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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05121376




Registration number
NCT05121376
Ethics application status
Date submitted
28/10/2021
Date registered
16/11/2021
Date last updated
16/05/2024

Titles & IDs
Public title
A Gene Therapy Study of BMN 331 in Subjects With Hereditary Angioedema
Scientific 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
Secondary ID [1] 0 0
331-201
Universal Trial Number (UTN)
Trial acronym
HAErmony-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hereditary Angioedema 0 0
HAE 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Dose 1 of BMN 331
Other interventions - Dose 2 of BMN 331
Other interventions - Dose 3 of BMN 331
Other interventions - Dose 4 of BMN 331
Other interventions - Dose 5 of BMN 331
Other interventions - Dose 6 of BMN 331
Other interventions - Dose 7 of BMN 331

Experimental: BMN 331 - AAV Gene Therapy Infusion


Other interventions: Dose 1 of BMN 331
BMN 331 AAV Gene Therapy

Other interventions: Dose 2 of BMN 331
BMN 331 AAV Gene Therapy

Other interventions: Dose 3 of BMN 331
BMN 331 AAV Gene Therapy

Other interventions: Dose 4 of BMN 331
BMN 331 AAV Gene Therapy

Other interventions: Dose 5 of BMN 331
BMN 331 AAV Gene Therapy

Other interventions: Dose 6 of BMN 331
BMN 331 AAV Gene Therapy

Other interventions: Dose 7 of BMN 331
BMN 331 AAV Gene Therapy
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with treatment-emergent adverse events following a single IV administration of BMN 331
Timepoint [1] 0 0
At 5 years
Secondary outcome [1] 0 0
Time-normalized number of investigator-confirmed HAE attacks
Timepoint [1] 0 0
At 5 years
Secondary outcome [2] 0 0
Time-normalized number of investigator-confirmed HAE attacks by severity (mild, moderate, severe)
Timepoint [2] 0 0
At 5 years
Secondary outcome [3] 0 0
Time-normalized use of HAE-specific medication
Timepoint [3] 0 0
At 5 years
Secondary outcome [4] 0 0
Plasma levels of functional C1-INH following BMN-331 infusion and change from baseline
Timepoint [4] 0 0
At 5 years
Secondary outcome [5] 0 0
Plasma levels of C1-INH antigen following BMN 331 infusion and change from baseline
Timepoint [5] 0 0
At 5 years
Secondary outcome [6] 0 0
Detection of total antibodies against AAV5 capsid following BMN 331 infusion
Timepoint [6] 0 0
At 5 years
Secondary outcome [7] 0 0
Detection of total antibodies against C1-INH following BMN 331 infusion
Timepoint [7] 0 0
At 5 years
Secondary outcome [8] 0 0
Detection of neutralizing antibodies against C1-INH following BMN 331 infusion
Timepoint [8] 0 0
At 5 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2028
Actual
Sample size
Target
44
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital, - Camperdown
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Mississippi
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Spain
State/province [13] 0 0
Barcelona
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BioMarin Pharmaceutical
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT05121376
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD Medical Director
Address 0 0
BioMarin Pharmaceutical
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries