Hereditary AngioedemaPhase 1/2HAErmony-1NCT05121376
A Gene Therapy Study of BMN 331 in Subjects With Hereditary Angioedema
A Phase 1/2 study testing Dose 1 of BMN 331, Dose 2 of BMN 331 and Dose 3 of BMN 331 in people with Hereditary Angioedema and HAE, run by BioMarin Pharmaceutical at 16 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Angioedema, HAE
- What is being tested?
- Dose 1 of BMN 331, Dose 2 of BMN 331 and Dose 3 of BMN 331
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 16 sitesin 3 countries
- Study dates
- 15 Feb 2022to Nov 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male adults ( ≥ 18 years old)
- 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
- 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
- Trained in self-administering acute attack treatment and is able to adequately manage acute attacks in a home setting
- Willingness to abstain from consumption of alcohol for at least 52 weeks post BMN 331 infusion and to use highly effective contraception
Who cannot join
- Evidence of active or chronic infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or any immunosuppressive disorder
- Contraindication to using glucocorticosteroids GCS, including a diagnosis of glaucoma or untreated osteoporosis
- 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
- Prior gene therapy treatment
- Prior use of high-dose attenuated androgens in the last 1 year prior to the study
- History or current clinically relevant liver disease (eg, nonalcoholic steatohepatitis [NASH], or chronic viral hepatitis B or C [HBV or HCV] or autoimmune hepatitis)
- Have a history or are at risk for clinically significant thromboembolic events (TEE) , or known underlying risk factor for thrombosis including thrombotic microangiopathy (TMA)
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
United States13 sites
AllerVie Clinical Research
Birmingham, Alabama, 35209
Institute For Asthma & Allergy
Chevy Chase, Maryland, 20815
University of Cincinnati (UC) Physicians Company, LLC
Cincinnati, Ohio, 45267
Asthma & Allergy Associates P.C.
Colorado Springs, Colorado, 80907
Optimed Research, LTD
Columbus, Ohio, 43235
AARA Research Center
Dallas, Texas, 75231
Duke Health
Durham, North Carolina, 27705
The Pennsylvania State University (Penn State) Milton S. Hershey Medical Center
Hershey, Pennsylvania, 16802
Mississippi Center for Advanced Medicine
Madison, Mississippi, 39110
Dr. Henry J. Kanarek Allergy, Asthma & Immunology
Overland Park, Kansas, 66211
University of California San Diego
San Diego, California, 92122
Medical Research of Arizona
Scottsdale, Arizona, 85251
Washington University School of Medicine
St Louis, Missouri, 63141
Spain2 sites
Hospital Universitario Vall d'Hebron
Barcelona
Hospital Universitario La Paz
Madrid
About this study
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
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.
Read the 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.
- Conditions
- Hereditary Angioedema, HAE
- Being tested
- 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
- Keywords
- HAE, Hereditary Angioedema, Gene Therapy, 331-201, 331, Haermony
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose 1 of BMN 331Genetic
BMN 331 AAV Gene Therapy
Dose 2 of BMN 331Genetic
BMN 331 AAV Gene Therapy
Dose 3 of BMN 331Genetic
BMN 331 AAV Gene Therapy
Dose 4 of BMN 331Genetic
BMN 331 AAV Gene Therapy
Dose 5 of BMN 331Genetic
BMN 331 AAV Gene Therapy
Dose 6 of BMN 331Genetic
BMN 331 AAV Gene Therapy
Dose 7 of BMN 331Genetic
BMN 331 AAV Gene Therapy
| Study group | Role | What they receive |
|---|---|---|
| BMN 331 | Experimental | AAV Gene Therapy Infusion Receives: 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; Genetic: Dose 6 of BMN 331; Genetic: Dose 7 of BMN 331 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At 5 years
Secondary outcomes (8)
Time-normalized number of investigator-confirmed HAE attacks
Measured: At 5 years
Time-normalized number of investigator-confirmed HAE attacks by severity (mild, moderate, severe)
Measured: At 5 years
Time-normalized use of HAE-specific medication
Measured: At 5 years
Plasma levels of functional C1-INH following BMN-331 infusion and change from baseline
Measured: At 5 years
Plasma levels of C1-INH antigen following BMN 331 infusion and change from baseline
Measured: At 5 years
Detection of total antibodies against AAV5 capsid following BMN 331 infusion
Measured: At 5 years
Detection of total antibodies against C1-INH following BMN 331 infusion
Measured: At 5 years
Detection of neutralizing antibodies against C1-INH following BMN 331 infusion
Measured: At 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2021
- Study start15 Feb 2022
- Primary completionNov 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD Medical Director, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05121376
- Sponsor's protocol ID
- 331-201
- Acronym
- HAErmony-1
- Status last verified
- May 2024
- First submitted
- 28 Oct 2021
- Last updated
- 16 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05121376
- Acronym / sponsor ID
- HAErmony-1 / 331-201
- Conditions
- Hereditary Angioedema, HAE
- Keywords
- HAE, Hereditary Angioedema, Gene Therapy, 331-201, 331, Haermony
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- 15 Feb 2022 (actual)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 16 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BMN 331 | Experimental | 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, Genetic: Dose 6 of BMN 331, Genetic: Dose 7 of BMN 331AAV Gene Therapy Infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Female or male adults ( ≥ 18 years old)
- 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
- 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
- Trained in self-administering acute attack treatment and is able to adequately manage acute attacks in a home setting
- Willingness to abstain from consumption of alcohol for at least 52 weeks post BMN 331 infusion and to use highly effective contraception
Key exclusion criteria (7 listed)
- Evidence of active or chronic infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or any immunosuppressive disorder
- Contraindication to using glucocorticosteroids GCS, including a diagnosis of glaucoma or untreated osteoporosis
- 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
- Prior gene therapy treatment
- Prior use of high-dose attenuated androgens in the last 1 year prior to the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dose 1 of BMN 331BMN 331 AAV Gene Therapy | Genetic | BMN 331 |
| Dose 2 of BMN 331BMN 331 AAV Gene Therapy | Genetic | BMN 331 |
| Dose 3 of BMN 331BMN 331 AAV Gene Therapy | Genetic | BMN 331 |
| Dose 4 of BMN 331BMN 331 AAV Gene Therapy | Genetic | BMN 331 |
| Dose 5 of BMN 331BMN 331 AAV Gene Therapy | Genetic | BMN 331 |
| Dose 6 of BMN 331BMN 331 AAV Gene Therapy | Genetic | BMN 331 |
| Dose 7 of BMN 331BMN 331 AAV Gene Therapy | Genetic | BMN 331 |
Primary outcome
Number of participants with treatment-emergent adverse events following a single IV administration of BMN 331
Time frame: At 5 years
Number of participants with treatment-emergent adverse events following a single IV administration of BMN 331
8 secondary outcomes
Time-normalized number of investigator-confirmed HAE attacks
Time frame: At 5 years
Time-normalized number of investigator-confirmed HAE attacks by severity (mild, moderate, severe)
Time frame: At 5 years
Time-normalized use of HAE-specific medication
Time frame: At 5 years
Plasma levels of functional C1-INH following BMN-331 infusion and change from baseline
Time frame: At 5 years
Plasma levels of C1-INH antigen following BMN 331 infusion and change from baseline
Time frame: At 5 years
Detection of total antibodies against AAV5 capsid following BMN 331 infusion
Time frame: At 5 years
Detection of total antibodies against C1-INH following BMN 331 infusion
Time frame: At 5 years
Detection of neutralizing antibodies against C1-INH following BMN 331 infusion
Time frame: At 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD Medical Director study director
BioMarin Pharmaceutical
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dose 1 of BMN 331, Dose 2 of BMN 331 and Dose 3 of BMN 331 in people with Hereditary Angioedema and HAE, run by BioMarin Pharmaceutical at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Spain, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-emergent adverse events following a single IV administration of BMN 331 (time frame: At 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.