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

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

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.

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Celecoxib; Other: Placebo- oral; Other: Placebo - SC; Drug: LY2951742

• Study Type: Interventional
• Enrollment (Actual): 268
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
  • California
    • Anaheim, California, United States, 92801
      • Dream Team Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • Upland, California, United States, 91786
      • Empire Clinical Research
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research
    • West Covina, California, United States, 91760
      • iM Research
  • Colorado
    • Denver, Colorado, United States, 80220
      • Horizons Clinical Research Center
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research LLC
    • Hialeah, Florida, United States, 33012
      • Palm Springs Research Institute
    • Hialeah, Florida, United States, 33012
      • AGA Clinical Trials
    • Miami, Florida, United States, 33173
      • Research Institute of South Florida, Inc.
    • Miami, Florida, United States, 33185
      • M&M Medical Center
    • Miami, Florida, United States, 33155
      • Community Research Foundation Inc
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Orlando, Florida, United States, 32806
      • Compass Research
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • United Osteoporosis Center
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Medex Healthcare Research, Inc.
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Buynak Clinical Research, P.C.
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Beacon Clinical Research, LLC
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, Inc
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • The Center for Clinical Trials, Inc.
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Arthritis, Rheumatic & Back Disease Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Clinical Research & Osteoporosis Center
  • New York
    • Hartsdale, New York, United States, 10530
      • Drug Trials of America
    • New York, New York, United States, 10016
      • Medex Healthcare Research, Inc.
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
  • Ohio
    • Wooster, Ohio, United States, 44691
      • Family Practice Center of Wooster
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • Rhode Island
    • Warwick, Rhode Island, United States, 02888
      • Greater Providence Clinical Research, LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
    • Greenville, South Carolina, United States, 29601
      • PCPMG Clinical Research Unit
  • Texas
    • Nassau Bay, Texas, United States, 77058
      • Accurate Clinical Research
    • San Antonio, Texas, United States, 78209
      • Quality Research, Inc.
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads Inc
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater
    • Norfolk, Virginia, United States, 23502
      • National Clinical Research - Norfolk Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Administered orally; Other: Placebo - SC; Administered SC
Active Comparator: Celecoxib + Placebo; 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).	Drug: Celecoxib; Administered orally; Other: Placebo - SC; Administered SC
Experimental: LY2951742 5 mg + Placebo; 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).	Other: Placebo- oral; Administered orally; Other: Placebo - SC; Administered SC; Drug: LY2951742; Administered subcutaneously (SC)
Experimental: LY2951742 50 mg + Placebo; 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).	Other: Placebo- oral; Administered orally; Other: Placebo - SC; Administered SC; Drug: LY2951742; Administered subcutaneously (SC)
Experimental: LY2951742 120 mg + Placebo; 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).	Other: Placebo- oral; Administered orally; Other: Placebo - SC; Administered SC; Drug: LY2951742; Administered subcutaneously (SC)
Experimental: LY2951742 300 mg + Placebo; 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).	Other: Placebo- oral; Administered orally; Other: Placebo - SC; Administered SC; Drug: LY2951742; Administered subcutaneously (SC)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Jin Y, Smith C, Monteith D, Brown R, Camporeale A, McNearney TA, Deeg MA, Raddad E, Xiao N, de la Pena A, Kivitz AJ, Schnitzer TJ. CGRP blockade by galcanezumab was not associated with reductions in signs and symptoms of knee osteoarthritis in a randomized clinical trial. Osteoarthritis Cartilage. 2018 Dec;26(12):1609-1618. doi: 10.1016/j.joca.2018.08.019. Epub 2018 Sep 18.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 14, 2014
• First Submitted That Met QC Criteria: July 14, 2014
• First Posted (Estimate): July 16, 2014

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: 15515; I5Q-MC-CGAF (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR