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A Gene Therapy Study of BMN 331 in Subjects With Hereditary Angioedema (HAErmony-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05121376
Recruitment Status : Recruiting
First Posted : November 16, 2021
Last Update Posted : April 11, 2023
Information provided by (Responsible Party):
BioMarin Pharmaceutical

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.

Condition or disease Intervention/treatment Phase
Hereditary Angioedema HAE Genetic: Dose 1 of BMN 331 Genetic: Dose 2 of BMN 331 Genetic: Dose 3 of BMN 331 Genetic: Dose 4 of BMN 331 Genetic: Dose 5 of BMN 331 Phase 1 Phase 2

Detailed Description:

BMN 331 is an investigational, single administration gene therapy intended to modify the disease course of HAE. Preclinical studies have shown that BMN 331 can transduce hepatocytes resulting in restoration of the deficient circulating levels of hC1-INH that cause HAE.

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. Subjects will be followed for 5 years following BMN 331 infusion. Part A of the study is a dose escalation phase designed to assess the preliminary safety of a single IV administration of BMN 331 and to determine whether there is a dose-dependent increase in C1-INH protein expression following administration of BMN 331. Part B is a dose expansion phase designed to demonstrate that up to three safe doses of BMN 331 (as determined in Part A) sustains a clinically meaningful increase in C1-INH levels.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label, Dose-Escalation Study to Determine the Safety Tolerability & Efficacy of BMN 331 an AAV Vector-Mediated Gene Transfer of Human SERPING1 Gene in Subjects With HAE Due to Human C1-INH Deficiency
Actual Study Start Date : February 15, 2022
Estimated Primary Completion Date : November 2028
Estimated Study Completion Date : November 2028

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BMN 331
AAV Gene Therapy Infusion
Genetic: Dose 1 of BMN 331
BMN 331 AAV Gene Therapy

Genetic: Dose 2 of BMN 331
BMN 331 AAV Gene Therapy

Genetic: Dose 3 of BMN 331
BMN 331 AAV Gene Therapy

Genetic: Dose 4 of BMN 331
BMN 331 AAV Gene Therapy

Genetic: Dose 5 of BMN 331
BMN 331 AAV Gene Therapy

Primary Outcome Measures :
  1. Number of participants with treatment-emergent adverse events following a single IV administration of BMN 331 [ Time Frame: At 5 years ]

Secondary Outcome Measures :
  1. Number and severity of investigator-confirmed HAE attacks [ Time Frame: At 5 years ]
  2. Annualized use of HAE medication [ Time Frame: At 5 years ]
  3. Plasma levels of functional C1-INH following BMN-331 infusion [ Time Frame: At 5 years ]
  4. Plasma levels of C1-INH antigen following BMN 331 infusion [ Time Frame: At 5 years ]
  5. Levels of total antibodies against AAV5 capsid following BMN 331 infusion [ Time Frame: At 5 years ]
  6. Levels of total antibodies against C1-INH following BMN 331 infusion [ Time Frame: At 5 years ]
  7. Levels of neutralizing antibodies against C1-INH following BMN 331 infusion [ Time Frame: At 5 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female or male adults ( ≥ 18 years old)
  2. Confirmed diagnosis of HAE due to C1-INH deficiency (Type I or II) confirmed by genotyping of SERPING1 gene
  3. 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
  4. Trained in self-administering acute attack treatment and is able to adequately manage acute attacks in a home setting
  5. Willingness to abstain from consumption of alcohol for at least 52 weeks post BMN 331 infusion and to use highly effective contraception

Exclusion Criteria:

  1. Evidence of active or chronic infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or any immunosuppressive disorder
  2. Contraindication to using glucocorticosteroids GCS, including a diagnosis of glaucoma or untreated osteoporosis
  3. 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
  4. Prior gene therapy treatment
  5. Prior use of high-dose attenuated androgens in the last 1 year prior to the study
  6. History or current clinically relevant liver disease (eg, nonalcoholic steatohepatitis [NASH], or chronic viral hepatitis B or C [HBV or HCV] or autoimmune hepatitis)
  7. Have a history or are at risk for clinically significant thromboembolic events (TEE) , or known underlying risk factor for thrombosis including thrombotic microangiopathy (TMA)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05121376

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Contact: Trial Specialist 1-800-983-4587

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United States, Alabama
AllerVie Clinical Research Recruiting
Birmingham, Alabama, United States, 35209
Contact: Esther Lange, CRNP    205-209-4131   
Principal Investigator: John Anderson, MD         
United States, California
University of California San Diego Recruiting
San Diego, California, United States, 92122
Contact: Roxanne Lacy    858-657-5366   
Principal Investigator: Marc Riedl, MD MS         
United States, Kansas
Dr. Henry J. Kanarek Allergy, Asthma & Immunology Recruiting
Overland Park, Kansas, United States, 66211
Contact: Kristin Fravel    913-451-8555   
Principal Investigator: Henry Kanarek, MD         
United States, Maryland
Institute For Asthma & Allergy Recruiting
Chevy Chase, Maryland, United States, 20815
Contact: Amie Koroma    301-986-9262   
Principal Investigator: Henry Li, MD         
United States, Mississippi
Mississippi Center for Advanced Medicine Recruiting
Madison, Mississippi, United States, 39110
Contact: Jesus Monico   
Principal Investigator: Ray Rodriguez, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Tarisa Mantia    314-996-8339   
Principal Investigator: James H Wedner, MD         
United States, North Carolina
Duke Health Recruiting
Durham, North Carolina, United States, 27710
Contact: Katherine Prince    919-681-8931   
Principal Investigator: Patricia Lugar, MD         
United States, Ohio
University of Cincinnati (UC) Physicians Company, LLC Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Heather Kimbrough    513-558-6987   
Principal Investigator: Jonathan Bernstein, MD         
Optimed Research, LTD Recruiting
Columbus, Ohio, United States, 43235
Contact: Katie Suchy    614-505-1967   
Principal Investigator: Donald McNeil, MD         
United States, Pennsylvania
The Pennsylvania State University (Penn State) Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 16802
Contact: Kristina Richwine    717-531-4506   
Principal Investigator: Timothy Craig, MD         
United States, Texas
AARA Research Center Recruiting
Dallas, Texas, United States, 75231
Contact: Taufiq Sayibu    214-365-0365   
Principal Investigator: William Lumry, MD         
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Laura Company Sapina    617908767   
Principal Investigator: Mar Guilarte, MD PhD         
Hospital Universitario La Paz Recruiting
Madrid, Spain
Contact: Olga Roche    34 91 727 77 07   
Principal Investigator: Teresa Caballero, MD, PhD         
Sponsors and Collaborators
BioMarin Pharmaceutical
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Study Director: MD Medical Director BioMarin Pharmaceutical
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Responsible Party: BioMarin Pharmaceutical Identifier: NCT05121376    
Other Study ID Numbers: 331-201
First Posted: November 16, 2021    Key Record Dates
Last Update Posted: April 11, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioMarin Pharmaceutical:
Hereditary Angioedema
Gene Therapy
Additional relevant MeSH terms:
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Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Immune System Diseases
Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes