A Study of Retatrutide (LY3437943) Once Weekly in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and efficacy of retatrutide once-weekly in participants who have obesity or are overweight and have osteoarthritis (OA) of the knee. The study will lasts about 77 weeks.

Official Title
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A Phase 3 Study to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Obesity, Overweight, Osteo Arthritis Knee

Intervention / Treatment
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* Drug: Retatrutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index (BMI) ≥27 kilogram/kg/m² at screening. Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight. Have index knee pain for >12 weeks prior to screening, and presence of index knee pain for >15 days over the previous month. Have knee X-ray with moderate radiographic changes (Kellgren-Lawrence Grade 2 or 3) per central reading at screening. Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA. Exclusion Criteria: Have had steroid joint injections within 90 days of screening. Have had other joint injections and procedures within 6 months of screening. Have joint disease other than osteoarthritis. Have a self-reported or documented change in body weight >5 kg (11 pounds) within 90 days prior to screening. Have been taking weight loss drugs, including over-the-counter medications, within 90 days prior to screening. Have a prior or planned surgical treatment for obesity. Have diabetes mellitus.

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: Retatrutide Dose 1<br>Participants will receive retatrutide subcutaneously (SC). | Drug: Retatrutide<br>* Administered SC<br>* Other names: LY3437943;|
| Experimental: Retatrutide Dose 2<br>Participants will receive retatrutide SC. | Drug: Retatrutide<br>* Administered SC<br>* Other names: LY3437943;|
| Placebo Comparator: Placebo<br>Participants will receive placebo. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score |  | Baseline, Week 68 | 
| Percent Change from Baseline in Body Weight |  | Baseline, Week 68 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the WOMAC Physical Function Subscale Score |  | Baseline, Week 68 | 
| Change from Baseline in Waist Circumference |  | Baseline, Week 68 | 
| Percent Change from Baseline in Total Cholesterol |  | Baseline, Week 68 | 
| Percent Change from Baseline in Triglycerides |  | Baseline, Week 68 | 
| Change from Baseline in Body Mass Index (BMI) |  | Baseline, Week 68 | 
| Change from Baseline in Systolic Blood Pressure (SBP) |  | Baseline, Week 68 | 
| Change from Baseline in Diastolic Blood Pressure (DBP) |  | Baseline, Week 68 | 
| Percent Change from Baseline in Fasting Insulin |  | Baseline, Week 68 | 
| Change from Baseline in Short Form 36-Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score |  | Baseline, Week 68 | 
| Change from Baseline in Average Pain Intensity Numeric Rating Score (API-NRS) Score |  | Baseline, Week 68 | 
| Change from Baseline in Worst Pain Intensity Numeric Rating Score (WPI-NRS) Score |  | Baseline, Week 68 |