MPS-IH (Hurler Syndrome)Phase 3HURCULESNCT06149403
A Study to Investigate the Efficacy and Safety of OTL-203 in Subjects With MPS-IH Compared With Standard of Care With Allogeneic HSCT
A Phase 3 study testing Experimental: OTL-203 and Active Comparator: Allo-HSCT in people with MPS-IH (Hurler Syndrome), run by Orchard Therapeutics at 5 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 28 days to 30 months
- Conditions the study is for
- MPS-IH (Hurler Syndrome)
- What is being tested?
- Experimental: OTL-203 and Active Comparator: Allo-HSCT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 11 Dec 2023to Mar 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 days to 30 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Netherlands2 sites
Princess Maxima Center
Utrecht, 3584 CS
UMC Utrecht
Utrecht, 3584 CX
United States1 site
University of Minnesota, Pediatrics
Minneapolis, Minnesota, 55455
United Kingdom1 site
Manchester University NHS Foundation Trust Blood and Marrow Transplant Programme, Royal Manchester Children's Hospital
Manchester, M13 9WL
About this study
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)
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).
Read the 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.
- Conditions
- MPS-IH (Hurler Syndrome)
- Being tested
- Experimental: OTL-203, Active Comparator: Allo-HSCT
- Keywords
- MPS-IH, Hurler, MPS-I, Mucopolysaccharidoses, Mucopolysaccharidosis type I, Hurler syndrome, Mucopolysaccharidosis IH, Gene Therapy, Transplantation, Autologous Lentiviral vector
- Medical subject headings
- Mucopolysaccharidosis I, Mucopolysaccharidoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental: OTL-203Genetic
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-HSCTGenetic
Active Comparator: Allogeneic hematopoietic stem cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Genetic: Active Comparator: Allo-HSCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival
Defined by events of death, rescue transplant, treatment failure, immunological complications, severe cognitive and/or growth impairment.
Measured: 2 years
Secondary outcomes (6)
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
Measured: 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
Measured: 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)
Measured: 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.
Measured: Up to 5 years post-treatment
Replication Competent Lentivirus (RCL)
Presence of RCL will be evaluated in subjects treated with OTL-203
Measured: Up to 5 years post-treatment
Immune response against IDUA enzyme
Anti-IDUA antibodies analysis will be evaluated in all subjects.
Measured: Up to 5 years post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2023
- Study start11 Dec 2023
- Primary completionMar 2028 (estimated)
- Study completionMar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MPS-IH (Hurler Syndrome)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel assignment
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orchard Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06149403
- Sponsor's protocol ID
- OTL-203-02
- Acronym
- HURCULES
- Status last verified
- Dec 2025
- First submitted
- 17 Nov 2023
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06149403
- Acronym / sponsor ID
- HURCULES / OTL-203-02
- Conditions
- MPS-IH (Hurler Syndrome)
- Keywords
- MPS-IH, Hurler, MPS-I, Mucopolysaccharidoses, Mucopolysaccharidosis type I, Hurler syndrome, Mucopolysaccharidosis IH, Gene Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Orchard TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 11 Dec 2023 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Mar 2031 (estimated)
- First posted
- 29 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel assignment
| Arm | Type | Receives |
|---|---|---|
| OTL-203 | Experimental | Genetic: Experimental: OTL-203Eligible 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. |
| Allo-HSCT | Active comparator | Genetic: Active Comparator: Allo-HSCTEligible 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. |
Who may qualify
- Ages
- 28 days to 30 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental: OTL-203Experimental: 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 | Genetic | OTL-203 |
| Active Comparator: Allo-HSCTActive Comparator: Allogeneic hematopoietic stem cell transplantation | Genetic | Allo-HSCT |
Primary outcome
Event-free survival
Time frame: 2 years
Defined by events of death, rescue transplant, treatment failure, immunological complications, severe cognitive and/or growth impairment.
6 secondary outcomes
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
Change from baseline to Year 2 in the ratio to the upper limit of normal (ULN) of urinary heparan sulfate levels
Time frame: Day 30 and multiple visits up to 5 years post-treatment
Safety of OTL-203 compared to allo-HSCT procedure
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).
Time frame: Up to 5 years post-treatment
Replication Competent Lentivirus (RCL)
Time frame: Up to 5 years post-treatment
Immune response against IDUA enzyme
Time frame: Up to 5 years post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Experimental: OTL-203 and Active Comparator: Allo-HSCT in people with MPS-IH (Hurler Syndrome), run by Orchard Therapeutics at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands, United States, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025; AzTrials last refreshed its copy on 8 Nov 2026.