A Phase I/II clinical trial of hematopoietic stem cell gene therapy for the treatment of Metachromatic Leukodystrophy - TIGET-MLD

Status

Active, not recruiting

Phases

Phase 1

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2009-017349-77-IT

Enrollment

Registered

2010-04-26

Start date

2010-03-15

Completion date

Unknown

Last updated

2024-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

metachromatic leukodystrophy MedDRA version: 9.1 Level: PT Classification code 10024381

Interventions

Product Name: autologous CD34+ cells transduced with a lentiviral vector encoding the ARSA cDNA Pharmaceutical Form: Suspension for injection Current Sponsor code: autologous CD34+ cells transduced wi

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Pre-symptomatic late infantile patients; Pre- or early-symptomatic early juvenile patients; Parental/guardian/patient signed informed consent. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: Patients will be excluded from the present study according to the following crite-ria: HIV-positive patients; Patients affected by neoplastic diseases; Patients with cytogenetic alterations typical of MDS/AML; Patients with end-organ functions or any other severe disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study; Patients enrolled in other trials; Patients who underwent allogeneic hematopoietic stem cell transplantation in the previous 6 months; Patients who underwent allogeneic hematopoietic stem cell transplantation with evidence of residual cells of donor origin.

Design outcomes

Primary

Measure	Time frame
Main Objective: Evaluation of the safety of gene therapy in MLD patients, considering both the conditioning regimen safety and the safety of LV-transduced cell infusion, short and long-term after the treatment. Evaluation of the efficacy of gene therapy, assessed as reduction in the progression of the clinical motor impairment in treated patients as compared to the progression measured in untreated MLD patients in our disease natural history study, accompanied by a significant increase of residual ARSA activity as compared to pre-treatment patients values. Motor functions will be measured by the clinically relevant GMFM scoring system. Indeed, there is a clear causal relationship between the potential beneficial outcome meas-ured with the GMFM and the treatment, being motor impairment consequent to the involvement of both central and peripheral nervous system, and less influenced by other variables. Residual ARSA activity will be measured on hematopoietic cells (PBMC and BM cells).;Secondary Objective: Evaluation of the efficacy of the procedure in reducing the progression of demyelination (and atrophy) in the central and peripheral nervous system in comparison with that documented in our historical controls, as assessed by validated instrumental parameters brain MR score and NCV Index at ENG recordings (see secondary efficacy end-points). Evaluation of the biological efficacy of the procedure in treated patients, which consists in the sustained engraftment of the transduced cells, essential prerequisite for achieving clinical benefit. Long-term transduced cell engraftment will prove that i) ARSA LV transduced HSC with long-term repopulation potential and ii) the conditioning regimen was adequate for allowing transduced cell engraftment.;Primary end point(s): Safety Primary endpoints ; Conditioning regimen related safety, consisting in the absence of engraftment failure or delayed hematological reconstitution (prolonged aplasia) and surveillance of non-hematolo	—

Measure

Time frame

Main Objective: Evaluation of the safety of gene therapy in MLD patients, considering both the conditioning regimen safety and the safety of LV-transduced cell infusion, short and long-term after the treatment. Evaluation of the efficacy of gene therapy, assessed as reduction in the progression of the clinical motor impairment in treated patients as compared to the progression measured in untreated MLD patients in our disease natural history study, accompanied by a significant increase of residual ARSA activity as compared to pre-treatment patients values. Motor functions will be measured by the clinically relevant GMFM scoring system. Indeed, there is a clear causal relationship between the potential beneficial outcome meas-ured with the GMFM and the treatment, being motor impairment consequent to the involvement of both central and peripheral nervous system, and less influenced by other variables. Residual ARSA activity will be measured on hematopoietic cells (PBMC and BM cells).;Secondary Objective: Evaluation of the efficacy of the procedure in reducing the progression of demyelination (and atrophy) in the central and peripheral nervous system in comparison with that documented in our historical controls, as assessed by validated instrumental parameters brain MR score and NCV Index at ENG recordings (see secondary efficacy end-points). Evaluation of the biological efficacy of the procedure in treated patients, which consists in the sustained engraftment of the transduced cells, essential prerequisite for achieving clinical benefit. Long-term transduced cell engraftment will prove that i) ARSA LV transduced HSC with long-term repopulation potential and ii) the conditioning regimen was adequate for allowing transduced cell engraftment.;Primary end point(s): Safety Primary endpoints ; Conditioning regimen related safety, consisting in the absence of engraftment failure or delayed hematological reconstitution (prolonged aplasia) and surveillance of non-hematolo

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Countries

Italy

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026