REACT for Chronic Kidney Disease

Overseen By Tierney Daigle

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Prokidney

Must be taking: Antihypertensives

Disqualifiers: Renal transplantation, Dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety of administering additional REACT injections to individuals with chronic kidney disease (CKD) who previously received REACT. REACT uses a person's own cells to support kidney function. Participants will receive two injections, spaced six months apart, and will be monitored for a year following the final injection. This trial may suit individuals who participated in a previous REACT study, still have CKD, but do not require dialysis. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants an opportunity to contribute to groundbreaking medical research.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antihypertensive medication, you must be on a stable regimen.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that REACT, or Renal Autologous Cell Therapy, has been tested in other studies to assess its safety for humans. In one study, patients received REACT injections directly into their kidneys to evaluate both the safety and effectiveness of these injections.

Previous patients generally tolerated the treatment well. Some unwanted side effects occurred, but they were not severe for most people. This indicates that while some may experience mild side effects, the treatment usually does not cause serious health problems.

Since the current trial is in the early stages, the main goal is to ensure safety. Early trials focus on this to confirm the treatment is not harmful before progressing to larger studies. Overall, earlier research has shown REACT to have a promising safety profile, but ongoing monitoring of its effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic kidney disease?

Unlike the standard treatments for chronic kidney disease, which often include medications like ACE inhibitors or dialysis to manage symptoms and slow progression, REACT (Renal Autologous Cell Therapy) offers a novel approach by using the patient's own cells to potentially regenerate kidney tissue. This treatment is unique because it involves two injections of autologous cells that might help repair and improve kidney function, a mechanism not seen in current therapies. Researchers are excited about REACT because of its potential to not just manage but actually improve kidney health, offering hope for more sustainable and effective outcomes for patients.

What evidence suggests that REACT might be an effective treatment for chronic kidney disease?

Research shows that REACT, which stands for Renal Autologous Cell Therapy, could benefit people with chronic kidney disease (CKD). Studies have found that REACT can repair damaged kidney cells, potentially stabilizing or even improving kidney function. In some trials, patients who received REACT injections experienced a slower progression to end-stage kidney disease. This therapy uses the patient's own cells to naturally restore kidney health. Early results suggest it could significantly improve outcomes for those with CKD. ^{1 2 4 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Prokidney

Are You a Good Fit for This Trial?

This trial is for adults aged 30-80 with chronic kidney disease who've had REACT treatment before. They must have stable blood pressure, possibly managed by medication, and not need dialysis yet. People can't join if they've been on dialysis over 30 days, tried other new treatments recently, have very high protein in their urine, a past kidney transplant or low hemoglobin unresponsive to anemia treatment.

Inclusion Criteria

My blood pressure is stable, and if I take medication for it, the dose hasn't changed recently.

You have been in a previous trial for chronic kidney disease and finished all follow-up appointments.

My kidney function is low but I don't need dialysis.

Exclusion Criteria

I have been on dialysis for over a month.

The participant has received any other investigational products after completion of REACT injections within 3 months of screening.

Your urine test shows a very high level of albumin compared to creatinine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 REACT injections separated by 6 months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• REACT

Trial Overview The study tests the safety of additional REACT injections in people with chronic kidney disease who previously received this therapy. It aims to see how well patients tolerate more doses of the same treatment they had earlier.

How Is the Trial Designed?

Group I: Renal Autologous Cell Therapy (REACT) Experimental Treatment 1 Intervention

Participants will receive 2 REACT injections separated by 6 months. All participants will be followed for 12 months post last supplemental REACT injection.

REACT is already approved in United States, European Union for the following indications:

Approved in United States as REACT for:

• Moderate to severe diabetic kidney disease

Approved in European Union as REACT for:

• Moderate to severe diabetic kidney disease

Who Is Running the Clinical Trial?

Prokidney

Lead Sponsor

Trials

10

Recruited

880+

Published Research Related to This Trial

High-dose immunosuppression followed by autologous haematopoietic stem cell therapy can lead to major clinical responses in about 65% of systemic lupus erythematosus (SLE) patients, with some experiencing durable effects for several years.

While earlier studies reported procedure-related mortality rates of up to 12%, recent larger studies show this has decreased to less than 5%, indicating improved safety in newer transplantation regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood stem cells as therapy for severe lupus. Illei, GG., Pavletic, SZ.[2019]

A multimodal intervention targeting urinary protein levels in 56 patients with heavy proteinuria led to a significantly slower decline in kidney function (GFR) compared to a matched historical group, with a median decline of -0.17 ml/min versus -0.56 ml/min over 4 years.

The intervention also resulted in a much lower incidence of end-stage renal disease (ESRD), with only 3.6% of patients reaching ESRD compared to 30.4% in the conventional therapy group, demonstrating the efficacy of proteinuria reduction in preserving kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of remission clinics in the longitudinal treatment of CKD. Ruggenenti, P., Perticucci, E., Cravedi, P., et al.[2022]

In a study of 178 lupus nephritis patients treated primarily with cyclophosphamide, 84.8% achieved a renal response, highlighting the efficacy of this treatment approach over 23 years.

Achieving a complete or partial renal response significantly improves both patient and kidney survival rates, with 15-year survival rates of 95% for complete responders compared to only 35% for nonresponders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive Treatment for Lupus Nephritis: Long-Term Results in 178 Patients. Zakharova, EV., Makarova, TA., Zvonova, EV., et al.[2018]

Autologous hematopoietic cell transplantation (ASCT) showed promising long-term outcomes for patients with refractory lupus nephritis (LN), with 90% renal survival and 100% overall survival over a 10-year follow-up period for the 20 patients studied.

Eighteen out of 20 patients achieved complete remission after ASCT, indicating that this treatment can effectively improve immunologic homeostasis in refractory LN, although a relapse rate of 45% was observed, necessitating further management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of autologous peripheral blood hematopoietic stem cell transplantation for refractory lupus nephritis-a series study of 20 patients. Yang, L., Ren, G., Chen, W., et al.[2022]

The REACT trial, involving 5 adults with congenital anomalies of the kidney and urinary tract (CAKUT) and chronic kidney disease (CKD) stages 3 and 4, shows promising safety with no complications related to the cell acquisition or injection procedures.

Preliminary results suggest that Renal Autologous Cell Therapy may stabilize or improve renal function, potentially delaying the need for dialysis in patients with CAKUT-associated CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol and Baseline Data on Renal Autologous Cell Therapy Injection in Adults with Chronic Kidney Disease Secondary to Congenital Anomalies of the Kidney and Urinary Tract. Stavas, J., Diaz-Gonzalez de Ferris, M., Johns, A., et al.[2022]

The REACT trial is a phase II multicenter study involving 83 adults with type 2 diabetic kidney disease (T2DKD), aiming to assess the safety and efficacy of a novel renal autologous cell therapy delivered via direct kidney injection to improve renal function.

The study will measure changes in estimated glomerular filtration rates (eGFR) over 24 months, comparing an active treatment group receiving REACT injections to a deferred treatment group, with a focus on monitoring for any adverse events related to the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Renal Autologous Cell Therapy for Type 2 Diabetes Mellitus Chronic Diabetic Kidney Disease: Clinical Trial Design. Stavas, J., Gerber, D., Coca, SG., et al.[2022]

In a study involving 22 adults with advanced type 2 diabetes-related chronic kidney disease (D-CKD), injections of autologous selected renal cells (SRCs) significantly improved the annualized estimated glomerular filtration rate (eGFR) slope from -4.63 to -1.69 ml/min per 1.73 m² per year, indicating a stabilization of kidney function after treatment.

The analysis of SRCs revealed cell markers associated with kidney development, suggesting that these cells may play a role in halting the progression of D-CKD, with no direct adverse effects linked to the injections or the REACT product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal Autologous Cell Therapy to Stabilize Function in Diabetes-Related Chronic Kidney Disease: Corroboration of Mechanistic Action With Cell Marker Analysis. Stavas, J., Filler, G., Jain, D., et al.[2022]

The STEADFAST study is a first-in-human trial assessing the safety and efficacy of TX200-TR101, a novel CAR-Treg therapy, in up to 15 living-donor renal transplant recipients, with a follow-up period of 84 weeks.

TX200-TR101 aims to enhance immunologic tolerance and prevent graft rejection in HLA-A∗02-mismatched kidney transplants, building on previous findings that Tregs are safe in renal transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study Design: Human Leukocyte Antigen Class I Molecule A∗02-Chimeric Antigen Receptor Regulatory T Cells in Renal Transplantation. Schreeb, K., Culme-Seymour, E., Ridha, E., et al.[2022]

The REACT trial, involving 10 adults with late-stage diabetic chronic kidney disease, demonstrated that autologous cell therapy is safe, with no cell-related adverse events reported and only minor procedure-related complications.

Participants experienced a delay in the need for dialysis by an average of 16 months, and 20% of patients showed stability in kidney function, suggesting that REACT may effectively stabilize renal function in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal Autologous Cell Therapy in Type 2 Diabetes with Late Stage 4 Diabetes-Related Chronic Kidney Disease: Trial Design and Early Analysis. Stavas, J., Thajudeen, B., Coca, S., et al.[2023]

A 26-year-old patient with severe lupus nephritis and nephrotic syndrome achieved complete clinical and immunologic remission five years after undergoing autologous peripheral stem cell transplantation (ASCT).

The case highlights ASCT as a powerful treatment option for patients with severe systemic lupus erythematosus (SLE), demonstrating its potential efficacy in managing refractory cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term complete remission of severe nephrotic syndrome secondary to diffuse global (IV-G) lupus nephritis following autologous, haematopoietic peripheral stem (CD34+) cell transplantation. Marmont, AM., Gualandi, F., van Lint, MT., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11151988/

Rilparencel (Renal Autologous Cell Therapy-REACT®) for ... This multicenter phase 2 RCT is designed to investigate the efficacy and safety of rilparencel with bilateral kidney dosing and compare two injection schedules.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05018416

NCT05018416 | Study of Renal Autologous Cell Therapy ... The purpose of this study is to assess the safety, efficacy, and durability of up to two REACT injections delivered percutaneously into biopsied and non- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03270956

NCT03270956 | A Study of Autologous Renal ... A Study of Autologous Renal Autologous Cell Therapy (REACT) in Patients With Diabetic Chronic Kidney Disease. ClinicalTrials.gov ID NCT03270956. Sponsor ...

4. investors.prokidney.com investors.prokidney.com/news-releases/news-release-details/prokidney-reports-statistically-and-clinically-significant

Releases Details ProKidney's lead product candidate, rilparencel (also known as REACT®), is a first-in-class, patented, proprietary autologous cellular therapy ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2468024923004795

WCN23-0428 RENAL AUTOLOGOUS CELL THERAPY ... Cell-based therapies may repair diseased nephrons and stabilize and enhance kidney function to delay the onset of end-stage kidney disease and improve ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38423000/

Rilparencel (Renal Autologous Cell Therapy-REACT®) for ... This multicenter phase 2 RCT is designed to investigate the efficacy and safety of rilparencel with bilateral kidney dosing and compare two ...