E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Metachromatic Leukodystrophy |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of inherited arylsulfatase A deficiency |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067609 |
E.1.2 | Term | Metachromatic leukodystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To collect long-term safety data in patients with MLD who are receiving HGT-1110 and have participated in study HGT-MLD-070 through Week 40. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate changes in gross motor function in patients who are receiving IT administration of HGT-1110
- To assess concentrations of HGT-1110 in cerebrospinal fluid (CSF) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patient has participated in Study HGT-MLD-070 through Week 40.
2.Patient must have no safety or medical issues that contraindicate participation.
3.The patient, patient’s parent or legally authorized representative(s) must provide written informed consent and/or assent (if applicable) prior to performing any study-related activities.
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E.4 | Principal exclusion criteria |
1.The patient is unable to comply with the protocol (eg, is unable to return for safety evaluations, or is otherwise unlikely to complete the study) as determined by the Investigator.
2.The patient has any known or suspected hypersensitivity to agents used for sedation or is thought to be at an unacceptably high risk for associated potential complications of airway compromise or other conditions
3.The patient is pregnant or breastfeeding.
4.The patient is enrolled in another clinical study that involves clinical investigations or use of any investigational product (drug or drug delivery device) other than those used in HGT-MLD-070 within 6 months prior to study enrollment or at any time during the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to collect long-term safety data of intrathecal HGT-1110 treatment in patients who participated through Week 40 of Study HGT-MLD-070. Safety will be measured by the following endpoints:
- Adverse events (by type and severity)
- Changes in clinical laboratory testing (serum chemistry including liver function tests, hematology, and urinalysis), vital signs, physical examinations and the neurological examinations
- Change from baseline in CSF chemistries (including cell counts, glucose, albumin, and protein)
- Development of anti-HGT-1110 antibodies in CSF and/or serum.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- AEs will be collected every other week
- Chemistry/hematology/urinalysis testing will be done every 12 weeks throughout the study
- CSF chemistries will be assessed every other week
- Anti-HGT-1110 antibodies in CSF and/or serum will be assessed every 12 weeks throughout the study |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of this study are:
- Change from baseline in motor function using the Gross Motor Function Measure-88 (GMFM-88) total raw score
- Concentrations of HGT-1110 in CSF at selected time points after single and repeated study drug administration
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- GMFM-88 will be conducted every 12 weeks for the 1st year of treatment and every 24 weeks for the subsequent years
- HGT-1110 in CSF will be evaluated every other week throughout the study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
extension to phase I/II trial |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Czech Republic |
Denmark |
France |
Germany |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |