Safety Dose Finding Study of ADVM-043 Gene Therapy to Treat Alpha-1 Antitrypsin (A1AT) Deficiency

NCT02168686 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: ADVM-043-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Alpha 1-Antitrypsin Deficiency

Keywords

alpha-1 antitrypsin deficiency; alpha1-antitrypsin deficiency; alpha-1-antitrypsin deficiency; alpha1AT; A1AT; ADVM-043; AAVrh.10halpha1AT; AAVrh.10hA1AT; Gene transfer vector; Gene therapy; Lung disease; Emphysema; COPD; ADVANCE study; ADVM-043-01

Outcome Measures

Primary Outcomes (2)

• Treatment-emergent Adverse Events Related to ADVM-043

  Number and proportion of subjects experiencing treatment-related adverse events related to ADVM-043

  From ADVM-043 infusion through End-of-Study visit at 52 weeks

• Abnormal Changes in Clinical Laboratory Parameters

  Number of participants with ≥1 abnormal shift from Baseline in neutrophil count, hemoglobin, important serum chemistry parameters

  From ADVM-043 infusion through End-of-Study visit at 52 weeks

Secondary Outcomes (2)

• Change in Plasma Concentrations of M-specific A1AT up to 52 Weeks

  At Week 52

• Changes in Total Plasma Concentrations of A1AT up to 52 Weeks

  At Week 52

Study Arms (5)

Part A: Dose 1

EXPERIMENTAL

ADVM-043, at the lowest dose of three planned dose levels, of 8E13 total vg (equivalent to 1E12 vg/kg based on an 80-kg patient) administered IV

Genetic: ADVM-043

Part A: Dose 2

EXPERIMENTAL

ADVM-043 at the intermediate dose of three planned dose levels, of 4E14 total vg (equivalent to 5E12 vg/kg based on an 80-kg patient) administered IV

Genetic: ADVM-043

Part A: Dose 3

EXPERIMENTAL

ADVM-043 at the highest dose of three planned dose levels, of 1.2E15 total vg (equivalent to 1.5E13 vg/kg based on an 80-kg patient) administered IV

Genetic: ADVM-043

Part A: Dose 4

EXPERIMENTAL

ADVM-043 administered at a dose that will be determined

Genetic: ADVM-043

Part B (optional): Intrapleural administration

EXPERIMENTAL

ADVM-043 administered intrapleurally at a dose that will be determined

Genetic: ADVM-043

Interventions

ADVM-043 GENETIC

Gene transfer vector administration

Also known as: AAVrh.10halpha1AT, AAVrh.10hA1AT

Part A: Dose 1; Part A: Dose 2; Part A: Dose 3; Part A: Dose 4; Part B (optional): Intrapleural administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adverum Biotechnologies, Inc.: lead

Study Sites (2)

University of Florida

Gainesville, Florida, 32610, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• Remih K, Amzou S, Strnad P. Alpha1-antitrypsin deficiency: New therapies on the horizon. Curr Opin Pharmacol. 2021 Aug;59:149-156. doi: 10.1016/j.coph.2021.06.001. Epub 2021 Jul 10.

  PMID: 34256305 DERIVED

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency; Lung Diseases; Emphysema; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes

Limitations and Caveats

Enrollment was stopped after dosing was complete for participants in Cohorts 1, 2, and 3 of Part A. Cohort 4 of Part A and Part B were not enrolled. Only 6 of the up to 25 potentially anticipated participants were enrolled and received study treatment.

Results Point of Contact

• Title: Chief Development Officer
• Organization: Adverum Biotechnology, Inc.

sseyedkazemi@adverum.com

650-649-1413

Study Officials

• Charlton Strange, MD

  Medical University of South Carolina, Charleston, SC, USA

  PRINCIPAL INVESTIGATOR

• Friedrich Kueppers, MD

  Temple University Hospital, Philadelphia, PA, USA

  PRINCIPAL INVESTIGATOR

• Mark Brantly, MD

  University of Florida, Gainesville, FL, USA

  PRINCIPAL INVESTIGATOR

• Kyle Hogarth, MD

  University of Chicago Medical Center, Chicago, IL, USA

  PRINCIPAL INVESTIGATOR

• Igor Barjakatarevic, MD

  Ronald Reagan UCLA Medical Center, Santa Monica, CA, USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, multicenter, dose-escalation clinical study to assess the safety and treatment effect of ADVM-043 in subjects with Alpha-1 Antitrypsin Deficiency.

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 20, 2014
• Study Start: November 28, 2017
• Primary Completion: August 29, 2019
• Study Completion: August 29, 2019
• Last Updated: October 5, 2023
• Results First Posted: August 8, 2022

Record last verified: 2023-09

Locations

US (2)