A Study of REACT in Subjects With Type 2 Diabetes Mellitus and Chronic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy (including durability) of up to 2 REACT injections given 3 months (+30 days) apart and delivered percutaneously into biopsied and non-biopsied contralateral kidneys in participants with T2DM and CKD.

Detailed Description
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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 undergo sham procedures and be followed to the global trial end date. Cohort 2 participants will receive 2 REACT injections 3 months apart (+30 days) and be followed to the global trial end date. This event driven study is estimated to have a total maximum duration of 5 years.

Official Title
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A Phase 3 Randomized Controlled Study of Renal Autologous Cell Therapy (REACT) in Subjects With Type 2 Diabetes and Chronic Kidney Disease (REGEN-006)

Conditions
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Type 2 Diabetes Mellitus, Chronic Kidney Diseases

Intervention / Treatment
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* Biological: Renal Autologous Cell Therapy (REACT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant is male or female, 30 to 80 years of age on the date of informed consent. The participant has a clinical diagnosis of T2DM in their health record. The participant has a clinical diagnosis of diabetic nephropathy as the underlying cause of renal disease (diagnosis does not have to be confirmed via renal biopsy) in their health record. The participant has a serum glycosylated hemoglobin (HbA1c) less than 10% at the Screening Visit. The participant has a documented clinical diagnosis of an eGFR greater than or equal to 20 and less than or equal to 50 mL/min/1.73m², not requiring renal dialysis. The participant has a urinary albumin-to-creatinine ratio (UACR) of greater than or equal to 300 and less than or equal to 5,000 mg/g. Exclusion Criteria: The participant has a history of type 1 diabetes mellitus. The participant has a history of renal transplantation. The participant has a mean systolic blood pressure greater than or equal to 140 mmHg and/or mean diastolic blood pressure greater than or equal to 90 mmHg at screening, across 3 measurements while seated. The participant has hemoglobin levels less than 10 g/dL and is not responsive to the standard medical intervention for CKD-related anemia prior to randomization.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Cohort 1<br>Participants randomized to Cohort 1 will receive 2 sham injections of REACT. Second injection to occur 3 months (+30 days) after the first REACT injection. Sham procedures simulate real procedure. No tissue is taken during biopsy and nothing is injected into kidney for injection. | Biological: Renal Autologous Cell Therapy (REACT)<br>* Participants will receive either 2 REACT injections or 2 Sham REACT injections into biopsied and non-biopsied contralateral kidneys 3 months apart.<br>|
| Experimental: Cohort 2<br>Participants randomized to Cohort 2 will receive 2 injections of REACT. The second injection to occur 3 months (+30 days) after the first REACT injection. | Biological: Renal Autologous Cell Therapy (REACT)<br>* Participants will receive either 2 REACT injections or 2 Sham REACT injections into biopsied and non-biopsied contralateral kidneys 3 months apart.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Composite Endpoint | The time from first injection to the earliest of: At least 40% reduction in eGFR, using the 2009 CKD-EPI serum creatinine equation, sustained for 30 days or eGFR <15 mL/min/1.73m² using the 2009 CKD-EPI serum creatinine equation, sustained for 30 days and/or chronic dialysis, and/or renal transplant or Renal or cardiovascular death | up to 60 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Composite Endpoint | The time from first injection to the earliest of: At least 40% reduction in eGFR, using the 2009 CKD-EPI serum creatinine equation, sustained for 30 days or eGFR <15 mL/min/1.73m² using the 2009 CKD-EPI serum creatinine equation, sustained for 30 days and/or chronic dialysis, and/or renal transplant Increase of UACR of at least 30% and of at least 30mg/g, using the random urine microalbumin/urine creatinine ratio sustained for 90 days or Renal or Cardiovascular death | up to 60 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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REACT®, Type 2 Diabetes Mellitus