NCT05121376

Brief Summary

This is a Phase 1/2, single-arm, open-label, dose-escalation and dose-expansion study of BMN 331 for the treatment of hereditary angioedema (HAE) due to C1 Esterase Inhibitor (C1-INH) protein deficiency. The study drug BMN 331is identified as AAV5 hSERPING1, an adeno-associated virus (AAV5)-based gene therapy vector that expresses wild-type human C1 Esterase Inhibitor (hC1-INH), under the control of a liver-selective promoter, and is being developed for the treatment of HAE with C1-INH deficiency. The pharmaceutical form of BMN 331 is a solution for intravenous infusion.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P50-P75 for phase_1

Timeline
31mo left

Started Feb 2022

Longer than P75 for phase_1

Geographic Reach
3 countries

16 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress63%
Feb 2022Nov 2028

First Submitted

Initial submission to the registry

October 28, 2021

Completed
19 days until next milestone

First Posted

Study publicly available on registry

November 16, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

February 15, 2022

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2028

Last Updated

May 16, 2024

Status Verified

May 1, 2024

Enrollment Period

6.7 years

First QC Date

October 28, 2021

Last Update Submit

May 15, 2024

Conditions

Hereditary AngioedemaHAE

Keywords

HAEHereditary AngioedemaGene Therapy331-201331Haermony

Outcome Measures

Primary Outcomes (1)

  • Number of participants with treatment-emergent adverse events following a single IV administration of BMN 331

    Number of participants with treatment-emergent adverse events following a single IV administration of BMN 331

    At 5 years

Secondary Outcomes (8)

  • Time-normalized number of investigator-confirmed HAE attacks

    At 5 years

  • Time-normalized number of investigator-confirmed HAE attacks by severity (mild, moderate, severe)

    At 5 years

  • Time-normalized use of HAE-specific medication

    At 5 years

  • Plasma levels of functional C1-INH following BMN-331 infusion and change from baseline

    At 5 years

  • Plasma levels of C1-INH antigen following BMN 331 infusion and change from baseline

    At 5 years

  • +3 more secondary outcomes

Study Arms (1)

BMN 331

EXPERIMENTAL

AAV Gene Therapy Infusion

Genetic: Dose 1 of BMN 331Genetic: Dose 2 of BMN 331Genetic: Dose 3 of BMN 331Genetic: Dose 4 of BMN 331Genetic: Dose 5 of BMN 331Genetic: Dose 6 of BMN 331Genetic: Dose 7 of BMN 331

Interventions

Dose 1 of BMN 331GENETIC

BMN 331 AAV Gene Therapy

BMN 331
Dose 2 of BMN 331GENETIC

BMN 331 AAV Gene Therapy

BMN 331
Dose 3 of BMN 331GENETIC

BMN 331 AAV Gene Therapy

BMN 331
Dose 4 of BMN 331GENETIC

BMN 331 AAV Gene Therapy

BMN 331
Dose 5 of BMN 331GENETIC

BMN 331 AAV Gene Therapy

BMN 331
Dose 6 of BMN 331GENETIC

BMN 331 AAV Gene Therapy

BMN 331
Dose 7 of BMN 331GENETIC

BMN 331 AAV Gene Therapy

BMN 331

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Female or male adults ( ≥ 18 years old)
  • Part A only: Confirmed diagnosis of Type I HAE due to C1-INH deficiency confirmed by genotyping of the SERPING1 gene Part B only: Confirmed diagnosis of Type I or II HAE due to C1-INH deficiency confirmed by genotyping of the SERPING1 gene
  • Currently using an HAE medication regimen that consists of a routine long-term prophylactic treatment for at least 6 months prior to enrollment or an on-demand therapy regimen for a documented attack frequency of at least 4 attacks within the last 12 months prior to enrollment or at least 2 attacks within the last 6 months prior to enrollment
  • Trained in self-administering acute attack treatment and is able to adequately manage acute attacks in a home setting
  • Willingness to abstain from consumption of alcohol for at least 52 weeks post BMN 331 infusion and to use highly effective contraception

You may not qualify if:

  • Evidence of active or chronic infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or any immunosuppressive disorder
  • Contraindication to using glucocorticosteroids GCS, including a diagnosis of glaucoma or untreated osteoporosis
  • Active malignancy (except non-melanoma skin cancer) autoimmune, metabolic (i.e., diabetes), hematologic, cardiac, or renal disease that is of clinical significance defined as requiring regular medical attention and treatment
  • Prior gene therapy treatment
  • Prior use of high-dose attenuated androgens in the last 1 year prior to the study
  • History or current clinically relevant liver disease (eg, nonalcoholic steatohepatitis \[NASH\], or chronic viral hepatitis B or C \[HBV or HCV\] or autoimmune hepatitis)
  • Have a history or are at risk for clinically significant thromboembolic events (TEE) , or known underlying risk factor for thrombosis including thrombotic microangiopathy (TMA)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

AllerVie Clinical Research

Birmingham, Alabama, 35209, United States

Location

Medical Research of Arizona

Scottsdale, Arizona, 85251, United States

Location

University of California San Diego

San Diego, California, 92122, United States

Location

Asthma & Allergy Associates P.C.

Colorado Springs, Colorado, 80907, United States

Location

Dr. Henry J. Kanarek Allergy, Asthma & Immunology

Overland Park, Kansas, 66211, United States

Location

Institute For Asthma & Allergy

Chevy Chase, Maryland, 20815, United States

Location

Mississippi Center for Advanced Medicine

Madison, Mississippi, 39110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63141, United States

Location

Duke Health

Durham, North Carolina, 27705, United States

Location

University of Cincinnati (UC) Physicians Company, LLC

Cincinnati, Ohio, 45267, United States

Location

Optimed Research, LTD

Columbus, Ohio, 43235, United States

Location

The Pennsylvania State University (Penn State) Milton S. Hershey Medical Center

Hershey, Pennsylvania, 16802, United States

Location

AARA Research Center

Dallas, Texas, 75231, United States

Location

Royal Prince Alfred Hospital,

Camperdown, 2050, Australia

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

MeSH Terms

Conditions

Angioedemas, Hereditary

Condition Hierarchy (Ancestors)

AngioedemaVascular DiseasesCardiovascular DiseasesHereditary Complement Deficiency DiseasesPrimary Immunodeficiency DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesUrticariaSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesHypersensitivity, ImmediateHypersensitivityImmune System DiseasesImmunologic Deficiency Syndromes

Study Officials

  • MD Medical Director

    BioMarin Pharmaceutical

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 28, 2021

First Posted

November 16, 2021

Study Start

February 15, 2022

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

November 1, 2028

Last Updated

May 16, 2024

Record last verified: 2024-05

Locations

AU(1)ES(2)US(13)