Alpha 1-Antitrypsin Deficiency
Conditions
Keywords
349, 349-102, AATD, MASH, PiZZ, PiMZ
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.
Interventions
DRUGBMN 349
250mg oral tablet
DRUGPlacebo
250mg oral tablet
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director, MD
BioMarin Pharmaceutical
Outcome results
None listed