|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the gene (GLA) that encodes the lysosomal enzyme α-galactosidase A.
|Medical condition in easily understood language
|Fabry disease is an inherited disorder that results from the buildup of a particular type of fat in the body's cells.
|Body processes [G] - Metabolic Phenomena [G03]
|E.1.2 Medical condition or disease under investigation
|Congenital, familial and genetic disorders
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To assess long-term safety of migalastat HCl in the treatment of subjects with Fabry
disease who completed treatment in a previous study of migalastat HCl.
|Secondary objectives of the trial
|To explore long-term efficacy/pharmacodynamics of migalastat HCl in subjects with Fabry disease who have completed treatment in a previous study of migalastat HCl.
|Trial contains a sub-study
|Principal inclusion criteria
|1.Subject with Fabry disease who completed treatment in a previous study of migalastat HCl given as monotherapy.
2. Male or female subjects 16 years of age or older.
Note: Subjects under the age of 18 will be enrolled only at sites with all required regulatory and ethics approvals to do so.
3. A female subject is eligible to participate if she is:
A. Of non-childbearing potential, or
B. Of childbearing potential and NOT pregnant or nursing, has a negative
urine pregnancy test at the Baseline Visit (Visit 1), and agrees to one of
the methods of avoiding pregnancy listed in Appendix 1 as per the study protocol from the time of
first dose of study medication until 30 days after study completion.
A female is considered “Non-childbearing potential” if she is status-post
hysterectomy, status-post surgical removal of both ovaries, has current, documented tubal ligation, or is postmenopausal and >2 years without
menses. Female subjects who are post-menopausal <2 years must be confirmed menopausal by Follicle Stimulating Hormone (FSH) and estradiol levels.
A female is considered “childbearingpotential” if she has functional ovaries, ducts, and uterus with no impairment that would cause sterility. This includes women with oligomenorrhea (even severe), and women who are
perimenopausal or who have just begun to menstruate.
4. Male subjects must agree to use one of the contraception methods listed in Appendix 1. This criterion must be followed from the time of the first dose of study medication until 30 days after study completion.
5. Subject is willing and able to provide written informed consent and authorization for use and disclosure of Personal Health Information (PHI) or has a legally authorized
representative who has given written informed consent.
6. French subjects: In France, a subject will be eligible for inclusion in this study only
if either affiliated to or a beneficiary of a social security category.
|Principal exclusion criteria
|1. The last available estimated glomerular filtration rate (eGFR) in the previous study
was <30 mL/min/1.73m2; unless there is measured GFR available within 3 months of Baseline Visit (Visit 1), which is >30 mL/min/1.73m2.
2. The subject has undergone, or is scheduled to undergo kidney transplantation or is currently on dialysis.
3. The subject is treated or has been treated with another investigational drug (except migalastat HCl) within 30 days of study start.
4. Subject is unable to comply with study requirements, or deemed otherwise unsuitable for study entry, in the opinion of the investigator.
5. Had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 12 months before Visit 1.
6. 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).
7. Has a history of allergy or sensitivity to AT1001 (including excipients) or other iminosugars (e.g., miglustat, miglitol).
8. Requires treatment with Glyset® (miglitol) or Zavesca® (miglustat).
9. 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.
10. Patients with severe or unsuitable concomitant medical condition (cardiovascular, neurological, hepatic, renal, metabolic, hematological, immunological, pulmonary, or gastrointestinal disorder). The medical monitor or designee must be contacted to discuss the stability of a subject's medical condition(s) and the potential impact of the
condition(s) on trial participation.
11. Patients with clinically significant abnormal laboratory value(s) and clinically significant electrocardiogram (ECG) findings at baseline. The medical monitor or designee must be contacted to discuss the stability of a subject's medical condition(s) and the potential impact of the condition(s) on trial participation.
|E.5 End points
|Primary end point(s)
|The safety assessments are:
• Adverse events (AEs), Possible Suicidality Related AEs (PSRAEs) and serious
adverse events (SAEs)
• Withdrawal due to AEs
• Vital signs (blood pressure and heart rate) and body weight
• Hematology, chemistry, and urinalysis parameters
• Stopping criteria
• Electrocardiograms (ECGs)
|Timepoint(s) of evaluation of this end point
|AEs will be collected from the start of study treatment (i.e., Visit 1) and until the follow-up contact.
|Secondary end point(s)
|•Measurement of LV internal dimension (LVIDd and LVIDs) and wall thickness, as assessed by echocardiography
•Fractional shortening, ass assessed by echocardiography
|Timepoint(s) of evaluation of this end point
|Change from baseline will be evaluated for each efficacy endpoint, where baseline is defined (as in Table 1 of the study protocol) as the value from the last treatment visit of the previous migalastat HCl study.
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|The duration of the treatment will vary among subjects. The sponsor is discontinuing Study AT1001-041 for logistical reasons and not due to either safety concerns or lack of efficacy. The investigator will discuss participation in a similar open-label, long-term AT1001 treatment study with the subject. Subjects will either transition to the new study once the site has received all required approvals or they will be discontinued from treatment.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days