A Phase 2 Multi-Center, Randomized Conversion Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Belatacept Administered to Pediatric Subjects With a Stable Renal Transplant
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 8
- 主要终点
- Total Body Clearance (CLT) of Belatacept
研究概览
简要总结
The purpose of this study is to evaluate how well adolescent kidney transplant patients tolerate a single dose of belatacept they receive at least 6 months after transplant surgery, and how their body handles the drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and Female subjects,12-17 years old
- •Receiving CNI-based maintenance immunosuppression since the time of renal transplantation in accordance with local standard of care
- •Stable renal function, in the opinion of the investigator, with a cGFR>45 mL/min/1.73m2 at the time of enrollment (per updated Schwartz Formula)
- •Adolescent Recipients of a renal allograft from a living donor or a deceased donor at least 6 months prior to enrollment
- •Subject must be receiving a calcineurin inhibitor (CNI)-based [cyclosporine (CsA) [any formulation] or Tacrolimus (TAC)] immunosuppressive regimen
- •Subject must be receiving adjunctive background maintenance immunosuppression with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS)/mycophenolic acid (MPA)
- •Subjects may be receiving maintenance corticosteroids in accordance with the local standard of care
- •Negative Interferon Gamma Release Assay (IGRA) such as QuantiFERON-TB Gold test or T-Spot-TB
- •FOCBP must have negative serum or urine pregnancy test within 24 hrs prior to start of study medication
- •Subject must have stable estimated glomerular filtration rate (GFR) ≥45 mL/min/1.73m2 (updated Schwartz formula)
排除标准
- •Epstein-Barr virus (EBV) serostatus negative or unknown at time of transplant and screening
- •History of any treated or biopsy proven acute rejection (BPAR) within 3 months prior to enrollment
- •Subjects who have experienced more than 1 episode of acute rejection (AR) of the current allograft or any antibody-mediated AR
- •Subjects with any active infection [including, but not limited to, positive cytomegalovirus (CMV) or BK viral (BKV) loads, BKV associated nephropathy (BKVAN), CMV retinitis, CMV colitis, etc.]
- •Urine albumin:creatinine ratio > 56.5 mg/mmol (> 0.5 mg albumin / mg creatinine) on a random voided urine specimen
研究组 & 干预措施
Belatacept
干预措施: Belatacept (Drug)
结局指标
主要结局
Total Body Clearance (CLT) of Belatacept
时间窗: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
CLT was the volume of abatacept cleared by the system, normalized by baseline body weight. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). CLT was measured in milliliters per hours per kilogram of body weight (mL/h/kg).
Volume of Distribution at Steady-state (Vss) of Belatacept
时间窗: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Vss was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Vss was measured in liters per kg body weight (L/kg).
Maximum Observed Serum Concentration (Cmax) of Belatacept
时间窗: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Cmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Cmax was measured in micrograms per milliliter.
Time of Maximum Observed Plasma Concentration (Tmax) of Belatacept
时间窗: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
Tmax was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). Tmax was measured in hours (h).
Half-Life of Elimination (T-Half) of Belatacept
时间窗: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
T-HALF was derived from serum concentration versus time data. Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL). T-HALF was measured in hours (h).
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC (0-T)) and Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC(INF)) of Belatacept
时间窗: Pre-dose (0), 0.5hr and 2hr from the start of infusion on Day 1, Day 29, and Day 57
AUC (0 - T) and AUC (0 - INF) were derived from serum concentration versus time data and measured in microgram hours per milliliter (µg\*h/mL). Serum samples were analyzed for abatacept by a validated enzyme-linked immunosorbent assay (ELISA) and were obtained at: pre-dose (0 hours), 0.5 and 2 hours from Start of Infusion on Day 1, Day 29, and Day 57. The results were summarized. The lower limit of assay quantitation (LLOQ) was set to "zero" which was 0.003 micrograms per milliliter (ug/mL).
次要结局
- Number of Participants With Positive Belatacept-induced Immunogenicity Response(Baseline/Day 1, Days 15, 29, and 57)
- Percentage of CD86 Receptor Occupancy(0.5 hours post dose on Day 1, Day 29 and Day 57)
- Number of Participants With Death, Serious Adverse Events (SAEs), and Treatment-related Adverse Event (AE)(Date of First Dose to 24 weeks post the last dose; approximately 26 weeks)