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Metazym for the Treatment of Patients With Late Infantile Metachromatic Leukodystrophy (MLD)

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ClinicalTrials.gov Identifier: NCT00418561
Recruitment Status : Completed
First Posted : January 5, 2007
Results First Posted : August 13, 2015
Last Update Posted : April 27, 2016
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Factorial Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metachromatic Leukodystrophy (MLD)
Intervention Drug: rhASA
Enrollment 13
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight. Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight. Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Period Title: Overall Study
Started 4 5 4
Completed 4 4 4
Not Completed 0 1 0
Reason Not Completed
Participant's (guardian's) decision             0             1             0
Arm/Group Title Cohort 1 Cohort 2 Cohort 3 Total
Hide Arm/Group Description Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight. Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight. Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight. Total of all reporting groups
Overall Number of Baseline Participants 4 5 4 13
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 4 participants 5 participants 4 participants 13 participants
36.25  (9.32) 41.80  (10.13) 30.75  (7.27) 36.69  (9.59)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 5 participants 4 participants 13 participants
Female
2
  50.0%
3
  60.0%
3
  75.0%
8
  61.5%
Male
2
  50.0%
2
  40.0%
1
  25.0%
5
  38.5%
1.Primary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) is any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurring in a participant, participating in a clinical study with study drug, regardless of causal relationship. TEAEs were AEs occurred after study drug administration that were absent before treatment or that worsened relative to pre-treatment state, up to Week 28 until evaluation (when last cohort had 26-week evaluation and data management performed within 4 weeks) completed.
Time Frame From study drug administration up to Week 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Measure Type: Number
Unit of Measure: participants
4 5 4
2.Primary Outcome
Title Change From Baseline in Gross Motor Function Measure (GMFM) at Week 26
Hide Description GMFM was measured using GMFM-88 item scores and summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score was between 0 (minimal) to 3 (maximum). The total GMFM-88 score was between 0 (minimal) and 264 (maximum). The decrease in GMFM score over time indicates worsening of disease over time. Relative change from baseline at Week 26 was calculated as percentage change from baseline divided by the age-difference in months between first and last visit. Adjusted mean and 95 percent (%) confidence intervals were reported.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Mean (95% Confidence Interval)
Unit of Measure: percent (%) change
-2.36
(-7.62 to 2.91)
-8.29
(-13.55 to -3.02)
-10.90
(-16.17 to -5.64)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1, Cohort 2, Cohort 3
Comments The comparisons of the three doses were done using analysis of variance (ANOVA) model including the baseline measurement as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0737
Comments Test for no difference between cohorts.
Method ANOVA
Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in Cerebrospinal Fluid (CSF) Sulfatide at Week 26
Hide Description Relative change from baseline at Week 26 was calculated as percentage change from baseline divided by the age-difference in months between first and last visit. Adjusted mean and 95 percent (%) confidence intervals were reported.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Mean (95% Confidence Interval)
Unit of Measure: percent (%) change
24.55
(0.44 to 48.66)
-3.77
(-22.33 to 14.80)
-4.32
(-28.17 to 19.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1, Cohort 2, Cohort 3
Comments The comparisons of the three doses were done using ANOVA model including the baseline measurement as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1115
Comments Test for no difference between cohorts.
Method ANOVA
Comments [Not Specified]
4.Primary Outcome
Title Number of Participants With Shift From Baseline to Week 26 in Sulfatide Levels in Urine
Hide Description Number of participants with shifts between negative (value=0) and positive (value=1) values in urine sulfatide levels from baseline at Week 26 is reported.
Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Here, the number of participants analyzed are the participants evaluable for this outcome.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 3 2 2
Measure Type: Number
Unit of Measure: participants
Negative(0) to negative(0) 0 0 0
Negative(0) to positive(1) 0 0 0
Positive(1) to negative(0) 0 0 0
Positive(1) to positive(1) 3 2 2
5.Primary Outcome
Title Change From Baseline in Mullen’s Scales of Early Learning at Week 26
Hide Description Mullen's Scales of Early Learning is used to assess performance and learning ability in young children. The scale consisted of 144 items that had specific scoring criteria for each item. The scores were converted to T-scores with a decrease in score indicating worsening of disease. Relative change from baseline at Week 26 was calculated as percentage change from baseline divided by the age-difference in months between first and last visit. Adjusted mean and 95 percent (%) confidence intervals were reported.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Mean (95% Confidence Interval)
Unit of Measure: percent (%) change
16.28
(0.72 to 31.84)
0.26
(-15.49 to 16.02)
-4.92
(-20.26 to 10.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1, Cohort 2, Cohort 3
Comments The comparisons of the three doses were done using ANOVA model including the baseline measurement as a covariate.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1268
Comments Test for no difference between cohorts.
Method ANOVA
Comments [Not Specified]
6.Primary Outcome
Title Maximum Plasma Drug Concentration (Cmax) of Recombinant Human Arylsulphatase A (rhASA)
Hide Description [Not Specified]
Time Frame Pre-dose and post-dose at 20, 40, 90 minutes, 3, 6 and 8 hours on Day 0, 40 minutes post-dose at Week 4, Pre-dose and post-dose at 20, 40, 90 minutes, 3, 6 and 8 hours at Week 8
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Due to quick disappearance of rhASA from plasma, rhASA levels were not possible to report.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Primary Outcome
Title Arylsulfatase A (ASA) Activity in Leukocytes
Hide Description [Not Specified]
Time Frame Pre-dose and post-dose at 24 hours on Day 0 and at Weeks 8 and 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data were not available to report as ASA activity in leukocytes was presented graphically, as per planned analysis.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Change From Baseline in Nerve Conduction Velocity at Week 26
Hide Description

An electrophysiological evaluation using standard electrophysiological and electromyography to measure the speed and extent of nerve conduction and units are expressed in meters per second.

Abbreviations: MN=Median Nerve; PN=Peroneal Nerve; SN=Sural Nerve; Dig.=Digit; FH=fibular hemimelia; L LM=left lateral medial; R LM=right lateral medial; MC=medial collateral.

Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Here, "N" signifies the number of participants who were evaluable for the respective category.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Mean (Standard Deviation)
Unit of Measure: meters per second
MN, Elbow Wrist: Baseline (N=4,5,4) 20.38  (6.99) 25.78  (17.72) 15.95  (5.68)
MN, Elbow Wrist: Change at Week 26 (N=4,4,4) -4.00  (1.10) 2.62  (4.42) -3.65  (3.33)
MN, Dig. II Wrist: Baseline (N=3,5,4) 39.83  (7.22) 36.82  (16.64) 23.30  (11.99)
MN, Dig. II Wrist: Change at Week 26 (N=3,4,4) -11.7  (5.78) -0.25  (4.39) -1.33  (4.72)
PN, Dig. Ankle FH: Baseline (N=4,4,4) 20.70  (9.08) 32.23  (21.41) 14.13  (5.92)
PN, Dig. Ankle FH: Change at Week 26 (N=4,3,4) -7.85  (3.92) -2.43  (1.59) -2.65  (3.61)
SN, Sensory L LM - MC: Baseline (N=4,4,4) 26.88  (9.29) 36.13  (20.61) 29.18  (15.93)
SN, Sensory L LM - MC: Change at Week 26 (N=3,3,4) -5.57  (4.18) 3.70  (9.79) -9.33  (10.64)
SN, Sensory R LM - MC: Baseline (N=4,4,4) 31.35  (6.46) 34.58  (17.74) 27.48  (13.91)
SN, Sensory R LM - MC: Change at Week 26 (N=0,0,0) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Since there were no participants evaluable for SN, Sensory R LM - MC category at Week 26, data could not be reported.
9.Secondary Outcome
Title Number of Participants Who Had Undergone Nerve Biopsy and Had a Normal Nerve at Both Baseline and Week 26
Hide Description [Not Specified]
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Measure Type: Number
Unit of Measure: participants
Baseline 0 2 0
Week 26 0 2 0
10.Secondary Outcome
Title Number of Participants With Shift From Baseline to Week 26 in Magnetic Resonance Imaging (MRI)-Loes Scores
Hide Description Loes scoring system is used to grade the demyelinating abnormalities on brain MRI. A total of 17 locations of the brain were scored from 0 (normal appearance) to 2 (dense appearance). The total score ranged from 0 to 34 with a score of 14 or greater being considered severe. Number of participants with any shift of score between 0 to 2 for each of the 17 locations (Parieto Occipital [PO]-Periventricular [P], Central [C], Subcortical [Sc]; Anterior Temporal [AT]-P, C, Sc; Frontal [F]-P, C, Sc; Corpus Callosum [CC]-Splenium [S], Genus [G]; Projection Fibers [PF]-Capsular interna [CI] ant, CI post, Brainstem [B]; Cerebellum [Cb]-Cortex, Atrophy; Basal Ganglia [BG]-BG, Thalamus [T]; Cerebral Atrophy [CA]-CA), are only reported.
Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Here, number of participants analyzed in the Cohort 2 are the participants evaluable for this outcome.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Number
Unit of Measure: participants
PO, P: 1 to 2 1 0 1
PO, P: 2 to 2 3 4 3
PO, C: 2 to 2 4 4 4
PO, Sc: 0 to 0 1 0 1
PO, Sc: 0 to 1 0 1 0
PO, Sc: 0 to 2 0 0 1
PO, Sc: 1 to 1 0 1 0
PO, Sc: 1 to 2 0 0 1
PO, Sc: 2 to 2 3 2 1
AT, P: 0 to 2 1 0 0
AT, P: 1 to 2 0 1 2
AT, P: 2 to 2 3 3 2
AT, C: 0 to 2 1 0 0
AT, C: 1 to 2 0 0 1
AT, C: 2 to 2 3 4 3
AT, Sc: 0 to 0 1 0 1
AT, Sc: 0 to 1 0 1 0
AT, Sc: 0 to 2 0 2 2
AT, Sc: 1 to 1 0 1 0
AT, Sc: 1 to 2 1 0 0
AT, Sc: 2 to 2 2 0 1
F, P: 0 to 2 1 0 1
F, P: 1 to 2 0 1 1
F, P: 2 to 2 3 3 2
F, C: 1 to 2 1 0 2
F, C: 2 to 2 3 4 2
F, Sc: 0 to 0 1 0 1
F, Sc: 0 to 2 0 2 2
F, Sc: 1 to 2 1 1 0
F, Sc: 2 to 2 2 1 1
CC, S: 1 to 0 0 1 1
CC, S: 1 to 2 1 0 0
CC, S: 2 to 0 1 1 1
CC, S: 2 to 1 2 1 0
CC, S: 2 to 2 0 1 2
CC, G: 0 to 2 1 1 0
CC, G: 1 to 1 0 1 0
CC, G: 1 to 2 0 0 2
CC, G: 2 to 1 1 0 1
CC, G: 2 to 2 2 2 1
PF, CI ant: 0 to 0 2 3 4
PF, CI ant: 0 to 1 1 1 0
PF, CI ant: 1 to 1 1 0 0
PF, CI post: 0 to 0 0 1 0
PF, CI post: 0 to 1 1 0 2
PF, CI post: 1 to 1 0 2 0
PF, CI post: 1 to 2 1 0 1
PF, CI post: 2 to 1 0 1 0
PF, CI post: 2 to 2 2 0 1
PF, B: 0 to 0 1 0 1
PF, B: 0 to 1 0 1 1
PF, B: 0 to 2 0 0 1
PF, B: 1 to 0 0 1 0
PF, B: 1 to 1 1 0 0
PF, B: 1 to 2 1 1 1
PF, B: 2 to 2 1 1 0
Cb, Cortex: 0 to 0 2 1 1
Cb, Cortex: 0 to 1 0 2 2
Cb, Cortex: 1 to 1 2 1 1
Cb, Atrophy: 0 to 0 1 1 3
Cb, Atrophy: 0 to 1 1 1 0
Cb, Atrophy: 1 to 1 2 2 1
Bg, Bg: 0 to 0 2 3 2
Bg, Bg: 0 to 1 0 0 2
Bg, Bg: 1 to 0 0 1 0
Bg, Bg: 1 to 1 2 0 0
Bg, T: 0 to 0 2 3 3
Bg, T: 1 to 0 0 1 1
Bg, T: 1 to 1 2 0 0
CA, CA: 0 to 0 1 0 2
CA, CA: 0 to 1 0 2 1
CA, CA: 1 to 1 1 1 1
CA, CA: 1 to 2 2 1 0
11.Secondary Outcome
Title Change From Baseline in Paediatric Evaluation of Disability Inventory (PEDI) Scores at Week 26
Hide Description PEDI is used for the clinical evaluation of functional capabilities, performance and changes in functional skills in children with disabilities. It consisted of 20 items scored on a scale from 0 (total assistance) to 5 (independent). Total score ranged from 0-100 with higher scores indicating better functioning. None, child, rehab, extensive are items in 3 domains (self-care, mobility and social functioning).
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Here, "N" signifies the number of participants who were evaluable for the respective category.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Mean (Standard Deviation)
Unit of Measure: units on a scale
Self-care, None: Baseline (N=4,5,4) 6.25  (0.96) 6.00  (1.41) 4.75  (2.06)
Self-care, None: Change at Week 26 (N=4,4,4) -0.75  (1.50) -1.50  (1.73) -1.50  (1.91)
Self-care, Child: Baseline (N=4,5,4) 1.75  (0.96) 2.00  (1.41) 3.25  (2.06)
Self-care, Child: Change at Week 26 (N=4,4,4) 0.75  (1.50) 1.25  (1.50) 0.75  (2.22)
Self-care, Rehab: Baseline (N=4,5,4) 0  (0) 0  (0) 0  (0)
Self-care, Rehab: Change at Week 26 (N=4,4,4) 0  (0) 0  (0) 0  (0)
Self-care, Extensive: Baseline (N=4,5,4) 0  (0) 0.20  (0.45) 0  (0)
Self-care, Extensive: Change at Week 26 (N=4,4,4) 0  (0) 0.25  (0.50) 0.50  (0.58)
Mobility, None: Baseline (N=4,5,4) 4.25  (1.89) 3.60  (1.14) 5.00  (0.82)
Mobility, None: Change at Week 26 (N=4,4,4) -0.75  (1.71) -0.50  (1.29) -1.25  (1.71)
Mobility, Child: Baseline (N=4,5,4) 2.50  (1.91) 2.40  (1.67) 1.25  (1.26)
Mobility, Child: Change at Week 26 (N=4,4,4) 0.00  (1.41) 0.25  (1.26) -0.50  (0.58)
Mobility, Rehab: Baseline (N=4,5,4) 0.00  (0.00) 1.00  (1.41) 0.75  (0.96)
Mobility, Rehab: Change at Week 26 (N=4,4,4) 1.00  (0.82) 0.25  (0.50) 0.50  (1.73)
Mobility, Extensive: Baseline (N=4,5,4) 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Mobility, Extensive: Change at Week 26 (N=4,4,4) 0.00  (0.00) 0.00  (0.00) 1.25  (1.50)
Social, None: Baseline (N=4,5,4) 4.25  (0.96) 4.60  (0.55) 4.75  (0.50)
Social, None: Change at Week 26 (N=4,4,4) 0.75  (0.96) -0.25  (0.50) 0.25  (0.50)
Social, Child: Baseline (N=4,5,4) 1.50  (2.38) 0.00  (0.00) 0.25  (0.50)
Social, Child: Change at Week 26 (N=4,4,4) -1.50  (2.38) 0.00  (0.00) -0.25  (0.50)
Social, Rehab: Baseline (N=4,5,4) 0.00  (0.00) 0.40  (0.55) 0.00  (0.00)
Social, Rehab: Change at Week 26 (N=4,4,4) 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Social, Extensive: Baseline (N=4,5,4) 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Social, Extensive: Change at Week 26 (N=4,4,4) 0.00  (0.00) 0.25  (0.50) 0.00  (0.00)
12.Other Pre-specified Outcome
Title Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Biochemistry
Hide Description

Number of participants with at least 1 shift from baseline to Week 26, are reported.

Abbreviations: ALT=Alanine transaminase; CK=Creatine kinase; AP=Amyloid P component; LDH=Lactate dehydrogenase.

Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Here, number of participants analyzed in the Cohort 2 are the participants evaluable for this outcome.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Number
Unit of Measure: participants
ALT-Serum: Low to low 2 0 1
ALT-Serum: Low to normal 1 1 0
ALT-Serum: Normal to low 0 1 2
ALT-Serum: Normal to normal 0 1 1
ALT-Serum: High to low 1 0 0
ALT-Serum: High to normal 0 1 0
Amylase-Serum: Normal to normal 4 4 4
AP-Serum: Normal to normal 4 4 4
Calcium-Serum: Normal to normal 4 3 4
CK-Serum: Normal to normal 4 3 2
CK-Serum: Normal to high 0 1 0
CK-Serum: High to normal 0 0 1
CK-Serum: High to high 0 0 1
Creatinine-Serum: Normal to normal 4 4 4
Iron-Serum: Low to normal 0 1 0
Iron-Serum: Normal to low 0 0 1
Iron-Serum: Normal to normal 3 3 3
Iron-Serum: Normal to high 1 0 0
LDH-Serum: Normal to normal 3 4 4
LDH-Serum: High to normal 1 0 0
Magnesium-Serum: Normal to normal 4 4 4
Phosphate-Serum: Normal to normal 2 3 3
Phosphate-Serum: Normal to high 1 0 0
Phosphate-Serum: High to normal 1 1 1
Potassium-Serum: Normal to normal 4 4 4
Sodium-Serum: Normal to normal 4 3 4
Sodium-Serum: High to normal 0 1 0
T Bilirubin-Serum: Normal to normal 4 3 4
T Bilirubin-Serum: High to normal 0 1 0
13.Other Pre-specified Outcome
Title Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Coagulation
Hide Description Number of participants with at least 1 shift from baseline to Week 26 are reported. The shift reported below for Cohort 1 was from low level at baseline to low level at Week 26.
Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Data for Cohorts 2 and 3 were not reported since there were no participants with shift from baseline to Week 26 in coagulation evaluations.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 0 0
Measure Type: Number
Unit of Measure: participants
4
14.Other Pre-specified Outcome
Title Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Genotyping
Hide Description

Number of participants with at least 1 shift from baseline to Week 26 are reported.

Abbreviations: CSF=Cerebrospinal fluid; NFP=Neurofilament proteins.

Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. The number of participants analyzed in the Cohort 2 are the participants evaluable for this outcome. Here, "N" signifies the number of participants who were evaluable for the respective category.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Number
Unit of Measure: participants
Albumin CSF: Normal to normal (N=3,4,4) 0 2 0
Albumin CSF: Normal to high (N=3,4,4) 1 0 0
Albumin CSF: High to high (N=3,4,4) 2 2 4
Albumin index: Normal to normal (N=3,4,4) 0 1 0
Albumin index: High to high (N=3,4,4) 3 3 4
Albumin Serum: Low to low (N=3,4,4) 2 2 2
Albumin Serum: Low to normal (N=3,4,4) 0 1 0
Albumin Serum: Normal to low (N=3,4,4) 0 0 1
Albumin Serum: Normal to normal (N=3,4,4) 1 1 1
Chitotriosidase CSF: Low to low (N=4,4,4) 1 0 0
Chitotriosidase CSF: High to high (N=4,4,4) 3 4 4
NFP CSF: Normal to high (N=4,4,4) 1 0 0
NFP CSF: High to high (N=4,4,4) 3 4 4
Sulfatide CSF: High to high (N=3,4,4) 3 4 4
Tauprotein CSF: High to low (N=4,4,4) 0 1 0
Tauprotein CSF: High to high (N=4,4,4) 4 3 4
15.Other Pre-specified Outcome
Title Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Hematology
Hide Description

Number of participants with at least 1 shift from baseline to Week 26 are reported.

Abbreviations: Abs=Absolute count; ERCS=Erythrocytes; MCHC=Mean corpuscular hemoglobin concentration; MCH=Mean cell hemoglobin.

Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. The number of participants analyzed in the Cohort 2 are the participants evaluable for this outcome. Here, "N" signifies the number of participants who were evaluable for the respective category.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 4 4
Measure Type: Number
Unit of Measure: participants
Basophils Abs - Blood: Normal to normal (N=4,4,4) 4 4 4
Eosinophil Abs - Blood: Normal to normal (N=4,4,4) 4 4 4
ERCS - Blood: Low to low (N=4,4,4) 1 0 0
ERCS - Blood: Normal to normal (N=4,4,4) 3 4 4
Haemoglobin - Blood: Low to low (N=4,4,4) 1 1 1
Haemoglobin - Blood: Low to normal (N=4,4,4) 1 0 1
Haemoglobin - Blood: Normal to low (N=4,4,4) 1 0 1
Haemoglobin - Blood: Normal to normal (N=4,4,4) 1 3 1
Lymphocyte Abs - Blood: Low to low (N=4,4,4) 0 1 0
Lymphocyte Abs - Blood: Normal to low (N=4,4,4) 2 2 2
Lymphocyte Abs - Blood: Normal to normal (N=4,4,4) 2 1 2
MCHC - Blood: Normal to normal (N=4,4,4) 3 3 4
MCHC - Blood: High to normal (N=4,4,4) 1 1 0
MCH - Blood: Low to low (N=4,4,4) 0 0 1
MCH - Blood: Normal to normal (N=4,4,4) 4 4 3
Monocytes Abs - Blood: Normal to normal (N=4,4,4) 4 4 3
Monocytes Abs - Blood: High to normal (N=4,4,4) 0 0 1
Neutropil Abs - Blood: Normal to normal (N=4,4,4) 4 4 3
Neutropil Abs - Blood: Normal to high (N=4,4,4) 0 0 1
Thrombocytes - Blood: Normal to low (N=4,3,4) 1 0 1
Thrombocytes - Blood: Normal to normal (N=4,3,4) 2 0 2
Thrombocytes - Blood: High to normal (N=4,3,4) 1 3 1
T Leucocytes - Blood: Low to normal (N=4,4,4) 0 0 1
T Leucocytes - Blood: Normal to low (N=4,4,4) 2 2 0
T Leucocytes - Blood: Normal to normal (N=4,4,4) 2 2 3
16.Other Pre-specified Outcome
Title Number of Participants With Abnormal Findings in Urine Analysis
Hide Description The parameters analyzed in urine were albumin/protein, glucose, leucocytes, acetoacetate/ketones, nitrite and pH. Urine analysis findings were considered abnormal as judged by the investigator.
Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Measure Type: Number
Unit of Measure: participants
0 0 0
17.Other Pre-specified Outcome
Title Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings
Hide Description Abnormal ECG findings were considered as clinically significant at the discretion of investigator.
Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Measure Type: Number
Unit of Measure: participants
0 0 0
18.Other Pre-specified Outcome
Title Change From Baseline in Chitotriosidase at Week 26
Hide Description [Not Specified]
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Here, "N" signifies the number of participants who were evaluable for the respective category.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Mean (Standard Deviation)
Unit of Measure: nanomole/hour/milliliter
Baseline (N=4, 5, 4) 924.0  (1431) 1481  (1165) 367.0  (179.0)
Change at Week 26 (N=4, 4, 4) -76.0  (393.9) -228  (692.7) 94.75  (103.6)
19.Other Pre-specified Outcome
Title Change From Baseline in Neurofilament Proteins (NFP), Glial Fibrillary Acidic Protein (GFAP) and Tauprotein in Cerebrospinal Fluid (CSF) at Week 26
Hide Description [Not Specified]
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Here, "N" signifies the number of participants who were evaluable for the respective category.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Mean (Standard Deviation)
Unit of Measure: nanogram/milliliter
NFP: Baseline (N=4, 5, 4) 5436  (3698) 7848  (4510) 12558  (3529)
NFP: Change at Week 26 (N=4, 4, 4) 1134  (8098) -3505  (2553) -4020  (9061)
GFAP: Baseline (N=4, 5, 4) 1758  (397.4) 1014  (524.3) 1415  (625.7)
GFAP: Change at Week 26 (N=4, 4, 4) 330.0  (380.3) 402.5  (460.5) 502.5  (285.4)
Tauprotein: Baseline (N=4, 5, 4) 1148  (143.4) 1014  (530.9) 1610  (543.4)
Tauprotein: Change at Week 26 (N=4, 4, 4) -288  (692.3) -273  (228.7) -118  (907.6)
20.Other Pre-specified Outcome
Title Change From Baseline in Amplitude at Week 26
Hide Description Abbreviations: MN=Median Nerve; PN=Peroneal Nerve; SN=Sural Nerve; Dig.=Digit; APB=abductor pollicis brevis; EDB=extensor digitorum brevis.
Time Frame Baseline, Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT. Here, "N" signifies the number of participants who were evaluable for the respective category.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 4 5 4
Mean (Standard Deviation)
Unit of Measure: millivolts
MN, Wrist-APB: Baseline (N=4,5,4) 5.63  (1.73) 7.88  (2.20) 4.30  (1.05)
MN, Wrist-APB: Change at Week 26 (N=4,4,4) 0.00  (2.84) 0.65  (0.74) -0.35  (1.66)
MN, Elbow-APB: Baseline (N=4,5,4) 3.85  (1.23) 6.34  (2.71) 2.65  (0.60)
MN, Elbow-APB: Change at Week 26 (N=4,4,4) 0.15  (2.05) 0.33  (0.57) -0.55  (0.65)
MN, Dig. II Wrist: Baseline (N=4,5,4) 2.68  (1.30) 11.64  (14.89) 1.78  (0.83)
MN, Dig. II Wrist: Change at Week 26 (N=4,4,4) -0.32  (1.00) 3.53  (6.60) -0.93  (0.85)
PN, Ankle EDB: Baseline (N=4,4,4) 1.85  (0.91) 5.40  (2.55) 1.30  (0.68)
PN, Ankle EDB: Change at Week 26 (N=4,3,4) -0.72  (1.66) -0.43  (1.56) 0.08  (0.96)
PN, FH EDB: Baseline (N=4,4,4) 2.43  (1.80) 4.98  (2.95) 0.95  (0.74)
PN, FH EDB: Change at Week 26 (N=4,3,4) -1.68  (2.06) -0.63  (1.46) 0.16  (0.75)
SN, Sensory L LM - MC: Baseline (N=4,4,4) 5.25  (6.31) 41.18  (51.50) 1.65  (2.28)
SN, Sensory L LM - MC: Change at Week 26 (N=4,3,4) -2.45  (4.18) 0.53  (21.75) -0.78  (2.34)
SN, Sensory R LM - MC: Baseline (N=4,4,4) 5.35  (5.45) 50.05  (56.13) 1.73  (2.01)
SN, Sensory R LM - MC: Change at Week 26 (N=0,0,0) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Since there were no participants evaluable for SN, Sensory R LM - MC category at Week 26, data could not be reported.
21.Other Pre-specified Outcome
Title Physical Examination Results
Hide Description Physical examination included general appearance, skin, head, ears, eyes, nose and throat, lymph nodes, heart, lungs, abdomen, extremities/joints, hip, neurological, mental status and, if appropriate, breasts, external genitalia, pelvic and rectal, and in addition weight, height and head circumference were recorded.
Time Frame Baseline up to Week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Physical examination results were not summarized since data were collected in participant’s listing only as planned.
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description:
Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description From study drug administration up to Week 28 until evaluation (when last cohort had 26-week evaluation and data management performed within 4 weeks)
 
Arm/Group Title Cohort 1 Cohort 2 Cohort 3
Hide Arm/Group Description Single dose of 25 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), thereafter, received repeated doses of 50 U/kg recombinant human Arylsulphatase A, once in every 2 weeks for a period of 26 weeks, as an intravenous (IV) infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight. Repeated doses of 100 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 30 minutes. Dosage adjustment was done monthly to account for changes in body weight. Repeated doses of 200 U/kg recombinant human Arylsulphatase A (Metazym, rhASA), once in every 2 weeks for a period of 26 weeks, as an IV infusion over 60 minutes. Dosage adjustment was done monthly to account for changes in body weight.
All-Cause Mortality
Cohort 1 Cohort 2 Cohort 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1 Cohort 2 Cohort 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/4 (25.00%)      2/5 (40.00%)      2/4 (50.00%)    
Infections and infestations       
Bronchitis acute  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Metabolism and nutrition disorders       
Malnutrition  1  0/4 (0.00%)  0 2/5 (40.00%)  2 2/4 (50.00%)  2
Respiratory, thoracic and mediastinal disorders       
Pneumonia aspiration  1  0/4 (0.00%)  0 1/5 (20.00%)  1 1/4 (25.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (8.2)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1 Cohort 2 Cohort 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      5/5 (100.00%)      4/4 (100.00%)    
Eye disorders       
Blindness  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Gastrointestinal disorders       
Vomiting  1  0/4 (0.00%)  0 2/5 (40.00%)  4 2/4 (50.00%)  3
Nausea  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Diarrhoea  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Constipation  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Abdominal pain upper  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Pharyngolaryngeal pain  1  1/4 (25.00%)  1 1/5 (20.00%)  1 0/4 (0.00%)  0
General disorders       
Pyrexia  1  1/4 (25.00%)  1 3/5 (60.00%)  6 2/4 (50.00%)  3
Discomfort  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Infusion related reaction  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Immune system disorders       
Type III immune complex mediated reaction  1  2/4 (50.00%)  12 1/5 (20.00%)  2 2/4 (50.00%)  2
Infections and infestations       
Bronchitis acute  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Tonsillitis  1  1/4 (25.00%)  1 0/5 (0.00%)  0 1/4 (25.00%)  1
Nasopharyngitis  1  1/4 (25.00%)  1 0/5 (0.00%)  0 1/4 (25.00%)  1
Influenza  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Herpangina  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Gastroenteritis  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Acute tonsillitis  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Viral infection  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Varicella  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Postoperative infection  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Otitis media  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Injury, poisoning and procedural complications       
Procedural pain  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Feeding tube complication  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Device occlusion  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Investigations       
Drug specific antibody present  1  2/4 (50.00%)  2 0/5 (0.00%)  0 0/4 (0.00%)  0
Hepatic enzyme increased  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Blood iron decreased  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Muscle spasms  1  1/4 (25.00%)  1 3/5 (60.00%)  3 1/4 (25.00%)  1
Nervous system disorders       
Muscle spasticity  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Convulsion  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Speech disorder developmental  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Mutism  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Psychiatric disorders       
Sleep disorder  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  1
Depression  1  0/4 (0.00%)  0 1/5 (20.00%)  1 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/4 (0.00%)  0 1/5 (20.00%)  1 1/4 (25.00%)  1
Pharyngeal oedema  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Vascular disorders       
Flushing  1  0/4 (0.00%)  0 0/5 (0.00%)  0 1/4 (25.00%)  2
Pallor  1  1/4 (25.00%)  1 0/5 (0.00%)  0 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (8.2)
ASA activity in leukocytes could not be included in basic results format as the results were presented graphically. Due to quick disappearance of rhASA from plasma, rhASA levels were not possible to report.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicentre publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicentre Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Name/Title: Study Physician
Organization: Shire
Phone: 1866-842-5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00418561     History of Changes
Other Study ID Numbers: rhASA-01
2006-005341-11 ( EudraCT Number )
First Submitted: January 4, 2007
First Posted: January 5, 2007
Results First Submitted: July 16, 2015
Results First Posted: August 13, 2015
Last Update Posted: April 27, 2016