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Trial record 1 of 1 for:    NCT06149403
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A Study to Investigate the Efficacy and Safety of OTL-203 in Subjects With MPS-IH Compared With Standard of Care With Allogeneic HSCT (HURCULES)

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ClinicalTrials.gov Identifier: NCT06149403
Recruitment Status : Recruiting
First Posted : November 29, 2023
Last Update Posted : April 16, 2024
Sponsor:
Information provided by (Responsible Party):
Orchard Therapeutics

Study Description
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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).

Condition or disease Intervention/treatment Phase
MPS-IH (Hurler Syndrome) Genetic: Experimental: OTL-203 Genetic: Active Comparator: Allo-HSCT Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 11, 2023
Estimated Primary Completion Date : March 2028
Estimated Study Completion Date : March 2031

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Arms and Interventions
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Arm Intervention/treatment
Experimental: OTL-203
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
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: Allo-HSCT
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
Active Comparator: Allogeneic hematopoietic stem cell transplantation


Outcome Measures
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Primary Outcome Measures :
  1. Event-free survival [ Time Frame: 2 years ]
    Defined by events of death, rescue transplant, treatment failure, immunological complications, severe cognitive and/or growth impairment.


Secondary Outcome Measures :
  1. Change from baseline to Year 2 in α-L-iduronidase (IDUA) activity in leukocytes [ Time Frame: Day 30 and multiple visits up to 5 years post-treatment ]
    IDUA activity in leukocytes will be used to measure post-treatment systemic correction of the biochemical defect that causes the disease

  2. Change from baseline to Year 2 in urinary heparan sulfate levels, defined as ratio to the upper limit of normal [ Time Frame: Day 30 and multiple visits up to 5 years post-treatment ]
    Urinary heparan sulfate levels will be used to measure post-treatment clearance of glycosaminoglycans accumulated within tissues and organs due to IDUA enzymatic deficiency

  3. Safety of OTL-203 compared to allo-HSCT procedure [ Time Frame: Up to 5 years post-treatment ]
    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)

  4. 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). [ Time Frame: Up to 5 years post-treatment ]
    Malignancy or ACP due to insertional oncogenesis will be evaluated in subjects treated with OTL-203.

  5. Replication Competent Lentivirus (RCL) [ Time Frame: Up to 5 years post-treatment ]
    Presence of RCL will be evaluated in subjects treated with OTL-203

  6. Immune response against IDUA enzyme [ Time Frame: Up to 5 years post-treatment ]
    Anti-IDUA antibodies analysis will be evaluated in all subjects.


Eligibility Criteria
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Ages Eligible for Study:   28 Days to 30 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  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 for drug product (DP) manufacturing.
  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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06149403


Contacts
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Contact: Orchard Medical Information +44 (0) 20 3808 8286 medinfo@orchard-tx.com

Locations
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United States, California
UCSF Benioff Children's Hospital Not yet recruiting
San Francisco, California, United States, 94143
United States, Minnesota
University of Minnesota, Pediatrics Recruiting
Minnesota, Minnesota, United States, 55455
Contact: Lauren Matzke, RN    612-624-5831    matzk042@umn.edu   
United States, Pennsylvania
The Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19041
Italy
Ospedale San Raffaele Not yet recruiting
Milan, Italy, 20131
Netherlands
Princess Maxima Center Not yet recruiting
Utrecht, Netherlands, 3584 CS
UMC Utrecht Not yet recruiting
Utrecht, Netherlands, 3584 CX
United Kingdom
Manchester University NHS Foundation Trust Blood and Marrow Transplant Programme, Royal Manchester Children's Hospital Not yet recruiting
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Orchard Therapeutics
More Information
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Responsible Party: Orchard Therapeutics
ClinicalTrials.gov Identifier: NCT06149403    
Other Study ID Numbers: OTL-203-02
First Posted: November 29, 2023    Key Record Dates
Last Update Posted: April 16, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Orchard Therapeutics:
MPS-IH
Hurler
MPS-I
Mucopolysaccharidoses
Mucopolysaccharidosis type I
 Hurler syndrome
Mucopolysaccharidosis IH
Gene Therapy
Transplantation
Autologous Lentiviral vector
Additional relevant MeSH terms:
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Mucopolysaccharidoses
Mucopolysaccharidosis I
Syndrome
Disease
Pathologic Processes
Carbohydrate Metabolism, Inborn Errors
 Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases