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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-006345-40 | EudraCT Number |
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This is a single center, open-label study of patients with late infantile MLD. All patients were previous treated 26 weeks in the phase I trial (EudraCT number: 2006-005341-11, NCT00418561). All patients will be offered continuing treatment in this study and will in this protocol receive 13 infusions, whereby the patients total have had 27 infusions of Metazym. One infusion will be given every other week. After a total of 52 weeks of treatment the subjects will continue treatment in a compassionate use protocol. Safety (AE/SAE) will be monitored at every visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Cohort 1: 50 U/kg Recombinant human Arylsulfatase A (rhASA) |
|
| Cohort 2 | Experimental | Cohort 2: 100 U/kg Recombinant human Arylsulfatase A (rhASA) |
|
| Cohort 3 | Experimental | Cohort 3: 200 U/kg Recombinant human Arylsulfatase A (rhASA) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant human Arylsulfatase A (rhASA) | Biological | intravenous infusion, every other week for 26 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Relative Changes (%) in Gross Motor Function Measurement (GMFM) | Change (percent change) in GMFM is measured from baseline to end of study (Week 52). GMFM is measured using GMFM-88. The GMFM-88 item scores can be summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score is between 0 (minimal) to 3 (maximum). The total GMFM-88 score is between 0 (minimal) to 264 (maximum). Relative changes in GMFM are calculated as percentage change from baseline divided by the age difference in months between first and last visit. The GMFM score decreases over time, which, indicates that the disease worsened over time. Score over time (SOT), data mentioned over mean represents the adjusted mean. | Baseline, 52 Weeks |
| Relative Change in Mullen's Scales of Early Learning | Changes in Mullen's Scales of Early Learning are measured from baseline to end of study (Week 52) using Mullen's Scales of Early Learning. T scores, percentile ranks, and age equivalents can be computed for the four scales separately (visual reception, fine motor, expressive language, and receptive language). Relative change is calculated as percentage change from baseline divided by the age-difference in months between first and last visit. When Mullen's score decreases over time, it indicates the disease worsened over time. Data mentioned over mean represents the adjusted mean. | Baseline, 52 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cerebrospinal Fluid (CSF) Sulfatide | Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean. | Baseline, 52 Weeks |
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Inclusion Criteria:
The patients from the Phase I trial must meet the following criteria to be enrolled in the study.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PhaseOneTrials A/S | Hvidovre | 2650 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33332761 | Derived | 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. |
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All participants that completed study recombinant human arylsulfatase A (rhASA-01) (NCT00418561) except 1 participant who did not complete (at week 18) the rhASA-01 (NCT00418561) participated in HGT-MLD-048/rhASA-03 (NCT00633139).
Children with an established diagnosis of late metachromatic leukodystrophy (MLD) due to arylsulfatase A (ASA) deficiency were recruited.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Participants received a single dose of rhASA at 25 units per kilogram (U/kg) intravenous (IV) infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52. |
| FG001 | Cohort 2 | Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52. |
| FG002 | Cohort 3 | Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Participants received a single dose of rhASA at 25 U/kg IV infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52. |
| BG001 | Cohort 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Relative Changes (%) in Gross Motor Function Measurement (GMFM) | Change (percent change) in GMFM is measured from baseline to end of study (Week 52). GMFM is measured using GMFM-88. The GMFM-88 item scores can be summed to calculate a total GMFM-88 score. For each GMFM-88 item, the score is between 0 (minimal) to 3 (maximum). The total GMFM-88 score is between 0 (minimal) to 264 (maximum). Relative changes in GMFM are calculated as percentage change from baseline divided by the age difference in months between first and last visit. The GMFM score decreases over time, which, indicates that the disease worsened over time. Score over time (SOT), data mentioned over mean represents the adjusted mean. | Intent to Treat (ITT) population included all the participants in the study. | Posted | Mean | 95% Confidence Interval | Relative % change in total GMFM-88 SOT | Baseline, 52 Weeks |
|
52 weeks of treatment
All other adverse events (AEs) (>5% reporting frequency) reported here are either probable (PRB) or definitely (DEF) related to drug administration.
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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 | Cohort 1: Participants received a single dose of rhASA at 25 U/kg IV infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| malnutrition | Metabolism and nutrition disorders | MedDRA v8.2 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Feeding tube complication | Injury, poisoning and procedural complications | MedDRA v8.2 | Systematic Assessment |
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| 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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|
Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52. |
| BG002 | Cohort 3 | Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Participants received a single dose of rhASA at 25 U/kg IV infusion in rhASA-01 (NCT00418561) study. Thereafter a repeated dose of rhASA at 50 U/kg, over 30 minutes was administered every other week up to Week 52.
| OG001 | Cohort 2 | Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52. |
| OG002 | Cohort 3 | Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52. |
|
|
|
| Primary | Relative Change in Mullen's Scales of Early Learning | Changes in Mullen's Scales of Early Learning are measured from baseline to end of study (Week 52) using Mullen's Scales of Early Learning. T scores, percentile ranks, and age equivalents can be computed for the four scales separately (visual reception, fine motor, expressive language, and receptive language). Relative change is calculated as percentage change from baseline divided by the age-difference in months between first and last visit. When Mullen's score decreases over time, it indicates the disease worsened over time. Data mentioned over mean represents the adjusted mean. | ITT population. | Posted | Mean | 95% Confidence Interval | Relative % change in Mullen's SOT | Baseline, 52 Weeks |
|
|
|
|
| Secondary | Change in Cerebrospinal Fluid (CSF) Sulfatide | Changes in CSF sulfatide from baseline to end of study (Week 52). Data mentioned over mean represents the adjusted mean. | ITT population | Posted | Mean | 95% Confidence Interval | %change in CSF sulfatide | Baseline, 52 Weeks |
|
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|
|
| 2 |
| 4 |
| 4 |
| 4 |
| EG001 | Cohort 2 | Cohort 2: Participants received a repeated dose of rhASA at 100 U/kg IV infusion over 30 minutes was administered every other week up to Week 52. | 2 | 5 | 5 | 5 |
| EG002 | Cohort 3 | Cohort 3: Participants received a repeated dose of rhASA at 200 U/kg IV infusion over 60 minutes was administered every other week up to Week 52. | 3 | 4 | 4 | 4 |
| bronchitis acute | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| pneumonia | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| vomiting | Gastrointestinal disorders | MedDRA v8.2 | Systematic Assessment |
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| pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA v8.2 | Systematic Assessment |
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| blindness | Eye disorders | MedDRA v8.2 | Systematic Assessment |
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| post procedural vomiting | Injury, poisoning and procedural complications | MedDRA v8.2 | Systematic Assessment |
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| peritonitis | Gastrointestinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Medical device complication | Injury, poisoning and procedural complications | MedDRA v8.2 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA v8.2 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA v8.2 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA v8.2 | Systematic Assessment |
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| Blood iron decreased | Investigations | MedDRA v8.2 | Systematic Assessment |
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| Blood iron increased | Investigations | MedDRA v8.2 | Systematic Assessment |
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| Drug specific antibody present | Investigations | MedDRA v8.2 | Systematic Assessment |
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| General physical condition abnormal | Investigations | MedDRA v8.2 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA v8.2 | Systematic Assessment |
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| Neutrophil count increased | Investigations | MedDRA v8.2 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA v8.2 | Systematic Assessment |
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| Leukodystrophy | Congenital, familial and genetic disorders | MedDRA v8.2 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Pharyngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Cognitive disorder | Nervous system disorders | MedDRA v8.2 | Systematic Assessment |
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| Hypotonia | Nervous system disorders | MedDRA v8.2 | Systematic Assessment |
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| Convulsion | Nervous system disorders | MedDRA v8.2 | Systematic Assessment |
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| Muscle spasticity | Nervous system disorders | MedDRA v8.2 | Systematic Assessment |
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| Mutism | Respiratory, thoracic and mediastinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Speech disorder developmental | Nervous system disorders | MedDRA v8.2 | Systematic Assessment |
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| Discomfort | General disorders | MedDRA v8.2 | Systematic Assessment |
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| Infusion related reaction | General disorders | MedDRA v8.2 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA v8.2 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA v8.2 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA v8.2 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA v8.2 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v8.2 | Systematic Assessment |
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| Acute tonsillitis | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Bronchitis acute | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Enterobiasis | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Herpangina | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Postoperative infection | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Varicella | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA v8.2 | Systematic Assessment |
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| 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 |