A Dose Response Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Methotrexate
- Conditions
- Rheumatoid Arthritis Inadequately Responding to Methotrexate
- Registration Number
- JPRN-jRCT2080223385
- Lead Sponsor
- Eisai Co., Ltd.
- Brief Summary
In Japanese RA subjects with inadequately responding to MTX, E6011 did not show statistically significant improvement in ACR20 response rate at Week 12 compared with placebo; however, a significant improvement was observed at Week 24 for E6011 200 mg and 400/200 mg. E6011 was well tolerated with no notable safety concerns at doses of 200 to 400 mg when administered subcutaneously every 2 weeks for up to 102 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 194
(1)Diagnosed with rheumatoid arthritis (RA) under the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) criteria >=12 weeks before informed consent
(2)Received methotrexate (MTX) treatment at 6 to 16 milligram (mg)/week for >=12 weeks before screening and presented >=6 tender joints (out of 68 joints) and >=6 swollen joints (out of 66 joints) in the Screening and Observation Phases
(3)Can continue stable dose regimen of MTX at 6 to 16 mg/week from 4 weeks before starting the study treatment until completion of the Extension Phase (or until study discontinuation)
(4)C-reactive protein (CRP) level >=0.6 mg/deciliter (dL) or erythrocyte sedimentation rate (ESR) >=28 millimeters per hour (mm/hr) in the Screening Phase
(5)Erosions at >=3 sites in radiographic image in the Screening Phase, or those with erosions at >=1 site and either positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody in the Screening Phase
(6)Weighs >=30 kilograms (kg) and <=100 kg in the Screening Phase
(7)Has voluntarily consented, in writing, to participate in this study. If a participant is below the age of 20, also consented, in writing, by a legally acceptable representative.
(8)Has been thoroughly briefed on the conditions for participation in the study, is able to understand, and is willing and able to comply with all aspects of the protocol
(1)Any history or complication of inflammatory arthritic disorder other than RA or Sjogren's syndrome
(2)Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class IV in the Screening Phase
(3)Received immunoglobulin preparations or blood products within 24 weeks before starting the study treatment
(4)Received a live vaccine within 12 weeks before starting the study treatment, or is planning to receive
(5)Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, or renal disease) that could affect the participant's safety or interfere with the study assessments in the opinion of the investigator or subinvestigator
(6)Complication of uncontrolled disorders such as acute cardiac infarction, unstable angina, brain infarct, or symptomatic intracerebral hemorrhage
(7)History of severe allergy (shock or anaphylactoid symptoms)
(8)History or current clinical condition of malignant tumor, lymphoma, leukemia, or lymphoproliferative disease, except for skin carcinoma (epithelial carcinoma or basal cell carcinoma) and cervix carcinoma which has completely excised and without metastasis or recurrence for more than 5 years before informed consent
(9)Immunodeficiency or history of human immunodeficiency virus (HIV) infection
(10)Infection requiring hospitalization or intravenous administration of antibiotics or disease requiring administration of antivirus drugs (e.g., herpes zoster) within 4 weeks before starting the study treatment
(11)History of tuberculosis or current complication of active tuberculosis
(12)History of clinically important vasculitis
(13)Tested positive for any of the following in the Screening Phase: HIV, hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis B virus core antibody (HBc antibody), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C virus antibody (HCV antibody), human T-lymphotrophic virus Type I antibody (HTLV-1 antibody), or syphilis
(14)Positive in tuberculosis test (QuantiFERONTB Gold Test or T-SPOT.TB Test) in the Screening Phase
(15)Findings indicating a history of tuberculosis on chest x-ray in the Screening Phase
(16)Neurological findings such as paralysis, visual impairment, or language disorder in the Screening Phase
(17)Demonstrated prolonged QTcF interval (>450 milliseconds [ms]) in repeated electrocardiogram examinations
(18)Females of childbearing potential who have a positive pregnancy test in the Screening or Observation Phase or are breastfeeding
(19)Females of childbearing potential who:
Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 70 days after study drug discontinuation
Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from being sexually active during the study period or for 70 days after study drug discontinuation
Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 70 days after stud
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method safety<br>efficacy<br>American College of Rheumatology 20 (ACR20) response rate at Week 12 [ Time Frame: Week 12 ]
- Secondary Outcome Measures
Name Time Method efficacy<br>-