Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency

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Brief Title

Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency

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

Brief Summary

      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

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Overall survival following gene therapy

Secondary Outcome

 Reduction in frequency of infections


Adenosine Deaminase Deficiency


EF1αS-ADA lentiviral vector transduced patient Cd34+ cells

Study Arms / Comparison Groups

 EF1αS-ADA lentiviral vector transduced patient Cd34+ cells


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

November 2012

Completion Date

December 2018

Primary Completion Date

December 2018

Eligibility Criteria

        Inclusion Criteria:

          1. Diagnosis of ADA-SCID confirmed by DNA sequencing or by confirmed absence of <3% of
             ADA enzymatic activity in peripheral blood (or for neonates) umbilical cord blood
             erythrocytes and/or leukocytes or in cultured fetal cells derived from either
             chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement

          2. Patients who lack a fully Human leukocyte antigen (HLA)-matched family donor

          3. Patients (male or female) <5 years of age OR Patients (male or female) ≥ 5 years to 15
             years of age who have preserved thymic function as evidenced by presence of >10 %
             naïve T cells (CD4+45RA+27+ cells)

          4. Parental/guardian signed informed consent

        Exclusion Criteria:

          1. Cytogenetic abnormalities on peripheral blood

          2. Evidence of active malignant disease

          3. Known sensitivity to busulfan

          4. If applicable, confirmed pregnancy (to be tested in patients above 12 years old)




N/A - 5 Years

Accepts Healthy Volunteers



Claire Booth, Dr, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Great Ormond Street Hospital for Children NHS Foundation Trust

Study Sponsor

Claire Booth, Dr, Principal Investigator, Great Ormond Street Hospital NHS Foundation Trust

Verification Date

August 2018