Gene therapy for Wiskott-Aldrich Syndrome (WAS)

ISRCTN	ISRCTN30718752
DOI	https://doi.org/10.1186/ISRCTN30718752
ClinicalTrials.gov (NCT)	NCT01347346
Protocol serial number	GTG003.08
Sponsor	Genethon (France)
Funder	Genethon (France)

Submission date: 03/05/2011
Registration date: 20/05/2011
Last edited: 11/04/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Haematological Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Alain Fischer
Scientific

Unité d'Immunologie et d'Hématologie Pédiatriques
Hôpital Necker-Enfants Malades
149 rue de Sèvres
Paris
75015
France

Study information

Primary study design	Interventional
Study design	Open labelled non-randomised single centre phase I/II cohort study
Secondary study design	Non randomised controlled trial
Study type	Participant information sheet
Scientific title	Phase I/II clinical trial of haematopoietic stem cell gene therapy for the Wiskott-Aldrich Syndrome
Study objectives	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(s)	Committee to Protect People (Comité de Protection des Personnes) - Ile de France 2 approved on 11th August 2009, (ref : 2009-04-01)
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Gene therapy
Primary outcome measure(s)	1. Safety of conditioning regimen (haematopoietic recovery within 6 weeks 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 1 x 106CD34+ cells per kg; retrospective undetectable (replication-competent lentiviruses)RCL; and cell viability equal to or greater than 70%, in accordance with the GMO 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 (as assessed by increased blood platelet counts, expected to rise above 50,000/mm3 and platelets size restoration)
Key secondary outcome measure(s)	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 (as assessed by clinical monitoring)
Completion date	31/12/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Male
Target sample size at registration	5
Key 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. Unless desease severity indicates that one cannot wait for 3 months (score 5; refractory thrombocytopenia with platelets < 5000 with bleeding or severe autoimmunity) 5. Lack of HLA-genotypically identical bone marrow after 3 month search 6. Lack of a 10/10 or 9/10 antigen HLA-matched unrelated donor after 3 month search 7. Lack of a HLA-matched cord blood after 3 month search 8. Parental, guardian, patient signed informed consent/assessment 9. Willing to return for follow-up during the 2 year study and lifelong for off study review 10. Only for patients who have received previous allogenic haematopoietic stem cell transplant 10.1. Failed allogenic haematopoietic stem cell transplant 10.2. Contraindication to repeat allogenic transplantation
Key exclusion criteria	1. Patient with HLA-genotypically identical bone marrow 2. Patient with 10/10 or 9/10 antigen HLA-matched unrelated donor or with HLA-matched cord blood 3. Contraindication to leukapheresis 3.1. Anaemia (Hb < 8g/dl) 3.2. Severe vascularitis 3.3. Refractory thrompopenia 3.3.1. Contraindication to bone marrow harvest 3.3.2. Contraindication to administration of conditioning medication 4. Human immunodeficiency virus (HIV) seropositive patient
Date of first enrolment	16/05/2011
Date of final enrolment	31/12/2013

Locations

Countries of recruitment

France

Study participating centre

Unité d'Immunologie et d'Hématologie Pédiatriques

Paris
75015
France

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	21/04/2015	11/04/2019	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

11/04/2019: Publication reference added.