of Enrollment United States | 100 Participants | 49 Participants | 149 Participants |
| Sex: Female, Male Female | 59 Participants | 24 Participants | 83 Participants |
| Sex: Female, Male Male | 41 Participants | 25 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 0 / 49 |
| other Total, other adverse events | 38 / 100 | 13 / 49 |
| serious Total, serious adverse events | 8 / 100 | 0 / 49 |
Outcome results
Primary
Change From Baseline for Average Pain Intensity as Measured by the NRS
The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals
Time frame: Baseline, up to Week 8
Population: All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Change From Baseline for Average Pain Intensity as Measured by the NRS | -1.57 score on a scale |
| Placebo | Change From Baseline for Average Pain Intensity as Measured by the NRS | -2.09 score on a scale |
95% CI: [-0.1, 1.14]Bayesian Mixed Model Analysis
Secondary
Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)
The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1=all of the time to 6=none of the time. MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes. Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
Time frame: Baseline, up to Week 8
Population: All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) | -0.02 score on a scale |
| Placebo | Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) | -0.08 score on a scale |
95% CI: [-0.4, 0.51]Bayesian Mixed Model Analysis
Secondary
Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI)
Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
Time frame: Baseline, up to Week 8
Population: All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI) | 2.93 score on a scale |
| Placebo | Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI) | 2.77 score on a scale |
95% CI: [-0.25, 0.58]Bayesian Mixed Model Analysis
Secondary
Change From Baseline for Worst Pain Intensity as Measured by NRS
The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
Time frame: Baseline, up to Week 8
Population: All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Change From Baseline for Worst Pain Intensity as Measured by NRS | -1.72 score on a scale |
| Placebo | Change From Baseline for Worst Pain Intensity as Measured by NRS | -2.20 score on a scale |
95% CI: [-0.19, 1.17]Bayesian Mixed Model Analysis
Secondary
Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)
The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than dead) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
Time frame: Baseline, up to Week 8
Population: All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States) | 0.03 score on a scale |
| Placebo | Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States) | 0.08 score on a scale |
95% CI: [-0.11, 0.01]Bayesian Mixed Model Analysis
Secondary
Change From Baseline on the Roland Morris Disability Questionnaire (RMDQ)
The RMDQ is a simple, sensitive, and reliable method to measure disability in patients with back pain that consists of 24 statements relating to the person's perceptions of back pain and associated disability based on physical ability/activity, sleep/rest, psychosocial, household management, eating, and pain frequency. Participants are asked if they feel the statement is descriptive of their own circumstance on that day. The total score is obtained by counting the number of ''Yes'' responses, ranging from: 0 = no disability to 24 = maximal disability. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
Time frame: Baseline, up to Week 8
Population: All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Change From Baseline on the Roland Morris Disability Questionnaire (RMDQ) | -2.36 score on a scale |
| Placebo | Change From Baseline on the Roland Morris Disability Questionnaire (RMDQ) | -3.40 score on a scale |
95% CI: [-0.46, 2.56]Bayesian Mixed Model Analysis
Secondary
Change From Baseline on the Visual Analog Scale (VAS) for Pain
VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence intervals.
Time frame: Baseline, up to Week 8
Population: All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Change From Baseline on the Visual Analog Scale (VAS) for Pain | -18.68 score on a scale |
| Placebo | Change From Baseline on the Visual Analog Scale (VAS) for Pain | -23.31 score on a scale |
95% CI: [-3.51, 12.59]Bayesian Mixed Model Analysis
Secondary
Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week
Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures. The Bayesian analyses include posterior probabilities instead of p-values, and 95% credible intervals instead of 95% confidence interval.
Time frame: Baseline up to Week 8
Population: All enrolled or randomized participants who received at least one dose of study drug. Here, the overall number of participants analyzed includes the number of participants with non-missing value at Week 8.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week | 312.51 mg per week |
| Placebo | Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week | 327.69 mg per week |
95% CI: [-206.43, 175.8]Bayesian Mixed Model Analysis