Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

May 19, 2021 updated by: Shire

A Single Center, Open-Label, Non-Randomized, Uncontrolled, Multiple-Dose, Dose Escalation Study of the Safety, Pharmacokinetics, Efficacy and Long Term Safety of HGT-1111 (Recombinant Human Arylsulfatase A [rhASA, Metazym]) for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

This is a single center, open-label study of patients with late infantile MLD. All patients were previous treated 26 weeks in the phase I trial (EudraCT number: 2006-005341-11, NCT00418561). All patients will be offered continuing treatment in this study and will in this protocol receive 13 infusions, whereby the patients total have had 27 infusions of Metazym. One infusion will be given every other week. After a total of 52 weeks of treatment the subjects will continue treatment in a compassionate use protocol. Safety (AE/SAE) will be monitored at every visit.

Study Overview

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Hvidovre, Denmark, 2650
        • PhaseOneTrials A/S

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 5 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

The patients from the Phase I trial must meet the following criteria to be enrolled in the study.

  • Subject's legally authorized guardian(s) must provide signed, informed consent prior to performing any study-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject)
  • The subject and his/her guardian(s) must have the ability to comply with the clinical protocol

Exclusion Criteria:

  • Spasticity so severe to inhibit transportation
  • Presence of known clinically significant cardiovascular, hepatic, pulmonary or renal disease or other medical condition that, in the opinion of the Investigator, would preclude participation in the trial
  • Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
  • Use of any investigational product other than rhASA within 30 days prior to study enrolment or currently enrolled in another study which involves clinical investigations

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA)
intravenous infusion, every other week for 26 weeks
Other Names:
  • Metazym
  • HGT-1111
Experimental: Cohort 2
Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA)
intravenous infusion, every other week for 26 weeks
Other Names:
  • Metazym
  • HGT-1111
Experimental: Cohort 3
Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA)
intravenous infusion, every other week for 26 weeks
Other Names:
  • Metazym
  • HGT-1111

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative Changes (%) in Gross Motor Function Measurement (GMFM)
Time Frame: Baseline, 52 Weeks
Change (percent change) in GMFM is measured from baseline to end of study (Week 52). GMFM is measured using GMFM-88. The GMFM-88 item scores can be summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score is between 0 (minimal) to 3 (maximum). The total GMFM-88 score is between 0 (minimal) to 264 (maximum). Relative changes in GMFM are calculated as percentage change from baseline divided by the age difference in months between first and last visit. The GMFM score decreases over time, which, indicates that the disease worsened over time. Score over time (SOT), data mentioned over mean represents the adjusted mean.
Baseline, 52 Weeks
Relative Change in Mullen's Scales of Early Learning
Time Frame: Baseline, 52 Weeks
Changes in Mullen's Scales of Early Learning are measured from baseline to end of study (Week 52) using Mullen's Scales of Early Learning. T scores, percentile ranks, and age equivalents can be computed for the four scales separately (visual reception, fine motor, expressive language, and receptive language). Relative change is calculated as percentage change from baseline divided by the age-difference in months between first and last visit. When Mullen's score decreases over time, it indicates the disease worsened over time. Data mentioned over mean represents the adjusted mean.
Baseline, 52 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Cerebrospinal Fluid (CSF) Sulfatide
Time Frame: Baseline, 52 Weeks
Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean.
Baseline, 52 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2007

Primary Completion (Actual)

November 25, 2008

Study Completion (Actual)

November 25, 2008

Study Registration Dates

First Submitted

February 29, 2008

First Submitted That Met QC Criteria

February 29, 2008

First Posted (Estimate)

March 11, 2008

Study Record Updates

Last Update Posted (Actual)

June 14, 2021

Last Update Submitted That Met QC Criteria

May 19, 2021

Last Verified

May 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Late Infantile Metachromatic Leukodystrophy

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