A Phase 3 Randomized Controlled Study of Renal Autologous Cell Therapy (REACT) in Subjects With Type 2 Diabetes and Chronic Kidney Disease (REGEN-006)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Prokidney
- 入组人数
- 685
- 试验地点
- 193
- 主要终点
- Clinical Endpoint
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of up to 2 REACT/rilparencel injections in participants with T2DM and CKD.
详细描述
Randomized multi-center, blinded intervention, two cohort, study whereby eligible participants will be randomized 1:1, prior to kidney biopsy, to 1 of 2 cohorts. Cohort 1 participants will have scripted sham procedures that mimic the sounds and activities of biopsy, injection procedures, and evaluations as a control for Cohort 2 participants who will have a kidney biopsy followed with a rilparencel injection into the biopsied kidney, then, approximately 12 weeks later with a second rilparencel injection into the contralateral kidney. All participants will be followed until the global trial end date is declared.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant is male or female, 30 to 80 years of age on the date of informed consent.
- •Documented diagnosis of type 2 diabetes mellitus (T2DM) and chronic kidney disease
- •Serum glycosylated hemoglobin (HbA1c) of 9.5% or lower at Screening.
- •Systolic blood pressure of ≤ 140 mm Hg and diastolic blood pressure of ≤ 90 mm Hg at Screening.
- •All participants should be strongly considered for treatment with sodium-glucose cotransporter 2 inhibitor (SGLT2i).
- •On a clinically relevant, maximally tolerated dose of an angiotensin converting-enzyme inhibitor (ACEI) OR an angiotensin receptor blocker (ARB), unless not tolerated or contraindicated.
- •Participant agrees and is able to refrain from using therapies that may increase bleeding risk for the specified pre-procedure and post-procedure durations.
- •Participant is willing and able to cooperate with all aspects of the protocol and provide signed informed consent.
排除标准
- •The participant has a history of type 1 diabetes mellitus.
- •The participant has a history of renal transplantation or other organ transplantation
- •The participant has any other known underlying cause of kidney disease
- •History of acute kidney injury or major surgery within 3 months prior to the Screening Visit.
- •Myocardial infarction, unstable angina, revascularization procedure or cerebrovascular accident within 12 weeks before randomization, or a revascularization procedure is planned during the trial.
- •Current or history of heart failure of New York Heart Association (NYHA) Class IV cardiac disease.
- •History of exclusionary malignancy within the past 3 years prior to Screening
- •Documented clinically significant liver disease, including acute or chronic hepatitis B or hepatitis C.
- •Known infection with HIV, active syphilis, or other unresolved active genitourinary infection, or active tuberculosis requiring treatment at Screening.
- •Immunocompromised condition or condition requiring chronic immunosuppressive agents, including individuals treated for chronic glomerulonephritis, within 3 months of signing ICF.
- •Has had a recent bleeding event or a known bleeding disorder(s) or increased risk of either thromboembolism or bleeding.
- •Kidney imaging reveals contraindications for undergoing biopsy or rilparencel injection
- •Maintained on any anticoagulant agents
- •History of anaphylactic or severe systemic reaction(s) to blood transfusions, Dextran 40, or bovine products, or contraindication(s) to above products due to medical reasons or participant preference.
- •History of severe systemic reaction(s) or any contraindication to local anesthetics or sedatives.
- •Use of an investigational product or device within 12 weeks prior to Randomization or previous treatment with rilparencel.
- •Participant's health status would, in the judgement of the Investigator, be jeopardized by participating in the study.
研究组 & 干预措施
Experimental (REACT/rilparencel injections)
Participants randomized to the experimental arm will receive 2 injections of REACT/ rilparencel.
干预措施: Renal Autologous Cell Therapy (REACT/ rilparencel) (Biological)
Sham Procedure
Participants randomized to the Sham Comparator arm will have 2 sham procedures.
干预措施: Sham Comparator (Procedure)
结局指标
主要结局
Clinical Endpoint
时间窗: up to 60 Months
The time from first injection to the earliest of: * At least 40% reduction in eGFR, sustained for 30 days, OR * eGFR \<15 mL/min/1.73m², sustained for 30 days and/or chronic dialysis, and/or kidney transplant OR * Renal or cardiovascular death
Surrogate / Intermediate Efficacy Endpoint -eGFR Slope
时间窗: 18 months after the 135th participant receives their first injection / sham.
The difference in annualized eGFR slope between the rilparencel and sham cohorts (approximately 18 months after the 135th participant receives their first injection/sham) using the 2021 Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) serum creatinine-based equation.
Clinical Endpoint
时间窗: From date of first injection until the date of first event: 40% reduction in eGFR, eGFR < 15 mL/min/1.73m² and/or chronic dialysis, and or renal transplant or date of renal or cardiovascular death, whichever came first, assessed up to 94 months.
The time from first injection to the earliest of: * At least 40% reduction in eGFR, sustained for 30 days, OR * eGFR \<15 mL/min/1.73m² with corresponding two-sided 95% CI, sustained for 30 days and/or chronic dialysis, and/or kidney transplant OR * Renal or cardiovascular death
次要结局
- Secondary Composite Endpoint: Change in eGFR from first injection to End Stage Renal Disease (ESRD)(up to 60 Months)
- Secondary Composite Endpoint: Mortality(up to 60 Months)
- Secondary Composite Endpoint: Quality of Life Changes(up to 60 Months)
- Secondary Composite Endpoint: Quality of Life(up to 60 Months)
- Secondary Endpoint: Time from first injection to at least a 40% reduction in eGFR sustained for 30 days.(From date of first injection until the date of 40% reduction in eGFR assessed up to 94 months.)
- Secondary Endpoint: Time from first injection to eGFR < 15 mL/min/1.73m² sustained for 30 days and/or chronic dialysis, and/or kidney transplant.(From date of first injection until the date of eGFR < 15 mL/min/1.73m² assessed up to 94 months.)
- Secondary Endpoint: All-cause mortality.(From date of first injection to all-cause mortality assessed up to 94 months.)
- Secondary Endpoint: Kidney Disease Quality of Life Changes(Week 52)
- Secondary Endpoint: Quality of Life(Week 52)