Last updated: 11/03/2018 21:21:16
This product has been transferred to Orchard Therapeutics Limited. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov
Gene Therapy for Wiskott-Aldrich SyndromeTIGET-WAS
GSK study ID
201228
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: A phase I/II clinical trial of hematopoietic stem cell gene therapy for the Wiskott-Aldrich syndrome
Trial description: This is phase I/II protocol to evaluate the safety and efficacy of WAS gene transfer into hematopoietic stem/progenitor cells for the treatment of Wiskott Aldrich Syndrome.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Conditioning regimen-related safety
Timeframe: two months after gene therapy
Safety of lentivirus gene transfer into HSC
Timeframe: 3 years
Sustained engraftment of genetically corrected haematopoietic stem cells in peripheral blood and/or in bone marrow
Timeframe: 1 year
Expression of vector-derived WASP
Timeframe: 1 year
Improved T-cell functions
Timeframe: 3 years
Antigen-specific responses to vaccination
Timeframe: >1year
Improved platelet count and MPV normalization
Timeframe: 3 years
overall survival
Timeframe: 3 years
Secondary outcomes:
Lack of immune response to transgene
Timeframe: 3 years
Reduced frequency of severe infections
Timeframe: 3 years
Reduced bruising and bleeding episodes
Timeframe: 3 years
Reduced autoimmunity phenomena and eczema
Timeframe: 3 years
Improved quality of life
Timeframe: 3 year
Multilineage engraftment of genetically corrected cells
Timeframe: 3 years
Overall safety of the treatment
Timeframe: 8 years
Interventions:
Genetic: Autologous CD34 positive cells transduced with WAS encoding lentiviral vector.
Enrollment:
8
Observational study model:
Not applicable
Primary completion date:
2018-22-10
Time perspective:
Not applicable
Clinical publications:
Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, Dionisio F, Calabria A, Giannelli S, Castiello MC, Bosticardo M, Evangelio C, Assanelli A, Casiraghi M, Di Nunzio S, Callegaro L, Benati C, Rizzardi P, Pellin D, Di Serio C, Schmidt M, Von Kalle C, Gardner J, Mehta N, Neduva V, Dow DJ, Galy A, Miniero R, Finocchi A, Metin A, Banerjee PP, Orange JS, Galimberti S, Valsecchi MG, Biffi A, Montini E, Villa A, Ciceri F, Roncarolo MG, Naldini L. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science. 2013 Aug 23;341(6148):1233151. doi: 10.1126/science.1233151. Epub 2013 Jul 11.
Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, Scaramuzza S, Andolfi G, Mirolo M, Brigida I, Tabucchi A, Carlucci F, Eibl M, Aker M, Slavin S, Al-Mousa H, Al Ghonaium A, Ferster A, Duppenthaler A, Notarangelo L, Wintergerst U, Buckley RH, Bregni M, Marktel S, Valsecchi MG, Rossi P, Ciceri F, Miniero R, Bordignon C, Roncarolo MG. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009 Jan 29;360(5):447-58. doi: 10.1056/NEJMoa0805817.
Aiuti A, Roncarolo MG. Ten years of gene therapy for primary immune deficiencies. Hematology Am Soc Hematol Educ Program. 2009:682-9. doi: 10.1182/asheducation-2009.1.682. Review.
Bosticardo M, Marangoni F, Aiuti A, Villa A, Grazia Roncarolo M. Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome. Blood. 2009 Jun 18;113(25):6288-95. doi: 10.1182/blood-2008-12-115253. Epub 2009 Apr 7. Review.
Boztug K, Dewey RA, Klein C. Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther. 2006 Oct;8(5):390-5. Review.
Burns S, Cory GO, Vainchenker W, Thrasher AJ. Mechanisms of WASp-mediated hematologic and immunologic disease. Blood. 2004 Dec 1;104(12):3454-62. Epub 2004 Aug 12. Review.
Charrier S, Dupré L, Scaramuzza S, Jeanson-Leh L, Blundell MP, Danos O, Cattaneo F, Aiuti A, Eckenberg R, Thrasher AJ, Roncarolo MG, Galy A. Lentiviral vectors targeting WASp expression to hematopoietic cells, efficiently transduce and correct cells from WAS patients. Gene Ther. 2007 Mar;14(5):415-28. Epub 2006 Oct 19.
Dupré L, Trifari S, Follenzi A, Marangoni F, Lain de Lera T, Bernad A, Martino S, Tsuchiya S, Bordignon C, Naldini L, Aiuti A, Roncarolo MG. Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction. Mol Ther. 2004 Nov;10(5):903-15.
Follenzi A, Sabatino G, Lombardo A, Boccaccio C, Naldini L. Efficient gene delivery and targeted expression to hepatocytes in vivo by improved lentiviral vectors. Hum Gene Ther. 2002 Jan 20;13(2):243-60.
Galy A, Roncarolo MG, Thrasher AJ. Development of lentiviral gene therapy for Wiskott Aldrich syndrome. Expert Opin Biol Ther. 2008 Feb;8(2):181-90. doi: 10.1517/14712598.8.2.181 . Review.
Marangoni F, Bosticardo M, Charrier S, Draghici E, Locci M, Scaramuzza S, Panaroni C, Ponzoni M, Sanvito F, Doglioni C, Liabeuf M, Gjata B, Montus M, Siminovitch K, Aiuti A, Naldini L, Dupré L, Roncarolo MG, Galy A, Villa A. Evidence for long-term efficacy and safety of gene therapy for Wiskott-Aldrich syndrome in preclinical models. Mol Ther. 2009 Jun;17(6):1073-82. doi: 10.1038/mt.2009.31. Epub 2009 Mar 3. Erratum in: Mol Ther. 2009 Jul;17(7):1300.
Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, Strina D, Patrosso MC, Ramenghi U, Sacco MG, et al. X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nat Genet. 1995 Apr;9(4):414-7.
Medical condition
Wiskott-Aldrich Syndrome
Product
GSK2696275
Collaborators
Not applicable
Study date(s)
April 2010 to September 2023
Type
Interventional
Phase
2
Participation criteria
Sex
Male
Age
Not applicable
Accepts healthy volunteers
No
- 1) Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:
- Severe WAS mutation
- 1) Patients positive for HIV-infection.
- 2) Patients affected by neoplasia.
Inclusion and exclusion criteria
Inclusion criteria:
- 1) Diagnosis of WAS defined by genetic mutation and at least one of the following criteria: -Severe WAS mutation -Absence of WASP expression -Severe clinical score (Zhu clinical score ≥ 3 2) No HLA-identical sibling donor 3) Negative search for a matched unrelated donor (10/10) or an adequate unrelated cord blood donor (5-6/6) within 4-6 months
- Patients of > 5 years of age who are not candidate to unrelated allogeneic transplant based on clinical conditions. 4) Parental/guardian/patient signed informed consent.
Exclusion criteria:
- 1) Patients positive for HIV-infection. 2) Patients affected by neoplasia. 3) Patients with cytogenetic alterations typical of MDS/AML. 4) Patients with end-organ functions or any other severe disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study. 5) Patients who underwent an allogeneic haematopoietic stem cell transplantation in the previous 6 months. 6) Patients who underwent an allogeneic haematopoietic stem cell transplantation with evidence of residual cells of donor origin.
Trial location(s)
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
No longer a GSK study
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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Access to clinical trial data by researchers
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