Trial Outcomes & Findings for Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants With Chronic Low Back Pain (NCT NCT04529096)

Last Updated: 2023-11-30

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

149 participants

Primary outcome timeframe

Baseline, up to Week 8

Results posted on

2023-11-30

Participant Flow

Participant milestones

Participant milestones
Measure	750 Mg-500 Milligram (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.	Placebo Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Overall Study STARTED	100	49
Overall Study Received at Least 1 Dose of Study Drug	100	49
Overall Study COMPLETED	86	43
Overall Study NOT COMPLETED	14	6

Reasons for withdrawal

Reasons for withdrawal
Measure	750 Mg-500 Milligram (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.	Placebo Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
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

1 participant had baseline data missing.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	750 Mg-500 mg LY3016859 n=100 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=49 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.	Total n=149 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=100 Participants	0 Participants n=49 Participants	0 Participants n=149 Participants
Age, Categorical Between 18 and 65 years	80 Participants n=100 Participants	33 Participants n=49 Participants	113 Participants n=149 Participants
Age, Categorical >=65 years	20 Participants n=100 Participants	16 Participants n=49 Participants	36 Participants n=149 Participants
Age, Continuous	53.2 years STANDARD_DEVIATION 13.4 • n=100 Participants	57.2 years STANDARD_DEVIATION 12.3 • n=49 Participants	54.5 years STANDARD_DEVIATION 13.2 • n=149 Participants
Sex: Female, Male Female	59 Participants n=100 Participants	24 Participants n=49 Participants	83 Participants n=149 Participants
Sex: Female, Male Male	41 Participants n=100 Participants	25 Participants n=49 Participants	66 Participants n=149 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=100 Participants	0 Participants n=49 Participants	1 Participants n=149 Participants
Race (NIH/OMB) Asian	2 Participants n=100 Participants	0 Participants n=49 Participants	2 Participants n=149 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=100 Participants	0 Participants n=49 Participants	0 Participants n=149 Participants
Race (NIH/OMB) Black or African American	15 Participants n=100 Participants	8 Participants n=49 Participants	23 Participants n=149 Participants
Race (NIH/OMB) White	79 Participants n=100 Participants	40 Participants n=49 Participants	119 Participants n=149 Participants
Race (NIH/OMB) More than one race	1 Participants n=100 Participants	1 Participants n=49 Participants	2 Participants n=149 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=100 Participants	0 Participants n=49 Participants	2 Participants n=149 Participants
Region of Enrollment United States	100 Participants n=100 Participants	49 Participants n=49 Participants	149 Participants n=149 Participants
Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)	5.68 score on a scale STANDARD_DEVIATION 1.46 • n=99 Participants • 1 participant had baseline data missing.	5.58 score on a scale STANDARD_DEVIATION 1.89 • n=49 Participants • 1 participant had baseline data missing.	5.65 score on a scale STANDARD_DEVIATION 1.61 • n=148 Participants • 1 participant had baseline data missing.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=80 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=41 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline for Average Pain Intensity as Measured by the NRS	-1.57 score on a scale Interval -1.94 to -1.21	-2.09 score on a scale Interval -2.6 to -1.59

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=86 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=43 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline on the Roland Morris Disability Questionnaire (RMDQ)	-2.36 score on a scale Interval -3.25 to -1.46	-3.40 score on a scale Interval -4.67 to -2.14

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=86 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=43 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change (PGI)	2.93 score on a scale Interval 2.69 to 3.17	2.77 score on a scale Interval 2.43 to 3.11

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=80 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=41 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline for Worst Pain Intensity as Measured by NRS	-1.72 score on a scale Interval -2.11 to -1.33	-2.20 score on a scale Interval -2.75 to -1.66

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=86 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=43 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline on the Visual Analog Scale (VAS) for Pain	-18.68 score on a scale Interval -23.37 to -13.94	-23.31 score on a scale Interval -29.8 to -16.68

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=86 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=43 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)	-0.02 score on a scale Interval -0.31 to 0.27	-0.08 score on a scale Interval -0.46 to 0.31

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=80 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=41 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week	312.51 mg per week Interval 202.94 to 421.49	327.69 mg per week Interval 172.77 to 484.06

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=86 Participants Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=43 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)	0.03 score on a scale Interval 0.0 to 0.07	0.08 score on a scale Interval 0.03 to 0.14

Adverse Events

750 Mg-500 mg LY3016859

Serious events: 8 serious events

Other events: 38 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	750 Mg-500 mg LY3016859 n=100 participants at risk Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=49 participants at risk Participants received placebo every 2 weeks by IV infusion for a total of 4 doses
Blood and lymphatic system disorders Disseminated intravascular coagulation	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Chest pain	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Covid-19 pneumonia	2.0% 2/100 • Number of events 2 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Fall	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Injury, poisoning and procedural complications Joint dislocation	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Psychiatric disorders Depression	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Vascular disorders Hypertension	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Other adverse events

Other adverse events
Measure	750 Mg-500 mg LY3016859 n=100 participants at risk Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Placebo n=49 participants at risk Participants received placebo every 2 weeks by IV infusion for a total of 4 doses
Gastrointestinal disorders Constipation	1.0% 1/100 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.1% 2/49 • Number of events 2 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Gastrointestinal disorders Diarrhoea	0.00% 0/100 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.1% 2/49 • Number of events 2 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Infusion site pain	4.0% 4/100 • Number of events 4 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Pyrexia	4.0% 4/100 • Number of events 4 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.0% 1/49 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
General disorders Xerosis	4.0% 4/100 • Number of events 4 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.1% 2/49 • Number of events 2 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Infections and infestations Covid-19	4.0% 4/100 • Number of events 4 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.0% 1/49 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Back pain	11.0% 11/100 • Number of events 12 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.0% 1/49 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Dizziness	4.0% 4/100 • Number of events 4 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.0% 1/49 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Nervous system disorders Headache	5.0% 5/100 • Number of events 6 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	6.1% 3/49 • Number of events 5 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Reproductive system and breast disorders Vulvovaginal erythema	0.00% 0/59 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.2% 1/24 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/100 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	4.1% 2/49 • Number of events 2 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Skin and subcutaneous tissue disorders Dry skin	8.0% 8/100 • Number of events 9 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	0.00% 0/49 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Skin and subcutaneous tissue disorders Pruritus	4.0% 4/100 • Number of events 5 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.	2.0% 1/49 • Number of events 1 • Baseline through Week 26 All enrolled or randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place