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

NCT06149403 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: OTL-203-02
• Study Type: interventional
• Target: 41
• Locations: 4 countries
• Sites: 5

Brief Summary

A multi-center randomized clinical trial to compare OTL-203 (gene therapy) with stem cell transplant (standard of care) in patients with MPS-IH (Hurler syndrome).

Conditions

MPS-IH (Hurler Syndrome)

Keywords

MPS-IH; Hurler; MPS-I; Mucopolysaccharidoses; Mucopolysaccharidosis type I; Hurler syndrome; Mucopolysaccharidosis IH; Gene Therapy; Transplantation; Autologous Lentiviral vector

Outcome Measures

Primary Outcomes (1)

• Event-free survival

  Defined by events of death, rescue transplant, treatment failure, immunological complications, severe cognitive and/or growth impairment.

  2 years

Secondary Outcomes (6)

• Change from baseline to Year 2 in α-L-iduronidase (IDUA) activity in leukocytes

  Day 30 and multiple visits up to 5 years post-treatment

• Change from baseline to Year 2 in the ratio to the upper limit of normal (ULN) of urinary heparan sulfate levels

  Day 30 and multiple visits up to 5 years post-treatment

• Safety of OTL-203 compared to allo-HSCT procedure

  Up to 5 years post-treatment

• Malignancy or abnormal clonal proliferation (ACP) using different tests and procedures (e.g., general clinical evaluation, blood counts, and specialized assessments such as integration site analysis).

  Up to 5 years post-treatment

• Replication Competent Lentivirus (RCL)

  Up to 5 years post-treatment

Study Arms (2)

OTL-203

EXPERIMENTAL

Eligible subjects randomized to Arm 1 will receive an intravenous (IV) infusion of OTL-203 gene therapy. Subjects will receive conditioning regimen with busulfan and fludarabine prior to OTL-203 infusion.

Genetic: Experimental: OTL-203

Allo-HSCT

ACTIVE COMPARATOR

Eligible subjects randomized to Arm 2 will receive allogeneic hematopoietic stem cell transplantation. Subjects will receive conditioning regimen with busulfan and fludarabine prior to allo-HSCT.

Genetic: Active Comparator: Allo-HSCT

Interventions

Experimental: OTL-203 GENETIC

Experimental: OTL-203: Autologous CD34+ enriched cell fraction that contains hematopoietic stem and progenitor cells transduced ex vivo using lentiviral vector encoding the human IDUA gene

OTL-203

Active Comparator: Allo-HSCT GENETIC

Active Comparator: Allogeneic hematopoietic stem cell transplantation

Allo-HSCT

Eligibility Criteria

• Age: 28 Days - 30 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Orchard Therapeutics: lead

Study Sites (5)

University of Minnesota, Pediatrics

Minneapolis, Minnesota, 55455, United States

Location

Ospedale San Raffaele

Milan, 20131, Italy

Location

Princess Maxima Center

Utrecht, 3584 CS, Netherlands

Location

UMC Utrecht

Utrecht, 3584 CX, Netherlands

Location

Manchester University NHS Foundation Trust Blood and Marrow Transplant Programme, Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I; Mucopolysaccharidoses

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel assignment

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: November 29, 2023
• Study Start: December 11, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2031
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); GB (1); IT (1); US (1)