Gene Therapy for Hereditary Angioedema

(HAErmony-1 Trial)

Recruiting at 15 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

Trial Summary

What is the purpose of this trial?

This trial tests BMN 331, a gene therapy given through an IV, for people with hereditary angioedema (HAE) who lack a specific protein. The therapy uses a virus to deliver a healthy gene to liver cells, enabling them to produce the missing protein. 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 cells, a method that has shown promise in treating various genetic disorders.

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.

What data supports the effectiveness of the treatment BMN 331 for hereditary angioedema?

Research on gene therapy for hereditary angioedema suggests that a one-time treatment using a virus to deliver the normal gene for C1 esterase inhibitor can maintain enough of this protein in the blood to prevent swelling episodes, which indicates potential effectiveness for BMN 331. ^{1 2 3 4 5}

Is gene therapy for hereditary angioedema safe for humans?

The research does not provide specific safety data for gene therapy in humans, but it suggests that gene therapy could potentially offer a one-time treatment for hereditary angioedema by restoring normal levels of a key protein. ^{1 3 4 6 7}

How is the treatment BMN 331 different from other treatments for hereditary angioedema?

BMN 331 is unique because it uses gene therapy to provide a one-time treatment that aims to maintain normal levels of C1 esterase inhibitor, potentially preventing swelling episodes without the need for repeated doses like current treatments. ^{1 2 3 4 6}

Research Team

MD Medical Director

Principal Investigator

BioMarin Pharmaceutical

Eligibility Criteria

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 am 18 years old or older.

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

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Hereditary angiodema: a current state-of-the-art review, IV: short- and long-term treatment of hereditary angioedema: out with the old and in with the new? [2019]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. Denmark pubmed.ncbi.nlm.nih.gov

Gene therapy for C1 esterase inhibitor deficiency in a Murine Model of Hereditary angioedema. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Hereditary angioedema due to C1 - inhibitor deficiency in Switzerland: clinical characteristics and therapeutic modalities within a cohort study. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

The hereditary angioedema syndromes. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Current and emerging management options for hereditary angioedema in the US. [2021]