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| ID | Type | Description | Link |
|---|---|---|---|
| 2006-005341-11 | EudraCT Number |
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Objectives: The overall objective is to evaluate the safety, efficacy and pharmacokinetics (PK) of rhASA treatment in patients with late infantile MLD.
Methodology: This is a single center, open-label study of patients with late infantile MLD. Twelve patients will be enrolled in this study receiving a total of thirteen intravenous infusions of Metazym. One infusion will be given every other week for a period of half a year. After the half year the subjects will continue treatment every other week until safety data is available. Safety (AE/SAE) will be monitored at every visit during this period.
Test product, dose, mode of administration, batch No.: The lowest dose level will be evaluated as a single dose of 25 U/kg. The three upper dose levels will be evaluated as repeated doses. Patients in each cohort will receive one dose of enzyme every other week for a period of eight weeks, a total of five doses. Dosing will be performed as follows: Cohort 1: 25 U/kg as a single dose - hereafter 50 U/kg; Cohort 2: 100 U/kg; Cohort 3: 200 U/kg. Patients receiving the lowest dose as a single dose will receive the next dose level as a repeated dose. After twenty six weeks the subjects will continue treatment every other week until safety data is available. Safety (AE/SAE) will be monitored at every visit during this period. The dose will be adjusted monthly to account for changes in body weight. The infusion length will be dependent on the dose. Doses of 25 U/kg, 50 U/kg and 100 U/kg will be diluted in 50 ml isotonic sodium chloride and infused over 30 minutes. Infusion of 200 U/kg will be administered in the same manner except for an infusion time of 60 minutes.
Duration of treatment: Half a year (26 weeks)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Metazym (Recombinant human arylsulfatase A (rhASA)): 25 U/kg as a single dose - hereafter 50 U/kg |
|
| Cohort 2 | Experimental | 100 U/kg Metazym (Recombinant human arylsulfatase A (rhASA)) |
|
| Cohort 3 | Experimental | 200 U/kg Metazym (Recombinant human arylsulfatase A (rhASA)) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rhASA - Dose Level 1 | Biological | Intravenous infusion 25 U/kg as a single dose - hereafter 50 U/kg every other week for 26 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | From study drug administration up to Week 28 |
| Change From Baseline in Gross Motor Function Measure (GMFM) at Week 26 | 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. | Baseline, Week 26 |
| Change From Baseline in Cerebrospinal Fluid (CSF) Sulfatide at Week 26 | 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. | Baseline, Week 26 |
| Number of Participants With Shift From Baseline to Week 26 in Sulfatide Levels in Urine | 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. | Baseline up to Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Nerve Conduction Velocity at Week 26 | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Biochemistry | 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. | Baseline up to Week 26 |
Inclusion Criteria:
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 patient must have a confirmed diagnosis of MLD as defined by:
ASA activity < 10 nmol/h/mg in leukocytes Presence of elevated sulfatide in urine
The patient must have a confirmed nerve conduction velocity < 2 standard deviations (from the appropriate age level)
The patient must have a residual level of voluntary function (as judged by the investigator), including presence of residual cognitive function (attention, executive and visual functions) as well as the presence of residual voluntary motor function in one upper or lower limb as a minimum.
The patient must have an age at the time of screening ≥ 1 year and < 6 years
The patient must have had onset of symptoms before the age of 4 years
The subject and his/her guardian(s) must have the ability to comply with the clinical protocol
The patients' medical record must document that the legal guardian(s) has had independent counselling or a consultation regarding stem cell transplantation in order to assure that the guardian(s) is fully informed regarding the risks and benefits of this alternative
Exclusion Criteria:
Patients will be excluded from this study if they do not meet the specific inclusion criteria, or if any of the following criteria apply:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet | Hvidovre | DK-2650 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26000324 | Result | Dali CI, Barton NW, Farah MH, Moldovan M, Mansson JE, Nair N, Duno M, Risom L, Cao H, Pan L, Sellos-Moura M, Corse AM, Krarup C. Sulfatide levels correlate with severity of neuropathy in metachromatic leukodystrophy. Ann Clin Transl Neurol. 2015 May;2(5):518-33. doi: 10.1002/acn3.193. Epub 2015 Mar 27. | |
| 33332761 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | 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. |
| FG001 | Cohort 2 | 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. |
| FG002 | Cohort 3 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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. | Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | From study drug administration up to Week 28 |
|
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From study drug administration up to Week 28 until evaluation (when last cohort had 26-week evaluation and data management performed within 4 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Malnutrition | Metabolism and nutrition disorders | MedDRA (8.2) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis acute | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| ID | Term |
|---|---|
| D007966 | Leukodystrophy, Metachromatic |
| ID | Term |
|---|---|
| D020279 | Hereditary Central Nervous System Demyelinating Diseases |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
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| rhASA - Dose Level 2 | Biological | Intravenous infusion 100 U/kg every other week for 26 weeks |
|
|
| rhASA - Dose Level 3 | Biological | Intravenous infusion 200 U/kg every other week for 26 weeks |
|
|
| Change From Baseline in Mullen's Scales of Early Learning at Week 26 |
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. |
| Baseline, Week 26 |
| Maximum Plasma Drug Concentration (Cmax) of Recombinant Human Arylsulphatase A (rhASA) | 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 |
| Arylsulfatase A (ASA) Activity in Leukocytes | Pre-dose and post-dose at 24 hours on Day 0 and at Weeks 8 and 26 |
| Baseline, Week 26 |
| Number of Participants Who Had Undergone Nerve Biopsy and Had a Normal Nerve at Both Baseline and Week 26 | Baseline, Week 26 |
| Number of Participants With Shift From Baseline to Week 26 in Magnetic Resonance Imaging (MRI)-Loes Scores | 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. | Baseline up to Week 26 |
| Change From Baseline in Paediatric Evaluation of Disability Inventory (PEDI) Scores at Week 26 | 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). | Baseline, Week 26 |
| Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Coagulation |
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. |
| Baseline up to Week 26 |
| Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Genotyping | Number of participants with at least 1 shift from baseline to Week 26 are reported. Abbreviations: CSF=Cerebrospinal fluid; NFP=Neurofilament proteins. | Baseline up to Week 26 |
| Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Hematology | 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. | Baseline up to Week 26 |
| Number of Participants With Abnormal Findings in Urine Analysis | 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. | Baseline up to Week 26 |
| Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings | Abnormal ECG findings were considered as clinically significant at the discretion of investigator. | Baseline up to Week 26 |
| Change From Baseline in Chitotriosidase at Week 26 | Baseline, Week 26 |
| Change From Baseline in Neurofilament Proteins (NFP), Glial Fibrillary Acidic Protein (GFAP) and Tauprotein in Cerebrospinal Fluid (CSF) at Week 26 | Baseline, Week 26 |
| Change From Baseline in Amplitude at Week 26 | Abbreviations: MN=Median Nerve; PN=Peroneal Nerve; SN=Sural Nerve; Dig.=Digit; APB=abductor pollicis brevis; EDB=extensor digitorum brevis. | Baseline, Week 26 |
| Physical Examination Results | 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. | Baseline up to Week 26 |
| 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. |
| Cohort 2 |
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. |
| BG002 | Cohort 3 | 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. |
| BG003 | Total | Total of all reporting groups |
| months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Cohort 2 | 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. |
| OG002 | Cohort 3 | 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. |
|
|
| Primary | Change From Baseline in Gross Motor Function Measure (GMFM) at Week 26 | 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. | ITT | Posted | Mean | 95% Confidence Interval | percent (%) change | Baseline, Week 26 |
|
|
|
|
| Primary | Change From Baseline in Cerebrospinal Fluid (CSF) Sulfatide at Week 26 | 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. | ITT | Posted | Mean | 95% Confidence Interval | percent (%) change | Baseline, Week 26 |
|
|
|
|
| Primary | Number of Participants With Shift From Baseline to Week 26 in Sulfatide Levels in Urine | 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. | ITT. Here, the number of participants analyzed are the participants evaluable for this outcome. | Posted | Number | participants | Baseline up to Week 26 |
|
|
|
| Primary | Change From Baseline in Mullen's Scales of Early Learning at Week 26 | 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. | ITT | Posted | Mean | 95% Confidence Interval | percent (%) change | Baseline, Week 26 |
|
|
|
|
| Secondary | Change From Baseline in Nerve Conduction Velocity at Week 26 | 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. | ITT. Here, "N" signifies the number of participants who were evaluable for the respective category. | Posted | Mean | Standard Deviation | meters per second | Baseline, Week 26 |
|
|
|
| Secondary | Number of Participants Who Had Undergone Nerve Biopsy and Had a Normal Nerve at Both Baseline and Week 26 | ITT. | Posted | Number | participants | Baseline, Week 26 |
|
|
|
| Secondary | Number of Participants With Shift From Baseline to Week 26 in Magnetic Resonance Imaging (MRI)-Loes Scores | 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. | ITT. Here, number of participants analyzed in the Cohort 2 are the participants evaluable for this outcome. | Posted | Number | participants | Baseline up to Week 26 |
|
|
|
| Secondary | Change From Baseline in Paediatric Evaluation of Disability Inventory (PEDI) Scores at Week 26 | 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). | ITT. Here, "N" signifies the number of participants who were evaluable for the respective category. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 26 |
|
|
|
| Other Pre-specified | Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Biochemistry | 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. | ITT. Here, number of participants analyzed in the Cohort 2 are the participants evaluable for this outcome. | Posted | Number | participants | Baseline up to Week 26 |
|
|
|
| Other Pre-specified | Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Coagulation | 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. | 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. | Posted | Number | participants | Baseline up to Week 26 |
|
|
|
| Other Pre-specified | Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Genotyping | Number of participants with at least 1 shift from baseline to Week 26 are reported. Abbreviations: CSF=Cerebrospinal fluid; NFP=Neurofilament proteins. | 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. | Posted | Number | participants | Baseline up to Week 26 |
|
|
|
| Other Pre-specified | Number of Participants With Shift From Baseline to Week 26 in Clinical Laboratory Evaluations: Hematology | 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. | 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. | Posted | Number | participants | Baseline up to Week 26 |
|
|
|
| Other Pre-specified | Number of Participants With Abnormal Findings in Urine Analysis | 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. | ITT | Posted | Number | participants | Baseline up to Week 26 |
|
|
|
| Other Pre-specified | Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings | Abnormal ECG findings were considered as clinically significant at the discretion of investigator. | ITT | Posted | Number | participants | Baseline up to Week 26 |
|
|
|
| Other Pre-specified | Change From Baseline in Chitotriosidase at Week 26 | ITT. Here, "N" signifies the number of participants who were evaluable for the respective category. | Posted | Mean | Standard Deviation | nanomole/hour/milliliter | Baseline, Week 26 |
|
|
|
| Other Pre-specified | Change From Baseline in Neurofilament Proteins (NFP), Glial Fibrillary Acidic Protein (GFAP) and Tauprotein in Cerebrospinal Fluid (CSF) at Week 26 | ITT. Here, "N" signifies the number of participants who were evaluable for the respective category. | Posted | Mean | Standard Deviation | nanogram/milliliter | Baseline, Week 26 |
|
|
|
| Other Pre-specified | Change From Baseline in Amplitude at Week 26 | Abbreviations: MN=Median Nerve; PN=Peroneal Nerve; SN=Sural Nerve; Dig.=Digit; APB=abductor pollicis brevis; EDB=extensor digitorum brevis. | ITT. Here, "N" signifies the number of participants who were evaluable for the respective category. | Posted | Mean | Standard Deviation | millivolts | Baseline, Week 26 |
|
|
|
| Primary | Maximum Plasma Drug Concentration (Cmax) of Recombinant Human Arylsulphatase A (rhASA) | Due to quick disappearance of rhASA from plasma, rhASA levels were not possible to report. | Posted | 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 |
|
|
| Primary | Arylsulfatase A (ASA) Activity in Leukocytes | Data were not available to report as ASA activity in leukocytes was presented graphically, as per planned analysis. | Posted | Pre-dose and post-dose at 24 hours on Day 0 and at Weeks 8 and 26 |
|
|
| Other Pre-specified | Physical Examination Results | 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. | Physical examination results were not summarized since data were collected in participant's listing only as planned. | Posted | Baseline up to Week 26 |
|
|
| 1 |
| 4 |
| 4 |
| 4 |
| EG001 | Cohort 2 | 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. | 2 | 5 | 5 | 5 |
| EG002 | Cohort 3 | 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. | 2 | 4 | 4 | 4 |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Bronchitis acute | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Herpangina | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Acute tonsillitis | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Postoperative infection | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (8.2) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (8.2) | Systematic Assessment |
|
| Discomfort | General disorders | MedDRA (8.2) | Systematic Assessment |
|
| Infusion related reaction | General disorders | MedDRA (8.2) | Systematic Assessment |
|
| Type III immune complex mediated reaction | Immune system disorders | MedDRA (8.2) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Pharyngolaryngeal pain | Gastrointestinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Pharyngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (8.2) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (8.2) | Systematic Assessment |
|
| Drug specific antibody present | Investigations | MedDRA (8.2) | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | MedDRA (8.2) | Systematic Assessment |
|
| Blood iron decreased | Investigations | MedDRA (8.2) | Systematic Assessment |
|
| Muscle spasticity | Nervous system disorders | MedDRA (8.2) | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA (8.2) | Systematic Assessment |
|
| Speech disorder developmental | Nervous system disorders | MedDRA (8.2) | Systematic Assessment |
|
| Mutism | Nervous system disorders | MedDRA (8.2) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (8.2) | Systematic Assessment |
|
| Feeding tube complication | Injury, poisoning and procedural complications | MedDRA (8.2) | Systematic Assessment |
|
| Device occlusion | Injury, poisoning and procedural complications | MedDRA (8.2) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (8.2) | Systematic Assessment |
|
| Pallor | Vascular disorders | MedDRA (8.2) | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA (8.2) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (8.2) | Systematic Assessment |
|
| Blindness | Eye disorders | MedDRA (8.2) | Systematic Assessment |
|
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.
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D052516 | Sulfatidosis |
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D056784 | Leukoencephalopathies |
| D003711 | Demyelinating Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
|
| Positive(1) to negative(0) |
|
| Positive(1) to positive(1) |
|
|
| MN, Dig. II Wrist: Baseline (N=3,5,4) |
|
| MN, Dig. II Wrist: Change at Week 26 (N=3,4,4) |
|
| PN, Dig. Ankle FH: Baseline (N=4,4,4) |
|
| PN, Dig. Ankle FH: Change at Week 26 (N=4,3,4) |
|
| SN, Sensory L LM - MC: Baseline (N=4,4,4) |
|
| SN, Sensory L LM - MC: Change at Week 26 (N=3,3,4) |
|
| SN, Sensory R LM - MC: Baseline (N=4,4,4) |
|
| SN, Sensory R LM - MC: Change at Week 26 (N=0,0,0) |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| PO, C: 2 to 2 |
|
| PO, Sc: 0 to 0 |
|
| PO, Sc: 0 to 1 |
|
| PO, Sc: 0 to 2 |
|
| PO, Sc: 1 to 1 |
|
| PO, Sc: 1 to 2 |
|
| PO, Sc: 2 to 2 |
|
| AT, P: 0 to 2 |
|
| AT, P: 1 to 2 |
|
| AT, P: 2 to 2 |
|
| AT, C: 0 to 2 |
|
| AT, C: 1 to 2 |
|
| AT, C: 2 to 2 |
|
| AT, Sc: 0 to 0 |
|
| AT, Sc: 0 to 1 |
|
| AT, Sc: 0 to 2 |
|
| AT, Sc: 1 to 1 |
|
| AT, Sc: 1 to 2 |
|
| AT, Sc: 2 to 2 |
|
| F, P: 0 to 2 |
|
| F, P: 1 to 2 |
|
| F, P: 2 to 2 |
|
| F, C: 1 to 2 |
|
| F, C: 2 to 2 |
|
| F, Sc: 0 to 0 |
|
| F, Sc: 0 to 2 |
|
| F, Sc: 1 to 2 |
|
| F, Sc: 2 to 2 |
|
| CC, S: 1 to 0 |
|
| CC, S: 1 to 2 |
|
| CC, S: 2 to 0 |
|
| CC, S: 2 to 1 |
|
| CC, S: 2 to 2 |
|
| CC, G: 0 to 2 |
|
| CC, G: 1 to 1 |
|
| CC, G: 1 to 2 |
|
| CC, G: 2 to 1 |
|
| CC, G: 2 to 2 |
|
| PF, CI ant: 0 to 0 |
|
| PF, CI ant: 0 to 1 |
|
| PF, CI ant: 1 to 1 |
|
| PF, CI post: 0 to 0 |
|
| PF, CI post: 0 to 1 |
|
| PF, CI post: 1 to 1 |
|
| PF, CI post: 1 to 2 |
|
| PF, CI post: 2 to 1 |
|
| PF, CI post: 2 to 2 |
|
| PF, B: 0 to 0 |
|
| PF, B: 0 to 1 |
|
| PF, B: 0 to 2 |
|
| PF, B: 1 to 0 |
|
| PF, B: 1 to 1 |
|
| PF, B: 1 to 2 |
|
| PF, B: 2 to 2 |
|
| Cb, Cortex: 0 to 0 |
|
| Cb, Cortex: 0 to 1 |
|
| Cb, Cortex: 1 to 1 |
|
| Cb, Atrophy: 0 to 0 |
|
| Cb, Atrophy: 0 to 1 |
|
| Cb, Atrophy: 1 to 1 |
|
| Bg, Bg: 0 to 0 |
|
| Bg, Bg: 0 to 1 |
|
| Bg, Bg: 1 to 0 |
|
| Bg, Bg: 1 to 1 |
|
| Bg, T: 0 to 0 |
|
| Bg, T: 1 to 0 |
|
| Bg, T: 1 to 1 |
|
| CA, CA: 0 to 0 |
|
| CA, CA: 0 to 1 |
|
| CA, CA: 1 to 1 |
|
| CA, CA: 1 to 2 |
|
|
| Self-care, Child: Baseline (N=4,5,4) |
|
| Self-care, Child: Change at Week 26 (N=4,4,4) |
|
| Self-care, Rehab: Baseline (N=4,5,4) |
|
| Self-care, Rehab: Change at Week 26 (N=4,4,4) |
|
| Self-care, Extensive: Baseline (N=4,5,4) |
|
| Self-care, Extensive: Change at Week 26 (N=4,4,4) |
|
| Mobility, None: Baseline (N=4,5,4) |
|
| Mobility, None: Change at Week 26 (N=4,4,4) |
|
| Mobility, Child: Baseline (N=4,5,4) |
|
| Mobility, Child: Change at Week 26 (N=4,4,4) |
|
| Mobility, Rehab: Baseline (N=4,5,4) |
|
| Mobility, Rehab: Change at Week 26 (N=4,4,4) |
|
| Mobility, Extensive: Baseline (N=4,5,4) |
|
| Mobility, Extensive: Change at Week 26 (N=4,4,4) |
|
| Social, None: Baseline (N=4,5,4) |
|
| Social, None: Change at Week 26 (N=4,4,4) |
|
| Social, Child: Baseline (N=4,5,4) |
|
| Social, Child: Change at Week 26 (N=4,4,4) |
|
| Social, Rehab: Baseline (N=4,5,4) |
|
| Social, Rehab: Change at Week 26 (N=4,4,4) |
|
| Social, Extensive: Baseline (N=4,5,4) |
|
| Social, Extensive: Change at Week 26 (N=4,4,4) |
|
|
| ALT-Serum: Normal to low |
|
| ALT-Serum: Normal to normal |
|
| ALT-Serum: High to low |
|
| ALT-Serum: High to normal |
|
| Amylase-Serum: Normal to normal |
|
| AP-Serum: Normal to normal |
|
| Calcium-Serum: Normal to normal |
|
| CK-Serum: Normal to normal |
|
| CK-Serum: Normal to high |
|
| CK-Serum: High to normal |
|
| CK-Serum: High to high |
|
| Creatinine-Serum: Normal to normal |
|
| Iron-Serum: Low to normal |
|
| Iron-Serum: Normal to low |
|
| Iron-Serum: Normal to normal |
|
| Iron-Serum: Normal to high |
|
| LDH-Serum: Normal to normal |
|
| LDH-Serum: High to normal |
|
| Magnesium-Serum: Normal to normal |
|
| Phosphate-Serum: Normal to normal |
|
| Phosphate-Serum: Normal to high |
|
| Phosphate-Serum: High to normal |
|
| Potassium-Serum: Normal to normal |
|
| Sodium-Serum: Normal to normal |
|
| Sodium-Serum: High to normal |
|
| T Bilirubin-Serum: Normal to normal |
|
| T Bilirubin-Serum: High to normal |
|
|
| Albumin CSF: High to high (N=3,4,4) |
|
| Albumin index: Normal to normal (N=3,4,4) |
|
| Albumin index: High to high (N=3,4,4) |
|
| Albumin Serum: Low to low (N=3,4,4) |
|
| Albumin Serum: Low to normal (N=3,4,4) |
|
| Albumin Serum: Normal to low (N=3,4,4) |
|
| Albumin Serum: Normal to normal (N=3,4,4) |
|
| Chitotriosidase CSF: Low to low (N=4,4,4) |
|
| Chitotriosidase CSF: High to high (N=4,4,4) |
|
| NFP CSF: Normal to high (N=4,4,4) |
|
| NFP CSF: High to high (N=4,4,4) |
|
| Sulfatide CSF: High to high (N=3,4,4) |
|
| Tauprotein CSF: High to low (N=4,4,4) |
|
| Tauprotein CSF: High to high (N=4,4,4) |
|
|
| ERCS - Blood: Low to low (N=4,4,4) |
|
| ERCS - Blood: Normal to normal (N=4,4,4) |
|
| Haemoglobin - Blood: Low to low (N=4,4,4) |
|
| Haemoglobin - Blood: Low to normal (N=4,4,4) |
|
| Haemoglobin - Blood: Normal to low (N=4,4,4) |
|
| Haemoglobin - Blood: Normal to normal (N=4,4,4) |
|
| Lymphocyte Abs - Blood: Low to low (N=4,4,4) |
|
| Lymphocyte Abs - Blood: Normal to low (N=4,4,4) |
|
| Lymphocyte Abs - Blood: Normal to normal (N=4,4,4) |
|
| MCHC - Blood: Normal to normal (N=4,4,4) |
|
| MCHC - Blood: High to normal (N=4,4,4) |
|
| MCH - Blood: Low to low (N=4,4,4) |
|
| MCH - Blood: Normal to normal (N=4,4,4) |
|
| Monocytes Abs - Blood: Normal to normal (N=4,4,4) |
|
| Monocytes Abs - Blood: High to normal (N=4,4,4) |
|
| Neutropil Abs - Blood: Normal to normal (N=4,4,4) |
|
| Neutropil Abs - Blood: Normal to high (N=4,4,4) |
|
| Thrombocytes - Blood: Normal to low (N=4,3,4) |
|
| Thrombocytes - Blood: Normal to normal (N=4,3,4) |
|
| Thrombocytes - Blood: High to normal (N=4,3,4) |
|
| T Leucocytes - Blood: Low to normal (N=4,4,4) |
|
| T Leucocytes - Blood: Normal to low (N=4,4,4) |
|
| T Leucocytes - Blood: Normal to normal (N=4,4,4) |
|
|
|
| GFAP: Baseline (N=4, 5, 4) |
|
| GFAP: Change at Week 26 (N=4, 4, 4) |
|
| Tauprotein: Baseline (N=4, 5, 4) |
|
| Tauprotein: Change at Week 26 (N=4, 4, 4) |
|
|
| MN, Elbow-APB: Baseline (N=4,5,4) |
|
| MN, Elbow-APB: Change at Week 26 (N=4,4,4) |
|
| MN, Dig. II Wrist: Baseline (N=4,5,4) |
|
| MN, Dig. II Wrist: Change at Week 26 (N=4,4,4) |
|
| PN, Ankle EDB: Baseline (N=4,4,4) |
|
| PN, Ankle EDB: Change at Week 26 (N=4,3,4) |
|
| PN, FH EDB: Baseline (N=4,4,4) |
|
| PN, FH EDB: Change at Week 26 (N=4,3,4) |
|
| SN, Sensory L LM - MC: Baseline (N=4,4,4) |
|
| SN, Sensory L LM - MC: Change at Week 26 (N=4,3,4) |
|
| SN, Sensory R LM - MC: Baseline (N=4,4,4) |
|
| SN, Sensory R LM - MC: Change at Week 26 (N=0,0,0) |
|