A Partially-blinded, Active-controlled, Multicenter, Randomized Study Evaluating Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in de Novo and Maintenance Kidney Transplant Recipients (CIRRUS I)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 418
- 试验地点
- 74
- 主要终点
- Percentage of Participants With Composite Efficacy Failure Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months Post-transplantation (Cohort 1)
研究概览
简要总结
This study was to compare CFZ533 to tacrolimus (TAC) in prevention of organ rejection in kidney transplant.
详细描述
The purpose of this study was to investigate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of three CFZ533 dose regimens in kidney transplant recipients.
Study CCFZ533A2201 was a randomized, planned 60-month (5 year) study comprising of 12-months treatment for the primary analysis plus an additional 48-month treatment period. The study had 2 different cohorts: adult de novo kidney transplant recipients and maintenance kidney transplant population (6-24 months post-transplant).
The study was terminated after the interim analysis.
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
- Triple (Participant, Care Provider, 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
- •for both cohorts
- •Written informed consent obtained before any assessment.
- •Male or female patient ≥ 18 years old.
- •Up to date vaccination as per local immunization schedules.
- •Key inclusion criteria specific to Cohort 1:
- •Recipients of a primary kidney transplant from a brain-dead donor, living unrelated or non-human leukocyte antigen (HLA) identical living related donors.
- •Recipients of a kidney with a cold ischemia time < 24 hours.
- •Key inclusion criteria specific to Cohort 2:
- •Recipients of a primary graft received 6 to 24 months prior enrollment, on a regimen containing TAC+MMF/ Enteric-coated mycophenolate sodium (EC-MPS)±corticosteroids (CS).
- •Patients with an actual eGFR according to Modification of Diet in Renal Disease (MDRD-4) ≥ 45 mL/min/1.73m2.
排除标准
- •for both cohorts
- •Recipient who tests positive for anti-HIV, HBsAg or anti-HCV (without proof of sustained viral response (SVR12) after anti-HCV treatment) within 28 days prior to baseline visit.
- •Recipient who tests negative for Epstein Barr virus (EBV) within 28 days prior to baseline visit.
- •Evidence of advanced liver disease (Child-Pugh C), or any sign of liver decompensation.
- •Patient with severe systemic infections, current or within the two weeks prior to randomization.
- •History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases, with the exception of localized excised non-melanomatous skin lesions.
- •Patients who weighed less than 30 kg or more than 180 kg.
- •Key exclusion criteria specific to Cohort 1:
- •Multi-organ transplant recipients, including en bloc and dual kidney transplantation, or prior kidney transplant
- •Recipients of an organ from a donor after cardiac death.
- •Recipient of an organ from an HLA identical living related donor.
- •ABO incompatible or complement-dependent lymphocytotoxic crossmatch positive transplant (isolated positive B cell crossmatches were not an exclusion criterion).
- •Recipients of kidneys from donors who were older than >65 years.
- •Recipients of kidneys from donors with terminal serum creatinine > 2 mg/dL.
- •Patients at high immunological risk for rejection as determined for assessment of anti-donor reactivity:
- •high panel reactive antibodies> 20% or
- •Presence of pre-formed DSA. Results 12 weeks prior to enrollment were acceptable if no blood transfusion or abortion occurred during this period.
- •Recipient of a kidney from a donor who tests positive for HIV, HBsAg or HCV.
- •Key exclusion criteria to Cohort 2
- •Recipients of a kidney re-transplant.
- •Recipient of a multi-organ transplant, including en bloc and dual kidney transplantation.
- •DSA within 12 weeks prior enrollment.
- •eGFR decline ≥10.0 mL/min within 12 weeks prior enrollment.
- •Ongoing rejection or rejection that required treatment within 12 weeks prior enrollment.
- •Severe humoral and/or cellular rejection (BANFF ≥ IIb) within 12 weeks before enrollment.
- •Proteinuria > 1 g/day or UPCR >1.2 mg/mg at time of enrollment
结局指标
主要结局
Percentage of Participants With Composite Efficacy Failure Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months Post-transplantation (Cohort 1)
时间窗: 12 Months
The composite efficacy failure event is defined as any of the following: (1) biopsy-proven acute rejection (BPAR) or (2) graft loss or (3) death. BPAR (BANFF ≥ 1A) is based on the central and adjudicated assessments. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. If the participant underwent allograft nephrectomy prior to start of permanent dialysis, the day of the nephrectomy was day of graft loss.
Percentage of Participants With Composite Efficacy Failure Event (BPAR, Graft Loss or Death) Over 12 Months Post-conversion (Cohort 2)
时间窗: 12 Months
The composite efficacy failure event is defined as any of the following: (1) biopsy-proven acute rejection (BPAR) or (2) graft loss or (3) death. BPAR (BANFF ≥ 1A) is based on the central and adjudicated assessments. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. If the participant underwent allograft nephrectomy prior to start of permanent dialysis, the day of the nephrectomy was day of graft loss.
次要结局
- Cohort 1: Mean Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-transplantation(12 months)
- Cohort 2: Mean Change in Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-conversion(12 months)
- Free CFZ533 Plasma Concentrations Over Time (Cohort 1)(Day 1-Pre-Dose to Month 30-Pre-Dose)
- Free CFZ533 Plasma Concentrations Over Time (Cohort 2)(Day 1-Pre-Dose to Month 30-Pre-Dose)
- Semi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 1)(24 Months)
- Semi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 2)(24 Months)