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

Sponsor

BioMarin Pharmaceutical (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06138327

Collaborator

(none)

Enrollment

Locations

Arms

12.2

Anticipated Duration (Months)

3.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyperoxaluria Nonalcoholic Fatty Liver Disease Kidney Stone	Drug: BMN 255 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 26, 2023

Anticipated Primary Completion Date :

Jul 31, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

The primary safety endpoint is the incidence of adverse events in adult participants with NAFLD and hyperoxaluria [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.]
- Including but not limited to acute liver or kidney injury

Secondary Outcome Measures

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]
Area under the plasma concentration-time curve (AUC)
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]
Maximum observed concentration (Cmax)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
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
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

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Department of Urology	Birmingham	Alabama	United States	35249
2	ProSciento, Inc.	Chula Vista	California	United States	91911
3	ProSciento, Inc.	Chula Vista	Florida	United States	91911
4	Georgia Clinical Research, LLC	Lawrenceville	Georgia	United States	30044
5	Medpace Clinical Pharmacology Unit	Cincinnati	Ohio	United States	45227
6	Centricity Research	Columbus	Ohio	United States	43213
7	Prolato Clinical Research Center	Houston	Texas	United States	77054