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 | 8.1 |
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 |
To evaluate the safety and tolerability of oral AT1001 in female patients with Fabry disease |
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E.2.2 | Secondary objectives of the trial |
To gain information about the pharmacokinetics of 3 dosages of oral AT1001 in female patients with Fabry disease. To gain information about the pharmacodynamics of 3 dosages of oral AT1001 in female patients with Fabry. To provide a preliminary assessment of cardiac, renal and CNS function in female patients with Fabry disease receiving AT1001.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must be adult females between 18 and 65 years of age (inclusive) and heterozygous for Fabry disease. Patients must have a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial) and enhanceable enzyme activity (in vitro test: meeting specific criteria for enhancement). The patients must be naïve to ERT and other therapies, except for palliative therapies for the signs and symptoms of Fabry disease or must stop ERT for at least 18 weeks or up to 13 months. Patients must have end organ dysfunction, even minimal, demonstrated by either evidence of left ventricular hypertrophy documented by abnormal ECG and echocardiogram or by cardiac biopsy, or renal insufficiency documented by common clinical assessments such as creatinine and glomerular filtration rate or by renal biopsy or brain tissue as documented by evidence of stroke (clinically or imaging), or peripheral nervous tissue documented by complaints of intolerance to heat or cold, decreased vibratory sense and propioception, decreased ability to perspire, or acroparesthesia. Patient agrees to be sexually abstinent or practice an effective method of contraception when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study for women of childbearing potential. Patients must be previously untreated by ERT or substrate depletion for Fabry disease and willing to undergo two renal and two skin biopsies. Patients must be willing and able to provide written informed consent.
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E.4 | Principal exclusion criteria |
The patient will be excluded from the study if: she is pregnant or lactating; she has a history of organ transplant; there is evidence of significant disease other than Fabry disease (e.g., end-stage renal disease; heart disease [per clinical history, documented event, testing or class III/IV according to the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes (unless HbA1c <= 8); or neurological disease that impairs her ability to participate in the study); serum creatinine is greater than 176 umol/L on day -2; QTc interval is > 450 msec; pacemaker or other contraindication for MRI scanning; taking a medication prohibited by the protocol or any experimental therapy for any indication. Patients who participated in a clinical trial in the last 30 days. Patients who have any other condition which, in the opinion of the investigator would jeopardize the safety of the patient or impact the validity of the study results. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to evaluate the safety and tolerability of AT1001 in this patient population. The primary endpoints are the following safety parameters: vital signs, clinical laboratory parameters (serum chemistry, hematology, and urinalysis), electrocardiograms (ECGs), echocardiograms (ECHO), physical examination, concomitant medications, and adverse events (AEs). |
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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 | No |
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 | Information not present in EudraCT |
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) | 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 | 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) | No |
E.8.2.2 | Placebo | No |
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 | No |
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 | 2 |
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 | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |