A Study in Participants With Moderate to Severe Rheumatoid Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01711359
• Date of registration: 18/10/2012
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Study in Participants With Moderate to Severe Rheumatoid Arthritis RA-BEGIN
• Scientific 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
• Date of first enrolment: November 2012
• Target sample size: 588
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01711359
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

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

Contacts

• Name: 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)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion 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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Methotrexate

Drug: Baricitinib

Drug: MTX Placebo

Drug: Baricitinib Placebo

Drug: Folic Acid

Primary Outcome(s)

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

Secondary Outcome(s)

Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) [Time Frame: Baseline, Week 24; Baseline, Week 52]

Change From Baseline in the Modified Total Sharp Score (mTSS) [Time Frame: Baseline, Week 24]

Percentage of Participants Achieving American College of Rheumatology 20% Improvement (ACR20) [Time Frame: Week 52]

Change From Baseline in Worst Tiredness Numeric Rating Scale (NRS) [Time Frame: Baseline, Week 24; Baseline Week 52]

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]

Change From Baseline in Clinical Disease Activity Index (CDAI) Score [Time Frame: Baseline, Week 24; Baseline, Week 52]

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]

Change From Baseline in Duration of Morning Joint Stiffness [Time Frame: Baseline, Week 52]

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [Time Frame: Baseline, Week 24]

Change From Baseline in Joint Space Narrowing and Bone Erosion Scores [Time Frame: Baseline, Week 24; Baseline, Week 52]

Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response [Time Frame: Week 12, Week 24, Week 52]

Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [Time Frame: Week 12, Week 24, Week 52]

Change From Baseline in Worst Joint Pain Numeric Rating Scale (NRS) [Time Frame: Baseline, Week 24; Baseline Week 52]

Percentage of Participants Who Achieved a Simplified Disease Activity Index (SDAI) Score =3.3 [Time Frame: Week 24]

Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Scores [Time Frame: Baseline, Week 24; Baseline Week 52]

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores [Time Frame: Baseline, Week 24; Baseline Week 52]

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]

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]

Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores [Time Frame: Baseline, Week 24; Baseline Week 52]

Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission [Time Frame: Week 12, Week 24, Week 52]

Secondary ID(s)

I4V-MC-JADZ

14062

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 15/08/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01711359