EUCTR2017-001730-26-ITActive, not recruitingPhase 1
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). - A clinical study using cryopreserved OTL-200 for treatment of MLD.
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Enrollment
- 10
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional clinical trial of medicinal product
Eligibility Criteria
- Sex
- All
Inclusion Criteria
- •1) Documented biochemical and molecular diagnosis of MLD, based on ARSA activity below the normal range and identification of two diseasecausing 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.
- •2) Eligible participants must have EITHER:
- •a) 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).
- •Participants will be classified as Late Infantile, Early Juvenile or Intermediate LI/EJ based on age of symptom onset in the index case and their ARSA genotype:
- •i. Late Infantile (LI): symptom onset in index case = 30 months of age; genotype typically 0/0
- •ii. Early Juvenile (EJ): symptom onset in index case >30 months and = 6 years of age; genotype typically 0/R
- •iii. Intermediate LI/EJ: symptom onset in index case = 6 years of age but unable to unambiguously characterize index case as LI or EJ
- •b) 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 patient has an early onset variant of MLD likely to benefit from gene therapy, and the patient is = 6 years of age (i.e. has not celebrated 7th birthday), the patient may be considered eligible after discussion and approval by the Orchard Therapeutics (Europe) medical monitor (Orchard- MM)
- •3) Parental/guardian signed and dated informed consent
- •Are the trial subjects under 18? yes
- •Number of subjects for this age range:
- •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
- •a) If LI MLD variant, clinical manifestations of the disease defined as EITHER one of the following:
- •i. Delay in the achievement of independent standing or walking, together with abnormal signs at neurological evaluation
- •ii. Documented neurological signs and symptoms of MLD associated with cognitive, motor or behavioral functional impairment or regression (substantiated by neurological exam and/or neuropsychological tests appropriate for age)
- •b) If EJ MLD variant, symptoms of MLD resulting in the loss of capacity of walking independently as defined by a GMFC>2 or symptoms consistent with cognitive impairment as defined by IQ<85 using age-appropriate
- •neurocognitive instruments
- •The following will not be exclusionary if present alone:
- •ii.Signs of the disease revealed at instrumental evaluations.
- •2)Documented HIV infection
- •3)Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome.Subjs with a prior successfully treated malignancy and a sufficient f-up to exclude recurrence can be included after discussion and approval by the MM.
- •4)Myelodysplasia, cytogenetic alterations characteristic of MDS and AML or other serious haematological disorders.
- •5)Pats currently enrolled in other interventional trials.
- •6)Has previously undergone allogeneic hematopoietic stem cell transplantation and has evidence of residual cells of donor origin.
- •7)Previous gene therapy.
- •8)Has symptomatic herpes zoster, not responsive to specific treatment. Subjs with a recent history of herpes zoster may be included in the study. In such cases, inclusion, additional monitoring and treatment of the condition must be discussed and approved by the OrchMM.
- •9)Evidence of TB based upon medical examination, chest imaging and TB testing i.e. QuantiFERON-TB Gold test and microbiological evidence. Subjs with latent TB, as documented by medical history and/or TB testing may be included in the study if receiving antibiotic prophylaxis (e.g. isoniazid). Inclusion, monitoring and treatment of TB in such subjects must be
- •discussed and approved by the OrchMM.
- •10)Acute or chronic stable Hepat B as evidenced by positive HBsAg test result at screening or within 3 months prior to onset of conditioning and/or posit HBV DNA.
- •Subjs with posit Hepat B core antibody due to prior resolved disease may be enrolled, only if a confirmatory negat Hepat B surface antigen and negat Hepat B DNA test are obtained.
- •Inclusion, monitoring and treatment of hepat in such subjs must be discussed and approved by the OrchMM.
- •11)Presence of posit HepatC RNA test result at screening; Pats who have previously tested posit for antibodies against hepat C can be treated, provided they demonstrate absence of ongoing infection using a nucleic acid test with a limit of quantification of =15 UI/ml. Negat test results are required on at least 3 sequential occasions over a period of at least 4 weeks, after completion of treatment for hepatC, with the final test conducted no more than 3 days prior to cell harvest. Inclusion, monitoring and treatment of hepatitis in such subs must be discussed and approved by the OrchMM.
- •12)End-organ dysfunction, severe active infection not responsive to treatment, or other severe disease or clinical condition which, in the judgment of the investigator, would make the subject inappropriate for entry into this study. In addition to the potential infections tested per protocol, the PI should consider testing for other transmissible infectiou
Investigators
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