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

Osteoarthritis Clinical Trial

Official title:

A Master Protocol for Randomized, Placebo-Controlled, Phase 2 Clinical Trials of Multiple Interventions for the Treatment of Chronic Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05080660
• Other study ID #: 17592
• Secondary ID: H0P-MC-OA02
• Status: Completed
• Phase: Phase 2
• Start date: October 12, 2021
• Est. completion date: June 6, 2022

Study information

• Verified date: August 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: June 6, 2022
• Est. primary completion date: June 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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 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 presence of index knee pain for >12 weeks at screening.

• Have an x-ray supporting diagnosis of osteoarthritis according to the American College of Rheumatology with a Kellgren-Lawrence grade 2 to 4 radiographic classification of index knee.

• Are men, or women able to abide by reproductive and contraceptive requirements.

Exclusion Criteria:

• 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.

• Have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision.

• Have fibromyalgia

• Have a substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association).

• 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.

• Are largely or wholly incapacitated and unable to participate fully in all protocol procedures, for example, bedridden or confined to a wheelchair, permitting little or no selfcare.

• Have presence of surgical hardware or other foreign body in the index knee.

• Have an unstable index joint (such as a torn anterior cruciate ligament).

• Have had a surgical procedure or therapeutic injection in the affected knee within 3 months prior to starting the washout period.

• Have chronic pain syndrome, or other concurrent medical or arthritic conditions that could interfere with the evaluation of the index knee.

• Have a history of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis, or amyloidosis.

• Have clinical signs and symptoms of active knee infection or crystal disease of the index knee.

• Have a history of infection in the index joint.

• Have a history of arthritis due to crystals (e.g., gout, pseudo gout).

• Have pain or functional impairment due to ipsilateral hip osteoarthritis.

• Are pregnant or breastfeeding.

Related Conditions & MeSH terms

• Chronic Pain
• Osteo Arthritis Knee
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• LY3526318
Administered orally.
• Placebo
Administered orally.

Locations

Country	Name	City	State
Puerto Rico	Ponce Medical School Foundation Inc.	Ponce
Puerto Rico	Latin Clinical Trial Center	San Juan
United States	VIN-Julie Schwartzbard	Aventura	Florida
United States	Great Lakes Research Group, Inc.	Bay City	Michigan
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Boston Clinical Trials	Boston	Massachusetts
United States	Synexus- Chandler	Chandler	Arizona
United States	Northwestern University	Chicago	Illinois
United States	Synexus Clinical Research US, Inc.	Chicago	Illinois
United States	Synexus - Cincinnati	Cincinnati	Ohio
United States	META Medical Research Institute	Dayton	Ohio
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	Synexus Clinical Research - Glendale	Glendale	Arizona
United States	CMR of Greater New Haven	Hamden	Connecticut
United States	Rocky Mountain Clinical Research	Idaho Falls	Idaho
United States	ActivMed Practices and Research	Methuen	Massachusetts
United States	New Horizon Research Center	Miami	Florida
United States	Suncoast Research Group	Miami	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	Synexus Clinical Research US, Inc - Orlando	Orlando	Florida
United States	Synexus Clinical Research US, Inc.	Pinellas Park	Florida
United States	Rainier Clinical Research Center	Renton	Washington
United States	Artemis Institute for Clinical Research	Riverside	California
United States	StudyMetrix Research	Saint Peters	Missouri
United States	Synexus - US	San Antonio	Texas
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Clinvest Research LLC	Springfield	Missouri
United States	Alliance for Multispecialty Research, LLC Tempe	Tempe	Arizona
United States	Synexus Clinical Research US, Inc - Orlando	The Villages	Florida
United States	MedVadis Research Corporation	Waltham	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (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 percent (%) credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 4
Secondary	Change From Baseline in Average Pain Intensity as Measured by the Numeric Rating Scale (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 was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 8
Secondary	Change From Baseline on the Western Ontario and McMaster University Arthritis Index (WOMAC®) Pain Subscale	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 repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 4
Secondary	Change From Baseline on the Western Ontario and McMaster University Arthritis Index (WOMAC®) Pain Subscale	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 repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 8
Secondary	Change From Baseline on the WOMAC® Stiffness Subscale	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 interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 4
Secondary	Change From Baseline on the WOMAC® Stiffness Subscale	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 interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 8
Secondary	Change From Baseline on the WOMAC® Physical Function Subscale	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, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 4
Secondary	Change From Baseline on the WOMAC® Physical Function Subscale	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, 95% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 8
Secondary	Overall Improvement as Measured by Patient's Global Impression of Change	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.	Week 4
Secondary	Overall Improvement as Measured by Patient's Global Impression of Change	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.	Week 8
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% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 4
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% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 8
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% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 4
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% credible interval was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 8
Secondary	Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep	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) is reported as the average number of hours slept each night during the past week (range 0 to 24 hours). Higher number of hours slept indicates improvement.; 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.	Baseline, Week 4
Secondary	Change From Baseline on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale) - Average Hours of Sleep	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) is reported as the average number of hours slept each night during the past week (range 0 to 24 hours). Higher number of hours slept indicates improvement.; 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.	Baseline, Week 8
Secondary	Total Amount of Rescue Medication Use as Measured by Average Daily Dosage (mg) Per Week	Total amount of rescue medication use as measured by average daily dosage (mg) per week. 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.	Baseline up to week 4
Secondary	Total Amount of Rescue Medication Use as Measured by Average Daily Dosage (mg) Per Week	Total amount of rescue medication use as measured by average daily dosage (mg) per week. 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.	Baseline up to week 8
Secondary	Change From Baseline on the EuroQuality of Life Five Dimensions (5D) Five Level (5L) 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% credible intervals was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 4
Secondary	Change From Baseline on the EuroQuality of Life Five Dimensions (5D) Five Level (5L) 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% credible intervals was derived using Bayesian mixed model repeated measures. Data presented are posterior mean with 95% credible interval.	Baseline, Week 8

External Links

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