A 12-month Randomized, Multiple Dose, Open-label, Study Evaluating Safety, Tolerability, Pharmacokinetics/Pharmacodynamics (PK/PD) and Efficacy of an Anti-CD40 Monoclonal Antibody, CFZ533, in Combination With Mycophenolate Mofetil (MMF) and Corticosteroids (CS), With and Without Tacrolimus (Tac), in de Novo Renal Transplant Recipients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Mean Tmax Pharmacokinetic Parameter - Part I
研究概览
简要总结
The purpose of this study was to investigate the safety, tolerability, pharmacokinetics (PK) and potential for CFZ533 to replace calcineurin inhibitors (CNI), while providing a similar rate of acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard criteria donors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Written informed consent must be obtained before any assessment is performed.
- •Recipients of a kidney transplant from a heart-beating deceased, living unrelated or non-human leukocyte antigen (HLA) identical living related donor.
- •Recipients of a kidney with a cold ischemia time (CIT) < 30 hours.
排除标准
- •Recipients of an organ from a non-heart beating donor.
- •ABO incompatible or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.
- •Subjects receiving a second kidney allograft, unless the first allograft was lost due to surgical complication.
- •Subjects at high immunological risk for rejection
- •Subjects at risk for tuberculosis (TB)
- •Subject with severe systemic infections, current or within the two weeks prior to randomization/enrollment.
- •Any additional contraindication to the use of tacrolimus or mycophenolate mofetil according to the national labeling information of these products (see local product label).
研究组 & 干预措施
Regimen A
CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
干预措施: CFZ533 (Biological)
Regimen A
CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
干预措施: Tacrolimus (Tac) (Drug)
Regimen A
CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
干预措施: Mycophenolate mofetil (MMF) (Drug)
Regimen A
CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
干预措施: Corticosteroids (CS) (Drug)
Regimen B
CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
干预措施: CFZ533 (Biological)
Regimen B
CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
干预措施: Mycophenolate mofetil (MMF) (Drug)
Regimen B
CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
干预措施: Corticosteroids (CS) (Drug)
Regimen B
CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
干预措施: anti-IL2 Induction (Biological)
Regimen C
Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]
干预措施: Tacrolimus (Tac) (Drug)
Regimen C
Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]
干预措施: Mycophenolate mofetil (MMF) (Drug)
Regimen C
Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]
干预措施: Corticosteroids (CS) (Drug)
Regimen C
Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]
干预措施: anti-IL2 Induction (Biological)
结局指标
主要结局
Mean Tmax Pharmacokinetic Parameter - Part I
时间窗: Day 1
Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
Mean AUClast Pharmacokinetic Parameter - Part I
时间窗: Day 1
Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II
时间窗: 3, 6, 9, and 12 months
To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale. An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy.
Mean Cmax Pharmacokinetic Parameter- Part I
时间窗: Day 1
Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I
次要结局
- CFZ533 Plasma PK Concentrations - Part II(throughout study period (day 84 to day 336))
- Anti-CFZ533 Antibodies - Part II(Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion))
- eGFR - Part II(Day 1, Day 29, Day 337,)
- Total sCD40 Plasma Concentrations - Part II(12 months)
- Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1(Baseline to end of study (Day 1, Day 29, Day 337))
- Free CD40 and Total CD40 on B Cells - Part II(Baseline to end of study (Day 1/predose))
- Anti-CFZ533 Antibodies - Part I(Baseline to end of study)