Clinical Trial: Multicenter Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy (MLD)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Multicenter Open-label Dose Escalation Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy

Brief Summary: The purpose of this study is to determine the safety of ascending doses of HGT-1110 administered by intrathecal (IT) injection for 38 weeks (20 injections) in children with metachromatic leukodystrophy (MLD).

Detailed Summary:

Metachromatic leukodystrophy (MLD) is an inherited, autosomal recessive disorder of lipid metabolism characterized by deficient activity of the lysosomal enzyme, arylsulfatase A (ASA). MLD is a rare disease that occurs in most parts of the world. The estimated overall incidence of the disease in the western world is approximately 1 in 100,000 live births that varies by geographic location. There are no approved therapies for MLD.

This is a multicenter, open-label, dose-escalation study designed to evaluate the safety of up to 3 dose levels (10, 30, or 100 mg) of HGT-1110 administered via an intrathecal drug delivery device (IDDD) every other week (EOW) for a total of 38 weeks (20 injections, Weeks 0 to 38) to children with MLD. The study also includes the assessment of HGT-1110 drug product produced with a revised drug substance manufacturing process (referred to as Process B) in a fourth cohort (Cohort 4). Approximately 24 patients will be enrolled and will receive treatment of HGT-1110. Patients will be sequentially enrolled into 4 dose cohorts, approximately 6 patients each. Patient enrollment will be staggered in this study to facilitate adequate safety monitoring per dose cohort.


Sponsor: Shire

Current Primary Outcome:

  • Cohorts 1-3: Safety of IT HGT-1110 administration [ Time Frame: 42 weeks ]
    Safety will be assessed by AEs (by type and severity), changes in clinical laboratory testing, electrocardiogram (ECG), vital signs, CSF chemistries and antibodies.
  • Cohort 4:Safety of the administration of IT HGT-1110 produced with a revised drug substance manufacturing pro [ Time Frame: 42 Weeks ]
    Safety will be assessed by AEs (by type and severity), changes in clinical laboratory testing, electrocardiogram (ECG), vital signs, CSF chemistries and antibodies.


Original Primary Outcome: Safety of IT HGT-1110 administration [ Time Frame: 40 weeks ]

Safety will be assessed by AEs (by type and severity), changes in clinical laboratory testing, electrocardiogram (ECG), vital signs, CSF chemistries and antibodies.


Current Secondary Outcome:

  • Clinical activity of IT administration of HGT-1110 on gross motor function [ Time Frame: 40 weeks ]
    Change from baseline in gross motor function
  • Serum Pharmacokinetic profile of HGT-1110 after single and repeated dose administration (weeks 0 and 38) [ Time Frame: 12 time points over 48 hours post-dose ]
    • Cmax: maximal serum concentration
    • Tmax: time to reach Cmax in plasma
    • AUC: area under the curve
  • Concentrations of HGT-1110 in CSF [ Time Frame: 40 weeks ]
    Concentrations of HGT-1110 in CSF prior to each IT administration


Original Secondary Outcome: Same as current

Information By: Shire

Dates:
Date Received: December 14, 2011
Date Started: August 2012
Date Completion:
Last Updated: January 31, 2017
Last Verified: February 2017