Alpha 1-Antitrypsin DeficiencyEarly Phase 1NCT00377416
Experimental Gene Transfer Procedure to Treat Alpha 1-Antitrypsin Deficiency
A Early Phase 1 study testing rAAV2-CB-hAAT Gene Vector in people with Alpha 1-Antitrypsin Deficiency, run by University of Massachusetts, Worcester at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alpha 1-Antitrypsin Deficiency
- What is being tested?
- rAAV2-CB-hAAT Gene Vector
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2004to Jan 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida, College of Medicine, Department of Pediatrics
Gainesville, Florida, 32610
UMass Medical School
Worcester, Massachusetts, 01655
About this study
Official title: Preclinical & Phase I/II Trials of AAV-AAT Vectors: Phase I Trial of Intramuscular Injection of a Recombinant Adeno-Associated Virus Alpha 1-Antitrypsin (rAAV2-CB-hAAT) Gene Vector to AAT-Deficient Adults
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.
Read the detailed description
AAT deficiency is a genetic disorder in which individuals have inadequate levels of the AAT protein. AAT protects the lungs from white blood cell enzymes that can damage air sacs within the lungs, potentially leading to emphysema. Experimental gene transfer procedures, in which normal copies of genes are inserted into cells, are being developed to treat many genetic diseases, including AAT deficiency. In this study, a modified virus, adeno-associated virus (AAV), has been genetically engineered to contain a normal copy of the AAT gene. When AAV is combined with the AAT gene, the resulting agent, rAAV2-CB-hAAT, is able to carry normal copies of the AAT gene into muscle cells to produce additional AAT. The purpose of this study is to evaluate the safety of injecting rAAV2-CB-hAAT into individuals with AAT deficiency.
This 13-month study will enroll individuals with AAT deficiency. Participants currently using AAT protein replacement will discontinue its use for 15 weeks during the study. Participants will first attend a baseline study visit, which will include a medical history review; a physical examination; an electrocardiogram (ECG) to record heart activity; blood, urine, and semen collection; pulmonary function tests; and chest and arm scans. Participants will then 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. Physical examinations will occur on all 5 inpatient days; pulmonary function testing, arm circumference measurements, and collection of blood, urine, and semen will occur on selected days of the inpatient stay. Follow-up study visits, with possible overnight stays, will occur on Days 14 and 90. On Days 30, 45, 60, 75, 180, 270, and 365, participants will have blood drawn at a local clinic. On these same days, study staff will contact participants by telephone to review their medical history and symptoms. Unused blood and semen samples will be frozen and stored for future research purposes. Participants will have yearly follow-up evaluations by either telephone or mail for a total of 15 years.
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Being tested
- rAAV2-CB-hAAT Gene Vector
- Keywords
- Gene Transfer Techniques, Gene Therapy
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | rAAV2-CB-hAAT Gene Vector Receives: Genetic: rAAV2-CB-hAAT Gene Vector |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arm circumference
Measured: Measured at Day 3
Presence of rAAV2-CB-hAAT vector in blood and semen
Measured: Measured at Day 14
Serum chemistries, hematology, urinalysis, immune response, and pulmonary function
Measured: Measured at Day 90
Human AAT levels and phenotype in the blood
Measured: Measured at Day 180
Adverse events
Measured: Measured at Year 1 and at yearly follow-up evaluations over 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2006 (estimated)
- Study startMar 2004
- Primary completionOct 2006
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alpha 1-Antitrypsin DeficiencyStudies of the same condition, open and under way.
- More trials run by University of Massachusetts, WorcesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Worcester
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Alpha-1 Foundation, University of Florida, National Center for Research Resources (NCRR)
- Responsible party
- Sponsor
- Investigators
- Terence R. Flotte, MD, Principal investigator, UMass Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00377416
- Sponsor's protocol ID
- 366
- Other IDs
- R01HL069877, NIH Protocol # 30104-465, UF GCRC # 567, UF IBC RD 2101, UF GTC TRF AAV001, IRB # 306-03
- Status last verified
- Apr 2020
- First submitted
- 14 Sep 2006
- Last updated
- 10 Apr 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 14965381Song 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.
PubMed 9826709Remih 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.
PubMed 34256305
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preclinical & Phase I/II Trials of AAV-AAT Vectors: Phase I Trial of Intramuscular Injection of a Recombinant Adeno-Associated Virus Alpha 1-Antitrypsin (rAAV2-CB-hAAT) Gene Vector to AAT-Deficient Adults
- ClinicalTrials.gov ID
- NCT00377416
- Acronym / sponsor ID
- 366
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Keywords
- Gene Transfer Techniques, Gene Therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of Massachusetts, WorcesterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Alpha-1 Foundation, University of Florida, National Center for Research Resources (NCRR)
- Study start
- Mar 2004
- Primary completion
- Oct 2006 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 18 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
AAT deficiency is a genetic disorder in which individuals have inadequate levels of the AAT protein. AAT protects the lungs from white blood cell enzymes that can damage air sacs within the lungs, potentially leading to emphysema. Experimental gene transfer procedures, in which normal copies of genes are inserted into cells, are being developed to treat many genetic diseases, including AAT deficiency. In this study, a modified virus, adeno-associated virus (AAV), has been genetically engineered to contain a normal copy of the AAT gene. When AAV is combined with the AAT gene, the resulting agent, rAAV2-CB-hAAT, is able to carry normal copies of the AAT gene into muscle cells to produce additional AAT. The purpose of this study is to evaluate the safety of injecting rAAV2-CB-hAAT into individuals with AAT deficiency.
This 13-month study will enroll individuals with AAT deficiency. Participants currently using AAT protein replacement will discontinue its use for 15 weeks during the study. Participants will first attend a baseline study visit, which will include a medical history review; a physical examination; an electrocardiogram (ECG) to record heart activity; blood, urine, and semen collection; pulmonary function tests; and chest and arm scans. Participants will then 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. Physical examinations will occur on all 5 inpatient days; pulmonary function testing, arm circumference measurements, and collection of blood, urine, and semen will occur on selected days of the inpatient stay. Follow-up study visits, with possible overnight stays, will occur on Days 14 and 90. On Days 30, 45, 60, 75, 180, 270, and 365, participants will have blood drawn at a local clinic. On these same days, study staff will contact participants by telephone to review their medical history and symptoms. Unused blood and semen samples will be frozen and stored for future research purposes. Participants will have yearly follow-up evaluations by either telephone or mail for a total of 15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Genetic: rAAV2-CB-hAAT Gene VectorrAAV2-CB-hAAT Gene Vector |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rAAV2-CB-hAAT Gene VectorParticipants 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. | Genetic | 1 |
Primary outcome
Arm circumference
Time frame: Measured at Day 3
Presence of rAAV2-CB-hAAT vector in blood and semen
Time frame: Measured at Day 14
Serum chemistries, hematology, urinalysis, immune response, and pulmonary function
Time frame: Measured at Day 90
Human AAT levels and phenotype in the blood
Time frame: Measured at Day 180
Adverse events
Time frame: Measured at Year 1 and at yearly follow-up evaluations over 15 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2020.
- Background: PubMed 14965381Flotte 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.
- Background: PubMed 9826709Song 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.
- Derived from this study: PubMed 34256305Remih 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Terence R. Flotte, MD principal investigator
UMass Medical School
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing rAAV2-CB-hAAT Gene Vector in people with Alpha 1-Antitrypsin Deficiency, run by University of Massachusetts, Worcester at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arm circumference (time frame: Measured at Day 3). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00377416, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2020.