MZE829 for Kidney Disease

Recruiting at 21 trial locations

Overseen By Maze Therapeutics

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Maze Therapeutics

Disqualifiers: Transplantation, Cancer, Bariatric surgery, Diabetes, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is purpose of this study is to evaluate the safety, tolerability, and effect on Albuminuria of MZE829 in Adults with APOL1 Kidney Disease

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is MZE829 (mizoribine) generally safe for humans?

Mizoribine (MZR), which may be related to MZE829, has been used in various studies for kidney-related conditions and has generally been found to be safe without serious adverse effects. It has been tested in conditions like lupus nephritis and kidney transplantation, showing no major safety concerns. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Maze Therapeutics

Eligibility Criteria

This clinical trial is for adults with a specific genetic risk (APOL1 high-risk genotype) for kidney disease who have chronic kidney disease with persistent albuminuria. It's not open to those who've had organ or bone marrow transplants, are pregnant or nursing, have conditions affecting drug absorption like past bariatric surgery, recent cancer history except certain low-risk types, or Type I diabetes.

Inclusion Criteria

I have a high-risk APOL1 genotype.

I have long-term kidney disease with ongoing protein in my urine.

Exclusion Criteria

I have had an organ or bone marrow transplant.

Pregnant or currently nursing

I have a condition that could change how drugs are absorbed, like a history of weight loss surgery.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MZE829 to evaluate safety, tolerability, and effect on albuminuria

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MZE829 (Other)

Trial Overview The study is testing MZE829 to see if it's safe and can be tolerated by patients. It also aims to find out how well the drug reduces protein in the urine (albuminuria), which is common in APOL1 kidney disease.

Participant Groups

Group I: MZE829 Experimental Treatment 1 Intervention

Cohort 1: Chronic kidney disease with concurrent diabetes Cohort 2: Chronic kidney disease without concurrent diabetes

Who Is Running the Clinical Trial?

Maze Therapeutics

Lead Sponsor

Trials

2

Recruited

180+

Findings from Research

In a study of 884 patients with primary proteinuric kidney disease, 60% were treated with steroids, and 62% of these patients experienced at least one steroid-associated adverse event (SAAE), with a frequency of 293 per 1000 person-years.

Steroid treatment was linked to a 40% increased risk of any SAAE, with higher doses significantly raising the risk; a 1-mg/kg per day increase in steroid dose resulted in a 2.5-fold increase in SAAE risk, highlighting the need for careful monitoring and potential steroid minimization strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroid-Associated Side Effects in Patients With Primary Proteinuric Kidney Disease. Oh, GJ., Waldo, A., Paez-Cruz, F., et al.[2022]

Mizoribine (MZR) showed similar efficacy to mycophenolate mofetil (MMF) in preventing acute rejection episodes in kidney transplant patients, with a noninferior rate of biopsy-proven acute rejection (6.4% for MZR vs 1.8% for MMF).

While MZR was effective, it was associated with a significant increase in uric acid levels compared to MMF, indicating a potential safety concern that needs to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mizoribine versus mycophenolate mofetil in combination therapy with tacrolimus for de novo kidney transplantation: evaluation of efficacy and safety. Ju, MK., Huh, KH., Park, KT., et al.[2017]

In a clinical study involving 11 lupus nephritis patients in China, mizoribine (MZR) demonstrated a high remission rate of 72.7% after 6 months, with significant reductions in proteinuria, indicating its efficacy as a treatment option.

No adverse events were reported during the study, suggesting that MZR is a safe option for inducing remission in lupus nephritis, even for patients who did not respond to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of the efficacy of mizoribine in lupus nephritis in Chinese patients. Zhang, M., Xing, CY., Liu, J.[2022]

In a pharmacokinetic study involving 9 patients with child-onset glomerulonephritis, mizoribine (MZR) was administered at doses of 60-300 mg/day, showing a peak serum concentration reached in about 2.94 hours and a half-life of approximately 1.96 hours.

The study provided important pharmacokinetic parameters for MZR, indicating a significant urinary excretion rate of 49.1%, which may help optimize treatment strategies for pediatric patients with glomerulonephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic study of mizoribine in child-onset glomerulonephritis. Abe, Y., Mikawa, T., Fuke, T., et al.[2017]

In a study of 40 kidney transplant patients, high-dose Mizoribine (6 mg/kg/day) combined with cyclosporine and other immunosuppressants achieved a 100% graft survival rate over two years, comparable to the 94.7% rate in the control group using mycophenolate mofetil.

The MZR group had a significantly lower incidence of cytomegalovirus (CMV) disease (0%) compared to the MMF group (18.4%), indicating that high-dose MZR may provide effective immunosuppression with a reduced risk of viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The beneficial effect of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroids on CMV infection in renal transplant recipients. Yoshimura, N., Ushigome, H., Akioka, K., et al.[2021]

References

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

Steroid-Associated Side Effects in Patients With Primary Proteinuric Kidney Disease. [2022]

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

Mizoribine versus mycophenolate mofetil in combination therapy with tacrolimus for de novo kidney transplantation: evaluation of efficacy and safety. [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

Study of the efficacy of mizoribine in lupus nephritis in Chinese patients. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Pharmacokinetic study of mizoribine in child-onset glomerulonephritis. [2017]

5. Japan pubmed.ncbi.nlm.nih.gov

The beneficial effect of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroids on CMV infection in renal transplant recipients. [2021]