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

Kidney Stone Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06138327
• Other study ID #: 255-102
• Status: Recruiting
• Phase: Phase 1
• Start date: September 26, 2023
• Est. completion date: October 2024

Study information

• Verified date: November 2023
• Source: BioMarin Pharmaceutical
• Contact: Trial Specialist
• Phone: 1-800-983-4587
• Email: medinfo[@]bmrn.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: October 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Hyperoxaluria
• Kidney Calculi
• Kidney Stone
• Liver Diseases
• Nephrolithiasis
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease

Intervention

Drug:
• BMN 255
Oral Capsule
• Placebo
Oral Capsule

Locations

Country	Name	City	State
United States	University of Alabama - Department of Urology	Birmingham	Alabama
United States	ProSciento, Inc.	Chula Vista	California
United States	ProSciento, Inc.	Chula Vista	Florida
United States	Medpace Clinical Pharmacology Unit	Cincinnati	Ohio
United States	Centricity Research	Columbus	Ohio
United States	Prolato Clinical Research Center	Houston	Texas
United States	Georgia Clinical Research, LLC	Lawrenceville	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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