Relinquished

Study Description:

This product has been transferred to Orchard Therapeutics Limited. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov

GSK2696274 is autologous cluster of differentiation 34+ (CD34+) cells transduced with lentiviral vector containing human arylsulfatase A (ARSA) complementary deoxyribonucleic acid (cDNA) used for the treatment of MLD. MLD is an autosomal recessive lysosomal storage disorder (LSD) characterized by severe and progressive demyelination affecting the central and peripheral nervous system. This study will assess safety and efficacy of treatment using cryopreserved formulation of GSK2696274 in pediatric subjects with pre-symptomatic Early Onset MLD (Late Infantile (LI) to Early Juvenile (EJ) MLD). Up to 10 subjects may be included in the study. A minimum of 3 subjects are planned to assess the primary endpoint. Subjects will be followed up for a minimum period of 8 years post treatment.

GSK Study ID:

205756


ClinicalTrials.gov Identifier:

NCT03392987


EudraCT Number:

2017-001730-26


Study Overview

Medical Conditions

Metabolism & Nutrition - Other

Product

GSK2696274;busulfan

Collaborators

Ospedale (Hospital) San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)


Date

December 2017 to August 2028

Type

Interventional

Phase

3


Gender

All

Age

N/A - N/A

Accepts Healthy Volunteers

No


Study Documents

No documents available
This study has Protocol summary on ClinicalTrial.gov. Click here to learn more.

Locations

Italy, Milan 20132Recruiting

Study Design

  • Primary Purpose: Treatment
  • Allocation: Not Available
  • Study Design: Single Group Assignment
  • Study Classification: Not Available
  • Masking: This will be an open label study. Hence, masking will not be provided.
  • Masked Subject: No
  • Masked Caregiver: No
  • Masked Investigator: No
  • Masked Assessor: No
Primary Outcomes:

  • Change in Gross Motor Function Measure (GMFM) score
    Timeframe: At 24 months post gene-therapy

Secondary Outcomes:

  • Change in Gross Motor Function Measure (GMFM) score
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in Gross Motor Function Classification (GMFC)-MLD score
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in neurological examinations
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in Nerve Conduction Velocity (NCV)
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in total score for brain magnetic resonance (MR) imaging
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in neurocognitive function (Intelligence Quotient [IQ])
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Engraftment measured by percent Lentiviral (LV) positive clonogenic progenitors in bone marrow
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Vector copy number (VCN) level in bone marrow mononuclear cells
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • VCN level in peripheral blood mononuclear cell (PBMCs)
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in ARSA activity in total PBMCs
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in ARSA activity in PB CD15+ cells
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in ARSA activity in PB CD14+ cells
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Change in ARSA activity in cerebrospinal fluid (CSF)
    Timeframe: At multiple visits up to 8 years post-gene therapy

  • Safety and tolerability as measured by recording of adverse events (AEs)
    Timeframe: Up to 8 years post-gene therapy

  • Safety and tolerability as measured by number of subjects not achieving hematological recovery by Day 60 (i.e., engraftment failure)
    Timeframe: By Day 60 post-gene therapy

  • Safety and tolerability as measured by number of subjects with incidences and titers of antibodies against ARSA
    Timeframe: Up to 8 years post-gene therapy

  • Safety and tolerability as measured by number of subjects with abnormal clonal proliferation (ACP)
    Timeframe: Up to 8 years post gene-therapy

  • Safety and tolerability as measured by number of subjects with replication competent lentivirus (RCL)
    Timeframe: Up to 8 years post gene-therapy

Arms:
  • 1

Interventions:

  • Drug: GSK2696274

Keyword:

  • GSK2696274, Cryopreserved formulation, Gene therapy, Metachromatic leukodystrophy
Inclusion / Exclusion Criteria: Click to view inclusion/exclusion criteria:
Enrollment: 10