A Moderate to Severe Rheumatoid Arthritis Study

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01721044
• Date of registration: 01/11/2012
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Moderate to Severe Rheumatoid Arthritis Study RA-BEACON
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors
• Date of first enrolment: January 2013
• Target sample size: 527
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01721044
• 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, Australia, Austria, Belgium, Canada, Croatia, Denmark, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Puerto Rico, Spain, Switzerland, Turkey, 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 the American
College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) 2010 Criteria
for the Classification of RA

- 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 = (greater than or equal to) 1 times the upper limit of normal (ULN)

- Have been treated at approved doses with at least 1 biologic tumor necrosis factor
(TNF)- alpha inhibitor for at least 3 months and either:

- experienced insufficient efficacy or loss of efficacy

- experienced intolerance of such treatment

- Have had regular use of at least 1 conventional disease-modifying antirheumatic drugs
(cDMARD) for at least the 12 weeks prior to study entry with a continuous, nonchanging
dose for at least 8 weeks prior to study entry

Exclusion Criteria:

- Have received a biologic treatment for RA within 28 days of planned randomization;
have received rituximab within 6 months of planned randomization

- Are currently receiving corticosteroids at doses > (greater than) 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

- Are currently receiving concomitant treatment with methotrexate (MTX),
hydroxychloroquine, and sulfasalazine or combination of any 3 cDMARDs

- 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 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 have 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 <
(less than) 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 (e.g. Fridericia's corrected QT
interval >500 millisecond [msec])

- 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: Placebo

Drug: cDMARD

Drug: Baricitinib

Primary Outcome(s)

Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response - Placebo Versus Baricitinib 4 mg [Time Frame: Week 12]

Secondary Outcome(s)

Change From Baseline in the Disease Activity Score Based on a 28-Joint Count (DAS-28) High Sensitivity C-Reactive Protein (hsCRP) - Placebo Versus Baricitinib 4 mg [Time Frame: Baseline, Week 12]

Percentage of Participants Achieving ACR20 Response - Placebo Versus Baricitinib 2 mg [Time Frame: Week 12]

Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 4 mg [Time Frame: Baseline, Week 12]

Change From Baseline in Worst Joint Pain NRS [Time Frame: Baseline, Week 24]

Percentage of Participants Achieving ACR20 Response [Time Frame: Week 24]

Change From Baseline in Clinical Disease Activity Index Score [Time Frame: Baseline, Week 24]

Change From Baseline in DAS28 - Erythrocyte Sedimentation Rate (ESR) [Time Frame: Baseline, Week 12]

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

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Scores [Time Frame: Baseline, Week 12, Week 24]

Percentage of Participants Achieving ACR/EULAR Remission - SDAI =3.3 - Placebo Versus Baricitinib 2 mg [Time Frame: Week 12]

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

Change From Baseline in European Quality of Life-5 Dimensions-5 Level Scores [Time Frame: Baseline, Week 12, Week 24]

Change From Baseline in HAQ-DI Score - Placebo Versus Baricitinib 2 mg [Time Frame: Baseline, Week 12]

Change From Baseline in the DAS28 - hsCRP - Placebo Versus Baricitinib 2 mg [Time Frame: Baseline, Week 12]

Percentage Change From Baseline in Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) Scores [Time Frame: Baseline, Week 12, Week 24]

Percentage of Participants Achieving ACR/EULAR Remission - Boolean Remission [Time Frame: Week 24]

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

Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of Baricitinib [Time Frame: Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.]

Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of Baricitinib [Time Frame: Week 0 (Baseline): 15 min. post-dose, 1 hour post-dose. Week 4 (Day 28 ±2 days): 2 to 4 hours post-dose. Week 8 (Day 56 ±3 days): 4 to 6 hours post-dose. Week 12 (Day 84 ±3 days): Pre-dose. Week 24 (Day 168 ±5 days): Pre-dose.]

Change From Baseline in Duration of Participant Reported Outcome - Morning Joint Stiffness [Time Frame: Baseline, Week 24]

Change From Baseline in Mental Component Score (MCS), 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 12, Week 24]

Change From Baseline in Measures of SDAI Score [Time Frame: Baseline, Week 24]

Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission - Simplified Disease Activity Index (SDAI) =3.3 - Placebo Versus Baricitinib 4 mg [Time Frame: Week 12]

Secondary ID(s)

14058

I4V-MC-JADW

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/01/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01721044