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

A Phase 1b, Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled, 2-Period Crossover Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of an Oral Administration of BMN 255 in Participants With Non-Alcoholic Fatty Liver Disease (NAFLD) And Hyperoxaluria

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.

Study Overview

• Status: Recruiting
• Conditions: Nonalcoholic Fatty Liver Disease; Kidney Stone; Hyperoxaluria
• Intervention / Treatment: Drug: Placebo; Drug: BMN 255

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Specialist; Phone Number: 1-800-983-4587; Email: medinfo@bmrn.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Recruiting
      • University of Alabama - Department of Urology
  • California
    • Chula Vista, California, United States, 91911
      • Recruiting
      • ProSciento, Inc.
  • Florida
    • Chula Vista, Florida, United States, 91911
      • Recruiting
      • ProSciento, Inc.
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • Recruiting
      • Georgia Clinical Research, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Recruiting
      • Medpace Clinical Pharmacology Unit
    • Columbus, Ohio, United States, 43213
      • Recruiting
      • Centricity Research
  • Texas
    • Houston, Texas, United States, 77054
      • Recruiting
      • Prolato Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Hyperoxaluria, as defined by 24-hour urine oxalate excretion ≥ 45 mg/24 hours/1.73m2 at 2 independent assessments during screening. The pre-dose 24-hour urine oxalate measure at Day 1 will be used for baseline but will not be required for inclusion in the study
3. 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.
4. Contraceptive use by men and women use throughout the study period
5. Participants must be capable of giving signed informed consent

Exclusion Criteria:

1. Clinical history (including family history) or genetic analyses consistent with primary hyperoxaluria (Type 1, 2, or 3).
2. 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).
3. 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.

4. 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).

5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMN 255 Investigational drug arm; Oral administration of BMN 255 at a dose of 100mg per day for 7 days in Treatment Period 1 or 2	Drug: BMN 255; Oral Capsule
Placebo Comparator: Placebo Comparative drug arm; Oral administration of Placebo at a dose of 100mg per day for 7 days in Treatment Period 1 or 2	Drug: Placebo; Oral Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the daily oral dose plasma pharmacokinetics of BMN 255 in adult participants with NAFLD and hyperoxaluria.	Area under the plasma concentration-time curve (AUC)	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.	Maximum observed concentration (Cmax)	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

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Medical Director, MD, BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2023
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Estimated): November 20, 2023

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: NAFLD; Nonalcoholic Fatty Liver Disease; Kidney Stones; Hyperoxaluria; MASLD; Metabolic Dysfunction-associated Steatotic Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Kidney Calculi; Nephrolithiasis
• Other Study ID Numbers: 255-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No