The Gene Therapy Center at the University of Florida

Alpha-1 Antitrypsin Deficiency Gene Transfer Research Study

Principal Investigator: Mark L. Brantly, MD
Co-Investigator: Terence R. Flotte, MD
Contact: Janet King, RN, phone: 352-273-6541 or toll free at 866-229-6312

The University of Florida in collaboration with the Alpha-1 Foundation, Shands Hospital, General Clinical Research Center, and the National Institutes of Health is conducting a Phase I non-randomized, open label, single dose escalation study of Gene Transfer.

The purpose of this study is to evaluate the safety of intramuscular injection of a Recombinant Adeno-Associated Virus Alpha 1-Antitrypsin (rAAV1-CB-hAAT) Gene Vector to AAT-Deficient Adults.

This will be the first time this specific study agent, vector, rAAV1-CB-hAAT, will be given to subjects.

Study Agent
Each subject will receive 9 injections of 1.1 ml of the study agent injected in the upper arm of their non-dominant hand.

• There will be four groups of three subjects; 12 subjects total.
  • First group will receive a very low dose of study agent.
  • The dose will increase with each group.
  • Each subject's dose will be dependent on the group he/she is admitted to.
  • The group will be determined by when the subject joins the study.

To be eligible, volunteers must:

• Have confirmed diagnosis of AAT Deficiency, and a phenotype or genotype for PI*ZZ or Z and another allele known to be associated with disease
• FEV₁ ≥ 30% predicted value post bronchodilator
• Be male or female ≥ 18 years of age
• Willing to discontinue AAT protein replacement for 15 weeks and drugs affecting blood clotting for 8 days
• Have liver function tests < two times the upper limit of normal; (bilirubin and gamma-glutamyl transpeptidase (ggt) < 1.2 times the upper limit of normal

Involvement in the study requires:

• Four weeks prior to receiving study agent each participant who is currently using AAT protein replacement will be asked to discontinue the use of it for 15 weeks.
• 4-7 visits to Shands Hospital, one visit requiring a 5 day admission, the remainder of the visits may be overnight.
• 4-7 follow-up days with telephone calls and shipment of blood specimen
• one year study with annual long-term contract

For further information please contact:
Janet King, RN, phone: 352-273-6541 or toll free at 866-229-6312