A Chronic Pain Master Protocol (CPMP): A Study of LY3857210 In Participants With Osteoarthritis Pain

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of LY3857210 in participants with Osteoarthritic Pain

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

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: LY3857210
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia. 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 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 fibromyalgia, 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, pseudogout). Have pain or functional impairment due to ipsilateral hip osteoarthritis. Have a history within 2 years prior to screening or current evidence of syncope, presyncope, uncontrolled vertigo, or postural dizziness, judged to be clinically significant by the investigator. Have clinically significant active thyroid disease, including Hashimoto's thyroiditis. Are taking metformin therapy. Are pregnant or breastfeeding. Have had any joint replacement such as knee of the lower extremity, such as hip, knee or ankle, in the past 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3857210<br>LY3857210 will be given orally | Drug: LY3857210<br>* Administered orally<br>|
| Placebo Comparator: Placebo<br>Placebo will be given orally | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline for Average Pain Intensity as measured by the Numeric Rating Scale (NRS) |  | Baseline, Up to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline for Disease State Assessment (DSA) |  | Baseline, Up to Week 8 | 
| Change from Baseline for Overall improvement as Measured by Patient's Global Impression of Change |  | Baseline, Up to Week 8 | 
| Change from Baseline for Worst Pain Intensity as Measured by NRS |  | Baseline, Up to Week 8 | 
| Percentage of Participants with a Pain Reduction from Baseline Greater than or equal to 30%, 50%, and 70% as Measured by the Average and Worst Pain Responses on the NRS |  | Baseline to Week 8 | 
| Percentage of Participants with at least 2-point Reduction from Baseline as Measured by the Average and Worst Pain Responses on the NRS |  | Baseline to Week 8 | 
| Time to First Pain Reduction of at Least 30%, 50%, and 70% from Baseline as Measured by the Average and Worst Pain Responses on the NRS |  | Baseline to Week 8 | 
| Time to First Pain Reduction of at least 2-point from Baseline as Measured by the Average and Worst Pain Responses on the NRS |  | Baseline to Week 8 | 
| Change from Baseline for on the Visual Analog Scale (VAS) for Pain |  | Baseline, Up to Week 8 | 
| Percentage of Participants with Pain Reduction from Baseline Greater than or equal to 30%, 50%, and 70% as Measured by VAS |  | Baseline to Week 8 | 
| Change from Baseline for on the Sleep Scale from the Medical Outcomes Study (MOS) Sleep Scale |  | Baseline, Up to Week 8 | 
| Percentage of Participants with Reduction from Baseline Greater Than or Equal to 30%, 50%, and 70% on the Physical Functioning Measures as described in the DSA |  | Baseline to Week 8 | 
| Summary of Frequency, Timing, and Amount of Rescue Medication used during the Treatment Phase |  | Baseline Through Week 8 | 
| Change from Baseline for Emotional Functioning as measured by the EuroQol-5D-5-Level Questionnaire (EQ-5D-5L) |  | Baseline to Week 8 |