NCT05086289

Chronic Pain Master Protocol (CPMP): A Study of LY3526318 in Participants With Chronic Low Back Pain

Completed Phase 2 Results posted Last updated 5 October 2023

What this trial tests

Phase 2 trial testing LY3526318 in Chronic Low-back Pain in 159 participants. Completed in 17 June 2022.

Timeline

25 October 2021

Primary endpoint
17 June 2022

17 June 2022

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	159
Start date	25 October 2021
Primary completion	17 June 2022
Estimated completion	17 June 2022
Sites	31 locations across Puerto Rico, United States

Drugs / interventions tested

• LY3526318 — full drug profile →
• Placebo

Conditions studied

• Chronic Low-back Pain — all drugs for Chronic Low-back Pain →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Chronic Low-back Pain. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline for Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) at Week 4 Primary · Baseline, Week 4

The NRS was used 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 percent (%) credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	-1.28	-1.59 – -0.97
Placebo	-0.90	-1.32 – -0.48

Change From Baseline for Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) Secondary · Baseline, Week 8

The NRS was used 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 was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	-1.47	-1.82 – -1.12
Placebo	-1.20	-1.67 – -0.73

Change From Baseline on the Roland Morris Disability Questionnaire (RMDQ) Secondary · Baseline, Week 4

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%

Group	Value	95% CI
250 mg LY3526318	-2.03	-2.82 – -1.25
Placebo	-1.42	-2.49 – -0.36

Change From Baseline on the Roland Morris Disability Questionnaire (RMDQ) Secondary · Baseline, 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%

Group	Value	95% CI
250 mg LY3526318	-2.55	-3.37 – -1.71
Placebo	-1.37	-2.49 – -0.25

Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change Secondary · Baseline, Week 4

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 where, 1=very much better, and 7=very much worse. Posterior mean, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	3.13	2.94 – 3.31
Placebo	3.25	2.99 – 3.50

Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change Secondary · Baseline, 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, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	3.00	2.76 – 3.24
Placebo	3.26	2.93 – 3.59

Change From Baseline for Worst Pain Intensity as Measured by NRS Secondary · Baseline, Week 4

The NRS was used 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% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	-1.45	-1.79 – -1.10
Placebo	-0.97	-1.43 – -0.50

Change From Baseline for Worst Pain Intensity as Measured by NRS Secondary · Baseline, Week 8

The NRS was used 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% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	-1.69	-2.09 – -1.28
Placebo	-1.18	-1.72 – -0.64

Change From Baseline on the Visual Analog Scale (VAS) for Pain Secondary · Baseline, Week 4

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% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	-14.84	-18.65 – -10.99
Placebo	-9.89	-14.97 – -4.80

Change From Baseline on the Visual Analog Scale (VAS) for Pain Secondary · Baseline, 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% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	-19.50	-23.74 – -15.30
Placebo	-14.72	-20.39 – -9.00

Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep Secondary · Baseline, Week 4

The MOS Sleep Scale consists of 12 questions addressing the past week. Question 1 asks time to fall asleep and it is reported in 5-point timeframe categories. Question 2 asks average hours of sleep. In the remaining 10 questions participants report how often a sleep symptom or problem was present on a scale ranging from '0=all of the time' to '5=none of the time.' MOS Sleep scale dimension scores range from 0 to 100 with lower score indicating improvement, except for the dimension of sleep adequacy, where higher scores indicate improvement. Here, the average hours of sleep (i.e., Question 2) i

Group	Value	95% CI
250 mg LY3526318	0.11	-0.09 – 0.32
Placebo	0.24	-0.04 – 0.52

Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep Secondary · Baseline, Week 8

The MOS Sleep Scale consists of 12 questions addressing the past week. Question 1 asks time to fall asleep and it is reported in 5-point timeframe categories. Question 2 asks average hours of sleep. In the remaining 10 questions participants report how often a sleep symptom or problem was present on a scale ranging from '0=all of the time' to '5=none of the time.' MOS Sleep scale dimension scores range from 0 to 100 with lower score indicating improvement, except for the dimension of sleep adequacy, where higher scores indicate improvement. Here, the average hours of sleep (i.e., Question 2) i

Group	Value	95% CI
250 mg LY3526318	5.04	0.08 – 9.95
Placebo	3.52	-2.96 – 10.02

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline through Week 8. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

250 mg LY3526318 Week 1 to 4

Serious: 2/105 (2%)

Deaths: 0/105

250 mg LY3526318/Placebo Week 5 to 8

Serious: 0/92 (0%)

Deaths: 0/92

Placebo Week 1 to 4

Serious: 0/54 (0%)

Deaths: 0/54

Placebo Week 5 to 8

Serious: 0/50 (0%)

Deaths: 0/50

Serious adverse events (2 terms)

Reaction	System	250 mg LY3526318 Week 1 to 4	250 mg LY3526318/Placebo W…	Placebo Week 1 to 4	Placebo Week 5 to 8
Hip fracture	Injury, poisoning and procedural complications	—	—	—	—
Suicidal ideation	Psychiatric disorders	—	—	—	—

Other adverse events (73 terms — click to expand)

Reaction	System	250 mg LY3526318 Week 1 to 4	250 mg LY3526318/Placebo W…	Placebo Week 1 to 4	Placebo Week 5 to 8
Nausea	Gastrointestinal disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Heavy menstrual bleeding	Reproductive system and breast disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—
Fatigue	General disorders	—	—	—	—
SARS-CoV-2 test positive	Investigations	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Abdominal distentation	Gastrointestinal disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—
Frequent bowel movements	Gastrointestinal disorders	—	—	—	—
Lip swelling	Gastrointestinal disorders	—	—	—	—
Balance disorder	Nervous system disorders	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—
Restless legs syndrome	Nervous system disorders	—	—	—	—
Tension headache	Nervous system disorders	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Gastroenteritis viral	Infections and infestations	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Concussion	Injury, poisoning and procedural complications	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—
Dental restoration failure	Injury, poisoning and procedural complications	—	—	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—	—	—
Post procedural complication	Injury, poisoning and procedural complications	—	—	—	—
Post procedural haematoma	Injury, poisoning and procedural complications	—	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—	—
Vaccination complication	Injury, poisoning and procedural complications	—	—	—	—
Chest discomfort	General disorders	—	—	—	—
Chest pain	General disorders	—	—	—	—
Chills	General disorders	—	—	—	—
Pain	General disorders	—	—	—	—

Most-reported serious reactions: Hip fracture, Suicidal ideation.

Data from ClinicalTrials.gov NCT05086289 adverse events section.

Sponsor's own description

The purpose of this study is to test whether LY3526318 is efficacious and safe in relieving chronic low back pain (CLBP). 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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Neuronal and non-neuronal TRPA1 as therapeutic targets for pain and headache relief.
   Iannone LF, Nassini R, Patacchini R, Geppetti P, et al · · 2023 · cited 18× · PMID 37187829 · DOI 10.1080/23328940.2022.2075218
2. Clinical proof-of-concept results with a novel TRPA1 antagonist (LY3526318) in 3 chronic pain states.
   Mellado Lagarde MM, Wilbraham D, Martins RF, Zhao HS, et al · · 2024 · cited 7× · PMID 39679712 · DOI 10.1097/j.pain.0000000000003487
3. The role of TRPA1 in lung cancer.
   O'Connor D, Finn SP, Gray SG. · · 2025 · cited 1× · PMID 41234585 · DOI 10.21037/tlcr-2025-114
4. When do platform trials in chronic pain make sense?
   Robinson-Papp J, Rathmell JP, Tarpey T, Troxel AB. · · 2026 · PMID 41380093 · DOI 10.1097/j.pain.0000000000003882
5. Physiological functions and pharmacological targeting of transient receptor potential channels.
   Chubanov V, Grimm C, Hill K, Schaefer M, et al · · 2025 · PMID 41118703 · DOI 10.1016/j.pharmr.2025.100089