PHASE 3B/4 RANDOMIZED SAFETY ENDPOINT STUDY OF 2 DOSES OF TOFACITINIB IN COMPARISON TO A TUMOR NECROSIS FACTOR (TNF) INHIBITOR IN SUBJECTS WITH RHEUMATOID ARTHRITIS
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 4,372
- 试验地点
- 339
- 主要终点
- Incidence Rate of Adjudicated Malignancies Excluding Non-melanoma Skin Cancers (NMSC)
研究概览
简要总结
This post-marketing study is designed to compare the safety of tofacitinib versus TNF inhibitor with respect to major cardiovascular adverse events and malignancies, excluding non-melanoma skin cancers when given to subjects with rheumatoid arthritis. Other safety events, including non-melanoma skin cancers, hepatic events, infections, and efficacy parameters will be collected and evaluated in the study.
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
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Moderate to severe rheumatoid arthritis
- •Taking methotrexate without adequate control of symptoms
- •Have at least one cardiovascular risk factor (eg, current smoker, high blood pressure, high cholesterol levels, diabetes mellitus, history of heart attack, family history of coronary heart disease, extra-articular RA disease)
排除标准
- •Current or recent infection
- •Clinically significant laboratory abnormalities
- •Pregnancy
研究组 & 干预措施
Treatment Arm 1
干预措施: tofacitinib (Drug)
Treatment Arm 2
干预措施: tofacitinib (Drug)
Treatment Arm 3
TNF inhibitor Arm - adalimumab will be used in US, Canada and Puerto Rico; etanercept will be used in all other countries.
干预措施: adalimumab (Biological)
Treatment Arm 3
TNF inhibitor Arm - adalimumab will be used in US, Canada and Puerto Rico; etanercept will be used in all other countries.
干预措施: etanercept (Biological)
结局指标
主要结局
Incidence Rate of Adjudicated Malignancies Excluding Non-melanoma Skin Cancers (NMSC)
时间窗: Baseline up to last contact date (maximum up to 72 months)
Incidence rate (number of participants with event per 100 participant year \[PY\]) was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. Malignancy events, excluding NMSC were adjudicated by a steering committee. The risk period (RP) was the last contact date. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
Incidence Rate of Adjudicated Major Adverse Cardiovascular Events (MACE)
时间窗: Baseline up to last contact date (maximum up to 72 months)
MACE included the cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke of any classification, including reversible focal neurologic defects with imaging evidence of a new cerebral lesion consistent with ischemia or hemorrhage. Incidence rate was defined as the total number of participants with admissible events divided by the total (for all qualifying participants) time at risk for the cohort/treatment group of interest. The risk period (RP) was the minimum of last contact date or last study treatment dose date + 60 days. The last contact date was the maximum of (AE start date, AE stop date, last study visit date, withdrawal date, telephone contact date). If a participant died, last contact date was the death date. First events were counted within the RP. If a participant did not have an event or had an event but outside the risk period, the participant was censored at the end of RP.
次要结局
- Number of Participants With an American College of Rheumatology 50% (ACR50) Response(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)
- Number of Participants With an American College of Rheumatology 70% (ACR70) Response(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)
- Percentage of Participants With Simplified Disease Activity Index (SDAI) Less Than or Equal to (<=) 3.3(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)
- Incidence Rate of Non-fatal Stroke(Baseline up to last contact date (maximum up to 72 months))
- Incidence Rate of Non-fatal Myocardial Infarction(Baseline up to last contact date (maximum up to 72 months))
- Incidence Rate of Adjudicated Opportunistic Infection Events Including Tuberculosis(Baseline up to last contact date (maximum up to 72 months))
- Incidence Rate of Adjudicated Hepatic Events(Baseline up to last contact date (maximum up to 72 months))
- Number of Participants With Reasons For Permanent or Temporary Discontinuation of Study Medication(Baseline up to last contact date (maximum up to 72 months))
- Change From Baseline in Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63(Baseline, Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63)
- Incidence Rate of Adjudicated Cardiovascular Events Other Than Major Adverse Cardiovascular Events (MACE)(Baseline up to last contact date (maximum up to 72 months))
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(AEs: Baseline up to minimum of last contact date or last study treatment dose date+28 days (maximum up to 72 months); SAEs: Baseline up to minimum of last contact date (maximum up to 72 months))
- Number of Participants With Clinically Significant Abnormal Laboratory Parameters(Baseline up to last contact date (maximum up to 72 months))
- Incidence Rate of Adjudicated All-Cause Deaths(Baseline up to last contact date (maximum up to 72 months))
- Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63(Baseline, Months 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63)
- Change From Baseline in Simplified Disease Activity Index (SDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63(Baseline, Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63)
- Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63(Baseline, Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60 and 63)
- Percentage of Participants Who Achieved Observed American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean Remission Criteria(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)
- Percentage of Participants With Clinical Disease Activity Index (CDAI) <=2.8(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)
- Percentage of Participants With Simplified Disease Activity Index (SDAI) <=11(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)
- Percentage of Participants With Clinical Disease Activity Index (CDAI) <=10(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)
- Percentage of Participants With Disease Activity Score 28-4 (DAS28-4) C-reactive Protein (CRP) <=3.2(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)
- Number of Participants With an American College of Rheumatology 20 Percent (%) (ACR20) Response(Month 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69 and 72)