A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01185353
First received: August 18, 2010
Last updated: September 18, 2012
Last verified: September 2012
  Purpose

The purpose of this trial is to evaluate the safety and efficacy of LY3009104 in participants with Rheumatoid Arthritis (RA).


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: LY3009104
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel-Group, Phase 2b Study of LY3009104 in Patients With Active Rheumatoid Arthritis on Background Methotrexate Therapy

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Percent of participants in the 4 mg and 8 mg dose groups who achieve an American College of Rheumatology (ACR) 20 Responder index (ACR20) response [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent of participants who achieve an American College of Rheumatology (ACR) 20 Responder index (ACR20) response - Model Based Dose Response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent of participants who achieve an American College of Rheumatology (ACR) 20 Responder index (ACR20) response [ Time Frame: 2 weeks, 4 weeks, 8 weeks, 12 weeks, 14 weeks, 16 weeks, 20 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Percent of participants who achieve an American College of Rheumatology (ACR) 50 Responder index (ACR50) response [ Time Frame: 2 weeks, 4 weeks, 8 weeks, 12 weeks, 14 weeks, 16 weeks, 20 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Percent of participants who achieve an American College of Rheumatology (ACR) 70 Responder index (ACR70) response [ Time Frame: 2 weeks, 4 weeks, 8 weeks, 12 weeks, 14 weeks, 16 weeks, 20 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Percent of participants who achieve an American College of Rheumatology (ACR) 50 Responder index (ACR50) - Model Based Dose Response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percent of participants who achieve an American College of Rheumatology (ACR) N - Model Based Dose Response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Mean tender and swollen joint counts [ Time Frame: Baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) score [ Time Frame: Baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Mean C-reactive protein (CRP) [ Time Frame: Baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Mean erythrocyte sedimentation rate (ESR) [ Time Frame: Baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Mean Physician Global Assessment of Disease Activity, Patient Global Assessment of Disease Activity and Patient Assessment of Pain [ Time Frame: Baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Mean Disease Activity Score based on the 28 diarthrodial joint count (DAS28) [ Time Frame: Baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Percent of responders according to European League Against Rheumatism Responder Index based on 28-joint count (EULAR28) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Percent of participants meeting low disease activity and remission based on the 28 diarthrodial joint count (DAS28) [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline through Week 12 endpoint in duration (minutes) of morning stiffness [ Time Frame: Baseline, 4 weeks, 8 weeks, 12 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline through Week 12 endpoint in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Health Component Summary (MCS) scores [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline through Week 12 endpoint in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-pain-in-the past-24-hours item score [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline through Week 12 endpoint in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) score [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  • Predicted Concentration Maximum (Cmax) of LY3009104 at each evaluated dose [ Time Frame: Baseline through 12 weeks ] [ Designated as safety issue: No ]
  • Predicted Area Under the Curve (AUC) of LY3009104 at each evaluated dose [ Time Frame: Baseline through 12 weeks ] [ Designated as safety issue: No ]
  • Mean change from baseline through Week 12 endpoint in the ENSEMBLE Minimum Data Set 1.0 [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 270
Study Start Date: October 2010
Estimated Study Completion Date: March 2014
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 mg LY3009104 once daily
Administered orally once daily for initial 12 weeks followed by randomization to either 4 mg once daily or 2 mg twice daily for an additional 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Drug: LY3009104
Administered orally
Other Names:
  • LY3009104
  • JAK1/JAK2 Inhibitor
  • Janus Kinase 1/2 Inhibitor
  • INCB028050
  • baricitinib
Experimental: 2 mg LY3009104 once daily
Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Drug: LY3009104
Administered orally
Other Names:
  • LY3009104
  • JAK1/JAK2 Inhibitor
  • Janus Kinase 1/2 Inhibitor
  • INCB028050
  • baricitinib
Experimental: 4 mg LY3009104 once daily
Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Drug: LY3009104
Administered orally
Other Names:
  • LY3009104
  • JAK1/JAK2 Inhibitor
  • Janus Kinase 1/2 Inhibitor
  • INCB028050
  • baricitinib
Experimental: 8 mg LY3009104 once daily
Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Drug: LY3009104
Administered orally
Other Names:
  • LY3009104
  • JAK1/JAK2 Inhibitor
  • Janus Kinase 1/2 Inhibitor
  • INCB028050
  • baricitinib
Placebo Comparator: Placebo once daily
Placebo administered orally once daily for initial 12 weeks followed by randomization to either 4 mg once daily or 2 mg twice daily for an additional 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Drug: Placebo
Administered orally
Experimental: 2 mg LY3009104 twice daily
(Not utilized in Part A) Administered orally twice daily for 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Drug: LY3009104
Administered orally
Other Names:
  • LY3009104
  • JAK1/JAK2 Inhibitor
  • Janus Kinase 1/2 Inhibitor
  • INCB028050
  • baricitinib

Detailed Description:

This study consists of the following:

  • Screening period: 4 to 28-days
  • Part A: a 12-week blinded, placebo controlled treatment period
  • Part B: a 12-week blinded extension period
  • Part C: an optional 52-week open-label extension period
  • Part D: an additional optional 52-week open-label extension period
  • Follow up period: 28 days
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have active RA
  • Must regularly use methotrexate (MTX) for at least 12 weeks before your participation in this study
  • Must have ACR functional class I, II, or III
  • Must have C-reactive protein (CRP) measurement > 1.2 times upper limit of normal (ULN) or Erythrocyte Sedimentation Rate (ESR) > upper limit of normal (28 mm/hr)
  • Have laboratory values that in the opinion of the investigator do not pose an unacceptable risk to the participants if study drug would be administered
  • Must have venous access sufficient to allow blood sampling as per the protocol
  • Must be reliable and willing to be available for the duration of the study and are willing to follow study procedures
  • Must be able to read, understand, and give written informed consent approved by Lilly or its designee and the ethical review board (ERB) governing the site
  • Male participants: agree to use two forms of highly effective methods of birth control with female partners of childbearing potential during the study
  • If you are a woman and you could become pregnant during this study, you must talk to the study doctor about birth control. You are required to use two forms of highly effective methods of birth control to avoid getting pregnant during the study
  • If you are a post menopausal woman, you must be at least 45 years of age and have not menstruated for the last 12 months
  • If you are a woman between 40 and 45 years of age, test negative for pregnancy, and have not menstruated during the last 12 months only, you must have an additional blood test to see if you can participate
  • For participants receiving corticosteroids, you must be on a dose not to exceed 10 mg of prednisone daily (or equivalent) and have been on the same dosing regimen for at least 6 weeks prior to randomization
  • Continue to meet inclusion criteria Parts A and B as applicable
  • Have completed the 52 weeks (Week 24 to Week 76) of participation in Part C of the study without permanent study drug discontinuation and have not completed the Follow-Up Visit (approximately 28 days after the last dose of study drug)

Exclusion Criteria:

  • Must not have received any parenteral corticosteroid administered by intra-articular, intramuscular, or intravenous (IV) injection
  • Must not be concomitantly using non-steroidal anti-inflammatory drugs (NSAIDS), unless you are on a stable dose within the last 4 weeks
  • Must not have received any prior biologic disease modifying anti-rheumatic drug (DMARD) therapy (such as TNFα, IL-1, IL-6, T-cell or B-cell target therapies)
  • Must not have used DMARDs other than methotrexate (MTX), hydroxychloroquine, or sulfasalazine within the last 8 weeks
  • Must not have used leflunomide within the last 12 weeks and have not received cholestyramine to speed up the elimination of leflunomide from your body
  • Must not have previously been randomized, completed or withdrawn from this study or any other study investigating LY3009104
  • Must not have received prior treatment with an oral Janus Kinase (JAK) inhibitor
  • Must not have a current or recent (within the last 30 days) viral, bacterial, fungal, or parasitic infection
  • Must not have had a serious infection (for example, pneumonia, cellulitis, or bone or joint infections) or atypical mycobacterial infection within the last 6 months
  • Must not have had symptomatic herpes zoster or herpes simplex infection within the last 90 days or have a history of disseminated/complicated herpes zoster
  • Must not have evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies
  • Must not have evidence of hepatitis C virus (HCV) or active hepatitis B
  • Must not have evidence or suspicion of active or latent tuberculosis (TB)
  • Must not have another serious disorder or illness
  • Must not be exposed to a live vaccine within the last 12 weeks
  • Must not have donated more than 500 mL of blood within the last month
  • Must not have had surgery on a joint that is to be assessed in the study within the last 2 months, or will require such during the study
  • Must not be currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an investigational drug or device or off-label use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Presence of significant uncontrolled cerebra-cardiovascular (eg, myocardial infarction (MI), unstable angina, unstable arterial hypertension, severe heart failure or cerebrovascular accident), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic or neuropsychiatric disorders, or abnormal laboratory values that in the opinion of the investigator pose an unacceptable risk to the participant if study drug would be administered
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01185353

  Show 68 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Incyte Corporation
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01185353     History of Changes
Other Study ID Numbers: 13854, I4V-MC-JADA, CTRI/2011/06/001834
Study First Received: August 18, 2010
Last Updated: September 18, 2012
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
India: Ministry of Health
Poland: Ministry of Health
Romania: Ministry of Public Health
Croatia: Ministry of Health and Social Care
Mexico: Federal Commission for Sanitary Risks Protection
Ukraine: Ministry of Health

Keywords provided by Eli Lilly and Company:
Rheumatoid Arthritis
RA

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 23, 2014