Metachromatic Leukodystrophy MedDRA version: 20.0 Level: PT Classification code 10067609 Term: Metachromatic leukodystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: OTL-200
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Not Applicable
Current Sponsor code: OTL-200
Other descriptive name: OTL-200 Dispersion for Infusion
Concentrati
Sponsors
Orchard Therapeutics (Europe) Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the pharmacodynamic effect of OTL-200 in CSF and the brain of patients with LJ MLD as compared to baseline ;Secondary Objective: -To evaluate the pharmacodynamic effect of OTL-200 in bone marrow and peripheral blood and on various brain metabolites in LJ MLD patients as compared to baseline, siblings and/or untreated historical controls -To evaluate engraftment of OTL-200 -To evaluate the clinical efficacy of OTL-200 in LJ MLD participants as compared to baseline, untreated historical controls or siblings -To evaluate the safety and tolerability of the HSPC-GT procedure and OTL-200;Primary end point(s): Co-primary pharmacodynamic efficacy endpoints: •Change in ARSA activity levels in CSF •Change in neuronal metabolite ratio NAA: Cr in white matter regions of interest of the brain ;Timepoint(s) of evaluation of this end point: from baseline to 24 months post-treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: •Change in ARSA activity levels in CSF from baseline to multiple visits over time •Change from baseline to multiple visits over time in neuronal metabolite ratio NAA: Cr in white matter regions of interest of the brain (may include but not limited to the centrum semiovale; parieto-occipital white matter) •Change from baseline to 24 months and multiple visits over time in ARSA levels in total PBMC, CD14+ and CD15+ •Neuronal metabolite ratios at 24 months and multiple visits over time relative to baseline and compared to untreated historical controls / siblings in treated participants (may include but not limited to Cho:Cr, mIns:Cr, Lac: Cr, Cho: NAA, NAA: H2O, Cho: H2O, mIns: H2O, Lac: H2O) in white matter regions of interest (may include but not limited to the centrum semiovale; frontal, occipital, and parieto-occipital white matter). •Engraftment as measured by %LV in BM progenitors (at D30 post gene therapy and at multiple visits over time) oBrain MRI assessments at 24 months and at multiple visits over time as compared to baseline, untreated historical controls or siblings oNeurocognitive assessments at 24 months and at multiple visits over time as compared to baseline, untreated historical controls or siblings oFull neurological clinical examination (NCE) at 24 months and at multiple visits over time as compared to baseline, untreated historical controls or siblings oGMFC-MLD at 24 months and at multiple visits over time as compared to baseline, untreated historical controls or siblings oAssessment of NCV at 24 months and at multiple visits over time as compared to baseline, untreated historical controls or siblings oVineland Adaptive Behavioural Scales at 24 months and at multiple visits over time as compared to baseline, untreated historical controls or siblings Safety as measured by: •Conditioning regimen related toxicity and AEs •Non-conditioning related AEs •Haematological reconstitution (ANC > 500/µL assoc | — |
Countries
Italy
Contacts
Public ContactClinical
Orchard Therapeutics (Europe) Limited
Outcome results
None listed