Clinical Trial: Open-Label Extension Study Evaluating Safety and Efficacy of HGT-1110 in Patients With Metachromatic Leukodystrophy

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: An Open-Label Extension of Study HGT-MLD-070 Evaluating Long Term Safety and Efficacy of Intrathecal Administration of HGT-1110 in Patients With Metachromatic Leukodystrophy

Brief Summary: The purpose of this study is to collect long-term safety data in patients with metachromatic leukodystrophy (MLD) who are receiving HGT-1110 and have participated in Study HGT-MLD-070 through Week 40.

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 study is a multicenter open-label study designed to evaluate safety and efficacy outcomes of HGT-1110 administered intrathecally in children with MLD who have participated in the dose escalation study, HGT-MLD-070, through Week 40 and are receiving study drug every other week (EOW).

Treatment groups will be identical to those in HGT-MLD-070, ie, patients assigned to Cohort 1 in Study HGT-MLD-070 will continue to receive a dose of 10 mg, patients assigned to Cohort 2 in Study HGT-MLD-070 will continue to receive a dose of 30 mg, and patients assigned to Cohorts 3 and 4 in Study HGT-MLD-070 will continue to receive a dose of 100 mg. Patients in Cohort 4 are to exclusively receive drug product produced with Process B in Study HGT-MLD-070 and will continue receiving this drug product in this study. Patients enrolled in this study from Cohorts 1 to 3 in Study HGT-MLD-070 were transitioned to Process B after all necessary approvals were obtained.

In HGT-MLD-071, all patients in the 10 mg dose cohort who experienced disease progression, as determined by the Investigator, increased to the 30 mg dose after agreement by the Medical Monitor. Based on the interim analysis results from HGT-MLD-070 (Cohorts 1-3), the dose of HGT-1110 will be increased to 100 mg for all patients in HGT-MLD-071 after all necessary approvals were obtained.


Sponsor: Shire

Current Primary Outcome: Safety of IT HGT-1110 administration [ Time Frame: Change from Baseline until End of Study (approximately 6 years) ]

Safety will be assessed by Adverse Events (AE; type and severity), changes in clinical laboratory testing, vital signs, physical examinations, neurological examinations, cerebrospinal fluid (CSF) chemistries and antibodies.


Original Primary Outcome: Safety of IT HGT-1110 administration [ Time Frame: Change from Baseline until End of Study (approximately 5.5 years) ]

Safety will be assessed by Adverse Events (AE; type and severity), changes in clinical laboratory testing, vital signs, physical examinations, neurological examinations, cerebrospinal fluid (CSF) chemistries and antibodies.


Current Secondary Outcome:

  • Clinical activity of IT administration of HGT-1110 on gross motor function [ Time Frame: Change from Baseline until End of Study (approximately 6 years) ]
    Evaluated using Gross Motor Function Measure-88 (GMFM-88)
  • Concentrations of HGT-1110 in CSF after single and repeated dose administration [ Time Frame: Baseline until End of Study ( approximately 6 years) ]


Original Secondary Outcome:

  • Clinical activity of IT administration of HGT-1110 on gross motor function [ Time Frame: Change from Baseline until End of Study (approximately 5.5 years) ]
  • Concentrations of HGT-1110 in CSF after single and repeated dose administration [ Time Frame: Baseline until Week 48 ]


Information By: Shire

Dates:
Date Received: June 20, 2013
Date Started: May 2013
Date Completion: October 2023
Last Updated: November 2, 2016
Last Verified: November 2016