A Study to Investigate the Efficacy and Safety of OTL-203 in Subjects With MPS-IH Compared With Standard of Care With Allogeneic HSCT

The study is a multi-center, randomized, active controlled clinical trial designed to evaluate the efficacy and safety of OTL-203 in patients with mucopolysaccharidosis type I, Hurler syndrome (MPS-IH) compared to standard of care with allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 40 patients with a confirmed diagnosis of MPS-IH who meet the study inclusion criteria will be randomized to receive either OTL-203 or allo-HSCT. The trial will comprise of a screening, baseline, and treatment period, with a follow-up period of 5 years post-treatment, and primary analysis performed at 2 years follow-up of the last treated subject.

Inclusion criteria

• Norm-referenced cognitive standard score of ≥70 measured by age-appropriate cognitive domains of either Bayley Scale of Infant Development (BSID)-III or Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-IV.
• Confirmed laboratory diagnosis of MPS-IH as demonstrated by biallelic mutation(s) in the gene coding for IDUA enzyme
• Final confirmation of MPS-IH diagnosis by a Diagnostic Review Committee (DRC).

Exclusion criteria

• Previous allo-HSCT or gene therapy
• Current enrollment or past treatment in any other interventional study/trial using a novel investigational agent and/or treated with prohibited medications listed in the protocol
• Positivity to serological testing for Human Immunodeficiency Virus (HIV)-1 or HIV-2, Human T Lymphotropic Virus (HTLV)-1 or HTLV-2, Hepatitis B Virus (HBV) core, Hepatitis C Virus (HCV), mycoplasma, active tuberculosis (TB) and not meeting the microbiology biological screening requirements.
• Malignant neoplasia (except local skin cancer).
• Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• History of uncontrolled seizures
• Subjects with an active infection not responsive to treatment, end-organ damage, or any other disease that contraindicates performance of any of the procedures detailed in the protocol, or medical conditions or extenuating circumstances that, in the opinion of the Investigator, might compromise the subject's well-being or safety, or the interpretability of the subject's clinical data.
• Subjects, who in the opinion of the Investigator, may not be able to comply with protocol requirements or cooperate fully with the study procedures and necessary long-term follow up