A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-188667 (Abatacept) or Placebo on a Background of Mycophenolate Mofetil and Corticosteroids in the Treatment of Subjects With Active Class III or IV Lupus Nephritis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 695
- 试验地点
- 42
- 主要终点
- Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
研究概览
简要总结
The purpose of this study is to evaluate (Abatacept) for treatment of lupus nephritis when used on a background of Cellcept (mycophenolate) and prednisone (corticosteroids)
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Potential subjects must have active lupus nephritis
- •Biopsy within 12 months prior to screening visit indicating active Class 3 or 4 proliferative lupus glomerulonephritis (lupus effecting your kidney)
- •Urine protein creatinine ratio (UPCR) ≥ 1 at Screening
- •Serum creatinine ≤ 3 mg/dL (ie, ≤ 265 micromol/L)
- •There must also be evidence of active disease within 3 months of Screening, based on at least one of the following:
- •Worsening of lupus nephritis OR
- •UPCR ≥ 3 at Screening OR
- •Active urine sediment OR
- •Biopsy within 3 months prior to screening visit indicating active Class 3 or Class 4 active proliferative lupus glomerulonephritis
- •Inclusion Criteria for the Long-Term Extension Period:
- •Signed Written Informed Consent
- •Subjects who achieve a complete or partial renal response after completing 2 years of double-blind treatment
排除标准
- •Systemic Lupus Erythematosus (SLE) must be the primary/main autoimmune diagnosis
- •Current symptoms of severe, progressive, or uncontrolled non-SLE related renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other concomitant medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study
- •Significant active Central nervous system (CNS) lupus with the exception of fatigue or mild stable cognitive
- •Subjects who are diagnosed as end-stage renal disease or whose kidney damage is too significant and irreversible
研究组 & 干预措施
Placebo + Mycophenolate mofetil + Prednisone
Placebo matching with BMS-188667 injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks
干预措施: Prednisone (Drug)
BMS-188667 + Mycophenolate mofetil + Prednisone
BMS-188667 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks
干预措施: BMS-188667 (Biological)
BMS-188667 + Mycophenolate mofetil + Prednisone
BMS-188667 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks
干预措施: Mycophenolate mofetil (Drug)
BMS-188667 + Mycophenolate mofetil + Prednisone
BMS-188667 30 mg/kg injection by intravenous on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks
干预措施: Prednisone (Drug)
Placebo + Mycophenolate mofetil + Prednisone
Placebo matching with BMS-188667 injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks
干预措施: Mycophenolate mofetil (Drug)
Placebo + Mycophenolate mofetil + Prednisone
Placebo matching with BMS-188667 injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks
干预措施: Placebo matching with BMS-188667 (Biological)
结局指标
主要结局
Percentage of Participants in Complete Renal Response (CR) of Lupus Glomerulonephritis at Day 365 of the Double-blind Period
时间窗: Day 365
Number of participants achieving CR was divided by the total number of participants in that arm and expressed as a percentage. CR defined as: eGFR is normal or no \<85% of the baseline; eGFR based on mean creatinine value from day 358 and 365. Proteinuria: UPCR\<0.5 mg/mg. Urine sediment: No cellular casts. Corticosteroid dose: Daily dose must be no \>10 mg prednisone or equiv. for at least 28 days prior to assessment. Participants with \>10mg/day prednisone or equivalent for non-renal disease within 28 days prior to day 365 will be imputed as having achieved CR if the following are true: Met all criteria for CR at day 337 and all criteria for CR except corticosteroid dose at day 365; Investigator confirms increase in steroid dose is not related to renal disease. Adjusted odds ratio is estimated from logistic regression model which includes treatment group, baseline ACEi/ARBs use (Yes/No), race (Asian/ Black/Caucasian/Other) and baseline UPCR as a continuous variable.
次要结局
- Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 365 of the Double-blind Period(Day 365)
- Adjusted Mean Change From Baseline in Urine Protein/Creatinine Ratio (UPCR) at Day 365 of the Double-blind Period in Nephrotic Participants(Baseline and Day 365)
- Adjusted Mean Change From Baseline in UPCR at Day 365 of the Double-blind Period in Overall Population(Day 1 and Day 365)
- Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During Year 1 of the Double-blind Period(Day 1 to Day 365)
- Number of Participants With Any Adverse Events (AEs) During Year 1 of the Double-blind Period(From Day 1 up to 56 days post last dose in Year 1 of the double-blind period)
- Median Time to Complete Renal Response During the Double-blind Period in All Participants(Day 365, Day 729)
- Percentage of Participants With Ranked Outcome of Complete Renal Response, Partial Renal Response (PR), and No Renal Response (NR) During the Double-blind Period(Day 365, Day 729)
- Median Time to Complete Renal Response During the Double-blind Period in Nephrotic Participants(Day 365, Day 729)
- Median Time to Partial Renal Response During the Double-blind Period in All Participants(Day 365, Day 729)
- Number of Participants With Other Marked Chemistry Laboratory Abnormalities in the Double Blind Period(Day 1 to Day 729)
- Number of Participants With Abatacept Induced Antibody Response Over Time in the Double-blind Period(Day 365, Day 729)
- Median Time to Partial Renal Response During the Double-blind Period in Nephrotic Participants(Day 365, Day 729)
- Adjusted Mean Change From Baseline in UPCR Over Time(Day 365; Day 729, includes data up to July 1st 2017 when double-blind therapy ended)
- Median Percent Change From Baseline in UPCR Over Time(Day 365, Day 729)
- Adjusted Mean Change From Baseline in eGFR Over Time(Day 365, Day 729)
- Median Time to First Sustained Change to No Response During the Double-blind Period(Day 365, Day 729)
- Number of Participants With Sustained Change From Higher Level of Response to no Response During the Double-blind Period(Day 365, Day 729)
- Adjusted Mean Change From Baseline in Disease Activity as Measured by BILAG 2004 Over Time During the Double-blind Period(Day 1 to Day 729; Day 365 to Day 729)
- Cmin (ug/mL): Trough Level Serum Concentration of Abatacept Prior to the Administration of the IV Infusion(Days 1 to 365)
- Cmax: Maximum Observed Serum Concentration Following Participants Receiving Active Abatacept IV(at 1 hour post Day 1 dose and 30 minutes post Day 337 dose)
- AUC (TAU): Area Under the Serum Concentration Time Curve Over a Dosing Interval(Days 337 to 365)
- Summary Statistics for Systolic Blood Pressure(Day 1 to Day 729)
- Summary Statistics for Diastolic Blood Pressure(Day 1 to Day 729)
- Summary Statistics for Heart Rate(Day 1 to Day 729)
- Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (U/L)(Day 729)
- Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (g/L)(Day 729)
- Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Percentage of Blood)(Day 729)
- Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (Umol/L)(Day 729)
- Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (mmol/L)(Day 729)
- Mean Change From Baseline in Laboratory Analytes During the Double-blind Period (x10^9 Cells/L)(Day 729)
- Number of Participants With Marked Hematology Laboratory Abnormalities During Year 1 of the Double Blind Period(Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier)
- Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities During Year 1 of the Double Blind Period(Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier)
- Number of Participants With Marked Electrolyte Laboratory Abnormalities During Year 1 of the Double Blind Period(Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier)
- Number of Participants With Marked Urinalysis Laboratory Abnormalities During Year 1 of the Double Blind Period(Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier)
- Number of Participants With Other Marked Chemistry Laboratory Abnormalities During Year 1 of the Double Blind Period(Day 1 to Day 365; includes data up to 56 days post last dose in year 1 of double-blind period or first dose date in the year 2 of double-blind period, whichever is earlier)
- Number of Participants With Any Adverse Events (AEs) During Year 2 of the Double-blind Period and Long-term Extension(From the first dose in Year 2 of the double-blind period up to 56 days post last dose)
- Percentage of Participants in Treatment Failure Over Time During the Double-blind Period(Day 365, Day 729)
- Median Time to First Treatment Failure and Overall Treatment Failure During the Double-blind Period(Day 365, Day 729)
- Percentage of Nephrotic Participants in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period(Day 729)
- Number of Participants With Marked Liver and Kidney Function Laboratory Abnormalities in the Double Blind Period(Day 1 to Day 729)
- Number of Participants With Marked Electrolyte Laboratory Abnormalities in the Double Blind Period(Day 1 to Day 729)
- Number of Participants With Marked Urinalysis Laboratory Abnormalities in the Double Blind Period(Day 1 to Day 729)
- Percentage of Participants in Overall Population in Complete Renal Response of Lupus Glomerulonephritis at Day 729 of the Double-blind Period(Day 729)
- Number of Participants With Marked Hematology Laboratory Abnormalities in the Double Blind Period(Day 1 to Day 729)