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A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD) | Clinical Trials | Clareo Health

COMPLETEDPHASE2

A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD)

A Single Arm, Open Label, Clinical Study of Cryopreserved Autologous CD34+ Cells Transduced With Lentiviral Vector Containing Human ARSA cDNA (OTL-200), for the Treatment of Early Onset Metachromatic Leukodystrophy (MLD)

NCT03392987•Orchard Therapeutics

View on ClinicalTrials.gov

Summary

OTL-200 is autologous CD34+ cells transduced with lentiviral vector containing human arylsulfatase A (ARSA) complementary deoxyribonucleic acid (cDNA) used for the treatment of MLD. MLD is an autosomal recessive lysosomal storage disorder (LSD) characterized by severe and progressive demyelination affecting the central and peripheral nervous system. This study will assess safety and efficacy of treatment using cryopreserved formulation of OTL-200 in pediatric subjects with pre-symptomatic Early Onset MLD (Late Infantile (LI) to Early Juvenile (EJ) MLD) and early symptomatic EJ MLD.

Eligibility

Age

0 - 6 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Documented biochemical and molecular diagnosis of MLD, based on ARSA activity below the normal range and identification of two disease-causing ARSA alleles, either known or novel mutations. Novel mutations will be analyzed with in silico prediction tools and excluded from being known common polymorphisms. In the case of a novel mutation(s), a 24-hour urine collection must show elevated sulfatide levels.
•Eligible subjects must have EITHER
•1. an older sibling affected by MLD (index case), whose age of symptom onset was \<=6 years of age (i.e., had not celebrated 7th birthday). Subjects will be classified as LI, EJ or intermediate LI/EJ based on age of symptom onset in the index case and their ARSA genotype; LI: symptom onset in index case \<=30 months of age and genotype typically 0/0; EJ: symptom onset in index case \>30 months and \<= 6 years of age with genotype typically 0/R; Intermediate LI/EJ: symptom onset in index case \<= 6 years of age but unable to unambiguously characterize index case as LI or EJ OR
•2. if MLD is diagnosed in a pre-symptomatic child without an older affected sibling, (e.g.) incidentally or via newborn screening) and the totality of the data available to the investigator strongly suggest that the subject has an early onset variant of MLD likely to benefit from gene therapy, and the subject is \<=6 years of age (i.e., has not celebrated 7th birthday), the subject may be considered eligible after discussion and approval by the Orchard medical monitor.
•Parental/guardian signed and dated informed consent.

Exclusion Criteria

•If LI MLD variant, clinical manifestations of the disease defined as EITHER of the following:
•* delay in expected achievement of independent standing or independent walking, together with abnormal signs at neurological evaluation
•* Or documented neurological signs and symptoms of MLD associated with cognitive, motor, or behavioural functional impairment or regression (substantiated by neurological examination and/or neuropsychological tests appropriate for age).
•If EJ MLD variant, symptoms of MLD resulting in the loss of capacity of walking independently as defined by a GMFC level ≥2 or symptoms consistent with cognitive impairment as defined by an IQ\<85 using age-appropriate neurocognitive instruments.
•NOTE: The following will not be exclusionary if present alone:
•Seizures
•Signs of the disease revealed at instrumental evaluations (Electroneurography \[ENG\] and brain MR)
•* Documented HIV infection (positive HIV RNA and/or anti-p24 antibodies).
•* Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome. Subjects with a prior successfully treated malignancy and a sufficient follow-up to exclude recurrence (based on oncologist opinion) can be included after discussion and approval by the Medical monitor.
•* Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), or other serious hematological disorders.
+10 more criteria

Locations (1)

Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)

Milan, Italy

Key Dates

Start Date

January 25, 2018

Primary Completion Date

April 6, 2022

Completion Date

March 10, 2026

Last Updated

March 16, 2026

Enrollment

ACTUAL participants

Conditions

Lysosomal Storage DiseaseMetachromatic Leukodystrophy

Interventions

OTL-200

GENETIC

The Myelin Disorders Biorepository Project

NCT03047369

LeukodystrophyWhite Matter Disease+64 more

View study

RECRUITINGNA

Lentiviral Hematopoietic Stem Cell Gene Therapy for MLD

NCT07046338

Metachromatic Leukodystrophy (MLD)

View study

ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 16, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD)

Inclusion Criteria

Exclusion Criteria

The Myelin Disorders Biorepository Project

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