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A 12-Week Safety and Pharmacodynamic Study of AT1001 in Female Patients With Fabry Disease

This study has been completed.
ClinicalTrials.gov Identifier:
First Posted: March 20, 2006
Last Update Posted: April 29, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Amicus Therapeutics
The purpose of this study is to determine whether AT1001 (migalastat hydrochloride) is safe and effective in female patients with Fabry disease.

Condition Intervention Phase
Fabry Disease Drug: AT1001 (migalastat hydrochloride) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multiple Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Female Patients With Fabry Disease

Resource links provided by NLM:

Further study details as provided by Amicus Therapeutics:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: Week 12 or Week 24 ]
    AEs; Vital signs (blood pressure, heart rate, temperature, respiratory rate); Clinical laboratory safety (hematology, serum chemistry, urinalysis); Electrocardiogram (ECGs); Echocardiogram (ECHO); Physical examination; Concomitant medications

Secondary Outcome Measures:
  • Pharmacodynamic parameters [ Time Frame: Week 12 or Week 24 ]
    PD in blood and urine

  • Functional parameters (cardiac, renal, CNS) [ Time Frame: Week 12 or Week 24 ]
    24 hour ECG, Cardiac MRI, GFR, kidney ultrasound, transcranial doppler, brain MRI, cognitive testing, QSART

Enrollment: 9
Study Start Date: May 2006
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose
Low dose of AT1001 every other day
Drug: AT1001 (migalastat hydrochloride)
25mg capsules every other day for 12 weeks
Experimental: Middle Dose
Middle dose of AT1001 every other day
Drug: AT1001 (migalastat hydrochloride)
25mg capsules every other day for 12 weeks
Experimental: High dose
High dose of AT1001 every other day
Drug: AT1001 (migalastat hydrochloride)
25mg capsules every other day for 12 weeks

Detailed Description:

This study will be a phase 2, open-label trial in previously untreated patients with Fabry disease. The trial will consist of a 4 week screening phase, a 12-week treatment phase that may be extended up to an additional 36 weeks, and a 2-week follow-up phase.

Twelve female patients are planned to be enrolled at two sites. The number of visits for the first part of the study is 7 and for the extension treatment part, a further 3. Once patients have completed treatment, they will be required to attend a follow up visit.

After determination of missense genotype, patients will be initially screened on Day -28 by collection of blood for evaluation of enhanceablity of α-Gal A in leukocytes. Patients will come to the treatment facility for Screening assessments on Day -2 and Day -1, and baseline assessments including α-Gal A and GL-3 in plasma (leukocytes), skin tissue, cardiac tissue, and renal tissue, GL-3 in urine, and baseline evaluation of safety, cardiac, renal, and CNS parameters as described in the schedule of assessments. From Day 1, patients will initiate AT1001 once every other day oral dosing for 12 weeks. Patients will be stratified by α-Gal A enzyme activity (high > 40%, and low ≤ 40%) then randomly assigned to receive one of three specified dose levels.

Patients will return to the treatment facility for Visits 1 through 4. Safety measures will be performed at all visits. Pharmacokinetic (PK) measures will be performed predose and up to 10 hours postdose on Days 1, 14 and 84. Pharmacodynamic measurements in the form of blood leukocyte measurements of α-Gal A and plasma and urine measurements of α-Gal A and GL-3 will be performed at each visit. A final set of skin, cardiac, and renal biopsies will be performed at Visit 4. Evaluations of cardiac and renal function parameters as described in the schedule of assessments will be performed at various timepoints: ECG and serum creatinine for Visits 1 through 4; glomerular filtration rate (GFR); and 24-hr Quantitative Holter monitor ECG, ECHO, cardiac MRI, natriuretic factor, treadmill cardiac stress test, renal ultrasound (to be performed at Porto Alegre site only), Brain MRI, QSART (to be performed at Porto Alegre site only) and transcranial Doppler at Screening and Visit 4. Cognitive Testing will be performed at Screening, Baseline, and Visit 4.

Patients will also come to the treatment facility at the end of the treatment period.

If they are not continuing into the 36-week treatment extension, patients will return to the clinic for a follow-up visit 2 weeks after the end of treatment. Patients continuing into the treatment extension will return to the clinic for additional visits at Weeks 24 (Visit 6), 36 (Visit 7) and 48 (Visit 8) for safety assessments and specific pharmacodynamic and functional measurements.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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: presence of residual Gal A activity [greater than or equal to 3% of normal] in lymphocytes and greater than or equal to 20% increase in activity after lymphocytes are incubated with AT1001).
  • 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.
  • 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 proprioception, 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, or be willing to temporarily stop treatment during this study, and be willing to undergo two renal, two cardiac, and two skin biopsies.
  • Patients must be willing and able to provide written informed consent.

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 less than or equal to 8);
  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00304512

United States, Georgia
Emory University Lysosomal Storage Disease Center
Decatur, Georgia, United States, 30033
Australia, Victoria
Royal Melbourne Hospital, Department of Nephrology
Parkville, Victoria, Australia, 3050
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre
Porto Alegre, Brazil
Canada, Quebec
Université de Montréal, Hôpital du Sacré-Coeur de Montréal
Montréal, Quebec, Canada, H4J 1C5
Hôpital Europeen Georges Pompidou
Paris, France
United Kingdom
Salford Royal NHS Trust, Hope Hospital
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Amicus Therapeutics
Principal Investigator: Roberto Giugliani, MD, PhD Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre
Principal Investigator: Stephen Waldek, FRCP Salford Royal NHS Trust, Hope Hospital
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT00304512     History of Changes
Other Study ID Numbers: FAB-CL-204
First Submitted: March 17, 2006
First Posted: March 20, 2006
Last Update Posted: April 29, 2015
Last Verified: April 2015

Additional relevant MeSH terms:
Fabry Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders