A Study of AT1001 in Patients With Fabry Disease

This study has been completed.
Information provided by (Responsible Party):
Amicus Therapeutics
ClinicalTrials.gov Identifier:
First received: September 13, 2005
Last updated: March 25, 2015
Last verified: March 2015

The purpose of this study is to determine whether AT1001 (migalastat hydrochloride) is safe and effective in patients with Fabry disease.

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Multicenter, Ascending-Dose, 12-Week Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AT1001 in Patients With Fabry Disease

Resource links provided by NLM:

Further study details as provided by Amicus Therapeutics:

Primary Outcome Measures:
  • Safety and tolerability of 3 dose levels of oral AT1001 [ Time Frame: Day -28, Day -15, Day -1, Day 1, Day 13, Day 27, Day 41, Day 83, Day 98, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 ] [ Designated as safety issue: Yes ]
    AEs; Clinical laboratory safety (hematology, serum chemistry, urinalysis); Vital signs (blood pressure, heart rate, temperature, respiratory rate); Physical examination; Electrocardiogram (ECGs); Concomitant medications

Secondary Outcome Measures:
  • Pharmacokinetics of 3 dose levels of oral AT1001 [ Time Frame: Day 1, Day 14, Day 28, Day 42, Week 24 ] [ Designated as safety issue: No ]
    PK blood sampling

  • Pharmacodynamic effects of oral AT1001 (effects on enzyme and substrate levels, cardiac function, renal function, and nerve conduction) [ Time Frame: Day -15, Day -1, Day 1, Day 14, Day 28, Day 42, Day 84, Day 98, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 ] [ Designated as safety issue: No ]
    PD blood draws, 12-lead ECGs, cardiac MRI, renal function tests on urine, QSART

Enrollment: 14
Study Start Date: September 2005
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 25 mg, capsule
AT1001 (migalastat hydrochloride) administered twice a day for weeks 1 and 2.
Drug: AT1001 (migalastat hydrochloride)
25 mg capsule, 100 mg capsule, 250 mg capsule, 50 mg capsule
Experimental: 100 mg, capsule
AT1001 (migalastat hydrochloride) administered twice a day for weeks 3 and 4.
Drug: AT1001 (migalastat hydrochloride)
25 mg capsule, 100 mg capsule, 250 mg capsule, 50 mg capsule
Experimental: 250 mg, capsule
AT1001 (migalastat hydrochloride) administered twice a day for weeks 5 and
Drug: AT1001 (migalastat hydrochloride)
25 mg capsule, 100 mg capsule, 250 mg capsule, 50 mg capsule
Experimental: 50 mg, capsule
AT1001 (migalastat hydrochloride) administered daily for the remainder of the subjects participation.
Drug: AT1001 (migalastat hydrochloride)
25 mg capsule, 100 mg capsule, 250 mg capsule, 50 mg capsule

Detailed Description:

This open-label study will be conducted in up to 20 patients at five clinical sites in the United States. Patients will undergo a 28-day screening period, including a 14-day run-in with AT1001 to assess eligibility for the study. Patients receiving enzyme replacement therapy or substrate depletion therapy for Fabry disease must undergo a 2-week washout of prior therapy before the 28-day screening period. Patients will receive a daily dose of AT1001 for 12 weeks during the treatment phase. The pharmacokinetics of AT1001 in plasma and urine will be assessed at regular intervals. Safety will be evaluated throughout the treatment period. At the end of the 12-week treatment period, the effect of AT1001 on pharmacodynamic parameters (alpha-Gal A in leukocytes, GL-3 in plasma and urine, and alpha-Gal A and GL-3 in skin biopsy samples) and functional parameters (cardiac function as assessed by electrocardiogram, echocardiogram, and MRI, and renal function as assessed by blood and urine tests, and nerve conduction as assessed by QSART and CASE IV tests) will be evaluated. If the safety profile is acceptable, patients will be permitted to enter a 36-week treatment extension period and continue to receive AT1001, with safety, pharmacodynamic, and functional assessments performed at 12-week intervals.


Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males between 18 and 55 years of age (inclusive)
  • Hemizygous for Fabry disease
  • Have a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
  • Have enhanceable enzyme activity
  • In the judgment of the investigator, must either be able safely to suspend enzyme replacement therapy (ERT) for a minimum of 18 weeks throughout the study, or be ERT naive
  • Agree to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following completion of the study
  • Willing and able to sign an informed consent form

Exclusion Criteria:

  • History of significant disease other than Fabry disease (eg, end-stage renal disease; Class III or IV heart disease [per 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 the patient's ability to participate in the study
  • History of organ transplant
  • Serum creatinine greater than 2 on Day -2
  • Screening 12-lead ECG demonstrating QTc > 450 msec prior to dosing
  • Taking a medication prohibited by the protocol: Fabrazyme (agalsidase beta), Replagal (agalsidase alfa), Glyset (miglitol), Zavesca(miglustat), or any experimental therapy for any indication
  • Participated in a previous clinical trial in the last 30 days
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00214500

United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Georgia
Emory University
Decatur, Georgia, United States, 30033
United States, Maryland
National Institute of Neurological Disorders and Stroke
Bethesda, Maryland, United States, 20892
United States, New York
New York University School of Medicine
New York, New York, United States, 10016
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Amicus Therapeutics
Study Director: Karin Ludwig, M.D. Amicus Therapeutics
  More Information

No publications provided

Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT00214500     History of Changes
Obsolete Identifiers: NCT00231036
Other Study ID Numbers: AA1565520 (FAB-CL-201)
Study First Received: September 13, 2005
Last Updated: March 25, 2015
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on May 03, 2015