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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
41
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
Active Comparator: Allogeneic hematopoietic stem cell transplantation
University of Minnesota, Pediatrics
Minneapolis, Minnesota, United States
Ospedale San Raffaele
Milan, Italy
Princess Maxima Center
Utrecht, Netherlands
UMC Utrecht
Utrecht, Netherlands
Event-free survival
Defined by events of death, rescue transplant, treatment failure, immunological complications, severe cognitive and/or growth impairment.
Time frame: 2 years
Change from baseline to Year 2 in α-L-iduronidase (IDUA) activity in leukocytes
IDUA activity in leukocytes will be used to measure post-treatment systemic correction of the biochemical defect that causes the disease
Time frame: 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
Urinary heparan sulfate levels will be used to measure post-treatment clearance of glycosaminoglycans accumulated within tissues and organs due to IDUA enzymatic deficiency
Time frame: Day 30 and multiple visits up to 5 years post-treatment
Safety of OTL-203 compared to allo-HSCT procedure
Measured by Overall incidence of adverse events (AEs) whether or not considered related to the study treatment, including conditioning regimen-related AEs, Study Procedure-related AEs, Disease-related AEs, Treatment related AEs, Serious adverse events (SAEs)
Time frame: 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).
Malignancy or ACP due to insertional oncogenesis will be evaluated in subjects treated with OTL-203.
Time frame: Up to 5 years post-treatment
Replication Competent Lentivirus (RCL)
Presence of RCL will be evaluated in subjects treated with OTL-203
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Manchester University NHS Foundation Trust Blood and Marrow Transplant Programme, Royal Manchester Children's Hospital
Manchester, United Kingdom
Time frame: Up to 5 years post-treatment
Immune response against IDUA enzyme
Anti-IDUA antibodies analysis will be evaluated in all subjects.
Time frame: Up to 5 years post-treatment