A Study to Assess the Steady-State Trough Serum Concentration, Safety, and Immunogenicity of Abatacept (BMS-188667) Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis Who Are Receiving Disease Modifying Ant-Rheumatic Drugs (DMARDs)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 87
- 试验地点
- 5
- 主要终点
- Short Term Period: Steady-state Trough Serum Concentration (Cmin) of Abatacept Following Weekly Subcutaneous Dosing in Participants With Active Rheumatoid Arthritis Receiving Disease Modifying Anti-rheumatic Drugs (DMARDS)
研究概览
简要总结
The purpose of this study is to study serum levels of Abatacept after subcutaneous dosing in subjects with RA.
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
- Double (Participant, Investigator)
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
- •Meet ARA criteria for diagnosis of RA with active disease.
- •RA diagnosis for at least 1 year.
- •> = 6 swollen joints.
- •> = 8 tender joints.
- •Taking methotrexate (MTX) or MTX plus not more than 1 added oral DMARD for > = 3 months and stable for 28 days prior to dosing.
排除标准
- •Serious acute or bacterial infection in last 3 months.
- •Chronic or recurrent bacterial infections.
- •History of TB within previous 3 years or old TB not adequately treated.
- •Specific lab test abnormalities
- •History of cancer within 5 years.
- •Exposure to CTLA4Ig (Cytotoxic T-lymphocyte (T-cell)-associated antigen 4Ig), belatacept, rituximab, efalizumab, alefacept, or other investigational drug or biologic.
- •Treatment with hydroxychloroquine, azathioprine, leflunomide, immunoadsorption columns, mycophenolate mofetil, cyclosporine, D-Penicillamine or calcineurin inhibitors.
- •Exposure to live vaccines.
研究组 & 干预措施
Group 1 (weight < 60 kg)
干预措施: Abatacept or Placebo (both as IV & SC solution) (Drug)
Group 2 (weight < 60 kg)
干预措施: Abatacept or Placebo (both as IV & SC solution) (Drug)
Group 3 (weight 60-100 kg)
干预措施: Abatacept or Placebo (both as IV & SC solution) (Drug)
Group 4 (weight > 100 kg)
干预措施: Abatacept or Placebo (both as IV & SC solution) (Drug)
Group 5 (weight > 100 kg)
干预措施: Abatacept or Placebo (both as IV & SC solution) (Drug)
Abatacept
Long Term
干预措施: Abatacept (Drug)
结局指标
主要结局
Short Term Period: Steady-state Trough Serum Concentration (Cmin) of Abatacept Following Weekly Subcutaneous Dosing in Participants With Active Rheumatoid Arthritis Receiving Disease Modifying Anti-rheumatic Drugs (DMARDS)
时间窗: Days 71 to 85
Participants received abatacept while also receiving DMARDS over a short term (ST) 12 Week period. To eliminate contribution from the IV loading dose of abatacept during the short term study period, Cmin values were selected from Days 71 to 85, when contribution from IV was negligible. Minimum trough serum concentration of abatacept (Cmin) was measured in micrograms/milliliter (µg/mL). Data are presented by treatment the participant actually received, not by what they were randomized to receive.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Reported During the Variable Dosing Phase of the Long Term Period (LTE)
时间窗: Day 85 to 56 days post last dose
AEs during variable dose phase of LTE + 56 days post last dose in the variable dose phase or start of the fixed dose phase, which ever came first; includes deaths reported during the variable dose phase including those that occurred greater than 56 days after last dose. Medical Dictionary for Regulatory Activities (MedDRA) version: 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (included hospitalizations for elective surgical procedures). Treatment-related=having certain, probable, possible, or missing relationship to study drug. Data presented by treatment the participant was randomized to and not what they actually received.
Number of Participants With Pre-specified AEs of Special Interest in the Variable Dosing Phase of Long Term Extension (LTE)
时间窗: Day 85 to Day 533
LTE period with variable abatacept dosing starting on Day 85 and continuing until Day 533 when LTE fixed dosing started. AEs of special interest: infection and/or infestation; neoplasms (malignant); pre-specified autoimmune disorder; infusional AEs (peri-infusional: pre-specified AEs occurring during first 24 hours (hrs) after start of the IV loading dose; acute infusional: pre-specified AEs occurring during the first hour after the start of the IV loading dose; systemic injection site reactions (SIR): pre-specified AEs for SIR; local injection site reaction: pre-specified AEs for local site reaction. Data are presented by treatment the participant was randomized to and not what they actually received.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Discontinuations Due to Adverse Events Summarized Over the Entire Long Term Extension (LTE) Period (Both Variable and Fixed Dosing)
时间窗: Day 533 to 56 Days Post last dose
On Day 85 participants rolled over into the LTE with variable dose phase first and at Day 533, a fixed dose phase of 125 mg abatacept SC weekly, irrespective of body weight. This summary includes AEs reported during entire LTE treatment plus 56 days post last dose; includes all deaths reported during the LTE including those that occurred greater than 56 days after last dose. MedDRA version: 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization (also included hospitalizations for elective surgical procedures). Treatment-related=having certain, probable, possible, or missing relationship to study drug.
次要结局
- Short Term Period: Mean Percent Change From Baseline on Day 85 in Participants Positive for Serum Rheumatoid Factor During Abatacept or Placebo Administration(Day 1 to Day 85 (or early termination))
- Short Term Period: Number of Participants With Laboratory Abnormalities in Hematology at Baseline (Day 1) to End of Period (Day 85)(Day 1 to Day 85 (or early termination))
- Short Term Period: Peak Serum Concentration (Cmax) of Abatacept at Steady State in Participants With Rheumatoid Arthritis Receiving DMARDS(Day 71 to Day 78)
- Short Term Period: Number of Participants With Laboratory Abnormalities in Serum Chemistry at Baseline and on Treatment up to Day 85(Day 1 to Day 85 (or early termination))
- Short Term Period: Mean Change From Baseline at Day 85 in Blood Pressure After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS(Day 1 to Day 85 (or early termination))
- Short Term Period: Area Under the Curve (AUC) in Time Interval of 7 Days [AUC(TAU)] of Abatacept in Participants With Rheumatoid Arthritis Receiving DMARDS(Day 71 to Day 78)
- Short Term Period: Summary of Adverse Events (AEs), Serious AEs, Deaths, and Discontinuations Due to AEs During 12 Weeks of Treatment With Either Abatacept or Placebo(Day 1 to Day 85 (or early termination))
- Short Term Period: Number of Participants With Pre-specified Adverse Events (AEs) of Special Interest After Administration of Abatacept or Placebo Over 12 Weeks(Day 1 to Day 85 (or early termination))
- Short Term Period: Mean Change From Screening at Day 85 in ECG (Heart Rate) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS(Screening to Day 85 (or early termination))
- Overall Study ST and LTE Periods: Number of Participants With Anti-abatacept Antibodies and/or Anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibodies(ST: Day 1 to Day 85; LTE: Day 85 to 168 days post last dose)
- Short Term Period: Mean Change From Baseline at Day 85 in Pulse Rate After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS(Day 1 to Day 85 (or early termination))
- Short Term Period: Mean Change From Screening to Day 85 in Electrocardiogram (QT, PR Intervals, QRS Width) After SC Administration of Abatacept or Placebo in Participants With Rheumatoid Arthritis Receiving DMARDS(Screening to Day 85 (or early termination))