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 |
Stage 1:
• to characterize the PK of migalastat in adolescents with Fabry disease and to validate extrapolation of migalastat plasma exposure in adults to adolescents weighing ≥ 45 kg for the 150 mg migalastat capsule administered every other day (QOD)
• to evaluate the 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
Stage 2:
• to evaluate the safety of migalastat treatment in pediatric subjects diagnosed with Fabry disease and who have GLA variants amenable to treatment with migalastat |
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E.2.2 | Secondary objectives of the trial |
• 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 evaluate the efficacy of migalastat in pediatric subjects diagnosed with Fabry disease and who have GLA variants amenable to treatment with migalastat
• to evaluate the relationship between exposure to migalastat and response
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.have a parent or legally-authorized representative who 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
2.male or female, diagnosed with Fabry disease aged between 12 and < 18 years at baseline, and who might benefit from specific treatment for their condition, in the opinion of the investigator
3.confirmed amenable GLA variant determined using the migalastat amenability assay
4.weight of ≥ 45 kg (99 pounds) at screening
5.treatment-naïve or discontinued ERT treatment at least 14 days prior to screening
6.have at least one complication (ie, historical or current laboratory abnormality and/or sign/symptom) of Fabry disease
7.able to swallow capsules
8.if of reproductive potential, agree to use medically accepted methods of contraception throughout the duration of the study and for up to 30 days after last dose of study medication
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E.4 | Principal exclusion criteria |
1.moderate or severe renal impairment (eGFR < 60 mL/min/1.73 m2 at screening)
2.advanced kidney disease requiring dialysis or kidney transplantation
3.history of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol)
4.subject has received any gene therapy at any time or anticipates starting gene therapy during the study period
5.requires treatment with Glyset® (miglitol) or Zavesca® (miglustat), within 6 months before screening or throughout the study
6.requires treatment with Replagal® (agalsidase alfa) or Fabrazyme® (agalsidase beta) within 14 days before screening or throughout the study
7.received any investigational/experimental drug, biologic or device within 30 days before screening
8.any intercurrent illness or condition at screening or baseline 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
9.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) |
1.incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug
2.changes in clinical laboratory test results
3.changes in vital signs
4.changes in physical examination findings
5.change in body weight and height percentile
6.changes in ECG results
7.changes in echocardiogram parameters
8.change in Tanner stage
9.use of concomitant medications
10.population pharmacokinetics (popPK) model that describes the relationship between weight and age and migalastat pharmacokinetics in pediatric subjects
11.popPK: Cmax :maximum observed plasma concentration
12.popPK: Cmin : minimum observed plasma concentration
13.popPK: tmax : time to reach Cmax
14.popPK: AUC0-T: area under the plasma concentration-time curve from time 0 over the dosing interval (ie, 48 hours)
15.popPK: t½ : terminal elimination half-life
16.popPK: CLss/F : apparent oral clearance at steady-state concentration
17.popPK: Vss/F concentration: apparent oral volume of distribution at steady-state
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Month 12
2. baseline over time; up to 12 months
3.baseline over time; up to 12 months
4.baseline over time; up to 12 months
5.baseline over time; up to 12 months
6.baseline over time; up to 12 months
7.baseline to Month 12/ET
8.baseline to Month 12/ET
9.baseline to Month 12/ET
10. baseline to Month 12/ET
11.Day 15-30, Months 6 and 12/ET
12.Day 15-30, Months 6 and 12/ET
13.Day 15-30, Months 6 and 12/ET
14.Time Frame: Day 15-30, Months 6 and 12/ET
15.Day 15-30, Months 6 and 12/ET
16.popPK: Day 15-30, Months 6 and 12/ET
17.popPK: Day 15-30, Months 6 and 12/ET
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E.5.2 | Secondary end point(s) |
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.baseline to Months 3, 6, and 12/ET
2.baseline to Months 3, 6, and 12/ET
3.baseline to Months 1, 3, 6, and 12/ET
4.baseline to Month 12/ET
5.baseline to Month 12/ET
6.Months 3, 6 , 9 and 12/ET
7.baseline to Month 12/ET
8.baseline to Month 12/ET
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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 | Yes |
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
| No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 |
Australia |
Germany |
Italy |
Spain |
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 |