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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: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT01380990
Date of registration: 23/06/2011
Prospective Registration: Yes
Primary sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Public title: Lentiviral (LV) Gene Therapy for Adenosine Deaminase (ADA) Deficiency
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 Autologous CD34+ Cells From ADA-deficient Individuals
Date of first enrolment: November 15, 2012
Target sample size: 36
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT01380990
Study type:  Interventional
Study design:  Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 1/Phase 2
Countries of recruitment
United Kingdom
Contacts
Name:     Claire Booth, Dr
Address: 
Telephone:
Email:
Affiliation:  Great Ormond Street Hospital NHS Foundation Trust
Key inclusion & exclusion criteria

Gene Therapy (On Trial)

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 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)

Gene Therapy (CUP)

A group of patients were treated under CUP (GOSH special license) either because the study
was not yet open and patients needed urgent treatment, or because they were outside of the
inclusion/exclusion criteria or received IMP followed a different process (ie, received in
two infusions). Patients followed the same protocol steps and study visits.

Historical 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 foetal cells derived from either
chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement
therapy

2. Patients (male or female) between 0-18 years at time of treatment

3. Patient treated with allogeneic haematopoietic stem cell transplantation since 2000



Age minimum: N/A
Age maximum: 15 Years
Gender: All
Health Condition(s) or Problem(s) studied
Adenosine Deaminase Deficiency
Severe Combined Immunodeficiencies (SCID)
Intervention(s)
Drug: Busulfan
Drug: Peg-Ada
Genetic: Infusion of autologous EFS-ADA LV CD34+ cells
Other: Haematopoietic Stem Cell Transplantation (HSCT)
Primary Outcome(s)
Analysis of the frequency of clonal expansion associated with vector integration near proto-oncogenes [Time Frame: 3 years]
Analysis of the frequency of vector integration into known proto-oncogenes [Time Frame: 3 years]
Clinical progress of patients [Time Frame: 3 years]
Comparison of OS and EvFS of subjects treated with IMP with those of patients treated with allogeneic HSCT [Time Frame: 1 year]
Event Free Survival (EvFS) of subjects treated with IMP [Time Frame: 1 year]
Hematological, and immunological progress of patients [Time Frame: 3 years]
Overall Survival (OS) of subjects treated with Investigational Medicinal Product (IMP) [Time Frame: 1 year]
Success of engraftment and resulting immunological and metabolic effects in subjects who received the IMP [Time Frame: 3 years]
Secondary Outcome(s)
Comparison of OS and EvFS outcomes at 2 and 3 years in subjects treated with IMP and patients who received allogeneic HSCT allogeneic Hematopoietic Stem Cell Transplantation (HSCT) [Time Frame: 2 and 3 years]
Reduction in the frequency of infections, evaluated at 1, 2, and 3 years post treatment on the basis of clinical history and examination [Time Frame: 1, 2 and 3 years]
Secondary ID(s)
10-MI-29
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Orchard Therapeutics
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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