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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
Sponsor:
Information provided by (Responsible Party):
Great Ormond Street Hospital for Children NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE June 23, 2011
First Posted Date  ICMJE June 27, 2011
Last Update Posted Date August 10, 2018
Study Start Date  ICMJE November 2012
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2011)
Overall survival following gene therapy [ Time Frame: 3 years follow up ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01380990 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2011)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency
Official Title  ICMJE 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

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adenosine Deaminase Deficiency
  • Severe Combined Immunodeficiencies (SCID)
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells
Intervention: Genetic: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 23, 2011)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2018
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 therapy
  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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE up to 5 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01380990
Other Study ID Numbers  ICMJE 10-MI-29
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Great Ormond Street Hospital for Children NHS Foundation Trust
Study Sponsor  ICMJE Great Ormond Street Hospital for Children NHS Foundation Trust
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Claire Booth, Dr Great Ormond Street Hospital NHS Foundation Trust
PRS Account Great Ormond Street Hospital for Children NHS Foundation Trust
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP