Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2008-000084-41 | EudraCT Number |
Not provided
Not provided
Not provided
Terminated prior to planned completion date due to lack of efficacy.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a multi-center, open-label, extension study of patients with late infantile MLD who have previously completed clinical study HGT-MLD-048 (NCT00633139), defined as the completion of all Week 52 procedures. This group of patients will be offered ongoing treatment with HGT-1111 in this protocol. One infusion will be given every other week until the product is commercially available, the patient discontinues, or the study is terminated by the Sponsor, provided no safety issues have emerged.
The primary objective of this study is to provide ongoing treatment of HGT-1111 to patients who have completed study HGT-MLD-048 (previously study rhASA-03 - NCT00633139) until HGT-1111 is commercially available or the study is terminated by the Sponsor, provided no safety concerns have emerged. The secondary objective of this study is to monitor disease progression and the safety profile of HGT-1111 administered to patients who have completed study HGT-MLD-048 (NCT00633139).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HGT-1111 100 U/kg | Experimental |
| |
| HGT-1111 200 U/kg | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HGT-1111 | Drug | Patients currently dosed with 100 U/kg or 200 U/kg will continue this treatment. Patients dosed with 50 U/kg will be equally randomized to treatment on 100 U/kg or 200 U/kg. The dose will be adjusted every 6-week to account for changes in body weight.The infusion length will be dependent on the dose. Infusion of 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Days of Exposure to HGT-1111 | End of study was defined as until HGT-1111 was commercially available, the participant's participation was discontinued, or the study was terminated by the Sponsor. | Baseline until end of study (Week 139) |
| Measure | Description | Time Frame |
|---|---|---|
| Level of Cerebrospinal Fluid (CSF) Sulfatide | Level of CSF sulfatide measured at 6-month intervals in HGT-MLD-049 (NCT00681811). | Baseline until end of study (Week 139) |
| Level of White Matter Metabolites |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet | Copenhagen | 2100 | 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. |
Not provided
Not provided
All participants who completed Study HGT-MLD-048 (NCT00633139) participated in this study.
Children with an established diagnosis of late metachromatic leukodystrophy (MLD) due to arylsulfatase A (ASA) deficiency were recruited.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 100 U/kg HGT-1111 | Participants received 100 units per kilogram (U/kg) of HGT1111 intravenous (IV) infusion every other week. |
| FG001 | 200 U/kg HGT-1111 | Participants received 200 U/kg of HGT1111 IV infusion every other week. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 100 U/kg HGT1111 | Participants received 100 U/kg of HGT1111 IV infusion every other week. |
| BG001 | 200 U/kg | Participants received 200 U/kg of HGT1111 IV infusion every other week. |
| 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 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Level of Cerebrospinal Fluid (CSF) Sulfatide | Level of CSF sulfatide measured at 6-month intervals in HGT-MLD-049 (NCT00681811). | Safety population. "Number of participants analysed" signifies participants who were evaluable for the respective arms under this outcome measure. | Posted | Mean | Standard Deviation | nanomole per liter (nmol/L) | Baseline until end of study (Week 139) |
|
Up to end of study (Week 139) which was defined as until HGT-1111 was commercially available, the patient's participation was discontinued, or the study was terminated by the Sponsor.
All other adverse events (>5% reporting frequency) reported here are related to drug administration, all were infusion-related reactions.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 100 U/kg HGT1111 | Participants received 100 U/kg of HGT1111 IV infusion every other week. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pallor | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
Early termination due to lack of efficacy.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
Not provided
| 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 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
Level of white matter metabolites [N-acetyl Aspartate (NAA)] measured at 6-month intervals in HGT-MLD-049 (NCT00681811).
| Baseline until end of study (Week 139) |
| Score of Gross Motor Function Measurement (GMFM) | Gross motor function was measured using GMFM-88 at 6-month intervals. The GMFM-88 item scores were 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) to 264 (maximum). Decrease in GMFM score indicates disease progression. | Baseline until end of study (Week 139) |
| Non-compliance |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Age at Week 54 or Week 56 in HGT-MLD-049 (NCT00681811) | Mean | Standard Deviation | months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG002 | 100 U/kg HGT-1111 (Month 12) | Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 12. |
| OG003 | 200 U/kg HGT-1111 (Month 12) | Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 12. |
| OG004 | 100 U/kg HGT-1111 (Month 18) | Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 18. |
| OG005 | 200 U/kg HGT-1111 (Month 18) | Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 18. |
| OG006 | 100 U/kg HGT-1111 (Month 24) | Participants received 100 U/kg of HGT1111 IV infusion every other week up to Month 24. |
| OG007 | 200 U/kg HGT-1111 (Month 24) | Participants received 200 U/kg of HGT1111 IV infusion every other week up to Month 24. |
|
|
| Secondary | Level of White Matter Metabolites | Level of white matter metabolites [N-acetyl Aspartate (NAA)] measured at 6-month intervals in HGT-MLD-049 (NCT00681811). | Safety population. "Number of participants analysed" signifies participants who were evaluable for the respective arms under this outcome measure. No participants were analysed after Month 18, hence, data were not available after Month 18. | Posted | Mean | Standard Deviation | nmol/L | Baseline until end of study (Week 139) |
|
|
|
| Secondary | Score of Gross Motor Function Measurement (GMFM) | Gross motor function was measured using GMFM-88 at 6-month intervals. The GMFM-88 item scores were 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) to 264 (maximum). Decrease in GMFM score indicates disease progression. | Safety population. "Number of participants analysed" signifies participants who were evaluable for the respective arms under this outcome measure. | Posted | Mean | Standard Deviation | scores on a scale | Baseline until end of study (Week 139) |
|
|
|
| Primary | Days of Exposure to HGT-1111 | End of study was defined as until HGT-1111 was commercially available, the participant's participation was discontinued, or the study was terminated by the Sponsor. | Safety population was defined as all enrolled participants who received at least one study infusion (or any portion of a dose) of HGT-1111. | Posted | Mean | Standard Deviation | Days | Baseline until end of study (Week 139) |
|
|
|
| 2 |
| 6 |
| 6 |
| 6 |
| EG001 | 200 U/kg HGT1111 | Participants received 200 U/kg of HGT1111 IV infusion every other week. | 4 | 5 | 5 | 5 |
| Lower respiratory track infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Catheter bacteraemia | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Bronchitis acute | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pseudomonas infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 8.1 | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Adverse drug reaction | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA 8.1 | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA 8.1 | Systematic Assessment |
|
| Phimosis | Reproductive system and breast disorders | MedDRA 8.1 | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Feeding tube complication | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Blood iron increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
| Increased bronchial secretion | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Dystonia | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Febrile convulsion | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hypotonia | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Muscle spasticity | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Conjunctival oedema | Eye disorders | MedDRA 8.1 | Systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA 8.1 | Systematic Assessment |
|
| Eyelid oedema | Eye disorders | MedDRA 8.1 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 8.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Reflux gastritis | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Regurgitation of food | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Urticaria generalised | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 8.1 | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA 8.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Herpes simplex | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Bronchitis acute | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Viral pharyngitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Scarlet fever | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
Not provided
| 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 |