Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency
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|ClinicalTrials.gov Identifier: NCT01380990|
Recruitment Status : Active, not recruiting
First Posted : June 27, 2011
Last Update Posted : August 10, 2018
Adenosine Deaminase (ADA) is an enzyme, needed by body to develop lymphocytes of the immune system. Children who are born in mutations with mutations in ADA gene have severe combined immunodeficiency (SCID). Children with ADA-deficient SCID generally die in the first year of life from severe infections because they do not have immune system that can fight against infections. ADA deficient individuals can be cured by bone marrow transplant, but the best results are obtained when there is fully matched family donor is available. In the absence of a matched related donor, transplants from unrelated or mismatched donors have a much worse outcome. There is a form of enzyme therapy (PEG-ADA) for ADA-deficient SCID, in which children receive injections of purified ADA enzyme 1-2 times each week. These injections can allow the immune system to recover to a level that protects children from infections.
However, these injections have to be given weekly and are very expensive (£ 125,000 - 200,000 annually) and the recovery of the immune system is not sustained over time.
Gene therapy for ADA-deficient SCID could be performed by introducing a normal copy of the human ADA gene into the blood forming stem cells of the patient's bone marrow by using a new type of gene delivery system (in this trial called a lentiviral vector). The gene corrected cells are then transplanted back into the patient after small dose of chemotherapy. These gene corrected stem cells can survive into the body and make lymphocytes. In this trial, we will determine whether gene therapy for ADA-deficient SCID using lentiviral vector is safe, feasible and effective
|Condition or disease||Intervention/treatment||Phase|
|Adenosine Deaminase Deficiency Severe Combined Immunodeficiencies (SCID)||Genetic: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II, Non-controlled, Open-label, Non-randomised, Single-centre Trial to Assess the Safety and Efficacy of EF1αS-ADA Lentiviral Vector Mediated Gene Modification of Autologous CD34+ Cells From ADA-deficient Individuals|
|Study Start Date :||November 2012|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
|Experimental: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells||
Genetic: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells
EF1αS-ADA lentiviral vector transduced patient Cd34+ cells will be infused in a volume of ~10-20 mls/kg intravenously over 30-45 minutes.
- Overall survival following gene therapy [ Time Frame: 3 years follow up ]
- Reduction in frequency of infections [ Time Frame: evaluated from 1st year after treatment by clinical history, complete physical examinations, haematological and microbiological tests ]
- Long term immune reconstitution as assessed by sustained improvement in thymic function [ Time Frame: 3 years follow up ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01380990
|Great Ormond Street Hospital for Children NHS Trust|
|London, United Kingdom, WC1N 3JH|
|Principal Investigator:||Claire Booth, Dr||Great Ormond Street Hospital NHS Foundation Trust|