BMN 255 for Non-alcoholic Fatty Liver Disease

No longer recruiting at 7 trial locations

Overseen By Trial Specialist

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BioMarin Pharmaceutical

Must be taking: Oral antihypertensives, oral AHAs

Must not be taking: Insulin, GLP-1 agonists

Disqualifiers: Primary hyperoxaluria, IBD, NASH, others

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BMN 255 to determine its safety and effectiveness for individuals with non-alcoholic fatty liver disease (NAFLD) who also have high levels of oxalate in their urine (hyperoxaluria). Participants will receive either BMN 255 or a placebo to compare effects. This trial suits individuals diagnosed with NAFLD, who have a history of kidney stones, and who experience hyperoxaluria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using most prescription medications 14 days before starting, except for certain oral medications for controlled hypertension, dyslipidemia, and diabetes, which you must have been taking consistently for 12 weeks before the trial. If you are on insulin, certain diabetes medications, or high doses of vitamin E, you cannot participate.

Is there any evidence suggesting that BMN 255 is likely to be safe for humans?

Research shows that BMN 255 is being tested for safety in people with non-alcoholic fatty liver disease (NAFLD) and high levels of oxalate in the urine (hyperoxaluria). This Phase 1 trial aims to determine how well participants tolerate the treatment and identify any side effects.

Phase 1 trials typically mark the first time a treatment is tested in humans, focusing primarily on safety. Detailed safety information might not yet be available. However, reaching this stage indicates that earlier lab or animal studies have shown enough promise to warrant human testing.

If BMN 255 performs well in Phase 1, it may be safe enough for testing in larger groups. Currently, researchers are monitoring for immediate side effects and how the body processes the drug. Participation in this study helps researchers learn more about the safety of BMN 255 for individuals with NAFLD and hyperoxaluria. ^{1 2 3 4 5}

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

Researchers are excited about BMN 255 for non-alcoholic fatty liver disease (NAFLD) because it offers a fresh approach compared to existing treatments like lifestyle changes and medications aimed at managing symptoms or related conditions. Unlike standard treatments, BMN 255 is an investigational drug that is administered orally and is being tested for its potential to quickly improve liver health. This drug targets the underlying causes of NAFLD, rather than just alleviating symptoms, which could lead to more effective management of the disease. While most treatments can take weeks or longer to show benefits, BMN 255 might offer improvements in just a few days, making it a promising option for patients.

What evidence suggests that BMN 255 might be an effective treatment for NAFLD?

Research suggests that BMN 255, which participants in this trial may receive, may help reduce high levels of oxalate in the urine for people with non-alcoholic fatty liver disease (NAFLD) and hyperoxaluria. Hyperoxaluria refers to having too much oxalate in the urine, which can lead to kidney stones. BMN 255 is designed to lower this excess oxalate. Early study results indicate that similar treatments have improved related health issues by reducing harmful substances in the body. Although more research is needed to confirm its effectiveness, BMN 255 shows promise because it addresses the root of the problem. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

BioMarin Pharmaceutical

Are You a Good Fit for This Trial?

This trial is for adults with Non-Alcoholic Fatty Liver Disease (NAFLD) and Hyperoxaluria, evidenced by high urine oxalate levels and a history of kidney stones. Participants must not have NASH or cirrhosis, inflammatory bowel disease, significant other medical conditions, or be on certain medications. They should have a liver fat content ≥ 8% confirmed by Fibroscan or MRI-PDFF.

Inclusion Criteria

I have had at least one kidney stone but no family history of specific stone types.

My body excretes a high amount of oxalate in urine, confirmed by two tests.

Contraceptive use by men and women use throughout the study period

Exclusion Criteria

I have or had inflammatory bowel disease or chronic issues absorbing fat.

I only use approved medications for hypertension, cholesterol, or diabetes and do not use insulin or specific diabetes drugs.

I have no major health issues apart from Type II diabetes, which is under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive either BMN 255 or placebo for 7 days

7 days

Day 1, Day 7 (in-person)

Washout

Participants undergo a washout period between treatment periods

7-9 days

Treatment Period 2

Participants receive the alternate treatment (BMN 255 or placebo) for 7 days

7 days

Day 1, Day 7 (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 days

What Are the Treatments Tested in This Trial?

Interventions

• BMN 255
• Placebo

Trial Overview The study tests the safety and effectiveness of BMN 255 in reducing urine oxalate levels compared to a placebo. It involves daily oral doses of BMN 255 for participants with NAFLD and hyperoxaluria to see if it can improve their condition.

How Is the Trial Designed?

Group I: BMN 255 Investigational drug arm Experimental Treatment 1 Intervention

Oral administration of BMN 255 at a dose of 100mg per day for 7 days in Treatment Period 1 or 2

Group II: Placebo Comparative drug arm Placebo Group 1 Intervention

Oral administration of Placebo at a dose of 100mg per day for 7 days in Treatment Period 1 or 2

Who Is Running the Clinical Trial?

BioMarin Pharmaceutical

Lead Sponsor

Trials

162

Recruited

115,000+

Alexander Hardy

BioMarin Pharmaceutical

Chief Executive Officer since 2023

MBA from INSEAD

Greg Friberg

BioMarin Pharmaceutical

Chief Medical Officer

MD from New York Medical College

Published Research Related to This Trial

In a study of 187 participants with nonalcoholic steatohepatitis (NASH) receiving placebo treatment, 20% showed a significant reduction in liver fat content (PDFF) after 12 weeks, highlighting a notable 'placebo effect' that can impact trial outcomes.

The analysis revealed an average decrease of 2.3 units in absolute PDFF values after 24 weeks of placebo treatment, suggesting that future clinical trials should account for this effect when calculating sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Nedrud, MA., Chaudhry, M., Middleton, MS., et al.[2023]

A systematic review of 11 randomized controlled trials involving 936 middle-aged individuals found that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduced liver fat content and serum liver enzyme levels in patients with nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH) over a median treatment duration of 26 weeks.

GLP-1 RAs, particularly liraglutide and semaglutide, also showed greater histological resolution of NASH without worsening liver fibrosis, indicating their potential as effective treatments for these liver conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Mantovani, A., Petracca, G., Beatrice, G., et al.[2021]

A 10-week diet plus exercise program significantly improved liver health and overall fitness in patients with nonalcoholic fatty liver disease (NAFLD), showing better results than exercise alone.

While both diet-plus-exercise and exercise-only programs improved health markers like body weight and insulin sensitivity, only the diet-plus-exercise group showed significant improvements in liver biochemistry, highlighting its greater efficacy in treating NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapeutic lifestyle program on ultrasound-diagnosed nonalcoholic fatty liver disease. Chen, SM., Liu, CY., Li, SR., et al.[2022]

Citations

1. clinicaltrials.biomarin.com clinicaltrials.biomarin.com/clinical-trial/a-study-of-bmn-255-in-participants-with-non-alcoholic-fatty-liver-disease-and-hyperoxaluria/

A Study of BMN 255 in Participants With Non-Alcoholic ... The purpose of this study is to test the safety of BMN 255 and to learn about the effect BMN 255 has on you and your hyperoxaluria ...

2. withpower.com withpower.com/trial/phase-1-liver-diseases-8-2023-1915d

BMN 255 for Non-alcoholic Fatty Liver Disease A 10-week diet plus exercise program significantly improved liver health and overall fitness in patients with nonalcoholic fatty liver disease (NAFLD), showing ...

3. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT06138327?keyword=%22MASLD%22

A Study of BMN 255 in Participants With Non-Alcoholic ... The purpose of this study is to test the safety of BMN 255 and to learn about the effect BMN 255 has on you and your hyperoxaluria associated with NAFLD, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9884828/

Advancements in the treatment of non-alcoholic fatty liver ... MD could improve overweight and visceral obesity, reduce hepatic steatosis, and reduce liver cirrhosis in NAFLD patients (12–14). It could also ...

5. barchart.com barchart.com/story/news/30493448/nonalcoholic-fatty-liver-disease-pipeline-2024-key-companies-moa-roa-and-clinical-trials-evaluation-by-delveinsight-eli-lilly-and-company-pfizer-boehringer-ingelheim-astrazeneca-inventiva

Non-Alcoholic Fatty Liver Disease Pipeline 2024 The MAESTRO-NASH OUTCOMES study is a double-blind, randomized, placebo-controlled Phase III trial that includes 845 patients with compensated NASH cirrhosis and ...

6. synapse.patsnap.com synapse.patsnap.com/drug/4aee424a0100401f8dd5039efdb802fa

BMN-255 - Drug Targets, Indications, Patents ... BMN 255 in Participants With Non-Alcoholic Fatty Liver Disease (NAFLD) And Hyperoxaluria. 100 Clinical Results associated with BMN-255. Login to view more data.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12321477/

MASLD development: From molecular pathogenesis toward ... Metabolic dysfunction-associated steatotic liver disease (MASLD) comprises a spectrum of liver injuries, including steatosis to steatohepatitis ...

8. go.drugbank.com go.drugbank.com/conditions/DBCOND0161012

Metabolic Dysfunction-associated Steatohepatitis (MASH) ... A Study of BMN 255 in Participants With Non-Alcoholic Fatty Liver Disease And Hyperoxaluria ... Safety and Efficacy of HL Tablet in Non-alcoholic Fatty Liver ...