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Clinical Trial Report
Gene Therapy Trial Report
Summary
ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
NCTID
NCT00598481
(View at clinicaltrials.gov)
Description
This is a phase I/II protocol to evaluate the safety and efficacy of ADA gene transfer into hematopoietic stem/progenitor cells for the treatment of adenosine deaminase (ADA)-deficiency. This condition is an autosomal recessive form of Severe Combined Immunodeficiency (SCID) characterized by impaired immune responses, recurrent infections, failure to thrive and systemic toxicity due to accumulation of purine metabolites. Transplants from an human leukocyte-antigen (HLA)-identical sibling donor is the treatment of choice, but available for a minority of patients. The use of alternative bone marrow donors or enzyme replacement therapy is associated with important drawbacks. The drug product studied in this protocol consists of autologous cluster of differentiation (CD)34+ hematopoietic stem/progenitor cells engineered ex vivo with a retroviral vector encoding the therapeutic gene ADA. The engineered CD34+ cells are infused following a nonmyeloablative conditioning with busulfan to make space in the bone marrow. The study objectives are: a) to evaluate the safety and the clinical efficacy of gene therapy, in the absence of enzyme replacement therapy; b) to evaluate the biological activity (engraftment, ADA expression) of ADA transduced CD34+ cells and their hematopoietic progeny. c) to evaluate the immunological reconstitution and purine metabolism after gene therapy.
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Development Status
Approved
Indication
Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID)
Disease Ontology Term
DOID:5810
Compound Name
STRIMVELIS
Compound Alias
GSK2696273
Compound Description
CD34+ cells transduced with MND-ADA retroviral vector
Sponsor
Fondazione Telethon
Funder Type
Other
Recruitment Status
Completed
Enrollment Count
12
Results Posted
View Results
Therapy Information
Target Gene/Variant
ADA
Therapy Type
Gene transfer
Therapy Route
Ex-vivo
Mechanism of Action
Functional gene replacement
Route of Administration
Intravenous
Drug Product Type
Autologous cells
Target Tissue/Cell
CD34+ cells
Delivery System
Viral transduction
Vector Type
MoMLV (RV)
Editor Type
Dose 1
Median dose: 11.6E6 CD34+ cells/kg (19 patients)
Dose 2
Median dose: 9.2E6 CD34+ cells/kg (22 patients)
Dose 3
Dose 4
Dose 5
Study Record Dates
Current Stage
Phase2
Submit Date
2008-01-10
Completion Date
2019-06-19
Last Update
2024-01-29
Participation Criteria
Eligible Age
<=17 Years
Standard Ages
Child
Sexes Eligible for Study
ALL
Locations
No.of Trial Sites
2
Locations
Italy,Israel
Regulatory Information
Has US IND
FDA Designations
Recent Updates
Product was initially developed by SR-TIGET, in-licensed by GlaxoSmithKline in 2010. EMA approval in May 2016. GSK sold Strimvelis in March 2018 to Orchard Therapeutics. Orchard discontinued the program in March 2022. Product license was transferred to Fondazione Telethon in July 2023
Resources/Links
Clinical Publications
Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients
Gene therapy for immunodeficiency due to adenosine deaminase deficiency
Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning
A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID
ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency
Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy
Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency
Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety
Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency
Gene therapy in peripheral blood lymphocytes and bone marrow for ADA- immunodeficient patients
News and Press Releases
SEC Form 10-Q: Orchard Therapeutics PLC 3Q2023
Preclinical Publications
Good Laboratory Practice Preclinical Safety Studies for GSK2696273 (MLV Vector-Based Ex Vivo Gene Therapy for Adenosine Deaminase Deficiency Severe Combined Immunodeficiency) in NSG Mice
An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency
Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID
Related NCTID
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