Clinical trial NCT06138327: A Study of BMN 255 in Participants With Non-Alcoholic Fatty Liver Disease And Hyperoxaluria
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Hyperoxaluria
Nonalcoholic Fatty Liver Disease
Kidney Stone
Keywords: Kidney Stones
Nonalcoholic Fatty Liver Disease
Hyperoxaluria
NAFLD
MASLD
Metabolic Dysfunction-associated Steatotic Liver Disease
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The primary safety endpoint is the incidence of adverse events in adult participants with NAFLD and hyperoxaluria
timeFrame: 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:
measure: To characterize the daily oral dose plasma pharmacokinetics of BMN 255 in adult participants with NAFLD and hyperoxaluria.
timeFrame: 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
measure: To characterize the daily oral dose plasma pharmacokinetics of BMN 255 in adult participants with NAFLD and hyperoxaluria.
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Department of Urology
state: Alabama
city: Chula Vista
country: United States
facility: ProSciento, Inc.
state: California
city: Chula Vista
country: United States
facility: ProSciento, Inc.
state: Florida
city: Lawrenceville
country: United States
facility: Georgia Clinical Research, LLC
state: Georgia
city: Cincinnati
country: United States
facility: Medpace Clinical Pharmacology Unit
state: Ohio
city: Columbus
country: United States
facility: Centricity Research
state: Ohio
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Director, MD
role: STUDY_DIRECTOR
References: