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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05121376
Other study ID # 331-201
Secondary ID
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date February 15, 2022
Est. completion date November 2028

Study information

Verified date May 2024
Source BioMarin Pharmaceutical
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

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)

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Australia,  Spain, 

Outcome

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
See also
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