A Study in Participants With Moderate to Severe Rheumatoid Arthritis (RA-BEGIN)

• ClinicalTrials.gov Identifier: NCT01711359
• Recruitment Status: Completed
• First Posted: October 22, 2012
• Results First Posted: August 15, 2017
• Last Update Posted: September 19, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: October 18, 2012
• First Posted Date: October 22, 2012
• Results First Submitted Date: March 10, 2017
• Results First Posted Date: August 15, 2017
• Last Update Posted Date: September 19, 2019
• Study Start Date: November 2012
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2017)

Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) [ Time Frame: Week 24 ]

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.

• Original Primary Outcome Measures (submitted: October 18, 2012): Proportion of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) [ Time Frame: Week 24 ]

Current Secondary Outcome Measures (submitted: July 14, 2017)

• Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) [ Time Frame: Week 52 ]
  ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). "ACR20 Responder" is a participant who has at least 20% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity using visual analog scale (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain due to arthritis, and high-sensitivity C-reactive protein (hsCRP). Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.
• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [ Time Frame: Baseline, Week 24 ]
  HAQ-DI 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 are averaged to calculate the HAQ-DI score, which ranges from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicates an improvement in the participant's condition.
• Change From Baseline in the Disease Activity Score Based on a 28-Joint Count and High-sensitivity C-reactive Protein (DAS28-hsCRP) [ Time Frame: Baseline, Week 24 ]
  Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), C-reactive protein (CRP) (milligrams per liter), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using the following formula: 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 1.0-9.4, where lower scores indicated less disease activity.
• Change From Baseline in the Modified Total Sharp Score (mTSS) [ Time Frame: Baseline, Week 24 ]
  X-rays of the hands/wrists and feet were scored for structural progression as measured using the mTSS (van der Heijde 2000). This methodology quantified the extent of bone erosions and joint space narrowing for 44 and 42 joints, with higher scores representing greater damage. The mTSS at a time point is the sum of the erosion (range from 0 to 280) and JSN (range from 0 to 168) scores, for a maximum score of 448.
• Percentage of Participants Who Achieved a Simplified Disease Activity Index (SDAI) Score ≤3.3 [ Time Frame: Week 24 ]
  SDAI is a tool for measurement of disease activity in RA that integrates TJC28, SJC28, acute phase response using C-reactive protein (milligrams per liter), Patient's Global Assessment of Disease Activity using VAS centimeters (cm), and Physician's Global Assessment of Disease Activity using VAS (cm). The SDAI is calculated by summing the values of the 5 components. Lower scores indicated less disease activity. An index-based definition of remission occurs with an SDAI score ≤3.3.
• Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: Week 12, Week 24, Week 52 ]
  ACR50 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR50 Responder" is a participant who has at least 50% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinued study or drug or were rescued before analysis time point were deemed non-responders.
• Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 12, Week 24, Week 52 ]
  ACR70 Responder Index is composite of clinical, laboratory, and functional measures in RA. "ACR70 Responder" is a participant who has at least 70% improvement in both tender and swollen joint counts and in at least 3 of the following 5 criteria: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, HAQ-DI, pain due to arthritis, and hsCRP. Participants with missing responses and participants who discontinued study or drug or were rescued before analysis timepoint were deemed non-responders.
• Change From Baseline in Clinical Disease Activity Index (CDAI) Score [ Time Frame: Baseline, Week 24; Baseline, Week 52 ]
  The CDAI is a tool for measurement of disease activity in RA that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition.
• Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) [ Time Frame: Baseline, Week 24; Baseline, Week 52 ]
  DAS28 consisted of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), erythrocyte sedimentation rate (ESR) (millimeters per hour), and Patient's Global Assessment of Disease Activity. DAS28 was calculated using the following formula: DAS28-ESR=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.70*natural log(ESR)+0.014*Patient's Global VAS. Scores ranged 1.0-9.4, where lower scores indicated less disease activity.
• Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission [ Time Frame: Week 12, Week 24, Week 52 ]
  The ACR/EULAR definitions of RA remission include a "Boolean-based definition". The Boolean-based definition of remission occurs when all 4 of the following criteria are met at the same visit: TJC28 ≤1, SJC28 ≤1, acute phase response using C-reactive protein (milligrams per deciliter) ≤1, Patient's Global Assessment of Disease Activity using VAS (cm) ≤1.
• Change From Baseline in Joint Space Narrowing and Bone Erosion Scores [ Time Frame: Baseline, Week 24; Baseline, Week 52 ]
  X-rays of the hands/wrists and feet were assessed for joint space narrowing (JSN) and bone erosions. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, is scored from 0 to 4, with 0 indicating no (normal) JSN and 4 indicating complete loss of joint space, bony ankylosis or luxation. JSN scores ranged from 0-168. A score of 0 would indicate no change and higher scores represent a worsening of joint space narrowing. The bone erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. Each joint is scored according to the surface area involved from 0 to 5 for hand joints and 0 to 10 for the foot joints, with 0 indicating no erosion and the highest score (5 for the hand and 10 for the foot) indicating extensive loss of bone from more than one half of the articulating bone. Erosion scores ranged from 0 (no erosion) to 280 (high erosion).
• Change From Baseline in Duration of Morning Joint Stiffness [ Time Frame: Baseline, Week 52 ]
  Participants reported the duration of their morning joint stiffness (MJS) in hours and minutes. The participants were asked about their duration of morning joint stiffness on the day prior to the study visit to capture actual symptoms, since the participant may have had an atypical morning routine on the day of the study visit. If morning joint stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. A decrease in duration of morning joint stiffness indicated an improvement in the participant's condition.
• Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS) [ Time Frame: Baseline, Week 24; Baseline Week 52 ]
  Participants rated their tiredness by selecting a number from 0 to 10 that best described their worst tiredness during the last 24 hours, where 0 represents "no tiredness" and 10 represents "as bad as you can imagine".
• Change From Baseline in Worst Joint Pain Numeric Rating Scale (NRS) [ Time Frame: Baseline, Week 24; Baseline Week 52 ]
  Participants rated their joint pain by selecting a number from 0 to 10 that best described their worst joint pain during the last 24 hours, where 0 represents "no pain" and 10 represents "pain as bad as you can imagine".
• Change From Baseline in Mental Component Score (MCS) and Physical Component Score (PCS) of the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute (SF-36v2 Acute) [ Time Frame: Baseline, Week 24; Baseline Week 52 ]
  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 emotional problems, general health, mental health, social functioning, vitality, and 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale with higher scores indicating better health status or functioning.
• Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores [ Time Frame: Baseline, Week 24; Baseline Week 52 ]
  European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. One component consists of a descriptive system of the respondent's health comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1. A higher score indicates better health state.
• Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores (Self-Perceived Health) [ Time Frame: Baseline, Week 24; Baseline Week 52 ]
  A second component of the EQ-5D-5L is a self-perceived health score which is assessed using a VAS that ranges from 0 to 100 millimeter (mm), where 0 indicates the worst health you can imagine and 100 indicates the best health you can imagine.
• Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores [ Time Frame: Baseline, Week 24; Baseline Week 52 ]
  The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's 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.
• Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores [ Time Frame: Baseline, Week 24; Baseline Week 52 ]
  The Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. It contains 6 items covering overall work productivity (health), overall work productivity (symptom), impairment of regular activities (health), and impairment of regular activities (symptom). Scores are calculated as impairment percentages. The WPAI-RA yields four types of scores: Absenteeism (work time missed), Presenteeism (impairment at work), Work productivity loss (overall work impairment), and Activity impairment.
• Population Pharmacokinetics (PK): Peak Concentration at Steady State (Cmax,ss) of Baricitinib [ Time Frame: Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose ]
• Population PK: Area Under the Concentration Versus Time Curve at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib [ Time Frame: Week 0: 15 and 60 minutes postdose; Week 4: 2 to 4 hours post-dose; Week 8: 4 to 6 hours post-dose; Week 12; Week 24; Week 32; Pre-dose ]

Original Secondary Outcome Measures (submitted: October 18, 2012)

• Change from Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score [ Time Frame: Baseline, Week 24 ]
• Change from Baseline in the Disease Activity Score based on a 28-Joint Count (DAS-28) [ Time Frame: Baseline, up to Week 52 ]
• Change from Baseline in the modified Total Sharp Score (mTSS) [ Time Frame: Baseline, Week 24 ]
• Proportion of Participants Achieving American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response [ Time Frame: Week 12, Week 24, Week 52 ]
• Change from Baseline in Patient Reported Outcomes [ Time Frame: Baseline, up to Week 52 ]
• Change from Baseline in Measures of Clinical Disease Activity and Severity [ Time Frame: Baseline, up to Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study in Participants With Moderate to Severe Rheumatoid Arthritis
• Official Title: A Randomized, Double-Blind, Active-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had Limited or No Treatment With Disease-Modifying Antirheumatic Drugs
• Brief Summary: The purpose of this study is to determine whether baricitinib therapy alone is noninferior to methotrexate (MTX) therapy alone in the treatment of moderate to severe active rheumatoid arthritis (RA) in those who have had limited or no treatment with MTX and are naive to other conventional or biologic disease-modifying antirheumatic drugs (DMARDs).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• Drug: Baricitinib
  Administered orally
  Other Name: LY3009104
• Drug: Methotrexate
  Administered orally
• Drug: Baricitinib Placebo
  Baricitinib placebo administered orally once daily.
• Drug: MTX Placebo
  MTX placebo administered orally once weekly.
• Drug: Folic Acid
  Administered orally every day

Study Arms

• Experimental: Baricitinib + MTX
  Baricitinib 4 milligram (mg) administered orally once daily through Week 52. Participants received methotrexate (MTX) orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
  Interventions:

  • Drug: Baricitinib
  • Drug: Methotrexate
  • Drug: Folic Acid
• Experimental: Baricitinib
  Baricitinib 4 mg administered orally once daily through Week 52. Participants received MTX placebo orally once weekly through Week 52. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
  Interventions:

  • Drug: Baricitinib
  • Drug: MTX Placebo
  • Drug: Folic Acid
• Active Comparator: MTX
  MTX administered orally once weekly with dose ranging from 10 to 20 mg per week through Week 52. Participants also received baricitinib placebo orally once daily. Starting at Week 24, participants who were nonresponders were rescued with baricitinib 4 mg orally once daily and MTX orally once weekly.
  Interventions:

  • Drug: Methotrexate
  • Drug: Baricitinib Placebo
  • Drug: Folic Acid

Publications *

• Taylor PC, Alten R, Alvaro Gracia JM, Kaneko Y, Walls C, Quebe A, Jia B, Bello N, Terres JR, Fleischmann R. Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy. RMD Open. 2022 Mar;8(1):e001994. doi: 10.1136/rmdopen-2021-001994.
• 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.
• van der Heijde D, Kartman CE, Xie L, Beattie S, Schlichting D, Mo D, Durez P, Tanaka Y, Fleischmann R. Radiographic Progression of Structural Joint Damage Over 5 Years of Baricitinib Treatment in Patients With Rheumatoid Arthritis: Results From RA-BEYOND. J Rheumatol. 2022 Feb;49(2):133-141. doi: 10.3899/jrheum.210346. Epub 2021 Sep 15.
• Emery P, Tanaka Y, Cardillo T, Schlichting D, Rooney T, Beattie S, Helt C, Smolen JS. Temporary interruption of baricitinib: characterization of interruptions and effect on clinical outcomes in patients with rheumatoid arthritis. Arthritis Res Ther. 2020 May 15;22(1):115. doi: 10.1186/s13075-020-02199-8. Erratum In: Arthritis Res Ther. 2020 Jul 2;22(1):166.
• Fleischmann R, Takeuchi T, Schiff M, Schlichting D, Xie L, Issa M, Stoykov I, Lisse J, Martinez-Osuna P, Rooney T, Zerbini CAF. Efficacy and Safety of Long-Term Baricitinib With and Without Methotrexate for the Treatment of Rheumatoid Arthritis: Experience With Baricitinib Monotherapy Continuation or After Switching From Methotrexate Monotherapy or Baricitinib Plus Methotrexate. Arthritis Care Res (Hoboken). 2020 Aug;72(8):1112-1121. doi: 10.1002/acr.24007.
• Smolen JS, Genovese MC, Takeuchi T, Hyslop DL, Macias WL, Rooney T, Chen L, Dickson CL, Riddle Camp J, Cardillo TE, Ishii T, Winthrop KL. Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment. J Rheumatol. 2019 Jan;46(1):7-18. doi: 10.3899/jrheum.171361. Epub 2018 Sep 15. Erratum In: J Rheumatol. 2019 Dec;46(12):1648-1649.
• 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.
• Schiff M, Takeuchi T, Fleischmann R, Gaich CL, DeLozier AM, Schlichting D, Kuo WL, Won JE, Carmack T, Rooney T, Durez P, Shaikh S, Hidalgo RP, van Vollenhoven R, Zerbini CAF. Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Res Ther. 2017 Sep 18;19(1):208. doi: 10.1186/s13075-017-1410-1.
• Fleischmann R, Schiff M, van der Heijde D, Ramos-Remus C, Spindler A, Stanislav M, Zerbini CA, Gurbuz S, Dickson C, de Bono S, Schlichting D, Beattie S, Kuo WL, Rooney T, Macias W, Takeuchi T. Baricitinib, Methotrexate, or Combination in Patients With Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment. Arthritis Rheumatol. 2017 Mar;69(3):506-517. doi: 10.1002/art.39953.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 14, 2017): 588
• Original Estimated Enrollment (submitted: October 18, 2012): 550
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a diagnosis of adult-onset rheumatoid arthritis (RA) as defined by American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 Criteria for the Classification of RA
• Have documented history of positive rheumatoid factor and/or cyclic citrullinated peptide (CCP) antibody test
• Have moderately to severely active RA defined as the presence of at least 6/68 tender joints and at least 6/66 swollen joints
• Have a C-reactive protein (CRP) or high-sensitivity C-reactive protein (hsCRP) measurement ≥1.2 times the upper limit of normal (ULN)
• Have had limited or no treatment with methotrexate (MTX)

Exclusion Criteria:

• Have received conventional disease-modifying antirheumatic drugs (DMARDs) other than MTX (eg, gold salts, cyclosporine, leflunomide, azathioprine, hydroxychloroquine, sulfasalazine or any other immunosuppressives)
• Are currently receiving corticosteroids at doses >10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6 weeks of planned randomization
• Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of study entry or within 6 weeks of planned randomization
• Have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry
• Have ever received any biologic DMARD
• Have received interferon therapy within 4 weeks prior to study entry or are anticipated to require interferon therapy during the study
• Have received any parenteral corticosteroid administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require a parenteral injection of corticosteroids during the study
• Have had 3 or more joints injected with intraarticular corticosteroids or hyaluronic acid within 2 weeks prior to study entry or within 6 weeks prior to planned randomization
• Have active fibromyalgia that, in the investigator's opinion, would make it difficult to appropriately assess RA activity for the purposes of this study
• Have a diagnosis of any systemic inflammatory condition other than RA, such as, but not limited to, juvenile chronic arthritis, spondyloarthropathy, Crohn's disease, ulcerative colitis, psoriatic arthritis, active vasculitis, or gout (Participants with secondary Sjogren's syndrome are not excluded.)
• Have a diagnosis of Felty's syndrome
• Have had any major surgery within 8 weeks of study entry or will require major surgery during the study that, in the opinion of the investigator in consultation with Lilly or its designee, would pose an unacceptable risk to the participant
• Have experienced any of the following within 12 weeks of study entry: myocardial infarction, unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure
• Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data
• Are largely or wholly incapacitated permitting little or no self care, such as, being bedridden or confined to a wheelchair
• Have an estimated Glomerular Filtration Rate (eGFR) based on the most recent available serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of <40 milliliter per minute per 1.73 m^2 (mL/min/1.73 m^2)
• Have a history of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the ULN or the most recent available total bilirubin ≥1.5 times the ULN
• Have a history of, lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for <5 years
• Have been exposed to a live vaccine within 12 weeks prior to planned randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination)
• Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection
• Have had symptomatic herpes zoster infection within 12 weeks prior to study entry
• Have a history of disseminated/complicated herpes zoster (eg, multidermatomal involvement, ophthalmic zoster, central nervous system involvement, postherpetic neuralgia)
• Are immunocompromised and, in the opinion of the investigator, are at an unacceptable risk for participating in the study
• Have a history of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
• Have screening laboratory test values, including thyroid-stimulating hormone (TSH), outside the reference range for the population or investigative site that, in the opinion of the investigator, pose an unacceptable risk for the participant's participation in the study
• Have screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator or the sponsor, are clinically significant and indicate an unacceptable risk for the participant's participation in the study
• Have symptomatic herpes simplex at the time of study enrollment
• Have evidence of active or latent tuberculosis (TB)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Belgium, Brazil, Canada, Germany, Greece, India, Italy, Japan, Korea, Republic of, Mexico, Portugal, Puerto Rico, Russian Federation, South Africa, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT01711359
• Other Study ID Numbers: 14062; I4V-MC-JADZ ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: September 2019