BMN 255 for Non-alcoholic Fatty Liver Disease

Recruiting at 6 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

Trial Summary

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.

What makes the drug BMN 255 unique for treating non-alcoholic fatty liver disease?

BMN 255 is a novel treatment option for non-alcoholic fatty liver disease, a condition for which no effective drugs have been developed yet. Unlike other treatments that focus on lifestyle changes or weight control, BMN 255 offers a new approach, although its specific mechanism of action or unique features compared to existing treatments are not detailed in the available research. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests the safety of BMN 255, an oral medication, in adults with NAFLD and hyperoxaluria. The goal is to see if it can reduce urine oxalate levels, potentially preventing kidney stones and other issues.

Research Team

Medical Director, MD

Principal Investigator

BioMarin Pharmaceutical

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

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

MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease. [2018]

3. Switzerland 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. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of therapeutic lifestyle program on ultrasound-diagnosed nonalcoholic fatty liver disease. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effect of orlistat on liver fat content in patients with nonalcoholic fatty liver disease with obesity: assessment using magnetic resonance imaging-derived proton density fat fraction. [2022]