NCT05080660

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

Completed Phase 2 Results posted Last updated 17 July 2024

What this trial tests

Phase 2 trial testing LY3526318 in Osteoarthritis in 160 participants. Completed in 6 June 2022.

Timeline

12 October 2021

Primary endpoint
6 June 2022

6 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	160
Start date	12 October 2021
Primary completion	6 June 2022
Estimated completion	6 June 2022
Sites	30 locations across Puerto Rico, United States

Drugs / interventions tested

• LY3526318 — full drug profile →
• Placebo

Conditions studied

• Osteoarthritis — all drugs for Osteoarthritis →
• Osteo Arthritis Knee — all drugs for Osteo Arthritis Knee →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

40 and older, any sex, with Osteoarthritis or Osteo Arthritis Knee. 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 in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) Primary · Baseline, Week 4

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 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	-0.95	-1.24 – -0.67
Placebo	-1.18	-1.58 – -0.78

Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (NRS) Secondary · Baseline, 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 was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.

Group	Value	95% CI
250 mg LY3526318	-1.26	-1.60 – -0.93
Placebo	-1.45	-1.92 – -0.99

Change From Baseline on the Western Ontario and McMaster University Arthritis Index (WOMAC®) Pain Subscale Secondary · Baseline, Week 4

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 5 questions on the pain subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no pain, and 4 = extreme pain. The scores for the pain subscale were calculated by summing the scores of the questions for each participant at each time point. The range of possible scores is 0 to 20 for the pain subscale. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed mode

Group	Value	95% CI
250 mg LY3526318	-1.87	-2.40 – -1.36
Placebo	-2.50	-3.21 – -1.79

Change From Baseline on the Western Ontario and McMaster University Arthritis Index (WOMAC®) Pain Subscale Secondary · Baseline, Week 8

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 5 questions on the pain subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0=no pain, and 4=extreme pain. The scores for the pain subscale were calculated by summing the scores of the questions for each participant at each time point. The range of possible scores is 0 to 20 for the pain subscale. Posterior mean change from baseline, 95% credible interval was derived using Bayesian mixed model re

Group	Value	95% CI
250 mg LY3526318	-2.51	-3.15 – -1.87
Placebo	-2.85	-3.69 – -1.99

Change From Baseline on the WOMAC® Stiffness Subscale Secondary · Baseline, Week 4

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 2 questions in the stiffness subscale and participants used a 0 to 4 Likert scale to answer each question for the current day: 0=no stiffness, and 4=extreme stiffness. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 8 for the stiffness subscale. Posterior mean change from baseline, 95% credible interva

Group	Value	95% CI
250 mg LY3526318	-1.04	-1.32 – -0.76
Placebo	-1.11	-1.48 – -0.75

Change From Baseline on the WOMAC® Stiffness Subscale Secondary · Baseline, Week 8

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 2 questions in the stiffness subscale and participants used a 0 to 4 Likert scale to answer each question for the current day: 0 = no stiffness, and 4 = extreme stiffness. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 8 for the stiffness subscale. Posterior mean change from baseline, 95% credible int

Group	Value	95% CI
250 mg LY3526318	-1.16	-1.46 – -0.86
Placebo	-1.26	-1.65 – -0.87

Change From Baseline on the WOMAC® Physical Function Subscale Secondary · Baseline, Week 4

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 17 questions in the physical function subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0=no difficulty, and 4=extreme difficulty. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 68 for the physical function subscale. Posterior mean change from baseline,

Group	Value	95% CI
250 mg LY3526318	-6.48	-8.21 – -4.76
Placebo	-8.46	-10.86 – -6.10

Change From Baseline on the WOMAC® Physical Function Subscale Secondary · Baseline, Week 8

The WOMAC® is a validated instrument that is extensively used to evaluate the response to medications for the treatment of Osteoarthritis pain. There are 17 questions in the physical function subscale, and participants used a 0 to 4 Likert scale to answer each question for the current day: 0=no difficulty, and 4=extreme difficulty. The scores for each subscale were calculated by summing the scores of the questions in each respective subscale for each participant at each time point. The range of possible scores is 0 to 68 for the physical function subscale. Posterior mean change from baseline,

Group	Value	95% CI
250 mg LY3526318	-8.04	-10.07 – -6.01
Placebo	-11.09	-13.82 – -8.33

Change From Baseline in 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: 1=very much better, and 7=very much worse. 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	3.18	2.97 – 3.40
Placebo	3.05	2.75 – 3.35

Change From Baseline in 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 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	2.96	2.74 – 3.18
Placebo	2.97	2.66 – 3.28

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

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% 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	-1.08	-1.38 – -0.79
Placebo	-1.38	-1.79 – -0.97

Change From Baseline for Worst Pain Intensity as Measured by NRS Secondary · Baseline, 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% 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	-1.41	-1.76 – -1.05
Placebo	-1.70	-2.19 – -1.21

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: 1/107 (1%)

Deaths: 0/107

250 mg LY3526318/Placebo (Week 5 to 8)

Serious: 0/99 (0%)

Deaths: 0/99

Placebo (Week 1 to 4)

Serious: 1/53 (2%)

Deaths: 0/53

Placebo (Week 5 to 8)

Serious: 0/51 (0%)

Deaths: 0/51

Serious adverse events (4 terms)

Reaction	System	250 mg LY3526318 (Week 1 t…	250 mg LY3526318/Placebo (…	Placebo (Week 1 to 4)	Placebo (Week 5 to 8)
Atrial fibrillation	Cardiac disorders	—	—	—	—
Diplopia	Eye disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Dysarthria	Nervous system disorders	—	—	—	—

Other adverse events (80 terms — click to expand)

Reaction	System	250 mg LY3526318 (Week 1 t…	250 mg LY3526318/Placebo (…	Placebo (Week 1 to 4)	Placebo (Week 5 to 8)
Headache	Nervous system disorders	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—	—
Abnormal dreams	Psychiatric disorders	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—
Balance disorder	Nervous system disorders	—	—	—	—
Dysarthria	Nervous system disorders	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—
Persistent genital arousal disorder	Nervous system disorders	—	—	—	—
Sedation	Nervous system disorders	—	—	—	—
Trigeminal neuralgia	Nervous system disorders	—	—	—	—
Hypoaesthesia	Nervous system disorders	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—
Eructation	Gastrointestinal disorders	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—
Abdominal pain lower	Gastrointestinal disorders	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Tendonitis	Musculoskeletal and connective tissue disorders	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—
Chronic sinusitis	Infections and infestations	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—

Most-reported serious reactions: Atrial fibrillation, Diplopia, Dizziness, Dysarthria.

Data from ClinicalTrials.gov NCT05080660 adverse events section.

Sponsor's own description

The purpose of this study is to test safety and efficacy of study drug LY3526318 in for the treatment of knee pain due to with osteoarthritis (OA). 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. Osteoarthritis Pain.
   Yu H, Huang T, Lu WW, Tong L, et al · · 2022 · cited 93× · PMID 35563035 · DOI 10.3390/ijms23094642
2. Ion channels in osteoarthritis: emerging roles and potential targets.
   Zhou R, Fu W, Vasylyev D, Waxman SG, et al · · 2024 · cited 39× · PMID 39122910 · DOI 10.1038/s41584-024-01146-0
3. 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
4. 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
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