A clinical trial to evaluate the effect of OTL-200, a gene therapy treatment in patients with Late Juvenile (LJ) Metachromatic Leukodystrophy (MLD)

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 6

Inclusion Criteria

1.Documented biochemical and molecular diagnosis of MLD, based on ARSA activity below the normal range and identification of two disease causing ARSA alleles. Novel mutations will be analysed within silico prediction tool 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.
2. O/R or R/R genotype or a genotype recognized as associated with the LJ variant of MLD.
3. a) if symptomatic: age at disease onset between =7 and <17 years of age (i.e. before their 17th birthday) OR b) if pre-symptomatic: participant must be <17 years of age at treatment (i.e before their 17th birthday) AND must have a sibling with a diagnosis of late-juvenile MLD variant based on age at disease onset (=7 and <17 years of age i.e before sibling's 17th birthday), with biochemical and molecular diagnosis.
4. Normal cognitive function as defined by an IQ= 85 on age appropriate cognitive scales.
5.a) If the participant is <7 years age (i.e before their 7th birthday): normal motor milestones achievement, normal gross motor function according to chronological age and normal neurological examination (if applicable based on the age of the subject, GMFC-MLD =0) OR b) If the participant is =7 years, normal gross motor function or mild gross motor function impairment, defined by a GMFC-MLD 0or 1 (i.e patient is able to walk independently).
6. If applicable, participant willing and capable of compliance with contraceptive requirements as detailed further in Protocol Section 7.1 Contraceptive use by men or women should be consistent with local regulations regarding he methods of contraception for those participating in clinical studies.
7. Participant (or if applicable, parent/legal guardian) providing signed informed consent as described in Section 17 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Documented HIV infection (positive HIV RNA and/or anti-p24 antibodies).
2.Malignant neoplasia (except localised skin cancer) or a documented history of hereditary cancer syndrome. Participants 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 OTL-MM.
3.Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) or other serious haematological disorders.
4.Patients currently enrolled in other interventional trials.
5.Has previously undergone allogeneic HSCT and has evidence of residual cells of donor origin.
6.Previous gene therapy.
7.Has symptomatic herpes zoster, not responsive to specific treatment
8.Evidence of active tuberculosis (TB)
9.Acute or chronic stable Hepatitis B (HBV)
10.Presence of positive Hepatitis C RNA test result at screening
11.End-organ dysfunction, severe active infection not responsive to treatment, or other severe disease or clinical condition which, in the judgement of the investigator, would make the participant inappropriate for entry into this study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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