Gene Therapy With Modified Autologous Hematopoietic Stem Cells for the Treatment of Patients With Mucopolysaccharidosis Type I, Hurler Variant

Phase I/II Study Evaluating Safety and Efficacy of Autologous Hematopoietic Stem and Progenitor Cells Genetically Modified With IDUA Lentiviral Vector Encoding for the Human α-L-iduronidase Gene for the Treatment of Patients Affected by Mucopolysaccharidosis Type I, Hurler Variant

This is a phase I/II study evaluating safety and efficacy of autologous hematopoietic stem and progenitor cells genetically modified with IDUA lentiviral vector encoding for the human α-L-iduronidase gene for the treatment of patients affected by Mucopolysaccharidosis Type I, Hurler variant

Pediatric patients with mucopolysaccharidosis type I will be treated with genetically modified autologous hematopoietic stem cells collected from mobilized peripheral blood (or bone marrow if mobilization is not feasible) and transduced with IDUA lentiviral vector encoding for the human α-L-iduronidase gene.

Participants will be followed for up to 15 years post treatment (per regulatory guidelines for follow up of patients treated with ATMPs, under this study (TigetT10_MPSIH) or via enrollment into a separate long term follow-up (LTFU) study for the overall OTL-203 Clinical Development Program, if one is set up prior to their Year 15 visit.

Inclusion Criteria:

• Written informed consent by parent/legal guardian
• Sex: Males and Females
• Age: ≥ 28 days and ≤ 11 years old
• Biochemically and molecularly proven MPS IH
• Lansky index >80%
• Indication to hematopoietic stem cell transplant
• Lack of a non-heterozygous (for mutated IDUA) HLA-matched sibling donor or a ≥7/8 (4 digits high-resolution typing) HLA-matched cord blood donor with a cellularity ≥5 x 10^7 Total Nucleated Cells (TNC)/Kg after 1-month search.(This criterion will not apply to patients whose country of origin does not offer unrelated donor cord blood transplantation).
• Adequate cardiac, renal, hepatic and pulmonary functions

Exclusion Criteria:

• Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents)
• Severe, active viral, bacterial or fungal infection at eligibility evaluation
• Patients affected by neoplasia or family history of familial cancer syndromes
• Cytogenetic alterations associated with high risk of developing hematological malignancies
• History of uncontrolled seizures
• Patients with end-organ damage or any other severe disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
• Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA and/or Treponema Pallidum or Mycoplasma active infection
• Patients with DQ/IQ <70
• Previous allogeneic hematopoietic stem cells transplantation or gene therapy with a different product
• Contraindications to PeIMP (G-CSF, Plerixafor, Busulfan, Fludarabine, Rituximab)