STUDY OF RENAL AUTOLOGOUS CELL THERAPY (REACT) IN SUBJECTS WITH TYPE 1 or 2 DIABETES AND CHRONIC KIDNEY DISEASE (REGEN-007)

• Status: Recruiting
• Trial end date: 2025-05-20
• Target enrollment: 0
• Participant gender: All

Summary

Multi-center, prospective, open-label, double-arm, randomized, redose study whereby eligible subjects will be randomized 1:1 after kidney biopsy to 1 of 2 cohorts. Cohort 1 subjects will receive 2 REACT injections in the biopsied and non-biopsied contralateral kidneys 3 months apart (+60 days). Cohort 2 subjects will receive 1 REACT injection into the biopsied kidney and if a pre-defined trigger is met, will undergo a second REACT injection into the contralateral kidney. Both cohorts will be followed for 24 months after the final REACT injection. If a Cohort 2 subject does not meet a trigger, the subject will be followed for 24 months after the first injection.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Prokidney

Criteria

Inclusion Criteria:

• Male or female aged 30 to 80 years, inclusive, on the date informed consent is signed.

• Clinical diagnosis of T1DM or T2DM, controlled per institutional standard of care.

• The subject has a clinical diagnosis of diabetic nephropathy as the underlying cause of renal disease (diagnosis does not have to be confirmed via renal biopsy).

• The subject has a serum glycosylated hemoglobin (HbA1c) level less than 10% at the Screening Visit.

• The subject has a documented clinical diagnosis of an eGFR between 20 and 50 mL/min/1.73m2 inclusive not requiring renal dialysis.

• The subject has stable blood pressure and is maintained on a stable anti-hypertensive medication regimen, if treatment for hypertension is necessary. If treatment includes an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), that treatment must be the maximum tolerated daily dose for at least 4 weeks prior to randomization or, if the treatment includes a sodium glucose cotransporter 2 inhibitor (SGLT2i) at any dose, for at least 4 weeks prior to randomization.

Note: A maximum tolerated daily dose of an ACEi or ARB is defined as the maximum tolerated dose for diabetic nephropathy (for agents with an approved indication for diabetic nephropathy in patients with T1DM or T2DM, i.e., losartan and irbesartan) or the maximum tolerated dose for hypertension (for agents without an approved indication for diabetic nephropathy), unless side effects or adverse events (AE) limit the use of the maximum dose. For subjects who are not on a maximum daily dose of an ACEi or ARB, Investigators will be required to document why a higher dose is contraindicated.

• A minimum of 3 measurements of eGFR (by sCr or cystatin C) must be obtained at least 3 months apart within 24 months prior to the Screening Visit to define the rate of progression of CKD.

• The subject agrees and is able to refrain from nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, clopidogrel, prasugrel, dipyridamole, and other platelet aggregation inhibitors during the period beginning 7 days before through 7 days following the percutaneous renal biopsy and REACT injection(s).

Note: Aspirin, at a dose of up to 100 mg/day, may be continued if doing so is the standard of care at the investigational site, is accepted for primary prevention of heart disease in subjects with diabetes who are older than 40 years of age or have additional risk factors for cardiovascular disease or stroke, and for whom the perceived benefits of aspirin therapy outweigh the risks associated with treatment.

• The subject agrees and is able to refrain from oral ingestion of fish oil supplements during the period beginning 7 days before through 7 days following the percutaneous renal biopsy and REACT injection(s).

• The subject is willing and able to cooperate with all aspects of the protocol.

• The subject is willing and able to provide signed informed consent.

Exclusion Criteria:

• The subject has a history of renal transplantation.

• The subject 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. Subjects with blood pressure outside of this range prior to biopsy/injection may continue if approved by the Medical Monitor.

• The subject has hemoglobin levels less than 10 g/dL and is not responsive to the standard medical intervention for CKD-related anemia prior to randomization.

• The subject appears to be at possibly increased risk of either thromboembolism or bleeding because of abnormal results at the Screening Visit for any of the following tests: activated partial thromboplastin time (APTT), prothrombin time-international normalized ratio (PT-INR), and platelet count.

• The subject has a bleeding disorder(s) or is maintained on any anticoagulant agents, including fractionated heparin preparations, Coumadin® (warfarin), or direct thrombin inhibitors, that cannot be discontinued for 7 days before and 7 days after biopsy or injections.

• The subject has a known allergy or contraindication(s), has experienced severe systemic reaction(s) to kanamycin/structurally similar aminoglycoside antibiotic(s), which may be a manufacturing process residual, or has a known hypersensitivity to dimethyl sulfoxide.

• The subject has a history of anaphylactic or severe systemic reaction(s) or contraindication(s) to human blood products, Dextran-40, or materials of animal origin (e.g., bovine).

• The subject is not a good candidate to undergo percutaneous REACT injection, in the judgment of the interventionalist or proceduralist who will perform the procedure. This includes confirming the subject has contraindications for undergoing the procedure based on depth of the kidneys, positioning limitations, body habitus, and if the kidneys are greater than 15 cm from skin surface to kidney capsule.

• The subject has a history of severe systemic reaction(s) or any contraindication to local anesthetics or sedatives.

• The subject has been diagnosed with acute kidney injury within 3 months of the Screening Visit.

• The subject has any of the following conditions: autosomal dominant and recessive polycystic kidney disease, focal segmental glomerulosclerosis, vasculitis-related CKD, IgA or IgG nephropathy, drug-induced or hypertension-related CKD and other types of CKD as determined by the Investigator that would interfere with biopsy and REACT injection procedure (such as horseshoe kidney variant and unexplained hydronephrosis), any other documented renal pathology that would interfere with the REACT injection procedure.

Note: Anatomic abnormalities and benign conditions are not exclusionary if the kidney remains accessible and meets the criteria to receive the REACT injection.

• The subject has poor diabetes control as evaluated by the Investigator, including, but not limited to, a history of diabetic ketoacidosis (DKA) in the year prior to screening, frequent hypoglycemic episodes, or hypoglycemia unawareness.

• The subject is awaiting a pancreas transplant.

• The subject has incapacitating cardiac neurologic, peripheral vascular, or pulmonary disorders as determined by the Principal Investigator.

• The subject has a history of malignancy within the past 3 years (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the Investigator, along with the Medical Monitor, is considered treated with minimal risk of recurrence).

• The subject has documented clinical diagnosis of chronic hepatic disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] greater than 3 times the upper limit of normal) at the Screening Visit.

• The subject has a positive test result for the hepatitis B virus (HBV) surface antigen, a positive test result for hepatitis C virus (HCV) antibodies, or a positive test result for human immunodeficiency virus (HIV) antibodies.

Note: At the discretion of the Investigator, a subject who gives a history of a treated and cured HCV infection may be screened with a test for viral ribonucleic acid (RNA) and, if a cure is demonstrated, the subject may be enrolled.

• The subject has a documented clinical diagnosis of active tuberculosis (TB) requiring treatment.

• The subject is immunocompromised or is receiving immunosuppressive agents, including individuals treated for chronic glomerulonephritis within 3 months of the Screening Visit.

Note: Inhaled corticosteroids, chronic low-dose corticosteroids (less than or equal to 7.5 mg prednisone equivalent per day), and brief pulsed corticosteroids for intermittent symptoms (e.g., asthma) are permitted.

• The female subject is pregnant, lactating (breast feeding), or planning a pregnancy during the course of the study. Or the female subject is of childbearing potential and is not using a highly effective method(s) of birth control, including sexual abstinence. Or the female subject is unwilling to continue Note: A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than one percent per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or a vasectomized partner.using a highly effective method of birth control throughout the duration of the study.

• The subject has a history of active alcohol and/or drug abuse that, in the judgment of the Investigator, would impair the subject's ability to comply with the protocol.

• The subject's health status would, in the judgment of the Investigator, be jeopardized by participating in the study.

• The subject has used an investigational product within 3 months prior to the Screening Visit without receiving written consent from the study assigned Medical Monitor.

• The subject has previously received treatment with REACT.