E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016016 |
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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 |
The primary objective of this study is to compare the effect of AT1001 versus placebo on kidney GL-3 as assessed by histological scoring of the number of inclusions in interstitial capillaries after 6 months of treatment. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of Stage 1 of this study are:  To compare the effect of AT1001 versus placebo on urine GL-3 levels as measured by LC-MS/MS  To compare the effect of AT1001 versus placebo on renal function (iohexol GFR, eGFR, 24-hour urine protein)  To compare the safety and tolerability of AT1001 versus placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female between the ages of 16 and 74 inclusive, diagnosed with Fabry disease Note: subjects under the age of 18 will be enrolled only at sites with all required regulatory and ethics approvals to do so. 2. Confirmed GLA mutation that has been shown to be responsive to AT1001 in vitro (as listed on pharmacogenetic reference table [Appendix A]) 3. Na�ve to ERT or has not received ERT for 6 consecutive months or longer before the screening visit for the study 4. Urine GL-3 greater than four times the upper limit of normal at Screening 5. Subjects taking angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) must be on a stable dose for a minimum of 4 weeks before the baseline visit 6. Male and female subjects of childbearing potential agree to use medically accepted methods of contraception during study and for 30 days after study completion 7. Subject is willing and able to provide written informed consent, and assent if applicable |
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E.4 | Principal exclusion criteria |
1. Subject has undergone or is scheduled to undergo kidney transplantation, or is currently on dialysis 2. eGFR < 30 mL/min/1.73m2 (CKD Stage 4 or 5) based on MDRD equation 3. QTc ≥ 450 msec for males or ≥ 470 msec for females 4. Pregnant or breast-feeding 5. History of allergy or sensitivity to study medication (including excipients) or other iminosugars (e.g., miglustat, miglitol) 6. Subject is treated or has been treated with any investigational drug within 30 days of the screening visit 7. Subject is currently treated or has ever been treated with AT1001 8. Any intercurrent condition or concomitant medication use considered to be an absolute contraindication to kidney biopsy or that may preclude accurate interpretation of study data 9. Otherwise unsuitable for the study, in the opinion of the Investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Kidney GL-3 (interstitial capillary histology): The average number of GL-3 inclusions per kidney interstitial capillary is assessed by a quantitative histological method used to count GL-3 inclusions in a sample of interstitial capillaries at baseline and at Month 6. |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 | Information not present in EudraCT |
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 |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |