Gene Transfer for ADA-SCID Using an Improved Lentiviral Vector (TYF-ADA)
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|ClinicalTrials.gov Identifier: NCT03645460|
Recruitment Status : Not yet recruiting
First Posted : August 24, 2018
Last Update Posted : October 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)||Genetic: TYF-ADA gene-modified autologous stem cells||Not Applicable|
This clinical trial will evaluate a safety and efficiency improved lentiviral vector system for delivering a therapeutic gene to patients with severe combined immunodeficiency (SCID) due to a defective adenosine deaminase (ADA) gene. This gene encodes for the adenosine deaminase enzyme, which is essential for the proper growth and function of infection-fighting white blood cells called T and B lymphocytes. Patients who lack this enzyme are vulnerable to frequent and severe infections.
ADA-SCID patients are normally rescued by a bone marrow transplant (BMT) from a matched healthy donor. However, matched donors are difficult to find and donor BMT is associated with high risk. This trial aims to treat ADA-SCID using a safety and efficiency improved self-inactivating lentiviral vector carrying a functional ADA gene to correct the genetic defect. By collecting an individual's stem cells and modifying them with a lentivirus, the gene-corrected cells can be returned to the patient to help produce normal healthy immune cells.The primary objectives are to evaluate the safety of the improved self-inactivating lentiviral vector TYF-ADA, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment. We will assess the lentiviral gene integration sites and the long-term effect of this gene transfer procedure.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Gene Transfer for Adenosine Deaminase-severe Combined Immunodeficiency (ADA-SCID) Using an Improved Self-inactivating Lentiviral Vector (TYF-ADA)|
|Estimated Study Start Date :||October 30, 2018|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: TYF-ADA-modified autologous stem cells
Autologous hematopoietic and/or mesenchymal stem cells transduced with lentiviral vector carrying the ADA gene
Genetic: TYF-ADA gene-modified autologous stem cells
Infusion of TYF-ADA-modified autologous stem cells at 1~10x10^6 gene-modified cells per kg body weight; or more infusions depending on the circumstances
- Overall survival up to a year [ Time Frame: 15 years ]Patient will be monitored for overall health condition, including immune cell assessments, blood biochemistry and metabolitic activities, metabolic detoxification, gene-modified cell percentage and vector copy number (VCN) in the blood, and continued follow-up for 15 years.
- 1. Success of immune reconstitution [ Time Frame: 12 month ]Immunological and metabolic values including all leukocyte counts (ALC), T, B and NK cell counts (CD3, CD4, CD8, CD19, CD56), T cell TREC levels, T cell repertoire diversity, PHA proliferation rate, immunoglobulins and dATP levels will be measured.
- 2. Change of infection status [ Time Frame: 12 month ]Immune recovery associated with reduction of infection episodes and frequencies, including viral, fungal and bacterial infections will be documented.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03645460
|Contact: Lung-Ji Chang, Ph.Dfirstname.lastname@example.org|
|Shenzhen Geno-immune Medical Institute||Recruiting|
|Shenzhen, Guangdong, China, 518000|
|Contact: Lung-Ji Chang, Ph.D 86-0755-86725195 email@example.com|
|Principal Investigator: XiaoDong Shi, M.D./P.H.D|
|Principal Investigator: Jie Zheng, M.D./P.H.D|
|Principal Investigator:||Lung-Ji Chang, Ph.D||Shenzhen Geno-Immune Medical Institute|