Gene Therapy for Hereditary Angioedema

(HAErmony-1 Trial)

Recruiting at 16 trial locations

Overseen By Trial Specialist

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioMarin Pharmaceutical

Must be taking: HAE medications

Must not be taking: High-dose androgens

Disqualifiers: Infection, Malignancy, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called BMN 331 for individuals with hereditary angioedema (HAE), a condition causing sudden and severe swelling due to a deficiency in a specific protein. The treatment uses a virus to deliver a gene that may help produce the missing protein and reduce these attacks. Individuals managing HAE with regular treatments or experiencing frequent attacks recently might be suitable for the study. The trial aims to determine if this gene therapy can effectively and safely reduce the number of swelling attacks. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop your current medications. However, it mentions that participants should have been on a routine long-term prophylactic treatment or an on-demand therapy regimen for HAE before enrolling, which suggests you may continue your current HAE medications.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that BMN 331 is an experimental gene therapy for hereditary angioedema (HAE). This therapy uses a virus to deliver a gene that helps produce a protein missing in people with HAE. Studies so far indicate that this type of gene therapy is generally well-tolerated.

Patients receiving similar gene therapies have reported mild side effects, such as headaches or mild fevers, which are common with many treatments. Some patients have experienced liver-related issues, but these were usually mild and temporary.

Since BMN 331 remains in the early stages of research, detailed information on its safety is limited. However, its testing in humans suggests that a basic level of safety has been established. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for hereditary angioedema (HAE) involve regular infusions of C1 inhibitors or medications that block specific proteins involved in the swelling attacks. But BMN 331 works differently by using gene therapy to deliver a functional copy of the defective gene causing HAE. This approach targets the root cause of the condition rather than just managing symptoms. Researchers are excited about BMN 331 because it has the potential to provide a long-term solution with possibly fewer treatments over time, improving quality of life for patients with HAE.

What evidence suggests that this gene therapy could be effective for hereditary angioedema?

Research has shown that BMN 331 is a promising gene therapy for hereditary angioedema (HAE). This treatment uses a virus to deliver a healthy version of a specific gene to the liver, helping patients produce more of the protein C1 Esterase Inhibitor, which they lack. Early results suggest that a single dose might address the protein deficiency in HAE. While researchers continue to collect human data, the therapy aims to reduce the frequency and severity of HAE attacks over time. ^{1 2 3 5 6}

Who Is on the Research Team?

MD Medical Director

Principal Investigator

BioMarin Pharmaceutical

Are You a Good Fit for This Trial?

Adults diagnosed with Hereditary Angioedema (HAE) due to C1-INH deficiency, who are on a stable HAE medication regimen or have had frequent attacks. Participants must be able to manage acute attacks at home, avoid alcohol for 52 weeks post-treatment, and use effective contraception. Excluded are those with recent high-dose androgen use, active infections including COVID-19, certain medical conditions like untreated osteoporosis or significant liver disease, prior gene therapy treatment, or risk of thrombosis.

Inclusion Criteria

I can manage my sudden health attacks at home.

Willingness to abstain from consumption of alcohol for at least 52 weeks post BMN 331 infusion and to use highly effective contraception

I have been on long-term HAE medication for 6 months or used on-demand medication for frequent attacks.

Exclusion Criteria

I cannot use steroids due to glaucoma or untreated osteoporosis.

I have used high-dose testosterone treatments in the past year.

I have received gene therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A: Dose escalation phase to assess preliminary safety and dose-dependent increase in C1-INH protein expression following a single IV administration of BMN 331

Varies

Dose Expansion

Part B: Dose expansion phase to demonstrate that up to three safe doses of BMN 331 sustain a clinically meaningful increase in C1-INH levels

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• BMN 331

Trial Overview The trial is testing BMN 331 gene therapy as a potential treatment for HAE. It involves different doses of the drug given through an IV infusion using an AAV5 virus vector designed to express normal human C1 Esterase Inhibitor in the liver. This Phase 1/2 study will gradually increase doses (dose-escalation) and then expand the number of participants at selected dose levels (dose-expansion).

How Is the Trial Designed?

Group I: BMN 331 Experimental Treatment 7 Interventions

AAV Gene Therapy Infusion

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

Patients with hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) tend to be older at disease onset and experience more abdominal and laryngeal attacks compared to those with HAE type I.

Icatibant is effective for treating angioedema attacks in both HAE-nC1 INH and HAE type I, but it takes longer to resolve attacks in HAE-nC1 INH patients, with no serious side effects reported, highlighting its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant. Bouillet, L., Boccon-Gibod, I., Launay, D., et al.[2018]

Emerging therapies for hereditary angioedema (HAE), including C1 esterase replacement, kallikrein inhibitors, and bradykinin receptor 2 antagonists, have shown promise in phase 1 and phase 2 trials, indicating their potential effectiveness in treating HAE.

The clinical trials are well-designed, being double-blind and placebo-controlled, and they focus on patients with confirmed low C1 inhibitor levels, suggesting a robust approach to developing new treatments for HAE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angiodema: a current state-of-the-art review, VI: novel therapies for hereditary angioedema. Frank, MM.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05121376

NCT05121376 | A Gene Therapy Study of BMN 331 in ... Study 331-201 is a two-part (part A and part B), first-in-human, Phase 1/2 study designed to assess the safety and efficacy of BMN 331 in patients with HAE.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2213219823013880

Clinical Progress in Hepatic Targeting for Novel ... A single intravenous dose of BMN 331 is intended to replace the defective SERPING1 gene and enable patients to produce functional C1INH. A first-in-human phase ...

3. withpower.com withpower.com/trial/phase-2-angioedema-10-2021-521b0

Gene Therapy for Hereditary Angioedema The study aims to see if this treatment is safe and effective over several years. BMN 331 is a gene therapy that uses a virus to deliver a healthy gene to liver ...

4. rarediseaseadvisor.com rarediseaseadvisor.com/hcp-resource/hereditary-angioedema-clinical-trials/

Hereditary Angioedema Clinical Trials A gene therapy study of BMN 331 in subjects with hereditary angioedema (HAErmony-1). ClinicalTrials.gov. November 16, 2021. Updated July 14, 2023. Accessed ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9141233/

Protocol for a Systematic Review and Network Meta-Analysis ... Hereditary angioedema (HAE) is a rare genetic disease that can lead to potentially life-threatening airway attacks [1]. Based on the nature of the disease, HAE ...

6. biomarin.com biomarin.com/news/press-releases/biomarin-provides-updates-on-progress-in-gene-therapy-programs/

BioMarin Provides Updates on Progress in Gene Therapy ... Finally, the Company announced that its Phase1/2 HAERMONY study to evaluate BMN 331, an investigational AAV5-mediated gene therapy for people living with ...