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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 20 July 2020
Main ID:  EUCTR2010-024253-36-GB
Date of registration: 09/05/2012
Prospective Registration: Yes
Primary sponsor: Great Ormond Street Hospital for Children NHS Trust
Public title: A clinical trial to study the effects of genetically modified patients' CD34+ cells
Scientific title: Phase I/II, historical controlled, open-label, non-randomised, single-centre trial to assess the safety and efficacy of EF1aS-ADA lentiviral vector mediated gene modification of autologus CD34+ cells from ADA-deficient individuals - LV Gene Therapy for ADA Deficiency
Date of first enrolment: 03/08/2012
Target sample size: 10
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024253-36
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: no
Open: yes
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: yes
Other trial design description: Historical control group
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: yes
Other specify the comparator: allogeneic haematopoietic stem cell transplantation control group
Number of treatment arms in the trial: 1
 
Phase:  Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
United Kingdom
Contacts
Name: Avani Shukla   
Address:  30 Guilford Street WC1N 1EH London United Kingdom
Telephone: 02079052863
Email: Avani.Shukla@gosh.nhs.uk
Affiliation:  UCL Institute of Child Health & GOSH R&D Office
Name: Avani Shukla   
Address:  30 Guilford Street WC1N 1EH London United Kingdom
Telephone: 02079052863
Email: Avani.Shukla@gosh.nhs.uk
Affiliation:  UCL Institute of Child Health & GOSH R&D Office
Key inclusion & exclusion criteria
Inclusion criteria:
Patients treated with Gene Therapy
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) in umbilical cord blood erythrocytes and/or leucocytes 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 HLA-matched family donor
3. Patients (male or female) <5yrs of age OR
Patients (male or female) >5yrs to 15 yrs 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

Historical HSCT control group
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) in umbilical cord blood erythrocytes and/or leucocytes or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement therapy
2. Patients (male or female) from all age
3. Patient treated with allogeneic haematopoietic stem cell transplantation

No exclusion criteria

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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)


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes
Health Condition(s) or Problem(s) studied
Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. If not treated in a way that restores immune function, children with SCID usually live only a year or two.
MedDRA version: 20.0 Level: LLT Classification code 10066372 Term: ADA deficiency System Organ Class: 100000012248
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Intervention(s)

Product Name: EF1aS-ADA lentiviral vector transduced patient CD34+ cells
Product Code: transduced patient CD34+ cells
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: EF1aS-ADA lentiviral vector gene modified autologous CD34+ cells
Other descriptive name: Autologous CD34+ HSCs transduced ex vivo with EFS lentiviral vector encoding for the human ADA gene
Concentration unit: Other
Concentration type: not less then
Concentration number: 500000-

Primary Outcome(s)
Main Objective: 1. To examine the safety and efficacy of lentiviral vector mediated gene therapy for ADA-deficient SCID.
2. To assess efficacy of treatment by measurement of ADA cDNA copy number in peripheral blood leukocytes using real-time PCR.
3. To assess efficacy of treatment by measurement of cellular and humoral immune system recovery
4. To assess efficacy of treatment by measurement of ADA activity and reduction in dATP in peripheral blood cells
5. To assess safety of treatment by clinical, haematological and immunological monitoring of patients
6. To assess safety of treatment by analysis of vector integration sites and analysis of clonal proliferation
7. To compare outcomes between patients treated with gene therapy and patients treated with allogeneic HSCT
Primary end point(s): 1) Overall survival following gene therapy after 1 year post gene therapy

2) Disease free survival as assessed by complete cessation of PEG-ADA 2 years post gene therapy

3) Engraftment of genetically corrected haematopoietic progenitors and/or differentiated cells in peripheral blood and/or in bone marrow (as assessed by evidence of vector copy number or transgene expression in the cells)

4) Reconstitution of cell mediated and humoral immunity 2 years post gene therapy (as assessed by evidence of changes in T cell function and circulating immunoglobulin levels).
5) Correction of metabolic abnormalities (as assessed by dATP at levels comparable to published data from HSCT treated patients and by evidence of ADA activity in erythrocytes)
6) Analysis of frequency of vector integration into known proto oncogene and analysis of frequency of clonal expansion associated with vector integration near proto oncogene
7) To compare overall survival and event-free survival between patients treated with gene therapy and patients treated with allogeneic HSCT
Secondary Objective: 1. To improve the overall health of the patient, including reduction in frequency of infections & promote growth.
2. To evaluate the longitudinal clinical effect in terms of improved immunity.
3. To evaluate tolerability of conditioning regimen
4. To evaluate feasibility of the transduction procedure


Timepoint(s) of evaluation of this end point: 3 years post-infusion of gene-modified cells.
Secondary Outcome(s)
Secondary end point(s): 1) Reduction in frequency of infections (evaluated from 1 year after treatment by clinical history, complete physical examinations at 3 years post-gene therapy, haematological tests) and improved weight parameter
2) Long term immune reconstitution as assessed by sustained improvement in thymic function assessed by TRECS after 2 years post-gene therapy
3) Tolerability of conditioning regimen assessed by hematopoietic recovery within 6 weeks as assessed by absolute neutrophil count (ANC) above 0.5 x 109 cells/l
4) Feasibility of the transduction procedure assessed by availability of greater than 0.5 x 106 CD34+ cells/kg after transduction; undetectable RCL (determined retrospectively); and CD45+ cell viability after transduction equal to or greater than 50%, in accordance with the final product release criteria
Timepoint(s) of evaluation of this end point: 3 years post-infusion of gene-modified cells.
Secondary ID(s)
10MI29
GTAC178
NCT01380990
Source(s) of Monetary Support
Department of Health, Internal Funder
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 30/01/2012
Contact:
Results
Results available: Yes
Date Posted: 09/07/2020
Date Completed: 23/12/2019
URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-024253-36/results
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