Safety & Efficacy Study of rAAV1-CB-hAAT for Alpha-1 Antitrypsin Deficiency

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01054339
• Date of registration: 21/01/2010
• Prospective Registration: Yes
• Primary sponsor: Applied Genetic Technologies Corp
• Public title: Safety & Efficacy Study of rAAV1-CB-hAAT for Alpha-1 Antitrypsin Deficiency
• Scientific title: A Multiple-Site, Phase 2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing Alpha-1 Antitrypsin (rAAV1-CB-hAAT) in Patients With Alpha-1 Antitrypsin Deficiency
• Date of first enrolment: June 2010
• Target sample size: 9
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01054339
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Ireland, United States

Contacts

• Name: Noel G. McElvaney, MB, BCh, BAO
• Affiliation: Beaumont Hospital, Dublin, Ireland

• Name: Robert A. Sandhaus, MD, PhD
• Affiliation: National Jewish Health, Denver, CO

• Name: Bruce C. Trapnell, MD
• Affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH

• Name: Terence R. Flotte, MD
• Affiliation: University of Massachusetts Medical School, Worcester, MA

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Have a diagnosis of AAT-deficiency, as defined by a serum AAT level of less than 11 µM
and a phenotype or genotype either homozygous for PI*Z or compound heterozygous
consisting of PI*Z and another allele known to be associated with disease

2. Be at least 18 and not more than 75 years of age

3. Have a forced expiratory volume at one second (FEV1) >25% of predicted value (post
bronchodilator)

4. Weigh = 90 kg

5. Not receiving AAT augmentation therapy currently or with the past 3 months, and not
planning to begin such therapy for at least 12 months after administration of
rAAV1-CB-hAAT

6. Be willing to discontinue aspirin, aspirin-containing products, and other drugs that
may alter platelet function, 7 days prior to dosing, resuming no earlier than 24 hours
after the dose has been administered

7. Have acceptable laboratory parameters:

- Hemoglobin = 11.2 g/dL for females, = 12.8 g/dL for males,

- White blood cell count 3,300 - 12,000 cells/mm3,

- Platelet count 125,000 - 550,000/mm3,

- Serum creatine kinase (CK) = 3 times upper normal range for study laboratory,

- Alanine aminotransferase (ALT) = 2 times upper normal range for study laboratory,

- Serum bilirubin = 1.5 times upper normal range for study laboratory,

- Serum creatinine within normal range for study laboratory,

- Prothrombin time (PT) = 14.5 seconds and partial thromboplastin time (PTT)

= 36 seconds,

- Normal urine dipstick (negative glucose, negative hemoglobin, and negative or
trace protein),

8. For females of childbearing potential:

- A negative pregnancy test (urine or serum) at screening and at baseline (within 2
days before administration of study agent)

- Agreement to consistently use barrier contraception (condoms, diaphragm or
cervical cap with spermicide) or another form of contraception (e.g. intrauterine
device or hormonal contraception) from the screening visit until 12 months after
administration of rAAV1-CB-hAAT, for sexual activity that could lead to pregnancy

9. For males of reproductive potential, agreement to consistently use barrier
contraception (condoms with spermicide) for 12 months after administration of
rAAV1-CB-hAAT, for sexual activity that could lead to pregnancy,

10. Provide signed informed consent before screening

Exclusion Criteria:

1. Prior receipt of any AAV gene therapy product

2. Use of anticoagulants or anti-platelet agents within 7 days prior to study agent
administration

3. History of immune response to human AAT augmentation therapy as indicated by clinical
history of an adverse immune response to infusion and/or decreased therapeutic effect
in combination with documentation of serum anti-AAT antibodies

4. Use of acute oral or intravenous antibiotic therapy for a respiratory infection within
28 days prior to study agent administration (long-term maintenance or chronic
suppressive oral antibiotics, and antibiotics for a non-respiratory indication, are
allowed)

5. Use of oral or systemic corticosteroids within 28 days prior to study agent
administration

6. Use of any investigational agent, or any immunosuppressive drug(s), within 3 months
prior to enrollment

7. For females of childbearing potential, a positive pregnancy test at screening or
baseline (within 2 days before rAAV1-CB-hAAT administration) Note: At the Cincinnati
Children's Hospital Medical Center site, women of childbearing potential were not
permitted to enroll in the study.

8. Females who are breast feeding

9. Have a significant abnormal EKG finding at screening and/or cardiac disease (e.g.
recent myocardial infarction or CHF) within past 6 months

10. Have had pulmonary edema or a pulmonary embolism within the past 6 months

11. Have a history of immunodeficiency or other medical condition which leads the
investigator to believe that the participant cannot comply with the protocol
requirements or that may place the participant at an unacceptable risk for
participation



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alpha-1 Antitrypsin Deficiency

Intervention(s)

Drug: rAAV1-CB-hAAT

Primary Outcome(s)

Frequency of Grade 3 or 4 Adverse Events [Time Frame: During 1 year after study agent administration]

Secondary Outcome(s)

Changes in Serum M-specific Alpha-1 Antitrypsin Concentration [Time Frame: During months 6-12 after study agent adminsitration]

Changes in Serum Total Alpha-1 Antitrypsin Concentrations [Time Frame: During months 6-12 after study agent adminstration]

Secondary ID(s)

R01HL069877

AGTC-AAT-002

2009-014286-20

R01FD003896

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Heart, Lung, and Blood Institute (NHLBI)

Results

• Results available: Yes
• Date Posted: 14/09/2012
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01054339