A Open-Label Extension Study Of CP-690,550 As Maintenance Therapy In Patients With Crohn's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 150
- 试验地点
- 74
- 主要终点
- Adjudicated Malignancy Events
研究概览
简要总结
The study hypothesis is to establish the safety and tolerability of long-term open-label (OL) CP-690,550 therapy in subjects with Crohn's disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who complete 26-week maintenance treatment of the A3921084 study or subjects who withdraw early due to A3921084 study treatment failure (see Appendix 5).
- •Women of childbearing potential must test negative for pregnancy prior to study enrolment.
- •Sexually active females of childbearing potential are required to use adequate contraceptive methods during the study period and until completion of the follow-up procedures. No specific contraceptive measures are required in male subjects during study participation.
排除标准
- •Subjects who have been discontinued due to protocol violation(s) (as determined by the Sponsor) in the A3921084 study.
- •Subjects who were discontinued from the A3921084 study due to an adverse event.
- •Subjects likely to require any non-elective surgery or surgery requiring overnight stay (with the exception of minor same day outpatient procedures that will not interfere with study drug dosing).
研究组 & 干预措施
5mg BID
干预措施: CP-690,550 (Drug)
10mg BID
干预措施: CP-690,550 (Drug)
结局指标
主要结局
Adjudicated Malignancy Events
时间窗: From baseline to Week 52
Pre-specified malignancy events were adjudicated by committees of external experts who were blinded to treatment assignment. pEoI were identified by the investigator, sponsor, potential primary event notifications (i.e. malignancies excluding non-melanoma skin cancers) for a specific protocol, events submitted for histopathology review for potential malignancies which met the criteria for potential malignancies, and by search of AE/SAE listings for events coded to Malignant tumors Standard Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQ) (20000194). IRs determined if the pEoI met the criteria for EoI classification according to the International Classification of Diseases for Oncology, a ten-digit multi-axial classification of the site (4 characters), morphology (4 digits), behavior (1 digit), and grading (1 digit) of neoplasms.
Adjudicated Potential Cardiovascular Events
时间窗: From baseline to Week 52
Pre-specified cardiovascular events were adjudicated by committees of external experts who were blinded to treatment assignment. Potential events of interest (pEoI) were identified by the investigator, sponsor, review of alerts from central electrocardiogram assessments, and by search of adverse events (AE)/serious adverse event (SAE) listings for events coded to death (coronary and non-coronary), myocardial infarction (non-fatal), all coronary revascularization, unstable angina, stroke (fatal and non-fatal), transient ischemic attack, congestive heart failure, peripheral arterial vascular disease, dyspnoea, and chest pain. The independent reviewers (IRs) determined if the pEoI met the criteria for EoI classification according to the definitions summarized from the Clinical Data Interchange Standards Consortium 'Standardized Definitions for End Point Events in Cardiovascular Trials' published October 2010.
Adjudicated Hepatic Injury Events
时间窗: From baseline to Week 52
Pre-specified liver injury events were adjudicated by blinded committees of external experts. pEoI were identified by investigator, sponsor \& search of clinical, safety \& laboratory databases (potential Hy's law event, ALT/AST ≥5 x ULN, events meeting hepatic discontinuation criteria, SAEs coded to MedDRA hepatobiliary system organ class (SOC), AEs/SAEs coded to MedDRA liver infections or infectious biliary disorders SMQ, AEs coded to MedDRA drug-induced liver injury (DILI) preferred term or any death with ALT or AST ≥3xULN, bilirubin ≥2xULN or jaundice). IRs determined if the pEoI met the criteria for EoI classification by assessing DILI (definite, highly likely, probable, possible, unlikely, unrelated or undetermined), pattern (hepatocellular, mixed, cholestatic or undetermined), likely, competing or alternative cause(s), severity (mild, moderate, severe, fatal/transplantation or undetermined), Hy's law case, recovery \& liver failure (all yes, no or undetermined).
Adjudicated Gastrointestinal (GI) Perforation Events
时间窗: From baseline to Week 52
Pre-specified GI perforation events were adjudicated by committees of external experts who were blinded to treatment assignment. The pEoI were identified via search of AE/SAE listings using the MedDRA GI Perforation SMQ. The IRs determined if the pEoI met the criteria for EoI classification based on whether a GI perforation occurred and if yes, the location within the GI tract, possible contributing medical conditions and/or concomitant medications.
Adjudicated Interstitial Lung Disease (ILD) Events
时间窗: From baseline to Week 52
Pre-specified ILD events were adjudicated by committees of external experts who were blinded to treatment assignment. pEoI were identified by searches of the clinical, safety \& laboratory databases (AEs coded to the MedDRA ILD SMQ and events nominated by the study clinician or clinical lead). The IRs determined if the pEoI met the criteria for EoI classification by assessment of the ILD event (probably ILD, possible ILD, alternative diagnosis likely, other or insufficient information to classify).
Adjudicated Opportunistic Infection Events
时间窗: From baseline to Week 52
Pre-specified opportunistic infection events were adjudicated by blinded committees of external experts. pEoI were identified by investigator, sponsor \& search of SAE listings for serious infections coded to MedDRA infections \& infestations SOC \&/or events meeting pre-specified criteria for IR pre-screening to determine if adjudication is required. IRs determined if the pEoI met the criteria for EoI classification according to definitions for opportunistic infections (invasive fungal infections per the European Organization for Research \& Treatment of Cancer/Invasive Fungal Infections Cooperative Group \& the National Institute of Allergy \& Infectious Diseases Mycoses Study Group \[EORTC/MSG\] Consensus Group definitions, endemic fungal infections per the EORTC/MSG Consensus Group definitions, other fungal infections, viral, bacterial \& parasitic infections \& vaccine dissemination) \& special interest infections (actinomycosis, Legionella \& mononucleosis-like toxoplasmosis).
次要结局
- Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study(Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up)
- Observed CDAI Score by Week(Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up)
- Observed Change From Baseline in High Sensitivity C-reactive Protein (CRP) by Week(Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up)
- Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 48/ET Visit(Baseline and Week 48/ET)
- Percentage of Participants With an IBDQ Total Score of Greater Than or Equal to (≥) 170 at Week 48/ET Visit(Week 48/ET)
- Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category(Week 48/ET visit)
- Percentage of Participants in Clinical Remission and Sustained Clinical Remission at Week 48(Week 48)
- Change From Baseline Observed CDAI Score by Week(Weeks 8, 16, 24, 36, 48 and 52/follow-up)
- Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit(Baseline and Week 48/ET visit)
- EuroQoL 5 Dimensions Questionnaire (EQ-5D) Utility Scores at Baseline and Week 48/ET Visit(Baseline and Week 48/ET visit)
- Percentage of Participants Hospitalized Due to Crohn's Disease(From baseline to Week 52/follow-up)
- Length of Hospitalizations Due to Crohn's Disease(From baseline to Week 52/follow-up)
- Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study(Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up)
- Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 48 - Among Subjects on Steroids at A3921086 Baseline(Week 48)
- Corticosteroid Use Over Time(Weeks 8, 16, 24, 36 and 48)
- Observed Change From Baseline in Fecal Calprotectin by Week(Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up)
- Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit(Baseline and Week 48/ET visit)
- Change From Baseline EQ-5D VAS Scores at Week 8/ET Visit(Baseline and Week 48/ET visit)
- Time to Relapse Among Participants in Clinical Remission at Baseline(From baseline to Week 52)
- Percentage of Participants Switching From 5 mg BID to 10 mg BID or 10 mg BID to 5 mg BID After Initial Assignment by Visit(From baseline to Week 48)
- Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit(Baseline and Week 48/early termination (ET))
- EQ-5D Visual Analogue Scale (VAS) Scores at Baseline and Week 8/ET Visit(Baseline and Week 48/ET visit)
- Change From Baseline EQ-5D Utility Scores at Week 48/ET Visit(Baseline and Week 48/ET visit)