| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
People with Fabry disease have a genetic disorder that prevents their
bodies from breaking down a particular lipid (a fat-like substance) in
their cells. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.0 |
| 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 |
|
| 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 |
| The primary efficacy parameter is the change from baseline in glomerular filtration rate (GFR) as assessed by plasma clearance of iohexol (“iohexol GFR”) |
|
| E.2.2 | Secondary objectives of the trial |
Change from baseline in:
-Estimated GFR; 24-hour urine protein; left ventricular mass and ejection fraction; urine GL-3; WBC α-galactosidase A activity; patient reported assessment of pain and Quality of Life as assessed by the BPI short form and Short Form 36
-Composite clinical outcome, as assessed by time to the first occurrence of the following events and number of subjects who experience any of the following events:
Renal events: A decrease in iohexol GFR ≥ 15 mL/min/1.73 m2, with the decreased GFR < 90 mL/min/1.73 m2 relative to baseline; An increase in 24-hour urine protein ≥ 33% , with the increased protein ≥ 300 mg relative to baseline
Cardiac events: Myocardial infarction; Unstable cardiac angina; New symptomatic arrhythmia requiring anti-arrhythmic medication, direct current cardioversion, pacemaker, or defibrillator implantation; Congestive heart failure, NYHA class III or IV
Cebrovascular events: Stroke; Transient ischemic attack/Death
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female, diagnosed with Fabry disease and between 16 and 74 years of age inclusive at Visit 1
2. Confirmed GLA mutation shown to be responsive to AT1001 in the in vitro HEK-293 cell-based assay, or a confirmed GLA mutation that is non-testable in this assay, but has evidence to suggest the potential to respond to AT1001.
3.Initiated treatment with ERT at least 12 months before Visit 2
4.Dose level and regimen of ERT have been stable for the 3 months before Visit 2 and is at least 80% of the currently labeled dose for this time period
5.GFR ≥ 30mL/min/1.73 m2
6.If taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) has been on a stable dose for at least the 4 weeks before Visit 1
7.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 protocol-defined study medication
7a. For sites in Italy: If of reproductive potential, agree to plan (or have their partner plan) with his/her physician a birth control strategy (or method) in order to avoid pregnancy throughout the duration of the study and for up to 30 days after the last dose of protocol defined study medication
8.Able to provide written informed consent, and assent if applicable. Subjects under 18 years of age will provide written informed assent, and written informed consent will be provided by their parent or legal guardian.
|
|
| E.4 | Principal exclusion criteria |
1.Undergone, or is scheduled to undergo, kidney transplantation or any other solid organ transplantation
2.On regular dialysis that is specifically for the treatment of chronic kidney disease
3.Had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 3 months before Visit 1
4.Has clinically significant unstable cardiac disease in the opinion of the investigator (e.g., cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or NYHA class III or IV congestive heart failure)
5.Is pregnant or breast-feeding
6.Has a history of allergy or sensitivity to AT1001 (including excipients) or other iminosugars (e.g., miglustat, miglitol)
7.Has absolute contraindication to iohexol and/or inability to undergo iohexol GFR testing
8.Requires treatment with Glyset® (miglitol) or Zavesca® (miglustat)
9.Has received any investigational/experimental drug, biologic, or device within 30 days of Visit 1
10.Has any intercurrent illness or condition 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
11. Is otherwise unsuitable for the study, in the opinion of the investigator
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| change from baseline in GFR as assessed by plasma clearance of iohexol (“iohexol GFR”) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Change from baseline in:
-Estimated GFR; 24-hour urine protein; left ventricular mass and ejection fraction; urine GL-3; WBC α-galactosidase A activity; patient reported assessment of pain and Quality of Life as assessed by the BPI short form and Short Form 36
-Composite clinical outcome, as assessed by time to the first occurrence of the following events and number of subjects who experience any of the following events: Renal events: A decrease in iohexol GFR ≥ 15 mL/min/1.73 m2, with the decreased GFR < 90 mL/min/1.73 m2 relative to baseline; An increase in 24-hour urine protein ≥ 33% , with the increased protein ≥ 300 mg relative to baseline
Cardiac events: Myocardial infarction; Unstable cardiac angina; New
symptomatic arrhythmia requiring anti-arrhythmic medication, direct
current cardioversion, pacemaker, or defibrillator implantation;
Congestive heart failure, NYHA class III or IV
Cebrovascular events: Stroke; Transient ischemic attack/Death |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 35 |
| 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 |
| Austria |
| Belgium |
| Brazil |
| Denmark |
| France |
| Germany |
| Greece |
| Hungary |
| Israel |
| Italy |
| Japan |
| Mexico |
| Poland |
| Russian Federation |
| Slovakia |
| Switzerland |
| Taiwan |
| Turkey |
| United Kingdom |
| United States |
|
| 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
|
| The end of trial is defined as the last visit of the last subject undergoing the trial. |
|
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | 11 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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