Gene Therapy for Metachromatic Leukodystrophy (MLD)
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ClinicalTrials.gov Identifier: NCT01560182 |
Recruitment Status :
Active, not recruiting
First Posted : March 22, 2012
Last Update Posted : October 7, 2021
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Condition or disease | Intervention/treatment | Phase |
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Lysosomal Storage Disease Metachromatic Leukodystrophy | Genetic: OTL-200 Gene Therapy | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 20 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Treatment of Metachromatic Leukodystrophy |
Actual Study Start Date : | April 9, 2010 |
Actual Primary Completion Date : | April 9, 2018 |
Estimated Study Completion Date : | April 9, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: OTL-200 Gene Therapy
CD34+ cells transduced ex vivo with lentiviral vector encoding ARSA cDNA
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Genetic: OTL-200 Gene Therapy
Autologous hematopoietic stem/progenitor cells collected from the bone marrow and transduced ex vivo with a Lentiviral vector encoding the human ARSA cDNA
Other Name: Previously GSK2696274 |
- Improvement of GMFM score [ Time Frame: 24 months after treatment ]An improvement of 10% of the total GMFM score in treated patients, when compared to the the GMFM scores in the historical control MLD population, evaluated 24 months after treatment.
- Increase of residual ARSA activity [ Time Frame: 24 months after treatment ]A significant increase of residual ARSA activity as compared to pre- treatment values, measured in total PBMC
- Conditioning regimen-related safety [ Time Frame: at +60 days after transplantation ]The absence of engraftment failure or delayed hematopoietic reconstitution (prolonged aplasia), defined as Absolute Neutrophil Count (ANC)<500/µl
- Conditioning regimen-related toxicity [ Time Frame: 3 years ]The absence of regimen related toxicity, as determined by a surveillance of AEs (NCI ≥2) and laboratory parameters (NCI ≥3) that will be applied in the short- and long-term follow-up of the treated patients in order to assess the degree of morbidity associated to the conditioning regimen
- The short-term safety and tolerability of lentiviral-transduced cell infusion [ Time Frame: 48 hours after transplant ]It will be evaluated evaluated on the basis of adverse events reporting and monitoring of the systemic reactions to cell infusion
- The long-term safety of lentiviral-transduced cell infusion [ Time Frame: baseline and after 1, 3, 6, 12 and 24 months ]Absence of Replication Competent Lentivirus (RCL): ELISA for HIV p24 antigen
- The absence of immune responses against the transgene (immunoblot analyses). [ Time Frame: every three months for the first year, then once a year. ]Even if an immune responses against the functional ARSA enzyme is not expected, treated subjects will be monitored for antibodies anti-ARSA on a defined schedule.
- Improvement in the NCV Index for ENG and in the total score for MR [ Time Frame: 24 months after treatment ]An improvement in the NCV Index for ENG and in the total brain MRI score.
- Transduced cell engraftment [ Time Frame: 12 months after treatment ]Transduced cell engraftment above 4% in bone marrow-derived clonogenic progenitor cells. Vector copy number (VCN) per cell in total PBMC, total BM, and peripheral blood (PB) and BM cell subpopulations will also be evaluated.
- IQ measurement above 55 [ Time Frame: 24, 30 and 36 months after treatment ]The measurement of an IQ above 55 (threshold for severe disability) at neuro-psychological testings

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Ages Eligible for Study: | up to 7 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Pre-symptomatic MLD patients with the late infantile variant;
- Pre- or early-symptomatic MLD patients with the early juvenile variant;
- Patients for whom parental/guardian signed informed consent has been obtained.
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01560182
Italy | |
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET) | |
Milan, Italy, 20132 |
Study Director: | Orchard Clinical Trials | Orchard Therapeutics |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Orchard Therapeutics |
ClinicalTrials.gov Identifier: | NCT01560182 |
Other Study ID Numbers: |
201222 Eudract 2009-017349-77 ( Other Identifier: IRCCS San Raffaele ) |
First Posted: | March 22, 2012 Key Record Dates |
Last Update Posted: | October 7, 2021 |
Last Verified: | September 2021 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
OTL-200 Metachromatic Leukodystrophy Gene Therapy MLD Previously GSK2696274 |
Leukodystrophy, Metachromatic Lysosomal Storage Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases Hereditary Central Nervous System Demyelinating Diseases Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Sulfatidosis Sphingolipidoses Lysosomal Storage Diseases, Nervous System Leukoencephalopathies Demyelinating Diseases Lipidoses Lipid Metabolism, Inborn Errors Lipid Metabolism Disorders |