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

NCT00633139 | Completed Phase 1 Results DMC

• 2 other identifiers: HGT-MLD-0482007-006345-40
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Late Infantile Metachromatic Leukodystrophy

Keywords

Metazym; Late infantile; Metachromatic leukodystrophy; Long-term safety

Outcome Measures

Primary Outcomes (2)

• Relative Changes (%) in Gross Motor Function Measurement (GMFM)

  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

  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 Outcomes (1)

• Change in Cerebrospinal Fluid (CSF) Sulfatide

  Baseline, 52 Weeks

Study Arms (3)

Cohort 1

EXPERIMENTAL

Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA)

Biological: Recombinant human Arylsulfatase A (rhASA)

Cohort 2

EXPERIMENTAL

Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA)

Biological: Recombinant human Arylsulfatase A (rhASA)

Cohort 3

EXPERIMENTAL

Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA)

Biological: Recombinant human Arylsulfatase A (rhASA)

Interventions

Recombinant human Arylsulfatase A (rhASA) BIOLOGICAL

intravenous infusion, every other week for 26 weeks

Also known as: Metazym, HGT-1111

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 1 Year - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

PhaseOneTrials A/S

Hvidovre, 2650, Denmark

Location

Related Publications (1)

• I Dali C, Groeschel S, Moldovan M, Farah MH, Krageloh-Mann I, Wasilewski M, Li J, Barton N, Krarup C. Intravenous arylsulfatase A in metachromatic leukodystrophy: a phase 1/2 study. Ann Clin Transl Neurol. 2021 Jan;8(1):66-80. doi: 10.1002/acn3.51254. Epub 2020 Dec 17.

  PMID: 33332761 DERIVED

MeSH Terms

Conditions

Leukodystrophy, Metachromatic

Condition Hierarchy (Ancestors)

Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sulfatidosis; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Leukoencephalopathies; Demyelinating Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2008
• First Posted: March 11, 2008
• Study Start: January 22, 2007
• Primary Completion: November 25, 2008
• Study Completion: November 25, 2008
• Last Updated: June 14, 2021
• Results First Posted: June 15, 2012

Record last verified: 2021-05

Locations

DK (1)