R3R01 for Alport Syndrome

No longer recruiting at 28 trial locations

Overseen By Guido Magni, MD, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: River 3 Renal Corp.

Must be taking: ACEi, ARB

Must not be taking: Bardoxolone, Rituximab, Cyclophosphamide, others

Disqualifiers: Uncontrolled diabetes, Hypertension, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of the drug R3R01 for individuals with Alport Syndrome who have high levels of protein in their urine despite standard treatments. Alport Syndrome is a genetic condition that can lead to kidney problems. The study will also include individuals with Focal Segmental Glomerulosclerosis (FSGS), a condition affecting kidney function that is difficult to treat with steroids. Participants must have a confirmed diagnosis of Alport Syndrome or FSGS and experience ongoing kidney-related issues despite current treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that patients continue their current ACE/ARB therapy at a stable dose for at least 4 weeks before and during the study. If you are taking steroids or SGLT2 inhibitors, those should also remain stable. However, you cannot use certain medications like bardoxolone, rituximab, cyclophosphamide, abatacept, or sparsentan during the trial.

Is there any evidence suggesting that R3R01 is likely to be safe for humans?

Research is examining the safety of R3R01 for individuals with Alport Syndrome and Focal Segmental Glomerulosclerosis (FSGS). Specific safety details from studies are not yet available. This trial is in an early stage (Phase 2), indicating that the treatment has shown some promise in earlier research, but more information is needed to fully understand its safety in humans.

Early-stage trials generally assess how well participants tolerate the treatment, including monitoring for any side effects. As R3R01 is still under investigation, participants receive close monitoring to quickly identify and manage any adverse effects. Considering participation means contributing to important research that helps determine if this treatment is safe and effective. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alport Syndrome?

Unlike the standard treatments for Alport Syndrome, which often involve managing symptoms with medications like ACE inhibitors or ARBs, R3R01 offers a fresh approach. R3R01 is an oral medication that targets the condition directly, potentially providing more precise control over the disease's progression. Researchers are particularly excited about its unique mechanism of action, which may offer benefits beyond current options by addressing underlying disease processes more effectively. This novel approach could lead to better outcomes for patients who have had limited options until now.

What evidence suggests that R3R01 might be an effective treatment for Alport Syndrome?

Research has shown that R3R01 might help treat Alport Syndrome, a genetic kidney disorder. In this trial, participants with Alport Syndrome will receive R3R01. Early findings suggest that R3R01 works by reducing proteinuria, a common issue in Alport Syndrome where too much protein leaks into the urine. Lowering protein levels in urine could help protect kidney function over time. Initial studies also indicated improvements in kidney health for patients taking R3R01. These promising results offer hope for better management of Alport Syndrome symptoms. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with Alport Syndrome or Focal Segmental Glomerulosclerosis who have uncontrolled proteinuria despite ACE/ARB therapy. Participants must be willing to follow study procedures and use contraception. Exclusions include uncontrolled diabetes, hypertension, recent investigational drug use, organ transplant recipients, active infections including COVID-19, and certain medication restrictions.

Inclusion Criteria

I agree to use condoms and will inform the investigator if my partner becomes pregnant during the study.

My condition did not improve or had side effects after long-term steroid use.

All Patients: Patient is able to communicate well with the investigator, understands and is willing to comply with all requirements of the study, and understands and signs the written informed consent form (ICF).

Exclusion Criteria

Females that are lactating.

Patient is not suitable to participate in the study for any reason (including, but not limited to co-morbidities, history of non-compliance with study visits, procedures, or drug administration) in the opinion of the investigator.

History of non-compliance such that patient is unlikely to be compliant with study visits, procedures or drug administration.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive R3R01 orally as 200 mg tablets twice daily for 84 days

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• R3R01

Trial Overview The trial is testing R3R01's safety, tolerability, efficacy, and how the body processes it in patients with Alport Syndrome or Focal Segmental Glomerulosclerosis. It's an open-label Phase 2 study where all participants will receive the experimental drug without a placebo comparison.

How Is the Trial Designed?

Group I: Cohort 3 (Focal Segmental Glomerulosclerosis Patients) Experimental Treatment 1 Intervention

R3R01 administered orally as 200 mg tablets twice daily for the 84 days.

Group II: Cohort 2 (Alport Syndrome Patients) Experimental Treatment 1 Intervention

R3R01 administered orally as 200 mg tablets twice daily for 84 days.

Who Is Running the Clinical Trial?

River 3 Renal Corp.

Lead Sponsor

Trials

2

Recruited

110+

Published Research Related to This Trial

In a study involving 157 patients with Alport syndrome, bardoxolone methyl demonstrated significant preservation of kidney function (eGFR) compared to placebo over 100 weeks, indicating its potential efficacy in managing this condition.

While bardoxolone methyl showed benefits in maintaining eGFR, it was associated with more treatment discontinuations due to increases in liver enzymes, highlighting the need for careful monitoring of safety in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Bardoxolone Methyl in Alport Syndrome. Warady, BA., Pergola, PE., Agarwal, R., et al.[2023]

The EARLY PRO-TECT Alport trial is a phase III study involving 120 pediatric patients with early stages of Alport syndrome, aiming to assess the safety and efficacy of ramipril, an ACE inhibitor, in delaying disease progression.

The primary endpoints of the trial include measuring the time to progression to the next disease level and the incidence of adverse drug events, which will provide crucial evidence for the use of ACE inhibitors in treating pediatric patients with kidney diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients. Gross, O., Friede, T., Hilgers, R., et al.[2021]

Alport syndrome (AS) is a hereditary kidney disease caused by mutations in type IV collagen genes, leading to kidney failure, and is often underrecognized in patients with chronic kidney disease (CKD).

Current treatments, such as RAAS inhibitors like ramipril, have been shown to delay the progression of kidney disease and are safe for use in children, while novel therapies targeting various pathways are being investigated to further improve outcomes for AS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Therapies for Alport Syndrome. Chavez, E., Rodriguez, J., Drexler, Y., et al.[2022]

Genetic testing is recommended as the gold standard for diagnosing Alport syndrome, which helps determine its mode of inheritance and identify affected family members, particularly in cases of X-linked Alport syndrome.

For males with X-linked Alport syndrome and individuals with autosomal recessive disease, early treatment with renin-angiotensin system blockers is advised, potentially before symptoms like proteinuria appear, to help manage the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. Savige, J., Gregory, M., Gross, O., et al.[2022]

A randomized, placebo-controlled trial involving 66 children with Alport syndrome showed that ramipril therapy was safe, with no significant adverse drug reactions reported over 216.4 patient-years.

While not statistically significant, ramipril appeared to reduce the risk of disease progression by nearly 50%, suggesting it may effectively slow the progression of renal failure in children with Alport syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, randomized, placebo-controlled, double-blind phase 3 trial with open-arm comparison indicates safety and efficacy of nephroprotective therapy with ramipril in children with Alport's syndrome. Gross, O., Tönshoff, B., Weber, LT., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05267262

Study to Evaluate R3R01 in Patients With Alport Syndrome ... This is a Phase 2, Multi-center, Open-Label Study to Assess Safety, Tolerability, Efficacy and Pharmacokinetics of R3R01 in Alport Syndrome Patients with ...

2. clinicaltrials.eu clinicaltrials.eu/inn/r3r01/

R3R01: A Promising New Drug for Kidney Diseases This article provides an overview of the ongoing research on R3R01, focusing on its potential benefits for patients with Alport Syndrome, Focal Segmental ...

3. nephcure.org nephcure.org/trials/r3r-asfsgs-trial-amsterdam-netherlands/

R3R ASFSGS Trial- Amsterdam, Netherlands A Phase II, Multi-center, Open-Label Study to Assess the Safety, Tolerability, Efficacy, and Pharmacokinetics of R3R01 in Alport Syndrome Patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11955716/

Systematic Review of Management Strategies for Alport ... Bardoxolone methyl, ramipril, and losartan demonstrated potential benefits in slowing renal disease progression in AS. Observational studies indicated that ...

5. trial.medpath.com trial.medpath.com/clinical-trial/496ff3baa838280b/euctr2021-004192-13-nl-r3r01-alport-syndrome-steroid-resistant-glomerulosclerosis

R3R01 in Alport Syndrome Patients and Primary Steroid ... All Patients: 1. Patient is able to communicate well with the investigator, understands and is willing to comply with all requirements of the study, and

6. nephcure.org nephcure.org/trials/r3r-asfsgs-trial-columbus-oh/

R3R ASFSGS Trial- Columbus, OH A Phase II, Multi-center, Open-Label Study to Assess the Safety, Tolerability, Efficacy, and Pharmacokinetics of R3R01 in Alport Syndrome Patients with ...

7. withpower.com withpower.com/trial/phase-2-focal-segmental-glomerulosclerosis-fsgs-2-2022-c43e3

R3R01 for Alport Syndrome · Info for Participants Bardoxolone methyl has been evaluated for safety in patients with Alport syndrome, but specific safety data from these studies are not detailed in the provided ...