NCT00377416

Brief Summary

Individuals with a deficiency of the Alpha 1-antitrypsin (AAT) protein are at risk for developing emphysema and liver damage. Researchers have developed a way to introduce normal AAT genes into muscle cells so that the AAT protein is produced at normal levels. This study will evaluate the safety of the experimental gene transfer procedure in individuals with AAT deficiency.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at P25-P50 for early_phase_1

Timeline
Completed

Started Mar 2004

Longer than P75 for early_phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2004

Completed
2.5 years until next milestone

First Submitted

Initial submission to the registry

September 14, 2006

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 18, 2006

Completed
13 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2006

Completed
13.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2020

Completed
Last Updated

April 10, 2020

Status Verified

April 1, 2020

Enrollment Period

2.6 years

First QC Date

September 14, 2006

Last Update Submit

April 8, 2020

Conditions

Alpha 1-Antitrypsin Deficiency

Keywords

Gene Transfer TechniquesGene Therapy

Outcome Measures

Primary Outcomes (5)

  • Arm circumference

    Measured at Day 3

  • Presence of rAAV2-CB-hAAT vector in blood and semen

    Measured at Day 14

  • Serum chemistries, hematology, urinalysis, immune response, and pulmonary function

    Measured at Day 90

  • Human AAT levels and phenotype in the blood

    Measured at Day 180

  • Adverse events

    Measured at Year 1 and at yearly follow-up evaluations over 15 years

Study Arms (1)

1

EXPERIMENTAL

rAAV2-CB-hAAT Gene Vector

Genetic: rAAV2-CB-hAAT Gene Vector

Interventions

rAAV2-CB-hAAT Gene VectorGENETIC

Participants will attend a 5-day inpatient visit, during which they will receive a series of injections consisting of one of four different doses of rAAV2-CB-hAAT.

1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosed with AAT deficiency
  • Forced expiratory volume in one second (FEV1) greater than 24% of predicted value (post bronchodilator)
  • Willing to discontinue AAT protein replacement 4 weeks prior to study entry, and to resume 11 weeks after rAAV2-CB-hAAT has been administered
  • Willing to discontinue aspirin, aspirin-containing products, and other drugs that may alter platelet function 7 days prior to study entry, and to resume 24 hours after rAAV2-CB-hAAT has been administered
  • Willing to use contraception throughout the study

You may not qualify if:

  • Required antibiotic therapy for a respiratory infection in the 28 days prior to rAAV2-CB-hAAT administration
  • Required oral or systemic corticosteroids in the 28 days prior to rAAV2-CB-hAAT administration
  • Liver disease
  • Currently receiving or has received an investigational study agent in the 30 days prior to study entry
  • Received gene transfer agents in the 6 months prior to study entry
  • Currently smokes cigarettes or uses illegal drugs
  • History of immune response to human AAT replacement
  • History of platelet dysfunction
  • Any other medical condition that the investigator deems unsuitable for study participation
  • Pregnant or breastfeeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of Florida, College of Medicine, Department of Pediatrics

Gainesville, Florida, 32610, United States

Location

UMass Medical School

Worcester, Massachusetts, 01655, United States

Location

Related Publications (3)

  • Flotte TR, Brantly ML, Spencer LT, Byrne BJ, Spencer CT, Baker DJ, Humphries M. Phase I trial of intramuscular injection of a recombinant adeno-associated virus alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults. Hum Gene Ther. 2004 Jan;15(1):93-128. doi: 10.1089/10430340460732490.

    PMID: 14965381BACKGROUND

  • Song S, Morgan M, Ellis T, Poirier A, Chesnut K, Wang J, Brantly M, Muzyczka N, Byrne BJ, Atkinson M, Flotte TR. Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14384-8. doi: 10.1073/pnas.95.24.14384.

    PMID: 9826709BACKGROUND

  • 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: 34256305DERIVED

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesSubcutaneous EmphysemaEmphysemaPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Terence R. Flotte, MD

    UMass Medical School

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 14, 2006

First Posted

September 18, 2006

Study Start

March 1, 2004

Primary Completion

October 1, 2006

Study Completion

January 1, 2020

Last Updated

April 10, 2020

Record last verified: 2020-04

Locations

US(2)