Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Marc Riedl, MD MS
Headshot of Marc Riedl
Marc Riedl

Description

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.

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

Details

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.

Keywords

Hereditary Angioedema HAE Gene Therapy 331-201 331 Haermony Angioedema Angioedemas, Hereditary Dose 1 of BMN 331 Dose 2 of BMN 331 Dose 3 of BMN 331 Dose 4 of BMN 331 Dose 5 of BMN 331

Eligibility

You can join if…

Open to people ages 18 years and up

  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 or an on-demand therapy for the last 6 months prior to enrollment for a documented attack frequency of at least 1 attack per month on average
  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

You CAN'T join if...

  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 attenuated androgens in the last 1 year prior 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)

Locations

  • University of California San Diego accepting new patients
    San Diego California 92122 United States
  • AARA Research Center accepting new patients
    Dallas Texas 75231 United States

Lead Scientist at UCSD

  • Marc Riedl, MD MS
    Dr. Riedl is Clinical Director of the US HAEA Angiodema Center at the UC San Diego. His professional focus is on angiodema conditions and primary immunodeficiency, and clinical pharmacology.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
BioMarin Pharmaceutical
ID
NCT05121376
Phase
Phase 1/2 Hereditary Angioedema Research Study
Study Type
Interventional
Participants
Expecting 34 study participants
Last Updated