A Seamless Phase 2/3 Randomized, Open-label Study to Investigate Efficacy and Safety of Frexalimab Versus Tacrolimus in Adult Kidney Transplant Recipients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Sanofi
- 入组人数
- 526
- 试验地点
- 26
- 主要终点
- Composite efficacy failure rate (BPAR, graft loss, and death) by 1 year post kidney transplantation
研究概览
简要总结
The purpose of this open-label, randomized, active-comparator-controlled study is to determine the efficacy and safety of frexalimab subcutaneous administrations up to 5 years compared to tacrolimus capsules in adults undergoing kidney transplantation. Participants aged 18 to 70 years who have low-to-moderate immunologic risk of graft rejection and receive their first kidney transplant are eligible if they meet all inclusion and no exclusion criteria. Study details include:
- The study and treatment duration will be up to approximately 5 years.
- The number of visits will be approximately 38.
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
- None
盲法说明
[Specify Complex Masking]
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who are scheduled to receive their first kidney transplant from a living or deceased donor.
- •Participants with low to moderate immunological risk.
排除标准
- •Deceased donor kidney graft qualified as expanded criteria donor or donor after cardiac death.
- •Positive T or B cell crossmatch, or positive virtual crossmatch per local practice at screening.
- •Participants receiving a kidney graft from HLA-identical living-related donors, or have current or previous solid organ, cell, or multi-organ transplantation, or paired kidney transplantation.
- •Participants whose primary causes of ESKD are idiopathic FSGS, C3 glomerulopathy, lupus nephritis, or thrombotic microangiopathy
- •Evidence of active or latent TB, HIV, HBV or HCV infection.
- •Participants who have known genetically predisposed thrombophilia, have history of thromboembolic events, or who need long-term anti-coagulation therapy.
- •Participants who have severe medical co-morbidities, active infection, or severely limited life expectancy due to underlying medical conditions that are generally precluded from kidney transplant.
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Tacrolimus
Tacrolimus
干预措施: Tacrolimus (Drug)
Frexalimab
The first dose of frexalimab will be given intravenously and subsequent doses of frexalimab will be administered subcutaneously via on-body delivery system(OBDS)
干预措施: mycophenolate sodium (Drug)
Frexalimab
The first dose of frexalimab will be given intravenously and subsequent doses of frexalimab will be administered subcutaneously via on-body delivery system(OBDS)
干预措施: mycophenolate mofetil (Drug)
Tacrolimus
Tacrolimus
干预措施: prednisone (Drug)
Tacrolimus
Tacrolimus
干预措施: methylprednisolone (Drug)
Tacrolimus
Tacrolimus
干预措施: rabbit anti-thymocyte globulin (Drug)
Frexalimab
The first dose of frexalimab will be given intravenously and subsequent doses of frexalimab will be administered subcutaneously via on-body delivery system(OBDS)
干预措施: rabbit anti-thymocyte globulin (Drug)
Frexalimab
The first dose of frexalimab will be given intravenously and subsequent doses of frexalimab will be administered subcutaneously via on-body delivery system(OBDS)
干预措施: prednisone (Drug)
Tacrolimus
Tacrolimus
干预措施: mycophenolate mofetil (Drug)
Frexalimab
The first dose of frexalimab will be given intravenously and subsequent doses of frexalimab will be administered subcutaneously via on-body delivery system(OBDS)
干预措施: Frexalimab (Drug)
Tacrolimus
Tacrolimus
干预措施: mycophenolate sodium (Drug)
Frexalimab
The first dose of frexalimab will be given intravenously and subsequent doses of frexalimab will be administered subcutaneously via on-body delivery system(OBDS)
干预措施: methylprednisolone (Drug)
结局指标
主要结局
Composite efficacy failure rate (BPAR, graft loss, and death) by 1 year post kidney transplantation
时间窗: by 1 year
BPAR is defined as biopsy confirmed T cell mediated and antibody mediated rejection as categorized by BANFF 2022; graft loss is defined as the first date the patients meet any of the following criteria: chronic dialysis for a least 56 days, day of allograft nephrectomy, or day of re-transplant.
次要结局
- Composite of participant and graft survival over time and at 6 months, 1 year, 2 years, 3 years, and 4 years post kidney transplantation(at 6 months, 1 year, 2 years, 3 years, and 4 years)
- Death-censored graft survival over time and at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation (including the causes of graft loss)(at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years)
- Participant survival over time and at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation (including the causes of death)(at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years)
- Incidence of BPAR (yearly and cumulative) up to 5 years post kidney transplantation(up to 5 years)
- Time to first BPAR(up to 5 years)
- Incidence of graft rejection at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation(at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years)
- Incidence of rejection episodes with clinical resolution up to 5 years post kidney transplantation(up to 5 years)
- Composite efficacy failure rate (BPAR, graft loss, and death) by 6 months post kidney transplantation(by 6 months)
- Incidence of de novo donor-specific antibodies at 1 year post kidney transplantation(at 1 year)
- Incidence of de novo donor-specific antibodies at 5 years post kidney transplantation(at 5 years)
- Participants with AEs, SAEs, AEs leading to permanent study intervention discontinuation, AESIs, and PCSAs in laboratory tests, ECG, and vital signs during the study period(until 5 years)
- Participants with medical device AEs, ADEs, medical device SAEs, SADEs, and device deficiencies during the study period(until 5 years)
- Side effects of immunosuppressive therapy evaluated by MTSOSD-59R score at Months 1, 2, 3, 4, 5, 6 and then every 6 months until the end of the study(at Months 1, 2, 3, 4, 5, 6 and then every 6 months until the end of the study)
- Frexalimab plasma concentration over time(up to 1 year)
- Incidence of ADA(until 5 years)
- Incidence of new-onset diabetes post kidney transplantation(until 5 years)
- Incidence of hypertension, anti-hypertensive regimen, and systolic and diastolic blood pressure(until 5 years)
- Incidence of dyslipidemia, lipid-lowering regimen, and measures of dyslipidemia, including serum TG and total, non-HDL, LDL, and HDL cholesterol(until 5 years)
- Titer of ADA(until 5 years)
- Persistence of ADA(until 5 years)
- Prevalence of hypertension, anti-hypertensive regimen, and systolic and diastolic blood pressure(until 5 years)
- Prevalence of dyslipidemia, lipid-lowering regimen, and measures of dyslipidemia, including serum TG and total, non-HDL, LDL, and HDL cholesterol(until 5 years)
- eGFR at 1 year post kidney transplantation(at 1 year)
- eGFR at 6 months, 2 years, 3 years, 4 years, and 5 years post kidney transplantation(at 6 months, 2 years, 3 years, 4 years, and 5 years)
- Change of eGFR from Month 3 over time up to 5 years post kidney transplantation(from Month 3 over time up to 5 years)
- Participant status of eGFR > 60 mL/min/1.73 m2 at 1, 2, 3, and 5 years post kidney transplantation(at 1, 2, 3, and 5 years)
- Participant status of eGFR < 60 mL/min/1.73 m² at Month 12 or with a > 10 mL/min/1.73 m² decrease in eGFR from Month 3 to 12(from Month 3 to 12)
- Proteinuria at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation(at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years)
- iBox score at 1 year post kidney transplantation(at 1 year)
- Composite of participant and graft survival at 5 years post kidney transplantation(at 5 years)