NCT02960438已完成2 期
A Dose Response Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Methotrexate
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 273
- 试验地点
- 5
- 主要终点
- Treatment Phase: Percentage of Participants Who Achieved an American College of Rheumatology 20 (ACR20) Response at Week 12 Based on Non-responder Imputation (NRI)
研究概览
简要总结
This study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study in rheumatoid arthritis participants inadequately responding to methotrexate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Any history or complication of inflammatory arthritic disorder other than RA or Sjogren's syndrome
- •Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class IV in the Screening Phase
- •Received immunoglobulin preparations or blood products within 24 weeks before starting the study treatment
- •Received a live vaccine within 12 weeks before starting the study treatment, or is planning to receive
- •Evidence of clinically significant disease (example, 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
- •Complication of uncontrolled disorders such as acute cardiac infarction, unstable angina, brain infarct, or symptomatic intracerebral hemorrhage
- •History of severe allergy (shock or anaphylactoid symptoms)
- •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
- •Immunodeficiency or history of human immunodeficiency virus (HIV) infection
- •Infection requiring hospitalization or intravenous administration of antibiotics or disease requiring administration of antivirus drugs (example, herpes zoster) within 4 weeks before starting the study treatment
- •History of tuberculosis or current complication of active tuberculosis
- •History of clinically important vasculitis
- •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
- •Positive in tuberculosis test (QuantiFERON®TB Gold Test or T-SPOT®.TB Test) in the Screening Phase
- •Findings indicating a history of tuberculosis on chest x-ray in the Screening Phase
- •Neurological findings such as paralysis, visual impairment, or language disorder in the Screening Phase
- •Demonstrated prolonged QTcF interval (>450 milliseconds [ms]) in repeated electrocardiogram examinations
- •Females of childbearing potential who have a positive pregnancy test in the Screening or Observation Phase or are breastfeeding
- •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 28 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 28 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 28 days after study drug discontinuation (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing]).
- •Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period or for 28 days after study drug discontinuation). No sperm donation is allowed during the study period or for 28 days after study drug discontinuation.
- •Scheduled for surgery during the study
- •Currently enrolled in another clinical study or used any investigational drug or device within 28 days (or 5* the half-life, whichever is longer) before informed consent
- •Has been treated with E6011 or any biologics for use in RA that has not been approved
- •Use of a psychotropic agent as recreational purpose other than therapeutic purpose
- •Any history of a medical condition or a concomitant medical condition that in the opinion of the investigator or subinvestigator would compromise the participant's ability to safely complete the study
研究组 & 干预措施
E6011 100 milligrams (mg)
Experimental
In the Treatment Phase, E6011 100 mg will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102.
干预措施: E6011 (Drug)
E6011 200 mg
Experimental
In the Treatment Phase, E6011 200 mg will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102.
干预措施: E6011 (Drug)
E6011 400 mg
Experimental
In the Treatment Phase, E6011 400 mg will be subcutaneously administered at Weeks 0, 1, 2, 4, 6, 8, and 10, and then E6011 200 mg will be subcutaneously administered every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102.
干预措施: E6011 (Drug)
Placebo
Placebo Comparator
In the Treatment Phase, placebo will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102.
干预措施: Placebo (Drug)
结局指标
主要结局
Treatment Phase: Percentage of Participants Who Achieved an American College of Rheumatology 20 (ACR20) Response at Week 12 Based on Non-responder Imputation (NRI)
时间窗: Week 12
The ACR20 response was defined as if the following 3 criteria (ACR components) were met: Greater than or equal to (\>=) 20 percent (%) reduction from baseline in the tender joint count (TJC) in 68 joints (TJC68); \>=20% reduction from baseline in the swollen joint count (SJC) in 66 joints (SJC66); \>=20% reduction from baseline in at least 3 of the following 5 assessments: Physician's Global Assessment of Disease Activity (visual analog scale \[VAS\]) , Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), Health Assessment Questionnaire disability index (HAQ-DI), and C-reactive protein (CRP).
次要结局
- Treatment Phase: Percentage of Participants Who Achieved an ACR50 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI(Weeks 2, 4, 8, 16, 20, and 24)
- Change From Baseline in Simple Disease Activity Index (SDAI) Values at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Treatment Phase: Percentage of Participants Who Achieved an ACR20 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI(Weeks 2, 4, 8, 16, 20, and 24)
- Treatment Phase: Percentage of Participants Who Achieved an ACR70 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI(Weeks 2, 4, 8, 16, 20, and 24)
- Change From Baseline in Tender Joint Counts (TJC) at Each Visit Based on Last Observation Carried Forward (LOCF)(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in Swollen Joint Counts (SJC) at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in Participant's Assessment of Pain Based on VAS Score at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in Participant's Global Assessment of Disease Activity Based on VAS Score at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on VAS Score at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Percentage of Participants Who Achieved CDAI Remission at Each Visit Based on NRI(Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in C-reactive Protein (CRP) Values at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in Disease Activity Score 28 (DAS28)-ESR Values at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in DAS28-CRP Values at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Values at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80,and 84)
- Number of Participants With a EULAR Good or Moderate Response Using DAS28-CRP at Each Visit Based on NRI(Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Percentage of Participants Who Achieved SDAI Remission at Each Visit Based on NRI(Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104)
- Change From Baseline in Modified Total Sharp Score (mTSS) at Each Visit Based on Observed Cases (OC)(Treatment Phase: Baseline and Week 24; Extension Phase: Baseline, Weeks 24, 52, 76, and 104)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Values at Each Visit Based on LOCF(Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Number of Participants With a European League Against Rheumatism (EULAR) Good, Moderate or No Response Using DAS28-ESR at Each Visit Based on NRI(Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
- Percentage of Participants Who Achieved Boolean Remission at Each Visit Based on NRI(Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84)
研究者
研究点 (5)
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