Clinical Trial to study effects of Baricitinib in Rheumatoid Arthritis patients with Inadequate Response to Conventional Drugs
Scientific Title of Study
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients with Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs with Moderately to Severely Active Rheumatoid Arthritis
Trial Acronym
RA BUILD
Secondary IDs if Any
Secondary ID
Identifier
I4V-MC-JADX amendment a dated 21 Aug 2012
Protocol Number
NCT01721057
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Tarun Puri
Designation
Medical Director
Affiliation
Eli Lilly and Company India Private Limited
Address
Eli Lilly and Company India Private Limited, Plot No. 92, Sec- 32
Eli Lilly and Company India Private Limited, Plot No. 92, Sec- 32
Gurgaon HARYANA 122001 India
Phone
0124-4753000
Fax
0124-4753013
Email
puri_tarun@lilly.com
Details of Contact Person Public Query
Name
Anil Seth
Designation
Director-Clinical Research
Affiliation
Eli Lilly and Company India Private Limited
Address
Eli Lilly and Company India Private Limited, Plot No. 92, Sec- 32
Gurgaon HARYANA 122001 India
Phone
0124-4753000
Fax
0124-4753013
Email
seth_anil@lilly.com
Source of Monetary or Material Support
Eli Lilly and Company
Primary Sponsor
Name
Eli Lilly and Company
Address
Corporate Center Indianapolis, IN 46285 USA
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Belgium Canada Croatia Czech Republic Germany Hungary India Italy Japan Mexico Poland Portugal Romania Russian Federation Slovakia South Africa Spain Taiwan United Kingdom United States of America
Sites of Study
No of Sites = 20
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Piyush Parikh
AMC MET Medical College and Seth LG General Hospital
Research Room, Rambag, Maninagar, Ahmedabad - 380008, Gujarat Ahmadabad GUJARAT
079-25472101 079-25472100 pnparikhlg@gmail.com
Dr Padmanabha Shenoy D
AMRITA Institute of Medical Sciences and Research Centre
Department of Rheumatology, AIMS Ponekkara Post, Kochi, Kerala - 682041 Ernakulam KERALA
919446567000 914842802131 pshenoy@aims.amrita.edu
Dr Shyamasish Bandhoypadhya
Apollo Gleneagles Hospitals
Department of Rheumatology, 58 Canal Circular Road, Kolkata 700054 Kolkata WEST BENGAL
91-9836576602 033-23201739 sambando@yahoo.co.uk
Dr Chandrasekara Srikantiah
Chanre Rheumatology & Immunology Centre for Research
15th Main, NHCL Water Tank Road, 4th Block, 3rd Stage, Basaveshwarnagar, Bangalore - 560079 Bangalore KARNATAKA
KLES Prabhakar Kore Hospital and Medical Research Centre
Department of Orthopaedics, KLES Dr. Prabhakar Kore Hospital & MRC, Jawaharlal Nehru Medical College, Belgaum, Karnataka - 590010 Belgaum KARNATAKA
08312470400 08312493099 drsvudapudi@gmail.com
Dr Jyotsana Oak
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
Department Of Rheumatology, Four Bungalows, Andheri (W)
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute – Mumbai - 400053 Mumbai MAHARASHTRA
Ethics Committee , M S Ramaiah Medical College and Hospital
Approved
Ethics Committee for Research in Human Subjects, Seth GS Medical College and KEM Hospital
Submittted/Under Review
Ethics Committee on Clinical Trials, Indraprastha Apollo Hospitals
Approved
Institute Ethics Committee, Sanjay Gandhi Post graduate Institute of Medical Sciences
Approved
Institutional Ethics Committee of Kings George Medical College
Approved
Institutional Ethics Committee, Amrita Institute of Medical and Research Centre
Approved
Institutional Ethics Committee, Apollo Gleneagles Hospital
Approved
Institutional Ethics Committee, Care Hospital
Approved
Institutional Ethics Committee, Chanre Rheumatology & Immunology Center & Research
Approved
Institutional Ethics Committee, Shalby Hospital
Approved
Institutional Scientific and Ethics Board, Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
Approved
IPGME&R Research Oversight Committee
Approved
KFRC Ethics Committee of KIMS foundation
Approved
KLE Universitys Ethics Committee
Approved
Manipal University Ethics Committee
Approved
Medanta Institutional Ethics Committee
Approved
St. John’s Medical College and Hospital, Institutional Ethical Review Board
Approved
Sumana Hospital Ethics Committee
Approved
Swastic Ethics Committee, Shri Nidan Hospital and Hope Fertility Centre
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Patients with Moderately to Severely Active Rheumatoid Arthritis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Baricitinib
Baricitinib 2 mg administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 24
Intervention
Baricitinib
Baricitinib 4 mg administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 mg orally once daily through Week 24
Comparator Agent
Placebo
Administered orally once daily through Week 24. Starting at Week 16, participants who are nonresponders will be rescued with baricitinib 4 milligram (mg) orally once daily through Week 24
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
-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) 1.2 times the upper limit of normal (ULN)
-Have had an insufficient response or are intolerant to conventional disease-modifying antirheumatic drugs (cDMARDs) and either:
Have had regular use of a 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
For participants not receiving a cDMARD at the time of entry, the investigator will document in the participants history that the participant had failed, was unable to tolerate, or had a contraindication to treatment with a cDMARD
ExclusionCriteria
Details
-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 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 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 investigators 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, Crohns disease, ulcerative colitis, psoriatic arthritis, active vasculitis or gout(participants with secondary Sjogrens syndrome are not excluded.)
-Have a diagnosis of Feltys 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 m2 (mL/min/1.73 m2)
-Have a history of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT)is greater than 1.5 times the ULN or the most recent available total bilirubin is greater than or equal to 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 less than 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 participants 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 participants participation in the study (eg, Fridericias corrected QT interval less than 500 millisecond [msec] for men and less than 520 msec for women)
-Have symptomatic herpes simplex at the time of study enrollment
-Have evidence of active or latent tuberculosis (TB)
Method of Generating Random Sequence
Method of Concealment
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Proportion of Participants Achieving American College of Rheumatology 20 percent Improvement (ACR20)
Time Frame: Week 12
Secondary Outcome
Outcome
TimePoints
-Change from Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
-Change from Baseline in the Disease Activity Score based on a 28-Joint Count (DAS-28)
-Change from Baseline in Patient Reported Outcomes
-Proportion of Participants Achieving American College of Rheumatology 50 percent (ACR50) and 70 percent (ACR70) Response
-Change from Baseline in Measures of Clinical Disease Activity and Severity
Time Frame: Baseline, Week 12
Time Frame: Baseline, Week 12
Time Frame: Baseline, up to Week 24
Time Frame: Week 12, Week 24
Time Frame: Baseline, up to Week 24
Target Sample Size
Total Sample Size="660" Sample Size from India="66" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
The purpose of this study is to determine whether baricitinib 4 milligram (mg) once daily (QD) is superior to placebo in the treatment of participants with moderately to severely active Rheumatoid Arthritis (RA) who have had inadequate response to or are intolerant to at least 1 conventional disease-modifying antirheumatic drug (cDMARD)(cDMARD-IR [inadequate response] participants) and who have not received a biologic disease-modifying antirheumatic drug (DMARD).