ClinicalTrials.gg
Active, not recruitingNCT03488394TigetT10_MPSIHUpdated Jul 16, 2026

Gene Therapy With Modified Autologous Hematopoietic Stem Cells for the Treatment of Patients With Mucopolysaccharidosis Type I, Hurler Variant

A Phase 1/2 interventional study of Frozen autologous CD34+ hematopoietic stem and progenitor cells genetically modified with the lentiviral vector IDUA LVV, encoding for the α-L-iduronidase cDNA, in their final formulation medium. in Mucopolysaccharidosis IH, sponsored by Orchard Therapeutics. Active, not recruiting at 1 site in Italy. Open to participants aged 28 Days to 11 Years. Per ClinicalTrials.gov, last updated 2026-07-16.

Sponsored by Orchard Therapeutics (part of Kyowa Kirin Co., Ltd.) · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
8
Allocation
Not applicable
Ages
28 Days to 11 Years
Sex
All
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Study summary

This is a phase I/II study evaluating safety and efficacy of autologous hematopoietic stem and progenitor cells genetically modified with IDUA lentiviral vector encoding for the human α-L-iduronidase gene for the treatment of patients affected by Mucopolysaccharidosis Type I, Hurler variant

Read the detailed description

Pediatric patients with mucopolysaccharidosis type I will be treated with genetically modified autologous hematopoietic stem cells collected from mobilized peripheral blood (or bone marrow if mobilization is not feasible) and transduced with IDUA lentiviral vector encoding for the human α-L-iduronidase gene.

Participants will be followed for up to 15 years post treatment (per regulatory guidelines for follow up of patients treated with ATMPs, under this study (TigetT10_MPSIH) or via enrollment into a separate long term follow-up (LTFU) study for the overall OTL-203 Clinical Development Program, if one is set up prior to their Year 15 visit.

02

Conditions studied

  • Mucopolysaccharidosis IH

Keywords

  • Mucopolysaccharidosis IH
  • Gene Therapy
  • Transplantation, Autologous
  • Lentiviral vector
03

In context

Mucopolysaccharidosis I

74 studies on the registry are indexed under Mucopolysaccharidosis I; 7 are open to participants now.

This study's enrollment of 8 is below the median of 14 across 47 interventional studies indexed under Mucopolysaccharidosis I.

Browse Mucopolysaccharidosis I studies →

Lead sponsor

Orchard Therapeutics is the lead sponsor of 5 studies on the registry; none are open to participants now.

First submitted before Orchard Therapeutics became part of Kyowa Kirin Co., Ltd..

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
28 Days to 11 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Written by parent/legal guardian
  • Sex: Males and Females
  • Age: ≥ 28 days and ≤ 11 years old
  • Biochemically and molecularly proven MPS IH
  • Lansky index >80%
  • Indication to hematopoietic stem cell transplant
  • Lack of a non-heterozygous (for mutated IDUA) HLA-matched sibling donor or a ≥7/8 (4 digits high-resolution typing) HLA-matched cord blood donor with a cellularity ≥5 x 10\^7 Total Nucleated Cells (TNC)/Kg after 1-month search.(This criterion will not apply to patients whose country of origin does not offer unrelated donor cord blood transplantation).
  • Adequate cardiac, renal, hepatic and pulmonary functions

Exclusion criteria

Exclusion Criteria:

  • Use of other agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents)
  • Severe, active viral, bacterial or fungal infection at eligibility evaluation
  • Patients affected by neoplasia or family history of familial cancer syndromes
  • Cytogenetic alterations associated with high risk of developing hematological
  • History of uncontrolled seizures
  • Patients with end-organ damage or any other severe disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • Positivity for (serology or RNA), and/or HbsAg and/or and/or and/or Treponema Pallidum or Mycoplasma active infection
  • Patients with DQ/IQ \<70
  • Previous hematopoietic stem cells transplantation or gene therapy with a different product
  • to PeIMP (G-CSF, Plerixafor, Busulfan, Fludarabine, Rituximab)
Terms in these criteria, in plain language(8)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
8 participants (actual)

Study arms

  • Experimental
    Treatment

    Gene therapy (autologous, CD34+ cell enriched cells fraction containing HSPCs, transduced with the IDUA LVV encoding for the human IDUA gene and cryopreserved in cryoformulation medium)

    Genetic: Frozen autologous CD34+ hematopoietic stem and progenitor cells genetically modified with the lentiviral vector IDUA LVV, encoding for the α-L-iduronidase cDNA, in their final formulation medium.

Interventions

  • GeneticFrozen autologous CD34+ hematopoietic stem and progenitor cells genetically modified with the lentiviral vector IDUA LVV, encoding for the α-L-iduronidase cDNA, in their final formulation medium.

    The drug product target dose is more or equal to 8x10\^6 CD34+ cells/Kg, with a minimum dose of 4x10\^6 CD34+ cells/Kg and a maximum dose of 35x10\^6 CD34+ cells/Kg. The product will be injected intravenously.

06

What researchers measure

Primary outcomes

  1. Overall survival

    Number and percentage of subjects alive at the end of the trial

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

  2. Achievement of haematological engraftment

    Percentage of subjects with both neutrophil count more than 500/mm3 and platelets more than 20,000/mm3 (in the absence of platelet transfusion for seven consecutive days) on 3 consecutive blood counts in the first 45 days from ATIMP injection.

    Time frame: within day +45 after gene therapy

  3. Safety of the administration of autologous haematopoietic stem cells transduced with IDUA LVV - Short term tolerability

    Percentage of subjects not experiencing short-term adverse events of any grade and systemic reactions

    Time frame: 0-24 hours from ATIMP injection

  4. Safety of the administration of autologous haematopoietic stem cells transduced with IDUA LVV - Absence of Replication Competent Lentivirus

    Percentage of subjects without Replication Competent Lentivirus

    Time frame: Assessed at multiple timepoints up to 8 years post-treatment, or if clinically indicated

  5. Safety of the administration of autologous haematopoietic stem cells transduced with IDUA LVV - Absence of malignancy or abnormal clonal proliferation

    Percentage of subjects without abnormal clonal proliferation

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

  6. Overall safety and tolerability (AE)

    The number of AEs (expected/unexpected and/or related/not related) and SAEs (expected/unexpected and/or related/not related) and the percentage of subjects experiencing AEs (expected/unexpected and/or related/not related) and SAEs (expected/unexpected and/or related/not related) will be summarized by severity and within body system involved. Narratives will also be presented. The rate of occurrence of these events will also be estimated.

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

  7. IDUA activity in blood (up to supraphysiologic levels) at 1-year post-treatment

    IDUA activity measured on peripheral dried blood spot

    Time frame: At 1 year post-treatment

Secondary outcomes

  1. Anti-IDUA antibody immune response

    Presence or absence and titer of anti-IDUA antibody on plasma or serum

    Time frame: Assessed at multiple timepoints up to 8 years post-treatment, or if clinically indicated

  2. Achievement of supraphysiologic IDUA activity in blood

    IDUA activity measured on peripheral dried blood spots up to supraphysiologic levels as compared with healthy donors. A supraphysiologic IDUA level is defined as \>24.31 μmol/L/h, which is the 97.5th percentile of the IDUA distribution in healthy children

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

  3. IDUA activity in plasma

    IDUA activity measured on plasma samples from peripheral blood.

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

  4. Engraftment of transduced cells ≥ 0.30 VCN/genome

    Percentage of subjects with engraftment of transduced cells ≥ 0.30 VCN/genome on peripheral blood mononuclear cells (PBMC) and/or bone marrow (BM) progenitor cells.

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

  5. Normalization of urinary GAGs

    Percentage of subjects achieving normalization of urinary GAG levels (heparan sulfate and dermatan sulfate) measured by HPLC

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

  6. Normalization of spleen and liver

    Percentage of subjects with normal spleen and liver assessed by clinical examination (palpation) and/or ultrasound

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

  7. Growth velocity

    Length/height for age (cm) per month vs. WHO percentiles

    Time frame: Assessed at multiple timepoints up to 15 years post-treatment

07

Study locations

1 site
08

References and documents

Publications

  • Consiglieri G, Tucci F, De Pellegrin M, Guerrini B, Cattoni A, Risca G, Scarparo S, Sarzana M, Pontesilli S, Mellone R, Gasperini S, Galimberti S, Silvani P, Filisetti C, Darin S, Forni G, Miglietta S, Santi L, Facchini M, Corti A, Fumagalli F, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Recupero S, Canarutto D, Doglio M, Tedesco L, Volpi N, Rovelli A, la Marca G, Valsecchi MG, Zancan S, Ciceri F, Naldini L, Baldoli C, Parini R, Gentner B, Aiuti A, Bernardo ME. Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome. Sci Transl Med. 2024 May;16(745):eadi8214. doi: 10.1126/scitranslmed.adi8214. Epub 2024 May 1. PubMed 38691622 ↗
  • Gentner B, Tucci F, Galimberti S, Fumagalli F, De Pellegrin M, Silvani P, Camesasca C, Pontesilli S, Darin S, Ciotti F, Sarzana M, Consiglieri G, Filisetti C, Forni G, Passerini L, Tomasoni D, Cesana D, Calabria A, Spinozzi G, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Miglietta S, Zonari E, Cheruku PS, Forni C, Facchini M, Corti A, Gabaldo M, Zancan S, Gasperini S, Rovelli A, Boelens JJ, Jones SA, Wynn R, Baldoli C, Montini E, Gregori S, Ciceri F, Valsecchi MG, la Marca G, Parini R, Naldini L, Aiuti A, Bernardo ME; MPSI Study Group. Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome. N Engl J Med. 2021 Nov 18;385(21):1929-1940. doi: 10.1056/NEJMoa2106596. PubMed 34788506 ↗
  • Tucci F, Uria Oficialdegui ML, Consiglieri G, Cossutta M, Filisetti C, Fumagalli F, Butera C, Santangelo R, Colombo M, Manitto MP, Stoppani M, Martina E, Dane G, Camesasca C, Risca G, De Pellegrin M, Scarparo S, Sarzana M, Puricelli C, Galimberti S, Darin S, Silvani P, Bonanomi S, Gasperini S, Naldini L, Gentner B, Parini R, Del Toro M, Diaz-de-Heredia C, Aiuti A, Bernardo ME. Non-neurological, non-skeletal outcomes after hematopoietic stem and progenitor cell-gene therapy (OTL-203) for Hurler syndrome. Mol Ther. 2026 Jan 7;34(1):443-454. doi: 10.1016/j.ymthe.2025.09.042. Epub 2025 Sep 27. PubMed 41017152 ↗

Individual participant data

Plan to share: Undecided

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 16, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03488394
Collaborators
Fondazione Telethon
Responsible party
Sponsor
First posted
Apr 5, 2018
Start date
May 11, 2018
Primary completion
Jan 2035 (estimated)
Completion
Mar 2035 (estimated)
Last update
Jul 16, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.

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