MZE829 for Kidney Disease

Recruiting at 84 trial locations

Overseen By Maze Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Maze Therapeutics

Disqualifiers: Transplantation, Cancer, Bariatric surgery, Diabetes, 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

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MZE829, a potential drug for individuals with a specific type of chronic kidney disease. The trial aims to determine the safety of MZE829, its tolerability, and its effectiveness in reducing albuminuria, a condition characterized by excessive protein in the urine. The trial includes two groups: one for participants with kidney disease and diabetes, and another for those with kidney disease without diabetes. Suitable candidates have a high-risk APOL1 gene type and ongoing kidney issues with high protein levels in their urine. 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 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 there any evidence suggesting that MZE829 is likely to be safe for humans?

Research shows that MZE829 is being tested for safety and tolerability. In earlier studies, healthy adults took MZE829 without major problems. This treatment is an oral pill designed to help with certain kidney diseases.

The earlier research found that most people tolerated MZE829 well, experiencing no severe reactions. Some had mild side effects, but serious ones were rare.

This trial is in the middle stage of testing (Phase 2), indicating that the treatment has shown some safety in earlier studies. However, researchers are still assessing its safety for people with kidney disease. ^{1 2 3 4 5}

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

Researchers are excited about MZE829 for kidney disease because it introduces a novel approach compared to current treatments like ACE inhibitors and angiotensin II receptor blockers. Unlike these standard options, which primarily focus on controlling blood pressure to slow kidney damage, MZE829 targets specific pathways involved in kidney inflammation and fibrosis, potentially offering more direct protection to kidney tissues. This unique mechanism could lead to improved outcomes for patients, especially those with chronic kidney disease both with and without diabetes.

What evidence suggests that MZE829 might be an effective treatment for kidney disease?

Research shows that MZE829 is a pill designed to block the APOL1 gene, which is linked to kidney disease. Studies suggest it could effectively treat kidney disease caused by this gene. Early results indicate that MZE829 may reduce the amount of albumin in urine, a marker of kidney damage, potentially slowing the progression of kidney disease. Positive initial data from human trials support its potential effectiveness and safety for individuals with this type of kidney disease. Participants in this trial will receive MZE829, with cohorts including those with chronic kidney disease, both with and without concurrent diabetes. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Maze Therapeutics

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• MZE829

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. ir.mazetx.com ir.mazetx.com/news-releases/news-release-details/maze-therapeutics-present-additional-data-highlighting

Maze Therapeutics to Present Additional Data Highlighting ... MZE829 is an oral, small molecule APOL1 inhibitor in development as a potential best-in-class treatment for APOL1-mediated kidney disease (AMKD) ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06830629

A Phase 2 Study of MZE829 in Adults With APOL1 Kidney ... An open-label Phase 2 study is designed to evaluate the safety, tolerability, and effect on Albuminuria of MZE829 in Adults with Proteinuric Chronic Kidney ...

3. ir.mazetx.com ir.mazetx.com/news-releases/news-release-details/maze-therapeutics-reports-positive-first-human-data-phase-1

Maze Therapeutics Reports Positive First-in-Human Data ... MZE829 is an oral, small molecule inhibitor of APOL1 that Maze is advancing as a potential treatment for people living with APOL1 kidney disease ...

4. asn-online.org asn-online.org/education/kidneyweek/2024/program-abstract.aspx?controlId=4126492

Kidney Week MZE829 is a highly potent, small molecule inhibitor of APOL1 currently under investigation for the treatment of APOL1-mediated kidney disease (AMKD).

5. finance.yahoo.com finance.yahoo.com/news/maze-therapeutics-present-additional-data-120000410.html

Maze Therapeutics to Present Additional Data Highlighting ... MZE782 is a novel, oral SLC6A19 inhibitor with the potential to be a best-in-class therapy for patients with phenylketonuria (PKU), an inherited ...

6. journals.lww.com journals.lww.com/jasn/fulltext/2024/10001/a_phase_1_study_in_healthy_adults_of_the_safety,.941.aspx?utm_source=chatgpt.com

A Phase 1 Study in Healthy Adults of the Safety,... MZE829 is a highly potent, small molecule inhibitor of APOL1 currently under investigation for the treatment of APOL1-mediated kidney disease (AMKD).

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-mze829-for-adults-with-apol1-kidney-disease/

Study of MZE829 capsules for adults with APOL1 kidney ... The purpose of this research is to evaluate how safe and well-tolerated MZE829 is in adults who have kidney disease with high levels of protein ...

8. ctv.veeva.com ctv.veeva.com/study/a-phase-2-study-of-mze829-in-adults-with-apol1-kidney-disease

A Phase 2 Study of MZE829 in Adults With APOL1 Kidney ... An open-label Phase 2 study is designed to evaluate the safety, tolerability, and effect on Albuminuria of MZE829 in Adults with Proteinuric Chronic Kidney ...