Clinical trial NCT06738017: Study of BMN 349 Single Dose in PiZZ and PiMZ/MASH Adult Participants
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Alpha 1-Antitrypsin Deficiency
Keywords: 349
349-102
AATD
MASH
PiZZ
PiMZ
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2024-12-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Participants must have confirmation of PiZZ or PiMZ genotype
* Females and males, of any race, 18 to 70 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

Primary outcomes:
measure: 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
timeFrame: 78 days
Secondary outcomes:
measure: C max
timeFrame: 78 days
measure: AUC 0-t
timeFrame: 78 days
measure: AUC 0-inf
timeFrame: 78 days
measure: CL/F
timeFrame: 78 days
measure: T max
timeFrame: 78 days
measure: t 1/2
timeFrame: 78 days
measure: Vz/F
timeFrame: 78 days
measure: Assess functional activity of circulating Alpha1 AntiTrypsin in participants
timeFrame: 78 days
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Cincinnati
country: United States
facility: Medpace Clinical Pharmacology Unit
state: Ohio
city: Charleston
country: United States
facility: The Medical University of South Carolina
state: South Carolina
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
state: UK
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
state: UK
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Director, MD
role: STUDY_DIRECTOR
References: