Back to resultsLong-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
Primary Purpose
Late Infantile Metachromatic Leukodystrophy
Status
Completed
Phase
Phase 1
Locations
Denmark
Study Type
Interventional
Intervention
Recombinant human Arylsulfatase A (rhASA)
Sponsored by
About this trial
This is an interventional treatment trial for Late Infantile Metachromatic Leukodystrophy focused on measuring Metazym, Late infantile, Metachromatic leukodystrophy, Long-term safety
Eligibility Criteria
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
Sites / Locations
- PhaseOneTrials A/S
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Arm Description
Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA)
Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA)
Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA)
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Change in Cerebrospinal Fluid (CSF) Sulfatide
Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00633139
Brief Title
Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
January 22, 2007 (Actual)
Primary Completion Date
November 25, 2008 (Actual)
Study Completion Date
November 25, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Late Infantile Metachromatic Leukodystrophy
Keywords
Metazym, Late infantile, Metachromatic leukodystrophy, Long-term safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA)
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA)
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA)
Intervention Type
Biological
Intervention Name(s)
Recombinant human Arylsulfatase A (rhASA)
Other Intervention Name(s)
Metazym, HGT-1111
Intervention Description
intravenous infusion, every other week for 26 weeks
Primary Outcome Measure Information:
Title
Relative Changes (%) in Gross Motor Function Measurement (GMFM)
Description
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.
Time Frame
Baseline, 52 Weeks
Title
Relative Change in Mullen's Scales of Early Learning
Description
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.
Time Frame
Baseline, 52 Weeks
Secondary Outcome Measure Information:
Title
Change in Cerebrospinal Fluid (CSF) Sulfatide
Description
Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean.
Time Frame
Baseline, 52 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
PhaseOneTrials A/S
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
12. IPD Sharing Statement
Citations:
PubMed Identifier
33332761
Citation
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.
Results Reference
derived
Learn more about this trial
Long-term Metazym Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)
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