Study of BMN 349 Single Dose in PiZZ and PiMZ/MASH Adult Participants

Phase 1

Recruiting

• Conditions: Alpha 1-Antitrypsin Deficiency
• Interventions: Drug: BMN 349; Drug: Placebo

• Registration Number: NCT06738017
• Lead Sponsor: BioMarin Pharmaceutical

Brief Summary

The goal of this clinical trial is to assess the safety and tolerability of a single oral dose of BMN 349 in participants with PiZZ or PiMZ/MASH.

Primary outcome measures include incidence of any adverse events (including serious adverse events, dose limit toxicities, and adverse events of special interest), incidence of any laboratory test abnormalities, incidence of lung function test abnormalities and 12-lead ECG parameters.

Participants will receive a single dose of either BMN 349 or placebo and then monitored for safety and tolerability.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-27
• Study First Submitted QC: 2024-12-12
• Study First Posted: 2024-12-17
• Study Start: 2025-02-21
• Status Verified: 2025-09
• Primary Completion: 2025-09
• Study Completion: 2025-09-01
• Last Update Submitted: 2025-09-02
• Last Update Posted: 2025-09-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Participants must have confirmation of PiZZ or PiMZ genotype
• Females and males, of any race, 18 to 75 years of age
• Nonsmokers, defined as not using tobacco or nicotine-containing products for at least 6 months prior to Screening

Exclusion Criteria

• International normalized ratio (INR) > 1.2
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels > 125 U/L
• Current or recent use of AAT augmentation therapy
• Participants with recent (last 3 months) diagnosis of pneumonia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A (PiZZ)	BMN 349	5:1 (349:Placebo)
Group A (PiZZ)	Placebo	5:1 (349:Placebo)
Group B (PiMZ)	BMN 349	5:1 (349:Placebo)
Group B (PiMZ)	Placebo	5:1 (349:Placebo)

Primary Outcome Measures

Name	Time	Method
Participant Adverse Events, Serious Adverse Events, Dose Limit Toxicities, Adverse Event of Special Interests, abnormal laboratory tests, abnormal pulmonary function tests, and 12-lead ECG parameters	78 days	Number of participant AEs, SAEs, DLTs, AESIs per physician's assessment, abnormal laboratory tests through whole blood samples, abnormal pulmonary function spirometry tests, and 12-lead ECG parameters changes from baseline following a single oral dose of BMN 349

Secondary Outcome Measures

Name	Time	Method
C max	78 days	Maximum observed plasma concentration
AUC 0-t	78 days	Area under the concentration-time curve from time 0 to the last measurable concentration
AUC 0-inf	78 days	Area under the concentration-time curve from time 0 to infinity
CL/F	78 days	Apparent total body clearance after oral dosing
T max	78 days	Time to reach maximum concentration
t 1/2	78 days	Terminal half-life in plasma
Vz/F	78 days	Apparent volume of distribution during terminal phase
Assess functional activity of circulating Alpha1 AntiTrypsin in participants	78 days	Changes in participant circulating AAT through whole blood samples following a single dose of BMN 349

Trial Locations

Locations (8)

University of California, San Diego; 🇺🇸 San Diego, California, United States

Saint Louis University; 🇺🇸 St Louis, Missouri, United States

Medpace Clinical Pharmacology Unit; 🇺🇸 Cincinnati, Ohio, United States

The Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

NHS Lothian; 🇬🇧 Edinburgh, UK, United Kingdom

Royal Free London NHS Foundation Trust; 🇬🇧 London, UK, United Kingdom

Nottingham University Hospitals; 🇬🇧 Nottingham, UK, United Kingdom

University Hospital Southampton NHS Foundation Trust; 🇬🇧 Southampton, UK, United Kingdom