BMN 349 for Alpha-1 Antitrypsin Deficiency

(PiZZ Trial)

Recruiting at 9 trial locations

Overseen By Trial Specialist

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BioMarin Pharmaceutical

Must not be taking: AAT augmentation therapy

Disqualifiers: INR > 1.2, ALT/AST > 125, pneumonia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and tolerability of a new drug, BMN 349, for individuals with Alpha-1 Antitrypsin Deficiency, a genetic condition that can impair lung function. Participants will receive a single dose of either BMN 349 or a placebo, and researchers will monitor them closely for any side effects or health changes. The trial is open to nonsmokers diagnosed with specific genetic types, PiZZ or PiMZ, of this condition. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does exclude those currently or recently using AAT augmentation therapy.

Is there any evidence suggesting that BMN 349 is likely to be safe for humans?

Research shows that BMN 349 is generally well-tolerated as a single oral dose. In earlier studies, participants who took BMN 349 did not experience any serious side effects, and no reactions required stopping the medication. Lab tests and heart checks (ECG) revealed no major issues, suggesting that BMN 349 is safe for humans at the tested dose. However, as this is early research, the full safety profile of BMN 349 is still under investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alpha-1 Antitrypsin Deficiency?

Most treatments for Alpha-1 Antitrypsin Deficiency (AATD), like augmentation therapy, focus on replacing the missing protein in the body but don't directly address the underlying genetic issue. BMN 349 is unique because it targets the root cause by potentially correcting the genetic deficiency itself. Researchers are excited about this approach as it offers a more direct and possibly long-lasting solution compared to current therapies that require regular infusions. This innovative method could significantly improve quality of life for individuals with AATD, reducing the need for frequent treatments.

What evidence suggests that BMN 349 might be an effective treatment for Alpha-1 Antitrypsin Deficiency?

Research is investigating BMN 349 as a potential treatment for alpha-1 antitrypsin deficiency (AATD), a genetic condition affecting the liver and lungs. Early results suggest that BMN 349 might help by addressing issues caused by the Z mutation in the alpha-1 antitrypsin gene. This mutation can lead to a deficiency of a protein that protects tissues from damage. Although limited data exists on BMN 349's effectiveness, the primary focus is on understanding its interaction with the body and its potential to improve symptoms in individuals with AATD. Participants in this trial will be divided into two groups: Group A (PiZZ) and Group B (PiMZ), each receiving BMN 349 or a placebo in a 5:1 ratio. Current studies primarily examine the drug's safety and how the body processes it. ^{1 2 3 4 5}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

BioMarin Pharmaceutical

Are You a Good Fit for This Trial?

This trial is for adults with Alpha-1 Antitrypsin Deficiency, specifically those with PiZZ or PiMZ/MASH genetic variations. Participants will be given a single dose of either the study drug BMN 349 or a placebo to assess safety.

Inclusion Criteria

My genetic test shows I have PiZZ or PiMZ genotype.

I haven't used tobacco or nicotine products in the last 6 months.

Exclusion Criteria

I was diagnosed with pneumonia in the last 3 months.

International normalized ratio (INR) > 1.2

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels > 125 U/L

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of BMN 349 or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

78 days

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• BMN 349

Trial Overview The study tests the safety and tolerability of BMN 349, an oral medication. Patients are randomly chosen to receive one dose of either BMN 349 or a placebo, followed by monitoring for any side effects and changes in lung function and heart health.

How Is the Trial Designed?

Group I: Group B (PiMZ) Experimental Treatment 2 Interventions

5:1 (349:Placebo)

Group II: Group A (PiZZ) Experimental Treatment 2 Interventions

5:1 (349:Placebo)

Who Is Running the Clinical Trial?

BioMarin Pharmaceutical

Lead Sponsor

Trials

162

Recruited

115,000+

Alexander Hardy

BioMarin Pharmaceutical

Chief Executive Officer since 2023

MBA from INSEAD

Greg Friberg

BioMarin Pharmaceutical

Chief Medical Officer

MD from New York Medical College

Published Research Related to This Trial

This study analyzed 1684 individuals tested for Alpha-1 antitrypsin deficiency (AATD) in Portugal from 2006 to 2015, revealing a significant prevalence of severe cases, with 24.7% of subjects classified as having severe to very severe AATD.

The findings indicate a low awareness of AATD among healthcare professionals, emphasizing the urgent need for a national registry and guidelines to improve diagnosis and management of this underrecognized condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-1 Antitrypsin Deficiency Detection in a Portuguese Population. Meira, L., Boaventura, R., Seixas, S., et al.[2019]

In a long-term study involving four Japanese patients with alpha1-antitrypsin deficiency, weekly intravenous infusions of 60 mg/kg Alpha-1 MP were found to be generally safe and well-tolerated over a period of 52 weeks, with most reported adverse events being mild.

The treatment did not lead to significant changes in pulmonary function tests or laboratory parameters, indicating that Alpha-1 MP does not adversely affect lung function or overall health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of Prolastin®-C, an alpha1-proteinase inhibitor, in Japanese patients with alpha1-antitrypsin deficiency. Seyama, K., Suzuki, M., Tasaka, S., et al.[2022]

In a long-term study of seven patients with Alpha-1-Antitrypsin Deficiency, weekly intravenous augmentation therapy significantly slowed the decline in lung function (FEV1) compared to the three years prior to the program, indicating its efficacy in managing COPD symptoms.

The home care program, 'Alpha-1-Mobile', was found to be safe and well-accepted, with minimal hospitalizations due to exacerbations and no adverse events related to the augmentation therapy, highlighting its practicality for ongoing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Longterm Homecare Augmentation Program in Alpha-1-Antitrypsin Deficient Patients]. Wilke, A., Semper, H., Gross, C., et al.[2022]

The study successfully purified a variant form of alpha1-antitrypsin from a subject with a mild deficiency, revealing that its molecular weight and trypsin inhibitory activity are similar to those of normal alpha1-antitrypsin proteins.

A key structural difference was identified: an amino acid substitution from glutamic acid to valine in the variant protein, which aligns with known changes in the Pi S-Christchurch variant, potentially impacting its function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular abnormality of PI S variant of human alpha1-antitrypsin. Yoshida, A., Ewing, C., Wessels, M., et al.[2020]

Two new alleles of the SERPINA1 gene, QOVigo and QOAachen, were identified in patients with Alpha-1 antitrypsin deficiency (AATD) that produce a null phenotype, meaning they do not produce functional AAT protein.

These alleles result from combined mutations with the common Pi*S allele, leading to severe AAT polymerization and almost undetectable AAT secretion, highlighting the importance of considering additional genetic variations for accurate diagnosis and understanding of AATD clinical variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New cis-Acting Variants in PI*S Background Produce Null Phenotypes Causing Alpha-1 Antitrypsin Deficiency. Matamala, N., Gomez-Mariano, G., Perez, JA., et al.[2020]

Citations

1. synapse.patsnap.com synapse.patsnap.com/drug/58c8e84906f14220ae572e78aeaf8276

BMN-349 - Drug Targets, Indications, Patents A randomized, double-blind, placebo-controlled, single oral dose study evaluating the safety and pharmacokinetics of BMN 349 in homozygous for the Z mutation.

2. clinicaltrials.biomarin.com clinicaltrials.biomarin.com/clinical-trial/study-of-bmn-349-single-dose-in-pizz-and-pimz-adult-participants/

Study of BMN 349 Single Dose in PiZZ and 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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06738017

NCT06738017 | Study of BMN 349 Single Dose in PiZZ ... A type of intervention model describing a clinical trial in which groups of participants receive two or more interventions in a specific order. For example, two ...

4. rarediseaseadvisor.com rarediseaseadvisor.com/news/new-study-assess-safety-efficacy-bmn-349-aatd/

New Study to Assess Safety and Efficacy of BMN 349 in ... A new study is recruiting patients to assess the safety and efficacy of BMN 349 in alpha 1 antitrypsin deficiency (AATD).

5. clinicaltrials.biomarin.com clinicaltrials.biomarin.com/areas-of-clinical-research/alpha-1-antitrypsin-deficiency/

Alpha-1 Antitrypsin Deficiency Learn about BioMarin's clinical trials for alpha-1 antitrypsin deficiency, a genetic condition that can cause worsening liver disease.