E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fabry disease and with amenable GLA variants |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016016 |
E.1.2 | Term | Fabry's disease |
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 |
Primary
•to assess the long-term safety of migalastat treatment in pediatric subjects diagnosed with Fabry disease and who have variants in the gene encoding α-galactosidase A (α-Gal A) (GLA) amenable to treatment with migalastat
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E.2.2 | Secondary objectives of the trial |
Secondary
•to characterize the pharmacodynamics (PD) of migalastat in pediatric subjects diagnosed with Fabry disease and who have GLA variants amenable to treatment with migalastat
•to assess the efficacy of migalastat in pediatric subjects diagnosed with Fabry disease and who have GLA variants amenable to treatment with migalastat
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female subjects diagnosed with Fabry disease > 12 years of age who completed Study AT1001-020
2.Subject’s parent or legally-authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent, if applicable
3.If of reproductive potential, both male and female subjects agree to use a medically accepted method of contraception throughout the duration of the study and for up to 30 days after their last dose of migalastat
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E.4 | Principal exclusion criteria |
1.Subject’s last available estimated glomerular filtration rate (eGFR) in the previous study was < 60 mL/min/1.73 m2
2.Subject has advanced kidney disease requiring dialysis or kidney transplantation
3.Subject received any investigational/experimental drug, biologic, or device within 30 days before baseline, with the exception of migalastat
4.Subject anticipates starting gene therapy during the study period
5.Subject has any intercurrent illness or condition at Visit 1 that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study
6.Subject has a history of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol)
7.Subject requires treatment with Replagal® (agalsidase alfa) or Fabrazyme® (agalsidase beta)
8.Subject requires treatment with Glyset® (miglitol) or Zavesca® (miglustat)
9.Female subject is pregnant or breast-feeding, or is planning to become pregnant during the study period
10.In the opinion of the investigator, the subject and/or parent or legally-authorized representative is unlikely or unable to comply with the study requirements
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety Endpoints:
1.incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to discontinuation of study drug
2.change from baseline in clinical laboratory test results over time
3.change from baseline in vital signs over time
4.change from baseline in physical examination findings over time
5.change from baseline in body weight and height over time
6.change from baseline in ECG results over time
7.change from baseline in echocardiogram parameters over time
8.change from baseline in Tanner Stage
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Month 60
2. baseline over time; up to 5 years
3.baseline over time; up to 5 years
4.baseline over time; up to 5 years
5.baseline over time; up to 5 years
6.baseline over time; up to 5 years
7.baseline over time; up to 5 years
8.baseline over time; up to 5 years
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E.5.2 | Secondary end point(s) |
Pharmacodynamic and Efficacy End Points:
1.change in plasma levels of lyso-Gb3
2.change in eGFR
3.change in urine protein and albumin levels
4.change in LVMi and other echocardiogram parameters
5.change in gastrointestinal signs and symptoms and pain, as measured by e-diary responses (Short FABPRO-GI and Pain Questionnaire)
6.mean Patient Global Impression of Change (PGI-C) values
7.change in FPHPQ scores
8.change in PedsQL scores
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.every 6 months, up to 5 years
2.every 6 months, up to 5 years
3.every 6 months, up to 5 years
4.every year, up to 5 years
5.every 3 months, up to 5 years
6.every 3 months, up to 5 years
7.every 3 months, up to 5 years
8.every 3 months, up to 5 years
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 1 |
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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 |
United Kingdom |
United States |
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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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The end of study is defined as date of database lock. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |