A Long-term, Open-label Follow-up Study Of Tofacitinib (Cp-690,550) For Treatment Of Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 4,488
- 试验地点
- 464
- 主要终点
- Initial Period: Primary Endpoints Were Standard Laboratory Safety Data (Chemistry, Hematology, Etc.) and Adverse Event (AE) Reports
研究概览
简要总结
The purpose of this study is to determine the long-term effectiveness and safety of CP-690,550 for the treatment of rheumatoid arthritis. Subjects are eligible for this study only after participating in another "qualifying" study of CP-690,550
A sub-study will be conducted within the A3921024 study, this study will evaluate the immune response to pneumococcal and influenza vaccines in patients receiving CP-690,550
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who have participated in a randomized "qualifying" study of CP-690,550 for the treatment of rheumatoid arthritis
- •Vaccine sub-study visit
- •Subjects actively participating in Study A3921024 must have completed at least 3 months of continuous 10 mg BID CP-690,550 treatment in A3921024 as defined by >80% compliance with prescribed dose consumption of CP-690,550 over the previous 3 months.
排除标准
- •Serious medical conditions that would make treatment with CP-690,550 potentially unsafe
- •Vaccine sub-study visit
- •Any documented influenza or pneumococcal infection within the last 3 months prior to randomization in this study
- •Received any vaccine within 1 month prior to randomization in this study
- •Received an influenza vaccine within 6 months or a pneumococcal vaccine within 5 years of randomization in this study.
研究组 & 干预措施
Open-Label Active Treatment Enrolled from Phase 3
Patients enrolling from Phase 3 studies
干预措施: CP-690,550 (Drug)
Open-Label Active Treatment Enrolled from Phase 2
Patients enrolling from Phase 2 studies
干预措施: CP-690,550 (Drug)
结局指标
主要结局
Initial Period: Primary Endpoints Were Standard Laboratory Safety Data (Chemistry, Hematology, Etc.) and Adverse Event (AE) Reports
时间窗: Includes laboratory test abnormality data for all visits and adverse event data up to 999 days after last dose of study drug
Treatment-emergent non serious AEs by System Organ Class (SOC) (all causalities) and Laboratory Test Abnormalities (without regard to baseline) The stated number of participants analyzed was the total number of participants in each group (AEs). The actual number of participants analyzed for each laboratory parameter varied, and is provided for each. Abs=absolute; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ESR=erythrocyte sedimentation rate; GGT=gamma glutamyl transferase; hgb=hemoglobin; HDL=high density lipids; LDL=low density lipids; LLN=lower limit of normal; qual=qualitative; Tot=total; ULN=upper limit of normal; WBC=white blood cell
Extension Period: Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs)
时间窗: Baseline (Day 1 at Entry of Extension Period) up to 28 days after last study drug dose in Extension Period (13 Months)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.
Extension Period: Number of Participants With Laboratory Test Abnormalities
时间窗: Baseline (Day 1 at Entry of Extension Period) up to 28 days after last study drug dose in Extension Period (13 Months)
Criteria for laboratory abnormalities: hemoglobin (Hg), hematocrit, red blood cell (RBC), high density lipoprotein (HDL) cholesterol:\<0.8\*lower limit of normal (LLN), platelet\<0.5\*LLN/\>1.75\*upper limit of normal (ULN), white blood cell (WBC)\<0.6\*LLN/\>1.5\*ULN, lymphocyte, neutrophil, protein, albumin \<0.8\*LLN/\>1.2\*ULN, basophil, eosinophil, monocyte, low density lipoprotein (LDL) cholesterol: \>1.2\*ULN; bilirubin\>1.5\*ULN, aspartate amino transferase(AT), alanine AT, gammaglutamyl transferase, alkaline phosphatase:\>3.0\*ULN; blood urea nitrogen, creatinine, cholesterol, triglyceride:\>1.3\*ULN; sodium \<0.95\*LLN/\>1.05\*ULN, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN/\>1.1\*ULN; glucose\<0.6\*LLN/\>1.5\*ULN; Urine (specific gravity\<1.003/\>1.030, pH\<4.5/\>8, glucose, ketone, protein, blood/Hg(\>=1; RBC, WBC\>=20; creatinine kinase\>2\*ULN).
Initial Period: The Long Term Safety and Tolerability of CP-690,550 5 Milligrams (mg) Twice Daily (BID) and 10 mg BID for the Treatment of Rheumatoid Arthritis
时间窗: Includes AEs for every visit and up to 999 days after last dose of study drug
Treatment-emergent AEs by SOC (all causalities) - all participants, by time. Data presented for Post Month 96 includes data up to and including Month 114.
Extension Period: Percentage of Participants With Adverse Events and Who Discontinued Treatment Due to Adverse Events to Assess Long-term Safety and Tolerability of Tofacitinib
时间窗: Baseline (Day 1 at Entry of Extension Period) up to Month 6 of Extension Period; Month 6 of Extension Period to Month 12 of Extension Period
Long term safety and tolerability of Tofacitinib was measured as following: percentage (%) of participants with AEs, percentage of participants who discontinued due to AEs. An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.
次要结局
- Extension Period: Change From Baseline in Disease Activity Score (DAS) 28-3 C-Reactive Protein (CRP)(DAS28-3 CRP) and DAS28-4 Erythrocyte Sedimentation Rate (ESR)(DAS28-4 ESR) at Month 3, 6, 9 and 12(Baseline (Month 0 at the entry of Initial period); Month 3, 6, 9 and 12 of Extension Period)
- Initial Period: Number (%) of Participants With DAS28-4 (ESR) and DAS28-3 (CRP) <2.6 and ≤3.2(Every visit until study completion)
- Initial Period: Percentage of Patients With American College of Rheumatology (ACR) 20, 50, and 70 Responses(Every visit until study completion)
- Extension Period: Percentage of Participants With American College of Rheumatology (ACR) 20, 50, and 70 Responses(Month 3, 6, 9 and 12 of Extension Period)
- Initial Period: Area Under American College of Rheumatology (ACR) n Curve(Not applicable as no data were collected for this endpoint.)
- Initial Period: Disease Activity Score (DAS)28 (C-reactive Protein [CRP]) and DAS28 (Erythrocyte Sedimentation Rate [ESR])(Every visit until study completion)
- Extension Period: Percentage of Participants With DAS28-4 (ESR) and DAS28-3 (CRP) Less Than (<) 2.6 and Less Than or (<=) 3.2(Baseline (Day 1 at the entry of Extension period); Month 3, 6, 9 and 12 of Extension Period)
- Initial Period: Health Assessment Questionnaire - Disability Index (HAQ-DI) Score(Every visit until study completion)
- Extension Period: Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Month 3, 6, 9 and 12(Baseline (Month 0 at the entry of Initial Period); Month 3, 6, 9, and 12 of Extension Period)
- Initial Period: Short-Form-36 Health Survey (SF-36) Score(Every visit until study completion)
- Initial Period: FACIT Fatigue Scale, EuroQol EQ 5D, Work Limitations Questionnaire, and RA Healthcare Resource Utilization Questionnaire (RA-HCRU)(Every visit until study completion)
- Initial Period: Preservation of Joint Structure in Participants Who Had Baseline Radiographs Obtained in Their Qualifying Index Study(Every 6 months until study completion)
- Vaccine Sub-study. Percent Achieving a Satisfactory Humoral Response to the Pneumococcal Vaccine as Defined by ≥ 2-fold Increase in Antibody Concentrations(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)
- Vaccine Sub-study. Percent Achieving a Satisfactory Humoral Response to the Seasonal Influenza Vaccine as Defined by ≥ 4-fold Increase in Antibody Titers(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)
- Vaccine Sub-study. Percentage of Participants Achieving Protective Antibody Titers to the Seasonal Influenza Vaccine as Measured by a Hemagglutination Inhibition (HI) Assay Titer of ≥ 1:40 in ≥ 2 of 3 Influenza Antigens at Vaccine Sub-study Visit 3 and 4(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)
- Vaccine Sub-study. Percentage of Participants Who Respond to Each of the 12 Pneumococcal Antigens as Defined by ≥ 2-fold Increase in Antibody Concentrations From Vaccine Sub-study Visit 2 (Vaccination Baseline) Measured at Vaccine Sub-study Visit 4(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)
- Vaccine Sub-study. Percentage of Participants Who Respond to Each of the 3 Influenza Antigens as Defined by ≥ 4-fold Increase in Antibody Titers From Vaccine Sub-study Visit 2 (Vaccination Baseline) Measured at Vaccine Sub-study Visit 4(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)
- Vaccine Sub-study. Titers of Anti-influenza Antibodies at Vaccine Sub-study Visit 3 and 4(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)
- Vaccine Sub-study. Concentrations of Anti-pneumococcal Antibodies at Vaccine Sub-study Visit 3 and 4(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)
- Vaccine Sub-study. Fold Increase of Anti-pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens Above Vaccination Baseline Values (Vaccine Sub-study Visit 2) at Vaccine Sub-study Visit 4(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)
- Vaccine Sub-study. Fold Increase of Anti-influenza Antibody Levels to Each of the 3 Influenza Antigens Above Vaccination Baseline Values (Vaccine Sub-study Visit 2) at Vaccine Sub-study Visit 4(From vaccine sub-study visit 2 (baseline) to sub-study visit 4)