Clinical Trials in Italy / NCT03488394
Active, not recruiting
Phase 1/2
Gene Therapy With Modified Autologous Hematopoietic Stem Cells for the Treatment of Patients With Mucopolysaccharidosis Type I, Hurler Variant
NCT03488394 · tracked via the Priya Life Science Italy tracker
Condition(s) studied
Mucopolysaccharidosis IH
Investigational drug(s) / intervention(s)
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.
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.: 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.
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
Eligibility
Inclusion Criteria:
* Written informed consent 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:
* Use of other investigational 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 malignancies
* 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 HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA and/or Treponema Pallidum or Mycoplasma active infection
* Patients with DQ/IQ \<70
* Previous allogeneic hematopoietic stem cells transplantation or gene therapy with a different product
* Contraindications to PeIMP (G-CSF, Plerixafor, Busulfan, Fludarabine, Rituximab)
Primary outcome measure(s)
- Overall survival — Assessed at multiple timepoints up to 15 years post-treatment
Number and percentage of subjects alive at the end of the trial - Achievement of haematological engraftment — within day +45 after gene therapy
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. - Safety of the administration of autologous haematopoietic stem cells transduced with IDUA LVV - Short term tolerability — 0-24 hours from ATIMP injection
Percentage of subjects not experiencing short-term adverse events of any grade and systemic reactions - Safety of the administration of autologous haematopoietic stem cells transduced with IDUA LVV - Absence of Replication Competent Lentivirus — Assessed at multiple timepoints up to 8 years post-treatment, or if clinically indicated
Percentage of subjects without Replication Competent Lentivirus - Safety of the administration of autologous haematopoietic stem cells transduced with IDUA LVV - Absence of malignancy or abnormal clonal proliferation — Assessed at multiple timepoints up to 15 years post-treatment
Percentage of subjects without abnormal clonal proliferation - Overall safety and tolerability (AE) — Assessed at multiple timepoints up to 15 years post-treatment
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. - IDUA activity in blood (up to supraphysiologic levels) at 1-year post-treatment — At 1 year post-treatment
IDUA activity measured on peripheral dried blood spot
Trial sites (1)
| Facility | City | Region | Status |
|---|---|---|---|
| Ospedale San Raffaele | Milan | Italy |
More Orchard Therapeutics trials in Italy
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT03488394 on ClinicalTrials.gov ↗ ← All trials in Italy