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)
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- BioMarin Pharmaceutical
- Enrollment
- 6
- Locations
- 15
- Primary Endpoint
- 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
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Group A (PiZZ)
5:1 (349:Placebo)
Intervention: BMN 349 (Drug)
Group A (PiZZ)
5:1 (349:Placebo)
Intervention: Placebo (Drug)
Group B (PiMZ)
5:1 (349:Placebo)
Intervention: BMN 349 (Drug)
Group B (PiMZ)
5:1 (349:Placebo)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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
Time Frame: 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 Outcomes
- C max(78 days)
- AUC 0-t(78 days)
- AUC 0-inf(78 days)
- CL/F(78 days)
- T max(78 days)
- t 1/2(78 days)
- Vz/F(78 days)
- Assess functional activity of circulating Alpha1 AntiTrypsin in participants(78 days)