A Study of LY2951742 in Participants With Mild to Moderate Osteoarthritis Knee Pain

Study Overview
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Brief Summary
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The main purpose of this study is to test if LY2951742 relieves mild to moderate knee pain. The study drugs will be given as an injection under the skin and as an oral capsule. The study will last about 28 weeks for each participant.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo and Active-Controlled Trial of LY2951742 in Patients With Mild to Moderate Osteoarthritis Pain of the Knee

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: LY2951742
* Other: Placebo- oral
* Other: Placebo - SC
* Drug: Celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have osteoarthritis (OA) of the knee joint based on American College of Rheumatology (ACR) criteria and confirmed with X-rays and ACR functional class of I to III Have been on stable dose of prescription Nonsteroidal Anti-Inflammatory Drugs (NSAIDS), celecoxib, tramadol, or acetaminophen of at least 2000 mg per day for at least 20 days in the past month Willing to stop all analgesics for OA pain during the study Experienced pain while walking in the target knee of 50-90 mm inclusive on 0-100 Visual Analog Scale (VAS) with an increase in pain while walking of at least 10 mm following washout of current Osteoarthritis pain medications at screening Exclusion Criteria: Allergic to LY2951742, celecoxib, other NSAIDS, including aspirin, and similar drugs Arthritis of the knee from other causes Uncontrolled hypertension Have OA pain that requires treatment with potent opioids, systemic corticosteroids, intra-articular injections, duloxetine, or venlafaxine Moderate to severe renal impairment Pregnant or lactating

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo capsule orally, once daily for approximately 16 weeks. Placebo subcutaneous (SC) once every 4 weeks for 16 weeks (Treatment period = 16 weeks). | Other: Placebo- oral<br>* Administered orally<br>Other: Placebo - SC<br>* Administered SC<br>|
| Active Comparator: Celecoxib + Placebo<br>Celecoxib 200 milligram (mg) capsule orally once daily for approximately 16 weeks. Placebo SC once every 4 weeks for 16 weeks (Treatment period = 16 weeks). | Other: Placebo - SC<br>* Administered SC<br>Drug: Celecoxib<br>* Administered orally<br>|
| Experimental: LY2951742 5 mg + Placebo<br>Placebo capsule orally, once daily for approximately 16 weeks. SC injections of 5 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks). | Drug: LY2951742<br>* Administered subcutaneously (SC)<br>Other: Placebo- oral<br>* Administered orally<br>Other: Placebo - SC<br>* Administered SC<br>|
| Experimental: LY2951742 50 mg + Placebo<br>Placebo capsule orally, once daily for approximately 16 weeks. SC injections of 50 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks). | Drug: LY2951742<br>* Administered subcutaneously (SC)<br>Other: Placebo- oral<br>* Administered orally<br>Other: Placebo - SC<br>* Administered SC<br>|
| Experimental: LY2951742 120 mg + Placebo<br>Placebo capsule orally, once daily for approximately 16 weeks. SC injections of 120 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks). | Drug: LY2951742<br>* Administered subcutaneously (SC)<br>Other: Placebo- oral<br>* Administered orally<br>Other: Placebo - SC<br>* Administered SC<br>|
| Experimental: LY2951742 300 mg + Placebo<br>Placebo capsule orally, once daily for 16 weeks. SC injections of 300 mg LY2951742 once every 4 weeks for 8 weeks followed by placebo SC once every 4 weeks for 8 weeks (Treatment period = 16 weeks). | Drug: LY2951742<br>* Administered subcutaneously (SC)<br>Other: Placebo- oral<br>* Administered orally<br>Other: Placebo - SC<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 to 8 Weeks in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale | The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis (OA) symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales. The WOMAC pain subscale was calculated for each participant at each time point for analysis as the mean score (range 0-100 millimeter [mm] VAS; 0=very good and 100=very poor) of all 5 questions related to pain. Bayesian posterior adjusted mean was calculated using a Bayesian Normal Dynamic Linear Model (NDLM) dose response model with baseline and pooled investigator site included as baseline covariates. | Baseline, 8 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 8 Weeks in the WOMAC Physical Function Subscale | The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales. The WOMAC Osteoarthritis Index version 3.1 was administered according to the study schedule. The WOMAC physical function subscale was calculated for each participant at each time point for analysis as the mean score (range 0-100 mm VAS; 0=very good and 100=very poor) of all 17 questions related to physical function. Least Square Mean (LSM) was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates. | Baseline, 8 Weeks | 
| Change in Baseline to 8 Weeks in Patient's Global Assessment of Osteoarthritis | The PGA is a patient-rated instrument that measures their assessment of overall OA symptoms. It is based on the participant's response to the question Considering all the ways your osteoarthritis affects you, how are you doing today? using a 100 mm VAS (0=very good and 100=very poor). LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates. | Baseline, 8 Weeks | 
| Number of Participants With a Response Rate Measured by the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI) | The responders according to OMERACT-OARSI criteria: participants with at least 50 % improvement in pain or in function scores, along with absolute improvement of 20 mm, were considered responders. Alternatively, participants were considered responders if they showed at least 20% improvement and absolute improvement of 10 mm in at least two of the following scores: pain, function and Patients Global Assessment (PGA) scores. | 8 Weeks | 
| Change From Baseline to 8 Weeks in the WOMAC Stiffness Subscale | The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales. The WOMAC stiffness subscale will be calculated for each participant at each time point for analysis as the mean score (range 0-100 mm VAS; 0=very good and 100=very poor) of 2 questions related to stiffness. LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates. LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates. | Baseline, 8 Weeks | 
| Change From Baseline to 8 Weeks in the WOMAC Total Score | The 24-question WOMAC Osteoarthritis Index assesses osteoarthritis symptoms using pain (5 questions), stiffness (2 questions) and physical function (17 questions) subscales.The WOMAC total score was calculated for each participant at each time point for analysis as the mean score (range 0-100 mm VAS; 0=very good and 100=very poor) of 24 questions. LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates. LSM mean was calculated using a mixed-effects model repeated measures (MMRM) approach with treatment, visit and the interaction of treatment and visit were fitted as fixed effects in the model and baseline and pooled investigator site as baseline covariates. | Baseline, 8 Weeks |