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Study of Atidarsagene Autotemcel for Treating Early Onset Metachromatic Leukodystrophy (MLD) in Patients

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What is this study about?

This clinical trial is focused on studying a rare genetic disorder called Metachromatic Leukodystrophy (MLD). MLD affects the nervous system and can lead to a decline in motor and cognitive functions. The study is testing a new treatment called OTL-200, which is a type of gene therapy. This treatment involves using a specially prepared form of the patient’s own cells, which are modified with a lentiviral vector containing the human Arylsulfatase A (ARSA) gene. The goal is to help the body produce the enzyme it lacks, which is necessary for breaking down certain fats in the body.

The purpose of the study is to evaluate how effective this gene therapy is in treating early onset MLD. Participants in the study will receive the treatment through a direct intravenous injection, which means it is delivered directly into the bloodstream. The study will follow participants over a period of time to monitor their progress and assess the treatment’s impact on their motor functions and overall health. This will include regular check-ups and various assessments, such as neurological exams and imaging tests like MRI scans, to see how the treatment is working.

Throughout the study, researchers will also keep track of any side effects or adverse events to ensure the safety and tolerability of the treatment. The study aims to provide valuable information on the potential benefits of this gene therapy for individuals with MLD, offering hope for a condition that currently has limited treatment options.

1 initial assessment

The trial begins with an initial assessment to confirm eligibility. This includes a documented biochemical and molecular diagnosis of Metachromatic Leukodystrophy (MLD). The diagnosis is based on ARSA activity below the normal range and identification of two disease-causing ARSA alleles.

Participants must meet specific criteria, such as having an older sibling affected by MLD or being diagnosed with MLD in a pre-symptomatic stage. The age of symptom onset and genetic factors are considered.

2 gene therapy administration

The treatment involves the administration of Libmeldy, a dispersion for infusion containing atidarsagene autotemcel. This is delivered through a direct intravenous injection.

The therapy uses a cryopreserved formulation of OTL-200, which is a gene therapy product designed to treat early onset MLD.

3 post-treatment monitoring

After the gene therapy, the patient’s gross motor function is measured at 24 months to evaluate the primary outcome.

Secondary outcomes include assessments of motor function, neurological examinations, nerve conduction velocity, brain imaging, and neurocognitive assessments at multiple visits over time.

4 safety and efficacy evaluations

Safety and tolerability are monitored through adverse event reporting. This includes any side effects related to the conditioning regimen and other non-conditioning related events.

Hematological recovery is assessed by checking the reconstitution of absolute neutrophil count and bone marrow recovery by day 60 post-gene therapy.

5 long-term follow-up

Long-term follow-up includes monitoring for the absence of malignancy or abnormal clonal proliferation, and ensuring there is no replication competent lentivirus.

The trial is expected to continue until July 2025, with ongoing assessments to ensure the safety and effectiveness of the treatment.

Who Can Join the Study?

  • The patient must have a confirmed diagnosis of Metachromatic Leukodystrophy (MLD). This is done by checking the activity of an enzyme called ARSA. If the activity is lower than normal and two specific changes (mutations) in the ARSA gene are found, the diagnosis is confirmed. If a new mutation is found, a 24-hour urine test must show high levels of a substance called sulfatide.
  • The patient must meet one of the following conditions:
    • Have an older brother or sister with MLD who started showing symptoms at or before the age of 6. The patient will be classified based on the age when the sibling started showing symptoms and their ARSA gene type:
      • Late Infantile (LI): Symptoms in the sibling started at or before 30 months of age; the ARSA gene type is usually 0/0.
      • Early Juvenile (EJ): Symptoms in the sibling started after 30 months but at or before 6 years of age; the ARSA gene type is usually 0/R.
      • Intermediate LI/EJ: Symptoms in the sibling started at or before 6 years of age, but it is unclear if they are LI or EJ.
    • If the patient is diagnosed with MLD before showing symptoms and does not have an older sibling with MLD, the patient may still be eligible if they are diagnosed early (for example, through newborn screening) and are likely to benefit from gene therapy. The patient must be 6 years old or younger, and this must be approved by a medical monitor from Orchard Therapeutics.
  • The study is open to both male and female patients.
  • The study includes patients who may be considered vulnerable, meaning they might need extra care or protection.

Who Cannot Join the Study?

Where you can join this trial?

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Site Name City Country Status
Ospedale San Raffaele S.r.l. Milan Italy

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Trial status

Country Status Recruitment Start
Italy Italy
Not recruiting
01.12.2017

Trial locations

Investigated drugs:

OTL200 is a treatment being studied for its effectiveness in treating early onset Metachromatic Leukodystrophy (MLD). It involves using a patient’s own CD34+ cells, which are collected and then modified with a lentiviral vector that contains human ARSA cDNA. This process aims to correct the genetic defect causing MLD, potentially slowing or stopping the progression of the disease.

Investigated diseases:

Metachromatic Leukodystrophy (MLD) – Metachromatic Leukodystrophy is a rare genetic disorder that affects the nervous system. It is caused by a deficiency of the enzyme arylsulfatase A, leading to the accumulation of sulfatides, which are toxic to the nervous system. This accumulation results in the progressive destruction of the myelin sheath, the protective covering of nerve cells. As the disease progresses, individuals may experience a decline in motor skills, muscle weakness, and difficulties with coordination and balance. Cognitive functions may also be affected, leading to changes in behavior and mental abilities. The progression of symptoms can vary, but it typically worsens over time.

Trial ID:
2024-511970-66-00
Protocol code:
205756
NCT ID:
NCT03392987
Trial Phase:
Therapeutic confirmatory (Phase III)

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