Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT01347242
Protocol/serial number
GTG002.07
Study information
Scientific title
Phase I/II clinical trial of haematopoietic stem cell gene therapy for the Wiskott-Aldrich Syndrome
Acronym
Study hypothesis
Studying the safety and efficacy of an ex vivo gene therapy using a lentiviral vector containing the human Wiskott-Aldrich Syndrome protein gene in patients with WAS
Ethics approval
Gene Therapy Advisory Committee (GTAC) (UK), 21/12/2009, GTAC 146
Study design
Open-labelled non-randomised single-centre phase I/II cohort study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Wiskott-Aldrich Syndrome
Intervention
Ex vivo gene therapy using patient's autologous CD34+ cells transduced with a lentiviral vector containing the human WASP gene.
Patients undergo either a bone marrow harvest or a leukapheresis. They then receive a conditioning myeloablative regimen while CD34+ cells are selected in their bone marrow and transduced with the lentiviral vector (3 days). Patients then receive their transduced CD34+ cells (as in autologous bone marrow transplantation).
There are no real doses, simply quantity of CD34+ cells transduced will depend on the amount of bone marrow harvest and quality of transduction. This is part of the parameters that are being assessed in the trial.
Duration of the study follow-up is 2 years.
Intervention type
Drug
Phase
Phase I/II
Drug names
Primary outcome measure
1. Safety of conditioning regimen (haematopoietic recovery within 6 weeks as assessed by absolute neutrophil count (ANC) above 0.5 x 109 /l )
2. Safety of the transduction procedure [as assessed by availability of greater than 0.5 x 106 cells per kg after transduction; undetectable replication-competent lentiviruses (RCL) (determined retrospectively); and cell viability after transduction equal to or greater than 50%, in accordance with the final product release criteria]
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 sequences or transgene expression in the cells)
4. Reconstitution of cell mediated and humoral immunity (as assessed by evidence of changes in T cell function and circulating immunoglobulin levels)
5. Correction of microthrombocytopenia (if not previously splenectomised, and as assessed by increased blood platelet counts, expected to rise above 50,000/mm3)
Secondary outcome measures
1. Reduction in frequency of infections (evaluated from 2nd year after treatment by clinical history, complete physical examinations, haematological and microbiological tests)
2. Resolution/reduction of autoimmunity (a decrease from baseline observations assessed by clinical examination)
3. Improvement in eczema (a decrease from baseline observations assessed by clinical examination)
4. Reduction in bruising and bleeding episodes when present (as assessed by clinical monitoring)
Overall trial start date
23/02/2010
Overall trial end date
31/12/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Males of all ages
2. Severe WAS (clinical score 3 5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry
3. Molecular confirmation by WAS gene DNA sequencing
4. Lack of HLA-genotypically identical bone marrow or of a 10/10 antigen HLA-matched unrelated donor or cord blood after 3 month search
5. Parental, guardian, patient signed informed consent/assessment
6. Willing to return for follow-up during the 2 year study and the 3 year long-term off study review
7. Only for patients who have received previous allogenic haematopoietic stem cell transplant:
7.1. Failed allogenic haematopoietic stem cell transplant
7.2. Contraindication to repeat allogeneic transplantation for example severe graft versus host disease
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
5
Participant exclusion criteria
1. Patient with HLA-genotypically identical bone marrow
2. Patient with 10/10 antigen HLA-matched unrelated donor or cord blood
3. Contraindication to leukapheresis
3.1. Anaemia (Hb < 8g/dl)
3.2. Cardiovascular instability
3.3. Severe coagulopathy
3.3.1. Contraindication to bone marrow harvest
3.3.2. Contraindication to administration of conditioning medication
3. Human immunodeficiency virus (HIV) positive patient
Recruitment start date
23/02/2010
Recruitment end date
31/12/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Institute of Child Health
London
WC1N 1EH
United Kingdom
Sponsor information
Organisation
Genethon (France)
Sponsor details
1 bis
rue de l'Internationale
Evry
91000
France
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Genethon (France)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28716862