Gene therapy for Wiskott-Aldrich Syndrome (WAS)
| ISRCTN | ISRCTN30718752 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN30718752 |
| ClinicalTrials.gov number | NCT01347346 |
| Secondary identifying numbers | GTG003.08 |
- 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
Scientific
Unité d'Immunologie et d'Hématologie Pédiatriques
Hôpital Necker-Enfants Malades
149 rue de Sèvres
Paris
75015
France
Study information
| Study design | Open labelled non-randomised single centre phase I/II cohort study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase I/II |
| Drug / device / biological / vaccine name(s) | Gene therapy |
| Primary outcome measure | 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) |
| 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 (as assessed by clinical monitoring) |
| Overall study start date | 16/05/2011 |
| Completion date | 31/12/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Male |
| Target number of participants | 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
75015
France
Sponsor information
Genethon (France)
Industry
Industry
1 bis, rue de l'Internationale
Evry
91000
France
| Website | http://www.genethon.fr |
|---|---|
"ROR" |
https://ror.org/03fj96t64 |
Funders
Funder type
Industry
Genethon (France)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 |
Editorial Notes
11/04/2019: Publication reference added.
