A Study of BMN 255 in Participants With Non-Alcoholic Fatty Liver Disease And Hyperoxaluria

NCT06138327 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 255-102
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 7

Brief Summary

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, and compare these effects with a placebo. The primary safety objective of the study is to assess the safety and tolerability of daily oral doses of BMN 255 in adult participants with NAFLD and hyperoxaluria. The primary efficacy objective of the study is to assess 24-hour urine oxalate levels (24-hour urine collection corrected for BSA) following daily oral doses of BMN 255 in adult participants with NAFLD and hyperoxaluria.

Conditions

Hyperoxaluria; Nonalcoholic Fatty Liver Disease; Kidney Stone

Keywords

Kidney Stones; Nonalcoholic Fatty Liver Disease; Hyperoxaluria; NAFLD; MASLD; Metabolic Dysfunction-associated Steatotic Liver Disease

Outcome Measures

Primary Outcomes (1)

• The primary safety endpoint is the incidence of adverse events in adult participants with NAFLD and hyperoxaluria

  \- Including but not limited to acute liver or kidney injury

  Treatment Periods 1 & 2 through a 15 day follow-up after period 2. Each treatment period is 7 days separated by a 7-9 day washout period.

Secondary Outcomes (2)

• To characterize the daily oral dose plasma pharmacokinetics of BMN 255 in adult participants with NAFLD and hyperoxaluria.

  Day 1, Day 7 of treatment periods 1 & 2, each treatment period is 7 days separated by a 7-9 day washout period and Day 15

• To characterize the daily oral dose plasma pharmacokinetics of BMN 255 in adult participants with NAFLD and hyperoxaluria.

  Day 1, Day 7 of treatment periods 1 & 2, each treatment period is 7 days separated by a 7-9 day washout period and Day 15

Study Arms (2)

BMN 255 Investigational drug arm

EXPERIMENTAL

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

Drug: BMN 255

Placebo Comparative drug arm

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

BMN 255 DRUG

Oral Capsule

BMN 255 Investigational drug arm

Placebo DRUG

Oral Capsule

Placebo Comparative drug arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of NAFLD with a liver fat content ≥ 8.0%, as determined by Fibroscan (transient elastography) or magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) during screening.
• History of kidney stones (at least 1 stone prior to screening based on medical history); participants with a known personal or family history of cystinuria or cystine kidney stones, calcium phosphate stones, struvite stones, or urate stones should not be included.
• Contraceptive use by men and women use throughout the study period
• Participants must be capable of giving signed informed consent

You may not qualify if:

• Clinical history (including family history) or genetic analyses consistent with primary hyperoxaluria (Type 1, 2, or 3).
• History or current evidence of inflammatory bowel disease (including, but not limited to: Crohn's disease, ulcerative colitis, celiac disease / gluten-sensitive enteropathy) or evidence of chronic fat malabsorption (steatorrhea) due to any cause (eg, pancreatic insufficiency).
• Significant history or clinical manifestation of any other allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator. Participants with Type II diabetes will be permitted to enroll but must meet the concomitant therapy requirements listed below.
• Use or intend to use any prescription medications/products within 14 days prior to Period 1 check-in, other than permitted oral medications to treat controlled hypertension, dyslipidemia and/or to lower triglycerides, and oral anti-hyperglycemic agents (AHAs), including, but not limited to, metformin, sulfonylureas, and dipeptidyl peptidase IV (DPP-IV) inhibitors, if approved by the investigator. Participants who require insulin injections, glucagon-like peptide-1 agonists, pioglitazone, or vitamin E ≥ 800 mg should not be included in the study.
• Note: Participants receiving lipid-modifying therapies and participants with controlled hypertension and/or diabetes must have been on a stable treatment regimen (medication, dose strength, dose interval) for 12 weeks prior to screening and no change in that regimen should be anticipated for the entire duration of this study (ie, from screening to final follow-up visit).
• Confirmed diagnosis or NASH or evidence of hepatic cirrhosis, based on clinical assessment (eg, physical examination), historical liver biopsy or other prior imaging study, or a liver stiffness value ≥ 14 kPa during the FibroScan® examination at screening.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (7)

University of Alabama - Department of Urology

Birmingham, Alabama, 35249, United States

Location

ProSciento, Inc.

Chula Vista, California, 91911, United States

Location

ProSciento, Inc.

Chula Vista Isles, Florida, 91911, United States

Location

Georgia Clinical Research, LLC

Lawrenceville, Georgia, 30044, United States

Location

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

Centricity Research

Columbus, Ohio, 43213, United States

Location

Prolato Clinical Research Center

Houston, Texas, 77054, United States

Location

MeSH Terms

Conditions

Hyperoxaluria; Non-alcoholic Fatty Liver Disease; Kidney Calculi

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases; Nephrolithiasis; Urolithiasis; Urinary Calculi; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Director, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: November 18, 2023
• Study Start: September 26, 2023
• Primary Completion: March 25, 2024
• Study Completion: March 25, 2024
• Last Updated: June 11, 2024

Record last verified: 2024-06

Locations

US (7)