Clinical trial NCT06149403: A Study to Investigate the Efficacy and Safety of OTL-203 in Subjects With MPS-IH Compared With Standard of Care With Allogeneic HSCT
Official title: A Multi-center, Randomized, Active Controlled Clinical Trial to Evaluate the Efficacy and Safety of OTL-203 in Subjects With Mucopolysaccharidosis Type I, Hurler Syndrome (MPS-IH) Compared to Standard of Care With Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: Orchard Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-11-29
Enrollment: 41
Sex: ALL
Minimum age (years): 28
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: TREATMENT

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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Confirmed laboratory diagnosis of MPS-IH as demonstrated by biallelic mutation(s) in the gene coding for IDUA enzyme
3. Final confirmation of MPS-IH diagnosis by a Diagnostic Review Committee (DRC).

Exclusion Criteria:

1. Previous allo-HSCT or gene therapy
2. 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
3. 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.
4. Malignant neoplasia (except local skin cancer).
5. Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
6. History of uncontrolled seizures
7. 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.
8. 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

Primary outcomes:
measure: Event-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Change from baseline to Year 2 in α-L-iduronidase (IDUA) activity in leukocytes
timeFrame: Day 30 and multiple visits up to 5 years post-treatment
measure: Change from baseline to Year 2 in the ratio to the upper limit of normal (ULN) of urinary heparan sulfate levels
timeFrame: Day 30 and multiple visits up to 5 years post-treatment
measure: Safety of OTL-203 compared to allo-HSCT procedure
timeFrame: Up to 5 years post-treatment
measure: 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).
timeFrame: Up to 5 years post-treatment
measure: Replication Competent Lentivirus (RCL)
timeFrame: Up to 5 years post-treatment
measure: Immune response against IDUA enzyme
timeFrame: Up to 5 years post-treatment
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota, Pediatrics
state: Minnesota
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Utrecht
country: Netherlands
facility: Princess Maxima Center
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust Blood and Marrow Transplant Programme, Royal Manchester Children's Hospital
Study officials:
References: