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Open-Label Phase 3 Long-Term Safety Study of Migalastat (AT1001-041)

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.
ClinicalTrials.gov Identifier: NCT01458119
Recruitment Status : Terminated (Amicus Therapeutics discontinued Study AT1001-041 for logistical reasons.)
First Posted : October 24, 2011
Results First Posted : October 2, 2018
Last Update Posted : October 2, 2018
Information provided by (Responsible Party):
Amicus Therapeutics

Tracking Information
First Submitted Date  ICMJE October 20, 2011
First Posted Date  ICMJE October 24, 2011
Results First Submitted Date  ICMJE August 10, 2018
Results First Posted Date  ICMJE October 2, 2018
Last Update Posted Date October 2, 2018
Actual Study Start Date  ICMJE October 14, 2011
Actual Primary Completion Date February 17, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline to End of Follow-up (30 days after the end of this 42-month study), with AE reporting occurring at each study visit, which occurred once every 6 months. ]
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered migalastat that did not necessarily have a causal relationship with the treatment. Each AE was recorded at the time of reporting; visits typically occurred every 6 months. A TEAE was defined as an AE starting on or after the first study drug administration date. Serious AEs were life-threatening or resulted in death, persistent or significant incapacitation, inpatient or prolonged hospitalization, or a congenital anomaly. The criteria for AE severity were: Mild: minimal discomfort, does not interfere with normal everyday activities; Moderate: sufficiently discomforting, interferes with normal everyday activities; Severe: prevents normal everyday activities. The number of participants experiencing TEAEs is presented for those who received migalastat treatment. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Original Primary Outcome Measures  ICMJE
 (submitted: October 20, 2011)
  • Incidence of adverse events (AEs) [ Time Frame: Up to 5 years ]
    non-serious AEs, serious AEs, and possible suicidality related AEs
  • Withdrawal from treatment due to AEs [ Time Frame: Up to 5 years ]
    including non-serious and serious AEs
  • Change from baseline in vital signs [ Time Frame: Up to 5 years ]
    blood pressure, heart rate
  • Change from baseline in laboratory parameters [ Time Frame: Up to 5 years ]
    blood chemistry, hematology, urinalysis
  • Change from baseline in echocardiogram (ECG) [ Time Frame: Up to 5 years ]
    12-lead ECG
  • Change from baseline in electrocardiography (ECHO) [ Time Frame: Up to 5 years ]
    ECHO ultrasound
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline, Every 6 m until the End of Study (42 m) ]
The annualized rate of change of the eGFR was assessed per participant by the slope of the simple linear regression between the observed values and the assessment times. It was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR [CKD-EPI]) and the Modification of Diet in Renal Disease (MDRD) equation (eGFR [MDRD]). The equations are as follows: eGFR [MDRD] = 175 * (Serum Creatinine)^-1.154 * (Age)^-0.203 * 1.212 (if black or African American) * 0.742 (if female); eGFR [CKD-EPI] = 141 * min(serum creatinine/kappa,1)^alpha * max(serum creatinine/kappa, 1)^-1.209 * 0.993^age * 1.1018(if female) * 1.159(if black or African American), where kappa is 0.7 for females and 0.9 for males, alpha is -0.329 for females and -0.411 for males, min is minimum of serum creatinine/kappa or 1, and max is the maximum of serum creatinine/kappa or 1. The number of participants with at least a Baseline and a post-Baseline value are presented.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2011)
  • Estimated glomerular filtration rate [ Time Frame: Up to 5 years ]
    based on the Modification of Diet in Renal Disease equation
  • Measurement of 24-hour urine [ Time Frame: Up to 5 years ]
    protein, albumin, creatinine and globotriaosylceramide (GL-3)
  • Evaluation of left ventricular mass index and ejection fraction [ Time Frame: Up to 5 years ]
    as measured by echocardiography
  • Evaluation of leukocyte alpha-galactosidase A (a-Gal A) activity [ Time Frame: Up to 5 years ]
    enzyme responsible for breaking down GL-3
  • Evaluation of patient reported assessment of pain [ Time Frame: Up to 5 years ]
    as assessed by the Brief Pain Inventory short form
  • Evaluation of patient reported Quality of Life [ Time Frame: Up to 5 years ]
    as assessed by the Short Form-36 survey
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Open-Label Phase 3 Long-Term Safety Study of Migalastat
Official Title  ICMJE An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in Subjects With Fabry Disease
Brief Summary This was a long-term, open-label study of migalastat (123 milligrams [mg] of migalastat [equivalent to 150 mg of migalastat hydrochloride]) (migalastat) in participants with Fabry disease who completed treatment in a previous monotherapy trial with migalastat.
Detailed Description

Study AT1001-041 was an open-label, noncomparative, multicenter, long-term extension study for participants with Fabry disease who completed treatment in one of three previous trials of migalastat (AT1001-011 [NCT00925301], AT1001-012 [NCT01218659], or FAB-CL-205 [NCT00526071]). In these trials, migalastat was given as monotherapy. This was an extension study designed to evaluate the long-term safety and efficacy of migalastat for the treatment of Fabry disease. Study visits occurred every 6 months (m). Visit evaluations included physical examinations, clinical laboratory parameters, adverse events, and participant reported outcomes.

The study consisted of a Baseline Visit, which was performed at the time of the final visit of the previous study, followed by clinic visits every 6 m for each year of the study. Study assessments included a physical examination, echocardiography, laboratory parameters, and participant-reported outcomes. Since participants enrolled in the study at varying time points based on the completion of the preceding migalastat study, treatment duration varied among participants. No maximum treatment duration was defined. There were no control groups in this study; all participants received migalastat as a 150-mg capsule taken orally once every other day (QOD) and inactive reminder capsules on alternate days.

The sponsor (Amicus Therapeutics) discontinued Study AT1001-041 for logistical reasons and not due to either safety concerns or lack of efficacy. For participants who were ongoing in Study AT1001-041 at the time of discontinuation, the investigators were offered participation in a similar open-label, long-term migalastat treatment study (AT1001-042 [NCT02194985]) for participants ongoing at discontinuation.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fabry Disease
Intervention  ICMJE Drug: migalastat hydrochloride
Oral capsule QOD
Other Names:
  • AT1001
  • Galafold
  • Migalastat
Study Arms  ICMJE Experimental: Migalastat
Migalastat 150-mg capsule taken orally QOD. The median duration of exposure was 23.5 m.
Intervention: Drug: migalastat hydrochloride
Publications * Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 29, 2016)
Original Estimated Enrollment  ICMJE
 (submitted: October 20, 2011)
Actual Study Completion Date  ICMJE February 17, 2016
Actual Primary Completion Date February 17, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Completed migalastat treatment in a previous Fabry disease protocol
  • Both male and female participants were enrolled
  • Age 16 years or older
  • Male and female participants had to agree to use protocol-identified acceptable contraception

Exclusion Criteria:

  • Estimated glomerular filtration rate (eGFR) in the previous study was <30 milliliters/minute/1.73 square meters (mL/min/1.73 m^2) unless there was a measured GFR available within 3 m of the Baseline Visit that was >30 mL/min/1.73 m^2
  • Had undergone, or was scheduled to undergo, kidney transplantation or was currently on dialysis
  • Pregnant or breast feeding
  • Treated with another investigational drug (except migalastat) within 30 days of study start
  • Unable to comply with study requirements, or deemed otherwise unsuitable for study entry, in the opinion of the investigator
  • Had documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 12 m before the Baseline Visit
  • Had clinically significant, unstable cardiac disease in the opinion of the investigator
  • Had a history of allergy or sensitivity to migalastat (including excipients) or to other iminosugars
  • Required treatment with Glyset (miglitol) or Zavesca (miglustat)
  • Had any intercurrent illness or condition that may have precluded the participant from fulfilling the protocol requirements
  • Had a severe or unsuitable concomitant medical condition
  • Had a clinically significant abnormal laboratory value and a clinically significant electrocardiogram finding at the Baseline Visit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   Denmark,   Egypt,   France,   Italy,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries Austria,   Japan
Administrative Information
NCT Number  ICMJE NCT01458119
Other Study ID Numbers  ICMJE AT1001-041
2011-004800-40 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Amicus Therapeutics
Original Responsible Party Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
Current Study Sponsor  ICMJE Amicus Therapeutics
Original Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor, Clinical Research Amicus Therapeutics
PRS Account Amicus Therapeutics
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP