Clinical trial
Phase 1/2 Study of Intravenous or Intrapleural Administration of a Serotype rh.10 Replication Deficient Adeno-associated Virus Gene Transfer Vector Expressing the Human Alpha-1 Antitrypsin cDNA to Individuals With Alpha-1 Antitrypsin Deficiency
Name
ADVM-043-01
Description
The ADVANCE study is being conducted by Adverum Biotechnologies, Inc. as an open-label, multicenter, dose-escalation study in order to assess the safety and protein expression of ADVM-043 following a single intravenous or intrapleural administration.
Trial arms
Trial start
2017-11-28
Estimated PCD
2019-08-29
Trial end
2019-08-29
Status
Completed
Phase
Early phase I
Treatment
ADVM-043
Gene transfer vector administration
Arms:
Part A: Dose 1, Part A: Dose 2, Part A: Dose 3, Part A: Dose 4, Part B (optional): Intrapleural administration
Other names:
AAVrh.10halpha1AT, AAVrh.10hA1AT
Size
6
Primary endpoint
Treatment-emergent Adverse Events Related to ADVM-043
From ADVM-043 infusion through End-of-Study visit at 52 weeks
Abnormal Changes in Clinical Laboratory Parameters
From ADVM-043 infusion through End-of-Study visit at 52 weeks
Eligibility criteria
Key Inclusion Criteria:
* Capable of providing informed consent
* Alpha1AT genotype of ZZ or Z Null
* Males and females 18 years and older
* Ongoing treatment with A1AT augmentation is not required, however any subject receiving A1AT augmentation therapy must be willing to washout. Washout is defined as at least 8 weeks between last augmentation therapy and pre-treatment plasma A1AT level
* Willing to remain off PAT for at least 3 months following treatment
* Body mass index 18 to 35 kg/m2
* Fertile men and women of childbearing potential must agree to use barrier contraception for 3 months after treatment
Key Exclusion Criteria:
* FEV1 \<35 percent of predicted value at the Screening visit
* Receiving systemic corticosteroids or other immunosuppressive medications
* Immunodeficiency disease or evidence of active infection of any type, including human immunodeficiency virus
* Abnormal liver function tests
* Organ transplant recipient or awaiting transplantation
* Participation in another current or previous gene transfer study
* AAVrh.10 neutralizing antibody titer ≥ 1:5
* Female who is pregnant or lactating
* History of alcohol or drug abuse within the past 5 years
* Any history of allergies that may prohibit study-specific investigations
* Receiving an investigational medicinal product or participating in another investigational study within 3 months prior to consent
* Cigarette smoking, or any other tobacco use, e-cigarettes or other recreational inhalant within 1 year of the Screening Visit
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Open-label, multicenter, dose-escalation clinical study to assess the safety and treatment effect of ADVM-043 in subjects with Alpha-1 Antitrypsin Deficiency.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 6, 'type': 'ACTUAL'}}
Updated at
2023-10-05
1 organization
1 product
1 indication
Organization
Adverum BiotechnologiesProduct
ADVM-043Indication
Alpha-1 Antitrypsin Deficiency