A Study Using Migalastat Hydrochloride to See the Long Term Safety and Effectiveness of the Drug in Patients with Fabry Disease

• Register: EUCTR
• Last refreshed on: 15 September 2020
• Main ID: EUCTR2014-002701-38-BE
• Date of registration: 04/12/2014
• Prospective Registration: Yes
• Primary sponsor: Amicus Therapeutics, Inc.
• Public title: A Study Using Migalastat Hydrochloride to See the Long Term Safety and Effectiveness of the Drug in Patients with Fabry Disease
• Scientific title: An Open-Label, Extension Study to Evaluate the Long Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in subjects with Fabry Disease
• Date of first enrolment: 09/02/2015
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002701-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Denmark, Egypt, France, Italy, Japan, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Patient Advocacy
• Affiliation: Amicus Therapeutics, Inc.

• Name: Patient Advocacy
• Affiliation: Amicus Therapeutics, Inc.

Key inclusion & exclusion criteria

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 18 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 medically accepted methods of avoiding pregnancy listed in Appendix 1 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 “childbearing potential” 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 medically accepted 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 research related health information or has a legally authorized representative who has given written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

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 3 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. The medical monitor or designee must be contacted to discuss the subject’s medical condition(s) and the potential impact of the condition(s) on continued trial participation.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the gene (GLA) that encodes the lysosomal enzyme a-galactosidase A.
MedDRA version: 18.1 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Intervention(s)

Product Name: Migalastat hydrochloride
Product Code: AT1001
Pharmaceutical Form: Capsule
INN or Proposed INN: migalastat
CAS Number: 75172-81-5
Current Sponsor code: AT1001
Other descriptive name: MIGALASTAT HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 123-

Product Name: Inactive Reminder Capsules
Product Code: Inactive Reminder Capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: NA
Other descriptive name: Inactive Reminder Capsules
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: AEs will be collected from the start of the study treatment (i.e., visit 1) and until the follow-up contact.

Main Objective: To assess long-term safety of migalastat HCl in the treatment of subjects with Fabry disease who have completed treatment in a previous study of migalastat HCl.

Primary end point(s): • Adverse events (AEs), possible suicidality related AEs (PSRAEs) and serious adverse events (SAEs)
• Withdrawal due to AEs
• Vital signs (blood pressure, body temperature, respiratory rate, and heart rate) and body weight
• Hematology, chemistry, and urinalysis parameters
• Echocardiography (ECHO)
• Electrocardiograms (ECGs)
• Stopping criteria

Secondary Objective: 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

Secondary Outcome(s)

Secondary end point(s): • Estimated glomerular filtration rate (eGFR) based on the Modification of Diet in Renal Disease (MDRD) equation and CKD-EPI equation
• Plasma lyso-Gb3
• Evaluation of left ventricular mass index (LVMi), as measured by echocardiography
• Ejection fraction, as measured by echocardiography
• Fractional shortening, as assessed by echocardiography
• Measurement of LV internal dimension (LVIDd and LVIDs) and wall thickness, as assessed by echocardiography
• Evaluation of white blood cell (WBC) a-Gal A activity
• Evaluation of subject reported Quality of Life as assessed by the Short Form 36 Survey (SF 36)

Timepoint(s) of evaluation of this end point: Change from baseline will be evaluated for each efficacy endpoint, when 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.

Secondary ID(s)

NCT02194985

2014-002701-38-AT

AT1001-042

Source(s) of Monetary Support

Amicus Therapeutics, Inc.

Ethics review

Status: Approved
Approval date: 09/02/2015
Contact: