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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hyperoxaluria, Nonalcoholic Fatty Liver Disease, Kidney Stone

Intervention / Treatment
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* Drug: BMN 255
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Stones, Nonalcoholic Fatty Liver Disease, Hyperoxaluria, NAFLD, MASLD, Metabolic Dysfunction-associated Steatotic Liver Disease