Last updated: 11/16/2018 17:00:18
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 GSK Clinical Study Register is no longer maintained for this study.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 Metachromatic LeukodystrophyTIGET-MLD
GSK study ID
201222
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 treatment of Metachromatic Leukodystrophy
Trial description: This is a phase I/II protocol aiming at the assessment of the safety and efficacy of ARSA gene transfer into hematopoietic stem/progenitor cells for the treatment of Metachromatic Leukodystrophy.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Conditioning regimen-related safety
Timeframe: at +60 days after transplantation
Conditioning regimen-related toxicity
Timeframe: 3 years
The short-term safety and tolerability of lentiviral-transduced cell infusion
Timeframe: 48 hours after transplant
Improvement of GMFM score
Timeframe: 24 months after treatment
Increase of residual ARSA activity
Timeframe: 24 months after treatment
The long-term safety of lentiviral-transduced cell infusion
Timeframe: 24 months after the treatment
Secondary outcomes:
The absence of immune responses against the transgene
Timeframe: every three months for the first year, then once a year.
Improvement in the NCV Index for ENG and in the total score for MR
Timeframe: 24 months after treatment
Transduced cell engraftment
Timeframe: 12 months after treatment
IQ measurement above 55
Timeframe: 24, 30 and 36 months after treatment
Interventions:
Genetic: Autologous CD34+ stem cells transduced with ARSA encoding lentiviral vector
Enrollment:
14
Observational study model:
Not applicable
Primary completion date:
2023-13-04
Time perspective:
Not applicable
Clinical publications:
Biffi A, Capotondo A, Fasano S, del Carro U, Marchesini S, Azuma H, Malaguti MC, Amadio S, Brambilla R, Grompe M, Bordignon C, Quattrini A, Naldini L. Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice. J Clin Invest. 2006 Nov;116(11):3070-82
Biffi A, Cesani M, Fumagalli F, Del Carro U, Baldoli C, Canale S, Gerevini S, Amadio S, Falautano M, Rovelli A, Comi G, Roncarolo MG, Sessa M. Metachromatic leukodystrophy - mutation analysis provides further evidence of genotype-phenotype correlation. Clin Genet. 2008 Oct;74(4):349-57. doi: 10.1111/j.1399-0004.2008.01058.x
Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S, Benedicenti F, Vallanti G, Biasco L, Leo S, Kabbara N, Zanetti G, Rizzo WB, Mehta NA, Cicalese MP, Casiraghi M, Boelens JJ, Del Carro U, Dow DJ, Schmidt M, Assanelli A, Neduva V, Di Serio C, Stupka E, Gardner J, von Kalle C, Bordignon C, Ciceri F, Rovelli A, Roncarolo MG, Aiuti A, Sessa M, Naldini L. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013 Aug 23;341(6148):1233158. doi: 10.1126/science.1233158. Epub 2013 Jul 11
Biffi A., De Palma M., Quattrini A., Del Carro U., Amadio S., Visigalli I., Sessa M., Fasano S., Brambilla R., Marchesini S., Bordignon C., and Naldini L. (2004). Correction of Metachromatic Leukodystrophy in the Mouse Model by Transplantation of Genetically Modified Hematopoietic Stem Cells. J. Clin. Invest. 113 (8): 1118-29
Capotondo A., Cesani M., Pepe S., Fasano S., Gregori S., Tononi L., Venneri M.A., Brambilla R., Quattrini A., Ballabio A., Cosma M.P., Naldini L., Biffi A. (2007). Over-expression of arylsulfatase A in target cells is safe and enables efficacious gene therapy of metachromatic leukodystrophy. Hum. Gene Ther. 18(9): 821-36
Cesani M, Capotondo A, Plati T, Sergi LS, Fumagalli F, Roncarolo MG, Naldini L, Comi G, Sessa M, Biffi A. Characterization of new arylsulfatase A gene mutations reinforces genotype-phenotype correlation in metachromatic leukodystrophy. Hum Mutat. 2009 Oct;30(10):E936-45. doi: 10.1002/humu.21093
Medical condition
Lysosomal Storage Disease
Product
GSK2696274
Collaborators
Fondazione TeleThon
Study date(s)
May 2010 to April 2023
Type
Interventional
Phase
1/2
Participation criteria
Sex
Female & Male
Age
Not applicable
Accepts healthy volunteers
No
- Pre-symptomatic late infantile patients
- Pre- or early-symptomatic early juvenile patients (IQ > 70 and ability to walk independently for >10 steps)
- HIV RNA and/or HCV RNA and/or HBV DNA positive patients
- Patients affected by neoplastic diseases
Inclusion and exclusion criteria
Inclusion criteria:
- Pre-symptomatic late infantile patients
- Pre- or early-symptomatic early juvenile patients (IQ > 70 and ability to walk independently for >10 steps)
- Parental/guardian/patient signed informed consent.
Exclusion criteria:
- HIV RNA and/or HCV RNA and/or HBV DNA positive patients
- Patients affected by neoplastic diseases
- Patients with cytogenetic alterations typical of MDS/AML
- Patients with end-organ functions or any other severe disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
- Patients enrolled in other trials.
- Patient who underwent allogeneic hematopoietic stem cell transplantation in the previous six months.
- Patient who underwent allogenic hematopoietic 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
Participate in clinical trial
Access to clinical trial data by researchers
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