Trial Outcomes & Findings for Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants With Diabetic Peripheral Neuropathic Pain (NCT NCT04476108)

Last Updated: 2023-11-14

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

125 participants

Primary outcome timeframe

Baseline, up to Week 8

Results posted on

2023-11-14

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	84	41
Overall Study Received at Least 1 Dose of Study Drug	83	41
Overall Study COMPLETED	76	38
Overall Study NOT COMPLETED	8	3

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	4	1
Overall Study Lost to Follow-up	1	0
Overall Study Inadvertent Enrollment	1	0
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants With Diabetic Peripheral Neuropathic Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	750 Mg-500 mg LY3016859 n=84 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 n=125 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	50 Participants n=5 Participants	24 Participants n=7 Participants	74 Participants n=5 Participants
Age, Categorical >=65 years	34 Participants n=5 Participants	17 Participants n=7 Participants	51 Participants n=5 Participants
Age, Continuous	61.6 years STANDARD_DEVIATION 8.5 • n=5 Participants	63.3 years STANDARD_DEVIATION 8.9 • n=7 Participants	62.2 years STANDARD_DEVIATION 8.7 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	14 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	27 Participants n=7 Participants	76 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) White	68 Participants n=5 Participants	33 Participants n=7 Participants	101 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	84 Participants n=5 Participants	41 Participants n=7 Participants	125 Participants n=5 Participants
Average Pain Intensity as Measured by the Numeric Rating Scale (NRS)	5.97 score on a scale STANDARD_DEVIATION 1.69 • n=5 Participants	6.30 score on a scale STANDARD_DEVIATION 1.62 • n=7 Participants	6.08 score on a scale STANDARD_DEVIATION 1.66 • n=5 Participants

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=70 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=38 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline in Average Pain Intensity as Measured by the NRS	-1.98 score on a scale Interval -2.42 to -1.55	-1.56 score on a scale Interval -2.17 to -0.96

SECONDARY outcome

Timeframe: Baseline, up to Week 8

The BPI-SF is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Interference scale), and other aspects of pain (for example, location of pain, relief from medications) in various disease states. BPI-SF score ranges from 0 = no pain to 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=75 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=38 Participants Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Change From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Total Interference Score	-2.11 score on a scale Interval -2.55 to -1.65	-1.74 score on a scale Interval -2.35 to -1.12

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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=76 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=38 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	2.48 score on a scale Interval 2.25 to 2.72	2.75 score on a scale Interval 2.41 to 3.09

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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=70 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=38 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	-2.10 score on a scale Interval -2.54 to -1.66	-1.66 score on a scale Interval -2.27 to -1.04

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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=76 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=38 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	-26.17 score on a scale Interval -31.48 to -20.84	-23.31 score on a scale Interval -30.8 to -15.88

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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=76 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=38 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)	0.21 score on a scale Interval -0.05 to 0.47	-0.14 score on a scale Interval -0.51 to 0.22

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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=70 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=38 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	271.58 mg per week Interval 162.12 to 381.44	271.24 mg per week Interval 118.0 to 426.01

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 death) 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.

Outcome measures

Outcome measures
Measure	750 Mg-500 mg LY3016859 n=76 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=38 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)	0.07 score on a scale Interval 0.03 to 0.11	0.03 score on a scale Interval -0.02 to 0.08

Adverse Events

750 Mg-500 mg LY3016859

Serious events: 3 serious events

Other events: 28 other events

Deaths: 1 deaths

Placebo

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	750 Mg-500 mg LY3016859 n=83 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=41 participants at risk Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Gastrointestinal disorders Nausea	1.2% 1/83 • 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% 0/41 • 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 Vomiting	1.2% 1/83 • 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% 0/41 • 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	1.2% 1/83 • 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% 0/41 • 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 Diabetic foot infection	0.00% 0/83 • 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.	2.4% 1/41 • 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.
Injury, poisoning and procedural complications Adverse event following immunisation	0.00% 0/83 • 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.	2.4% 1/41 • 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.
Injury, poisoning and procedural complications Overdose	1.2% 1/83 • 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% 0/41 • 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 Post-traumatic stress disorder	1.2% 1/83 • 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% 0/41 • 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

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

Measure	750 Mg-500 mg LY3016859 n=83 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=41 participants at risk Participants received placebo every 2 weeks by IV infusion for a total of 4 doses.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/83 • 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.	4.9% 2/41 • 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	3.6% 3/83 • 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% 0/41 • 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 Nausea	4.8% 4/83 • 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% 0/41 • 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	4.8% 4/83 • 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% 0/41 • 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	3.6% 3/83 • Number of events 3 • 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% 0/41 • 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	0.00% 0/83 • 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.	7.3% 3/41 • Number of events 3 • 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 Sinusitis	3.6% 3/83 • Number of events 3 • 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% 0/41 • 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.
Investigations Glomerular filtration rate decreased	0.00% 0/83 • 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.	4.9% 2/41 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	3.6% 3/83 • Number of events 3 • 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.	4.9% 2/41 • 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.
Musculoskeletal and connective tissue disorders Back pain	3.6% 3/83 • Number of events 3 • 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% 0/41 • 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 Muscle spasms	0.00% 0/83 • 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.	4.9% 2/41 • 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.
Nervous system disorders Headache	3.6% 3/83 • 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.	2.4% 1/41 • 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.
Skin and subcutaneous tissue disorders Dry skin	3.6% 3/83 • Number of events 3 • 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% 0/41 • 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	4.8% 4/83 • 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.	4.9% 2/41 • 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 Rash	7.2% 6/83 • Number of events 7 • 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% 0/41 • 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.