Hereditary Angioedema Clinical Trial
— HAErmony-1Official 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
Verified date | May 2024 |
Source | BioMarin Pharmaceutical |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 44 |
Est. completion date | November 2028 |
Est. primary completion date | November 2028 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Female or male adults ( = 18 years old) 2. 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 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) |
Country | Name | City | State |
---|---|---|---|
Australia | Royal Prince Alfred Hospital, | Camperdown | |
Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
Spain | Hospital Universitario La Paz | Madrid | |
United States | AllerVie Clinical Research | Birmingham | Alabama |
United States | Institute For Asthma & Allergy | Chevy Chase | Maryland |
United States | University of Cincinnati (UC) Physicians Company, LLC | Cincinnati | Ohio |
United States | Asthma & Allergy Associates P.C. | Colorado Springs | Colorado |
United States | Optimed Research, LTD | Columbus | Ohio |
United States | AARA Research Center | Dallas | Texas |
United States | Duke Health | Durham | North Carolina |
United States | The Pennsylvania State University (Penn State) Milton S. Hershey Medical Center | Hershey | Pennsylvania |
United States | Mississippi Center for Advanced Medicine | Madison | Mississippi |
United States | Dr. Henry J. Kanarek Allergy, Asthma & Immunology | Overland Park | Kansas |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | University of California San Diego | San Diego | California |
United States | Medical Research of Arizona | Scottsdale | Arizona |
Lead Sponsor | Collaborator |
---|---|
BioMarin Pharmaceutical |
United States, Australia, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Time-normalized number of investigator-confirmed HAE attacks | At 5 years | ||
Secondary | Time-normalized number of investigator-confirmed HAE attacks by severity (mild, moderate, severe) | At 5 years | ||
Secondary | Time-normalized use of HAE-specific medication | At 5 years | ||
Secondary | Plasma levels of functional C1-INH following BMN-331 infusion and change from baseline | At 5 years | ||
Secondary | Plasma levels of C1-INH antigen following BMN 331 infusion and change from baseline | At 5 years | ||
Secondary | Detection of total antibodies against AAV5 capsid following BMN 331 infusion | At 5 years | ||
Secondary | Detection of total antibodies against C1-INH following BMN 331 infusion | At 5 years | ||
Secondary | Detection of neutralizing antibodies against C1-INH following BMN 331 infusion | At 5 years |
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