Advertisement

Topics

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

2014-07-24 14:10:13 | BioPortfolio

Summary

This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector expressing alpha-1 antitrypsin in patients with alpha-1 antitrypsin deficiency. Three groups of three subjects each will receive the study drug by intramuscular injection, with progressively larger doses in the second and third groups.

Description

The study is a non-randomized, open-label, multi-center, sequential, three-arm, Phase 2 clinical trial evaluating the safety and efficacy of administration of a rAAV1-CB-hAAT vector administered by IM injection. Each participant will receive rAAV1-CB-hAAT on a single occasion. Three groups of three subjects each will receive rAAV1-CB-hAAT at dosage levels of 6 x 10e11 vg/kg, 1.9 x 10e12 vg/kg or 6 x 10e12 vg/kg by IM injection. Subjects in group 1 will receive a total of 10 IM injections distributed across a single muscle site, subjects in group 2 will receive a total of 32 IM injections distributed across three muscle sites, and subjects in group 3 will receive 100 IM injections distributed across 10 muscle sites. Each injection will be given in a volume of 1.35 mL, at the appropriate vector concentration to achieve the desired total vector dose, and the injection density at each administration site (nine IM injections per 4 cm2 skin surface area) will be the same as the injection density that was well tolerated in a previous Phase 1 clinical trial with rAAV1-CB-hAAT. Safety will be monitored by evaluation of adverse events, hematology and clinical chemistry parameters, histological examination of muscle biopsies, and measurement of serum antibodies to AAT. Efficacy will be measured by evaluation of serum concentrations of M-specific AAT and total AAT and serum AAT phenotype determined on isoelectric focusing gels. Additional information to be collected will include presence of the vector in blood or semen, changes in serum anti-AAV antibody titers, and changes in T cell responses to AAV and AAT.

Study Design

Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Alpha-1 Antitrypsin Deficiency

Intervention

rAAV1-CB-hAAT

Location

National Jewish Health
Denver
Colorado
United States
80206

Status

Recruiting

Source

Applied Genetic Technologies Corp

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-24T14:10:13-0400

Clinical Trials [787 Associated Clinical Trials listed on BioPortfolio]

Experimental Gene Transfer Procedure to Treat Alpha 1-Antitrypsin Deficiency

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...

Experimental Gene Transfer Procedure to Treat Alpha 1-Antitrypsin Deficiency

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...

Safety Study of an Aerosolized, Recombinant Alpha 1-Antitrypsin in Subjects With Alpha 1-Antitrypsin Deficiency

The purpose of this randomized, double-blind, placebo-controlled study is to evaluate the short-term safety of inhaled recombinant alpha 1-antitrypsin (rAAT) in subjects with alpha 1-antit...

Alpha-1 Antitrypsin Deficiency Adult Liver Study

The investigators hypothesize that there is liver injury (inflammation, fibrosis, cirrhosis) in adults with Alpha-1 Antitrypsin Deficiency (AATD), which is asymptomatic, under-recognized, ...

The Safety and Tolerability of Alpha-1 MP In Subjects With Alpha-1-Antitrypsin (AAT) Deficiency

The purpose of this clinical study is to assess the safety and tolerability of Alpha-1 MP in adult Alpha1-antitrypsin deficient patients.

PubMed Articles [3244 Associated PubMed Articles listed on BioPortfolio]

Comparison of exercise training responses in COPD patients with and without Alpha-1 antitrypsin deficiency.

The benefits of pulmonary rehabilitation (PR) on fatigue-resistant skeletal muscle fibre type I have been found to be smaller in COPD patients with alpha-1 antitrypsin deficiency (AATD) than in those ...

Intensive smoking diminishes the differences in quality of life and exacerbation frequency between the alpha-1-antitrypsin deficiency genotypes PiZZ and PiSZ.

Alpha-1-antitrypsin deficiency (AATD) is a rare genetic disorder that is associated with low levels of circulating alpha-1-antitrypsin in serum. In comparison to the genotype PiZZ, PiSZ usually leads ...

Retrospective analysis of children with α-1 antitrypsin deficiency.

α-1 Antitrypsin (AAT) deficiency is the most frequently occurring genetic liver disorder. The association among classical α-1 antitrypsin deficiency (AATD), chronic liver disease, and cirrhosis is c...

Could autophagy induced by misfolded mutant alpha-1-antitrypsin Z in synovitis explain the association of ATZ with increased ACPA production in RA?

We read with interest the paper "Genetic variation of the alpha-1-antitrypsin (AT) gene is associated with increased autoantibody production in rheumatoid arthritis" by McCarthy et al. A strong assoc...

Therapeutic Genome Editing With CRISPR/Cas9 in a Humanized Mouse Model Ameliorates α1-antitrypsin Deficiency Phenotype.

α1-antitrypsin (AAT) is a circulating serine protease inhibitor secreted from the liver and important in preventing proteolytic neutrophil elastase associated tissue damage, primarily in lungs. In hu...

Medical and Biotech [MESH] Definitions

Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN, leading primarily to degradation of elastin of the alveolar walls, as well as other structural proteins of a variety of tissues. (From Scriver, Beaudet, Sly, & Valle, The Metabolic and Molecular Bases of Inherited Disease, 7th ed, p4125)

A trypsin-like enzyme of spermatozoa which is not inhibited by alpha 1 antitrypsin.

Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.

Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.

A transcription factor that regulates the expression of a large set of hepatic proteins including SERUM ALBUMIN; beta-fibrinogen; and ALPHA 1-ANTITRYPSIN. It is composed of hetero- or homo-dimers of HEPATOCYTE NUCLEAR FACTOR 1-ALPHA and HEPATOCYTE NUCLEAR FACTOR 1-BETA.

More From BioPortfolio on "Safety & Efficacy Study of rAAV1-CB-hAAT for Alpha-1 Antitrypsin Deficiency"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Pharmacy
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Rheumatology
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...


Searches Linking to this Trial