R3R01 for Alport Syndrome

Recruiting at 26 trial locations

Overseen By Guido Magni, MD, PhD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests R3R01, a new drug that lowers fat in kidney cells to improve kidney function and reduce damage. It targets patients with Alport Syndrome and steroid-resistant FSGS who have high protein levels in their urine because their conditions are not improving with current treatments. Another drug has shown promise in reducing protein levels and kidney damage in animal studies.

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 the treatment R3R01 (bardoxolone methyl) safe for humans?

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 research articles. However, it is mentioned as a novel therapeutic approach under investigation, suggesting ongoing evaluation of its safety profile. ^{1 2 3 4 5}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• R3R01 (Unknown)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Egypt 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. [2021]

2. United States 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of Bardoxolone Methyl in Alport Syndrome. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Therapies for Alport Syndrome. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. [2022]