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A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy

Primary Purpose

Arthritis, Rheumatoid

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

LY3009104

Placebo

Methotrexate

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Rheumatoid Arthritis, RA

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Must have active RA
Must regularly use methotrexate (MTX) for at least 12 weeks before your participation in this study
Must have American College of Rheumatology (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) > ULN [28 millimeters/hour (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 2 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 2 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
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 for Parts A and B as applicable
Part D only: 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 (IM), or intravenous (IV) injection within 6 weeks prior to baseline
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 Tumor necrosis factor-alpha (TNFα), interleukin (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 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 milliliters (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 cerebro-cardiovascular [for example (eg), myocardial infarction (MI), unstable angina (UA), unstable arterial hypertension, severe heart failure or cerebrovascular accident], respiratory, hepatic, renal, gastrointestinal (GI), 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

Sites / Locations

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

1 mg LY3009104 once daily

2 mg LY3009104 once daily

4 mg LY3009104 once daily

8 mg LY3009104 once daily

Placebo once daily

2 mg LY3009104 twice daily

Arm Description

Administered orally once daily for initial 12 weeks followed by randomization to either 4 mg LY3009104 once daily or 2 mg LY3009104 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.

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.

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: 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.

Placebo administered orally once daily for initial 12 weeks followed by randomization to either 4 mg LY3009104 once daily or 2 mg LY3009104 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.

(Not utilized in Part A) After 12 weeks treatment with 1 mg LY3009104 once daily or Placebo once daily 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.

Outcomes

Primary Outcome Measures

Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100.

Secondary Outcome Measures

Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) * 100.

Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100.

Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) * 100.

Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128

Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24

ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) * 100.

Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128

Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) * 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

ACR Percent Improvement (ACR-N)

ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of a) % of improvement in TJC, b) % of improvement in SJC, and c) third highest percentage of improvement of remaining 5 ACR core criteria: If ≥3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to a range of -100 to 100 to minimize impact of outliers (greater scores indicate greater % improvement) and negative scores indicate a decline. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)

TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.

Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC

Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.

Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score

Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.

Mean Change From Baseline to Weeks 76 and 128 in hsCRP

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.

Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)

ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.

Mean Change From Baseline to Weeks 76 and 128 in ESR

ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.

Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Physician's and Patient's Assessments of Disease Activity (DA) assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeters (mm), where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis was also assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).

Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Physician's and Patient's assessments of DA assessed using a VAS that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).

Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.

Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (patient's global VAS). DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.

Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24

EULAR28 categorizes clinical response based upon improvement since baseline in DAS modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: TJC28, SJC28, CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score >5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by >0.6 units but ≤1.2 units or post-baseline DAS28 score >3.2 with improvement by >1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by >1.2 units).

Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128

EULAR28 categorizes clinical response based upon improvement since baseline in Disease Activity Score modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score >5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by >0.6 units but ≤1.2 units or post-baseline DAS28 score >3.2 with improvement by >1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by >1.2 units).

Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24

Disease Activity Score (DAS) modified to include 28-joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP [milligrams per liter (mg/L)], and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores <2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.

Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores <2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.

Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness

The Investigator asked participants about the duration of their morning stiffness (in minutes) in and around the joints and recorded the duration. The Investigator asked the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses.

Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains (physical functioning, bodily pain, role limitations due to physical problems and also emotional problems, general health, mental health, social functioning and vitality) and 2 component scores (PCS and MCS). The PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. The MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher scores indicating better health or functioning.

Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score

The BPI-sf modified is a self-administered questionnaire developed for the rapid assessment of pain. The BPI-sf modified provides information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The questionnaire asks questions about pain relief, pain quality, and the participant's perception of the cause of pain. The BPI-sf modified uses a numeric rating scale from 0 ("No pain") to 10 ("Pain as bad as you can imagine"). Since pain can be quite variable over a day, the BPI-sf modified asked participants to rate their pain at the time of responding to the questionnaire (right now), and also at its worst, least and average over the last 24 hours.

Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score

The FACIT-F Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 ("Not at all") to 4 ("Very much") for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.

Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104

Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104

Mean Change From Baseline Through Week 12 in the ENSEMBLE Minimum Data Set 1.0

Full Information

NCT ID

NCT01185353

First Posted

August 18, 2010

Last Updated

May 22, 2017

Sponsor

Eli Lilly and Company

Collaborators

Incyte Corporation

1. Study Identification

Unique Protocol Identification Number

NCT01185353

Brief Title

A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

October 2010 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

Collaborators

Incyte Corporation

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arthritis, Rheumatoid

Keywords

Rheumatoid Arthritis, RA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

301 (Actual)

8. Arms, Groups, and Interventions

Arm Title

1 mg LY3009104 once daily

Arm Type

Experimental

Arm Description

Arm Title

2 mg LY3009104 once daily

Arm Type

Experimental

Arm Description

Arm Title

4 mg LY3009104 once daily

Arm Type

Experimental

Arm Description

Arm Title

8 mg LY3009104 once daily

Arm Type

Experimental

Arm Description

Arm Title

Placebo once daily

Arm Type

Placebo Comparator

Arm Description

Arm Title

2 mg LY3009104 twice daily

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

LY3009104

Other Intervention Name(s)

Janus Kinase (JAK)1/JAK2 Inhibitor, JAK1/2 Inhibitor, INCB028050, baricitinib

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered orally

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Intervention Description

Administered orally as background therapy

Primary Outcome Measure Information:

Title

Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12

Description

Time Frame

Baseline through Week 12

Secondary Outcome Measure Information:

Title

Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response

Description

Time Frame

Baseline through Week 12

Title

Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24

Description

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) * 100.

Time Frame

Baseline through Weeks 2, 4, 8, 12, 16, 20, 24

Title

Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128

Description

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) * 100.

Time Frame

Baseline through Weeks 76 and 128

Title

Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24

Description

Time Frame

Baseline through Weeks 2, 4, 8, 12, 16, 20, 24

Title

Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128

Description

Time Frame

Baseline through Weeks 76 and 128

Title

Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24

Description

Time Frame

Baseline through Weeks 2, 4, 8, 12, 16, 20, 24

Title

Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128

Description

Time Frame

Baseline through Weeks 76 and 128

Title

Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response

Description

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) * 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

Time Frame

Baseline through Week 12

Title

ACR Percent Improvement (ACR-N)

Description

Time Frame

Baseline through Week 12

Title

Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC

Description

Time Frame

Baseline, Weeks 76 and 128

Title

Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score

Description

Time Frame

Baseline, Weeks 76 and 128

Title

Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)

Description

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.

Time Frame

Baseline, Weeks 12 and 24

Title

Mean Change From Baseline to Weeks 76 and 128 in hsCRP

Description

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.

Time Frame

Baseline, Weeks 76 and 128

Title

Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)

Description

ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.

Time Frame

Baseline, Weeks 12 and 24

Title

Mean Change From Baseline to Weeks 76 and 128 in ESR

Description

ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.

Time Frame

Baseline, Weeks 76 and 128

Title

Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Description

Time Frame

Baseline, Weeks 76 and 128

Title

Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)

Description

Time Frame

Baseline, Weeks 12 and 24

Title

Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP

Description

Time Frame

Baseline, Weeks 76 and 128

Title

Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24

Description

Time Frame

Baseline through Weeks 12 and 24

Title

Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128

Description

Time Frame

Baseline, Weeks 76 and 128

Title

Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24

Description

Time Frame

Baseline through Weeks 12 and 24

Title

Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128

Description

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores <2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.

Time Frame

Baseline through Weeks 76 and 128

Title

Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness

Description

Time Frame

Baseline, Weeks 4, 8, 12

Title

Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

Description

Time Frame

Baseline, Week 12

Title

Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score

Description

Time Frame

Baseline, Week 12

Title

Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score

Description

Time Frame

Baseline, Week 12

Title

Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104

Time Frame

Baseline through 24 weeks

Title

Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104

Time Frame

Baseline through 24 weeks

Title

Mean Change From Baseline Through Week 12 in the ENSEMBLE Minimum Data Set 1.0

Time Frame

Baseline, 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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 American College of Rheumatology (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) > ULN [28 millimeters/hour (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 2 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 2 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 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 for Parts A and B as applicable Part D only: 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 (IM), or intravenous (IV) injection within 6 weeks prior to baseline 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 Tumor necrosis factor-alpha (TNFα), interleukin (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 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 milliliters (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 cerebro-cardiovascular [for example (eg), myocardial infarction (MI), unstable angina (UA), unstable arterial hypertension, severe heart failure or cerebrovascular accident], respiratory, hepatic, renal, gastrointestinal (GI), 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

City

Paradise Valley

State/Province

Arizona

ZIP/Postal Code

85253

Country

United States

Facility Name

City

Peoria

State/Province

Arizona

ZIP/Postal Code

85381

Country

United States

Facility Name

City

Covina

State/Province

California

ZIP/Postal Code

91723

Country

United States

Facility Name

City

Santa Maria

State/Province

California

ZIP/Postal Code

93454

Country

United States

Facility Name

City

Westlake Village

State/Province

California

ZIP/Postal Code

91361

Country

United States

Facility Name

City

Aventura

State/Province

Florida

ZIP/Postal Code

33180

Country

United States

Facility Name

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33432

Country

United States

Facility Name

City

Daytona Beach

State/Province

Florida

ZIP/Postal Code

32117

Country

United States

Facility Name

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32607

Country

United States

Facility Name

City

Jupiter

State/Province

Florida

ZIP/Postal Code

33458

Country

United States

Facility Name

City

Lake Mary

State/Province

Florida

ZIP/Postal Code

32746

Country

United States

Facility Name

City

Melbourne

State/Province

Florida

ZIP/Postal Code

32901

Country

United States

Facility Name

City

Naples

State/Province

Florida

ZIP/Postal Code

34102

Country

United States

Facility Name

City

Orlando

State/Province

Florida

ZIP/Postal Code

32804

Country

United States

Facility Name

City

Palm Harbor

State/Province

Florida

ZIP/Postal Code

34684

Country

United States

Facility Name

City

Vero Beach

State/Province

Florida

ZIP/Postal Code

32960

Country

United States

Facility Name

City

South Bend

State/Province

Indiana

ZIP/Postal Code

46601

Country

United States

Facility Name

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40504

Country

United States

Facility Name

City

Columbia

State/Province

Maryland

ZIP/Postal Code

21045

Country

United States

Facility Name

City

Flowood

State/Province

Mississippi

ZIP/Postal Code

39216

Country

United States

Facility Name

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63117

Country

United States

Facility Name

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68516

Country

United States

Facility Name

City

Freehold

State/Province

New Jersey

ZIP/Postal Code

07728

Country

United States

Facility Name

City

Toms River

State/Province

New Jersey

ZIP/Postal Code

08755

Country

United States

Facility Name

City

Lake Success

State/Province

New York

ZIP/Postal Code

11042

Country

United States

Facility Name

City

Middleburg Heights

State/Province

Ohio

ZIP/Postal Code

44130

Country

United States

Facility Name

City

Toledo

State/Province

Ohio

ZIP/Postal Code

43606

Country

United States

Facility Name

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73103

Country

United States

Facility Name

City

Duncansville

State/Province

Pennsylvania

ZIP/Postal Code

16635

Country

United States

Facility Name

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

City

Houston

State/Province

Texas

ZIP/Postal Code

77008

Country

United States

Facility Name

City

Osijek

ZIP/Postal Code

31000

Country

Croatia

Facility Name

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

City

Ceska Lipa

ZIP/Postal Code

470 01

Country

Czechia

Facility Name

City

Hlucin

ZIP/Postal Code

748-01

Country

Czechia

Facility Name

City

Hostivice

ZIP/Postal Code

253-01

Country

Czechia

Facility Name

City

Hustopece

ZIP/Postal Code

693 01

Country

Czechia

Facility Name

City

Prague

ZIP/Postal Code

128 50

Country

Czechia

Facility Name

City

Zlin

ZIP/Postal Code

760 01

Country

Czechia

Facility Name

City

Budapest

ZIP/Postal Code

1027

Country

Hungary

Facility Name

City

Debrecen

ZIP/Postal Code

4032

Country

Hungary

Facility Name

City

Kistarcsa

ZIP/Postal Code

2143

Country

Hungary

Facility Name

City

Veszprem

ZIP/Postal Code

8200

Country

Hungary

Facility Name

City

Ahmedabad

ZIP/Postal Code

532004

Country

India

Facility Name

City

Hyderabaad

ZIP/Postal Code

500082

Country

India

Facility Name

City

Pune

ZIP/Postal Code

411007

Country

India

Facility Name

City

Trivandrum

ZIP/Postal Code

695011

Country

India

Facility Name

City

Cuauhtemoc

ZIP/Postal Code

06090

Country

Mexico

Facility Name

City

Guadalajara

ZIP/Postal Code

44158

Country

Mexico

Facility Name

City

Leon

ZIP/Postal Code

37000

Country

Mexico

Facility Name

City

Mexico City

Country

Mexico

Facility Name

City

San Luis Potosi

ZIP/Postal Code

78200

Country

Mexico

Facility Name

City

Czestochowa

ZIP/Postal Code

42-200

Country

Poland

Facility Name

City

Elblag

ZIP/Postal Code

82-300

Country

Poland

Facility Name

City

Krakow

ZIP/Postal Code

30-349

Country

Poland

Facility Name

City

Poznan

ZIP/Postal Code

60-773

Country

Poland

Facility Name

City

Torun

ZIP/Postal Code

87-100

Country

Poland

Facility Name

City

Warsaw

ZIP/Postal Code

02-507

Country

Poland

Facility Name

City

Bacau

ZIP/Postal Code

600114

Country

Romania

Facility Name

City

Bucharest

ZIP/Postal Code

10584

Country

Romania

Facility Name

City

Cluj-Napoca

ZIP/Postal Code

400006

Country

Romania

Facility Name

City

Galati

ZIP/Postal Code

800587

Country

Romania

Facility Name

City

Iasi

ZIP/Postal Code

700656

Country

Romania

Facility Name

City

Kiev

ZIP/Postal Code

03151

Country

Ukraine

Facility Name

City

Kyiv

ZIP/Postal Code

01601

Country

Ukraine

Facility Name

City

Simferopol

ZIP/Postal Code

95017

Country

Ukraine

Facility Name

City

Ternopil

ZIP/Postal Code

46002

Country

Ukraine

Facility Name

City

Vinnytsya

ZIP/Postal Code

21018

Country

Ukraine

12. IPD Sharing Statement

Citations:

PubMed Identifier

34706874

Citation

Taylor PC, Takeuchi T, Burmester GR, Durez P, Smolen JS, Deberdt W, Issa M, Terres JR, Bello N, Winthrop KL. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022 Mar;81(3):335-343. doi: 10.1136/annrheumdis-2021-221276. Epub 2021 Oct 27.

Results Reference

derived

PubMed Identifier

30842122

Citation

Combe B, Balsa A, Sarzi-Puttini P, Tony HP, de la Torre I, Rogai V, Durand F, Witt S, Zhong J, Dougados M. Efficacy and safety data based on historical or pre-existing conditions at baseline for patients with active rheumatoid arthritis who were treated with baricitinib. Ann Rheum Dis. 2019 Aug;78(8):1135-1138. doi: 10.1136/annrheumdis-2018-214261. Epub 2019 Mar 6. No abstract available.

Results Reference

derived

PubMed Identifier

30647190

Citation

Peterfy C, DiCarlo J, Emery P, Genovese MC, Keystone EC, Taylor PC, Schlichting DE, Beattie SD, Luchi M, Macias W. MRI and Dose Selection in a Phase II Trial of Baricitinib with Conventional Synthetic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis. J Rheumatol. 2019 Aug;46(8):887-895. doi: 10.3899/jrheum.171469. Epub 2019 Jan 15.

Results Reference

derived

PubMed Identifier

29463520

Citation

Taylor PC, Kremer JM, Emery P, Zuckerman SH, Ruotolo G, Zhong J, Chen L, Witt S, Saifan C, Kurzawa M, Otvos JD, Connelly MA, Macias WL, Schlichting DE, Rooney TP, de Bono S, McInnes IB. Lipid profile and effect of statin treatment in pooled phase II and phase III baricitinib studies. Ann Rheum Dis. 2018 Jul;77(7):988-995. doi: 10.1136/annrheumdis-2017-212461. Epub 2018 Feb 20.

Results Reference

derived

PubMed Identifier

28811354

Citation

Keystone EC, Genovese MC, Schlichting DE, de la Torre I, Beattie SD, Rooney TP, Taylor PC. Safety and Efficacy of Baricitinib Through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis. J Rheumatol. 2018 Jan;45(1):14-21. doi: 10.3899/jrheum.161161. Epub 2017 Aug 15.

Results Reference

derived

PubMed Identifier

25431052

Citation

Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, Lee CH, Fidelus-Gort RK, Luchi ME, Rooney TP, Macias WL, Genovese MC. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Ann Rheum Dis. 2015 Feb;74(2):333-40. doi: 10.1136/annrheumdis-2014-206478. Epub 2014 Nov 27.

Results Reference

derived

Learn more about this trial

A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy

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