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

A Randomized, Double-Blind, Placebo-Controlled, Single Oral Dose Study Evaluating the Safety and Pharmacokinetics of BMN 349 in Homozygous for the Z Mutation of Alpha 1 Antitrypsin Gene (PiZZ) and Heterozygous for the Z Mutation (PiMZ/MASH)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alpha 1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: BMN 349; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • Edinburgh, UK, United Kingdom
      • NHS Lothian
    • London, UK, United Kingdom
      • Royal Free London NHS Foundation Trust
    • Southampton, UK, United Kingdom
      • University Hospital Southampton NHS Foundation Trust
• United States
  • California
    • San Diego, California, United States, 92037
      • University of California, San Diego
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Saint Louis University
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Medpace Clinical Pharmacology Unit
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • The Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group A (PiZZ); 5:1 (349:Placebo)	Drug: BMN 349; 250mg oral tablet; Drug: Placebo; 250mg oral tablet
Other: Group B (PiMZ); 5:1 (349:Placebo)	Drug: BMN 349; 250mg oral tablet; Drug: Placebo; 250mg oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	78 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Medical Director, MD, BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2025
• Primary Completion (Estimated): August 19, 2026
• Study Completion (Estimated): August 19, 2026

Study Registration Dates

• First Submitted: November 27, 2024
• First Submitted That Met QC Criteria: December 12, 2024
• First Posted (Actual): December 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: AATD; PiZZ; MASH; PiMZ; 349; 349-102
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; alpha 1-Antitrypsin Deficiency; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 349-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No