A Phase 2 interventional study of OTL-200 in Lysosomal Storage Disease and Metachromatic Leukodystrophy, sponsored by Orchard Therapeutics. Completed at 1 site in Italy. Open to participants aged Up to 6 Years. Per ClinicalTrials.gov, last updated 2026-03-16.
Sponsored by Orchard Therapeutics (part of Kyowa Kirin Co., Ltd.) · Phase 2, Interventional, and Treatment
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.
49 studies on the registry are indexed under Leukodystrophy, Metachromatic; 11 are open to participants now.
This study's enrollment of 10 is below the median of 19 across 28 interventional studies indexed under Leukodystrophy, Metachromatic.
Browse Leukodystrophy, Metachromatic studies →Orchard Therapeutics is the lead sponsor of 5 studies on the registry; none are open to participants now.
First submitted before Orchard Therapeutics became part of Kyowa Kirin Co., Ltd..
Compared within Leukodystrophy, Metachromatic, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Lysosomal Storage Diseases. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Eligible subjects must have EITHER
Exclusion Criteria:
If LI MLD variant, clinical manifestations of the disease defined as EITHER of the following:
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:
Signs of the disease revealed at instrumental evaluations (Electroneurography [ENG] and brain MR)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Eligible subjects will receive intravenous (IV) infusion of OTL-200 gene therapy. Subjects will also receive conditioning regimen with busulfan.
Genetic: OTL-200
OTL-200 is an autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with lentiviral vector that encodes for the human ARSA cDNA sequence
Also known as: Previously GSK2696274
Change in Gross Motor Function Measure (GMFM) score
GMFM will evaluate subject's ability to perform specific tasks in different positions. The scoring range is between 100 percent and 0 percent, with 0 percent corresponding to loss of all voluntary movement.
Time frame: At 24 months post gene-therapy
Change in Gross Motor Function Measure (GMFM) score
GMFM will evaluate subject's ability to perform specific tasks in different positions. The scoring range is between 100 percent and 0 percent, with 0 percent corresponding to loss of all voluntary movement.
Time frame: At 24 months and multiple visits up to 5 years post-gene therapy
Change in Gross Motor Function Classification (GMFC)-MLD score
GMFC-MLD will evaluate the change in motor function according to seven clinically relevant levels of walking, sitting, locomotion, trunk and head control. The scoring range is from 0 (walking without support with quality of performance normal for age) to 6 (loss of any locomotion as well as loss of any head and trunk control).
Time frame: At 24 months and multiple visits up to 5 years post-gene therapy
Change in neurological examinations
Neurological examinations will be performed to identify any signs and symptoms of MLD disease.
Time frame: At 24 months and multiple visits up to 5 years post-gene therapy
Change in Nerve Conduction Velocity (NCV)
NCV will be assessed by electroneurography which is a technique used to test and quantify the nerve conduction and impulse propagation along motor and sensory peripheral nerves.
Time frame: At 24 months and multiple visits up to 5 years post-gene therapy
Change in total score for brain magnetic resonance (MR) imaging
Brain MR will be assessed using modified Loes score where normal brain has a score of zero and increasing score reflects worsening disease and demyelination.
Time frame: At 24 months and multiple visits up to 5 years post-gene therapy
Change in neurocognitive function (Intelligence Quotient [IQ])
Standardized, age-appropriate IQ tests will be administered.
Time frame: At 24 months and multiple visits up to 5 years post-gene therapy
Engraftment measured by percent Lentiviral (LV) positive clonogenic progenitors in bone marrow
Engraftment of transduced cells will be determined by measuring the percentage of hematopoietic colony-forming cells harboring the integrated vector by quantitative polymerase chain reaction (qPCR).
Time frame: At Day 30 and multiple visits up to 5 years post-gene therapy
Vector copy number (VCN) level in bone marrow mononuclear cells
Engraftment of transduced cells will be determined by measuring the VCN per genome in bone marrow-derived cells.
Time frame: At Day 30 and multiple visits up to 5 years post-gene therapy
VCN level in peripheral blood mononuclear cell (PBMCs)
Engraftment of transduced cells will be determined by measuring the VCN per genome in PBMCs.
Time frame: At Day 60 and multiple visits up to 5 years post-gene therapy
Change in Arylsulfatase A (ARSA) activity in total PBMCs
Measured to assess the pharmacodynamic activity of OTL-200 in circulating total PBMCs post-treatment.
Time frame: At Day 60 and multiple visits up to 5 years post-gene therapy
Change in ARSA activity in PB CD15+ cells
Measured to assess the pharmacodynamic activity of OTL-200 in circulating CD15+ cells post-treatment.
Time frame: At Day 60 and multiple visits up to 5 years post-gene therapy
Change in ARSA activity in PB CD14+ cells
Measured to assess the pharmacodynamic activity of OTL-200 in circulating CD14+ cells post-treatment.
Time frame: At Day 60 and multiple visits up to 5 years post-gene therapy
Change in ARSA activity in cerebrospinal fluid (CSF)
Measured to assess the pharmacodynamic activity of OTL-200 in the Central Nervous System (CNS) post-treatment.
Time frame: At Day 90 and multiple visits up to 5 years post-gene therapy
Safety and tolerability as measured by recording of adverse events (AEs), including conditioning regimen related toxicity and AEs, and non-conditioning related AEs
An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as an serious adverse event (SAE).
Time frame: Up to 5 years post-gene therapy
Safety and tolerability as measured by number of subjects not achieving hematological recovery (i.e., engraftment failure)
Hematological recovery will be defined as reconstitution of absolute neutrophil count (ANC ) \> 500 neutrophils per microliter, associated with evidence of bone marrow recovery by Day 60.
Time frame: By Day 60 post-gene therapy
Safety and tolerability as measured by incidences and titers of anti-ARSA antibodies
Serum samples will be collected for anti-ARSA antibody analysis.
Time frame: Up to 5 years post-gene therapy
Safety and tolerability as measured by absence of abnormal clonal proliferation (ACP)
Malignancy or ACP due to insertional oncogenesis will be evaluated using different tests and procedures.
Time frame: Up to 5 years post gene-therapy
Safety and tolerability as measured by absence of replication competent lentivirus (RCL)
Molecular monitoring of RCL will be carried out using an enzyme-linked immunosorbent assay (ELISA) test for serum human immunodeficiency virus (HIV) p24 antigen. A positive HIV p24 test result is subject to second level testing including: a) DNA PCR for vesicular stomatitis virus G (VSV-G) envelope (PBMC), and b) reverse transcription (RT)-PCR for serum HIV-pol ribonucleic acid (RNA) (plasma).
Time frame: baseline, 1, 3, 6, and 12 months, then once a year up to 5 years post gene-therapy
This study is completed, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
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Leukodystrophy, Metachromatic →