Chronic Kidney Diseases, Type 2 Diabetes Mellitus
Conditions
Keywords
REACT®, Type 2 Diabetes Mellitus, Rilparencel, Proact
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALRenal Autologous Cell Therapy (REACT/ rilparencel)
Participants will have a kidney biopsy followed approximately12 weeks later with a rilparencel injection into the biopsied kidney, then, approximately 12 weeks later a rilparencel injection into their contralateral kidney.
PROCEDURESham Comparator
Participants will have sham procedures that simulate real biopsy and injection procedure. No tissue is taken during biopsy and nothing is injected into kidney. The 2 injection/ sham procedures will occur approximately 12 weeks apart.
Sponsors
Prokidney
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. The participant is male or female, 30 to 80 years of age on the date of informed consent. 2. Documented diagnosis of type 2 diabetes mellitus (T2DM) and chronic kidney disease 3. Serum glycosylated hemoglobin (HbA1c) of 9.5% or lower at Screening. 4. Systolic blood pressure of ≤ 140 mm Hg and diastolic blood pressure of ≤ 90 mm Hg at Screening. 5. All participants should be strongly considered for treatment with sodium-glucose cotransporter 2 inhibitor (SGLT2i). 6. 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. 7. Participant agrees and is able to refrain from using therapies that may increase bleeding risk for the specified pre-procedure and post-procedure durations. 8. Participant is willing and able to cooperate with all aspects of the protocol and provide signed informed consent. Key
Exclusion criteria
1. The participant has a history of type 1 diabetes mellitus. 2. The participant has a history of renal transplantation or other organ transplantation 3. The participant has any other known underlying cause of kidney disease 4. History of acute kidney injury or major surgery within 3 months prior to the Screening Visit. 5. Myocardial infarction, unstable angina, revascularization procedure or cerebrovascular accident within 12 weeks before randomization, or a revascularization procedure is planned during the trial. 6. Current or history of heart failure of New York Heart Association (NYHA) Class IV cardiac disease. 7. History of exclusionary malignancy within the past 3 years prior to Screening 8. Documented clinically significant liver disease, including acute or chronic hepatitis B or hepatitis C. 9. Known infection with HIV, active syphilis, or other unresolved active genitourinary infection, or active tuberculosis requiring treatment at Screening. 10. Immunocompromised condition or condition requiring chronic immunosuppressive agents, including individuals treated for chronic glomerulonephritis, within 3 months of signing ICF. 11. Has had a recent bleeding event or a known bleeding disorder(s) or increased risk of either thromboembolism or bleeding. 12. Kidney imaging reveals contraindications for undergoing biopsy or rilparencel injection 13. Maintained on any anticoagulant agents 14. 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. 15. History of severe systemic reaction(s) or any contraindication to local anesthetics or sedatives. 16. Use of an investigational product or device within 12 weeks prior to Randomization or previous treatment with rilparencel. 17. Participant's health status would, in the judgement of the Investigator, be jeopardized by participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Surrogate / Intermediate Efficacy Endpoint -eGFR Slope | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | • Time from first injection to at least a 40% reduction in eGFR sustained for 30 days. |
| 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. | • Time from first injection to eGFR \< 15 mL/min/1.73m² sustained for 30 days and/or chronic dialysis, and/or kidney transplant. |
| Secondary Endpoint: All-cause mortality. | From date of first injection to all-cause mortality assessed up to 94 months. | The time from first injection to all-cause mortality. |
| Secondary Endpoint: Kidney Disease Quality of Life Changes | Week 52 | • Changes from Baseline in patient-reported outcome from the Burden of Kidney Disease domain at Week 52 from the Kidney Disease Quality of Life (KDQOL) Questionnaire. The survey is used to assess the burden, symptoms/problems, and effects of kidney disease on a patient's quality of life. |
| Secondary Endpoint: Quality of Life | Week 52 | Changes from Baseline in patient-reported outcome EuroQol 5-Dimension 5-Level (EQ5D-5L) at Week 52. The descriptive system is divided into 5 levels of perceived problems with level 1 (indicating no problem) and level 5 (indicating extreme problems). |
Countries
Mexico, Puerto Rico, Taiwan, United States
Contacts
STUDY_DIRECTORStudy Director
Prokidney
Outcome results
None listed