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Study to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease

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: NCT01218659
Recruitment Status : Completed
First Posted : October 11, 2010
Results First Posted : November 1, 2018
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Study Description
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Brief Summary:
Study to compare the efficacy and safety of migalastat and enzyme replacement therapy (ERT) in male and female participants with Fabry disease who are currently receiving ERT and who have an alpha galactosidase-A (α Gal-A) mutation that is amenable to migalastat, based on the clinical trial human embryonic kidney cell (HEK) assay.

Condition or disease Intervention/treatment Phase
Fabry Disease Drug: migalastat hydrochloride Biological: agalsidase Phase 3

Detailed Description:
This was a Phase 3, randomized, open-label, active-controlled study to evaluate the efficacy and safety of 150 milligrams (mg) of migalastat hydrochloride (migalastat) (equivalent to 123 mg of migalastat) once every other day (QOD) and ERT in male and female participants with Fabry disease who were receiving ERT and who have an α Gal-A mutation that is amenable to migalastat, based on the clinical trial HEK assay. This was a 2-part study. Part 1, the 18-month randomized phase, evaluated participants who received either migalastat 150 mg QOD or ERT per prescribing physicians' instructions for efficacy and safety. Part 2, the optional 12-month open-label extension (OLE) phase in which all participants received migalastat, also explored efficacy and safety. For Part 2, all participants who received ERT in Part 1 were given migalastat. Data presented in this posting include efficacy data from the 18-month randomized period and safety data from the entire study (18-month randomized period and 12-month optional OLE [total of 30 months]).
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label Study to Compare the Efficacy and Safety of AT1001 and Enzyme Replacement Therapy (ERT) in Patients With Fabry Disease and AT1001-Responsive GLA Mutations, Who Were Previously Treated With ERT
Actual Study Start Date : September 8, 2011
Actual Primary Completion Date : May 27, 2014
Actual Study Completion Date : May 28, 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Migalastat
Participants received 150 mg migalastat orally QOD during the 18-month randomized treatment period and the optional 12-month OLE period. Participants received an inactive reminder capsule on alternate days during both treatment periods.
 Drug: migalastat hydrochloride
150-mg capsule administered orally QOD
Other Names:
  • AT1001
  • Migalastat
  • Galafold
Active Comparator: ERT
Participants received ERT (either agalsidase alfa or agalsidase beta) as prescribed by the participant's treating physician and administered in accordance with the approved prescribing information during the 18-month randomized treatment period. Participants were required to be given >80% of the currently labeled dose and regimen during the 18-month randomized treatment period. During the optional 12-month OLE period, participants received 150 mg migalastat orally QOD. Participants received an inactive reminder capsule on alternate days during the OLE.
 Biological: agalsidase
Agalsidase via intravenous infusion as prescribed by the participant's treating physician and in accordance with the approved prescribing information
Other Names:
  • agalsidase beta; Fabrazyme
  • agalsidase alfa; Replagal


Outcome Measures
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Primary Outcome Measures :
  1. Annualized Rate Of Change From Baseline To Month 18 In Measured Glomerular Filtration Rate [ Time Frame: Baseline to Month 18 ]
    To assess renal function, measured glomerular filtration rate (GFR) was measured by the plasma clearance of unlabeled iohexol (mGFR-iohexol), a non-ionic contrast agent. The annualized rate of change in mGFR-iohexol from Baseline to Month 18 was analyzed using an analysis of covariance (ANCOVA) model with the following factors as covariates: treatment group, sex, age, Baseline GFR (mGFR-iohexol), and Baseline 24-hour (hr) urine protein. A threshold of <2.2 milliliter (mL)/minute (min)/1.73 meter squared (m^2)/year was established to compare migalastat to ERT. This difference of 2.2 mL/min/1.73 m2/year is based on the smallest expected rate of decline in estimated glomerular filtration rate (eGFR) for participants treated with agalsidase alfa for 18 months.

  2. Annualized Rate Of Change From Baseline To Month 18 In eGFR [ Time Frame: Baseline to Month 18 ]

    The eGFR assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was calculated using the following:

    eGFR-CKD-EPI = 141 x min (Serum Creatinine/κ,1)^(α) x max(Serum Creatinine/κ,1)^(-1.209) x 0.993^(Age) x 1.1018 (if female) x 1.159 (if African American or black) where: κ is 0.7 for females and 0.9 for males; α is -0.329 for females and -0.411 for males; min indicates the minimum of Serum Creatinine/κ or 1; max indicates the maximum of Serum Creatinine/κ or 1.

    The annualized rate of change in eGFR-CKD-EPI from Baseline to Month 18 was analyzed using an ANCOVA model with the following factors as covariates: treatment group, sex, age, Baseline GFR (eGFR-CKD-EPI), and Baseline 24-hr urine protein. A threshold of <2.2 mL/min/1.73m^2/year was established to compare migalastat to ERT. This difference of 2.2 mL/min/1.73 m2/year is based on the smallest expected rate of decline in eGFR for participants treated with agalsidase alfa for 18 months.



Secondary Outcome Measures :
  1. Annualized Rate Of Change From Baseline To Month 18 In eGFR By The Modification Of Diet In Renal Disease Equation [ Time Frame: Baseline to Month 18 ]

    The GFR estimated by the Modification Of Diet In Renal Disease equation (eGFR-MDRD) was calculated using the following equation: eGFR-MDRD = 175 x (Serum Creatinine)^(-1.154) x (Age)^(-0.203) x 1.212 (if participant's race is black or African American) x 0.742 (if participant is female).

    The eGFR-MDRD from Baseline to Month 18 was analyzed using an ANCOVA model with the following factors as covariates: treatment group, sex, age, Baseline GFR (eGFR-CKD-EPI), and Baseline 24-hr urine protein.



Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 74 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female between the ages of 16 and 74 diagnosed with Fabry disease
  • Confirmed α Gal-A mutation that is amenable to migalastat, based on the clinical trial HEK assay
  • Participant has been on ERT for at least 12 months before screening/baseline
  • Dose level and regimen of ERT have been stable for 3 months before screening/baseline and is at least 80% of the currently labeled dose and regimen for this time period
  • Glomerular filtration rate (GFR) ≥ 30 milliliter (mL)/minute (min) /1.73 m^2
  • Participants taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be on a stable dose for at least 4 weeks before screening/baseline
  • Women who can become pregnant and all men agree to be sexually abstinent or use medically accepted methods of birth control throughout the duration of the study and for up to 30 days after last dose of study medication
  • Participant is willing and able to provide written informed consent and assent if applicable

Exclusion Criteria:

  • Participant has undergone, or is scheduled to undergo, kidney transplantation or any other solid organ transplantation
  • Participant is on regular dialysis that is specifically for the treatment of chronic kidney disease
  • Participant has had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 3 months before screening/baseline
  • Participant has clinically significant unstable cardiac disease in the opinion of the investigator (for example, cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or New York Heart Association (NYHA) class III or IV congestive heart failure)
  • Pregnant or breast-feeding
  • History of allergy or sensitivity to study medication (including excipients) or other iminosugars (for example, miglustat, miglitol)
  • Participant has absolute contraindication to iohexol and/or inability to undergo iohexol GFR testing
  • Participant requires treatment with Glyset® (miglitol), or Zavesca® (miglustat)
  • Participant received any investigational/experimental drug, biologic or device within 30 days of screening/baseline
  • Any intercurrent illness or condition that may preclude the participant from fulfilling the study requirements or suggests to the investigator that the participant may have an unacceptable risk by participating in this study
Contacts and Locations
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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): NCT01218659


Locations
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United States, California
Los Angeles, California, United States, 90048
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Decatur, Georgia, United States, 30033
United States, Michigan
Grand Rapids, Michigan, United States, 49525
United States, Oregon
Portland, Oregon, United States, 97239
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15224
United States, Virginia
Fairfax, Virginia, United States, 22030
United States, Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia, Victoria
Parkville, Victoria, Australia, 03050
Australia, West Australia
Perth, West Australia, Australia, 6000
Austria
Vienna, Austria, 1090
Belgium
Edegem, Belgium, 2650
Brazil
Sao Paulo, Brazil, 14048-900
Denmark
Copenhagen, Denmark, 2100
France
Garches, France, 92380
Lille, France, 59037
Italy
Firenze, Italy, 50129
Japan
Niigata, Japan, 951-8520
Osaka, Japan, 545-8586
Osaka, Japan, 565-0871
Tokyo, Japan, 105-8471
United Kingdom
Cambridge, United Kingdom, CB2 0QQ
London, United Kingdom, NW3 2QG
London, United Kingdom, WC1N 3BG
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Amicus Therapeutics
Investigators
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Study Director: Medical Monitor, Clinical Research Amicus Therapeutics
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT01218659    
Other Study ID Numbers: AT1001-012
ATTRACT ( Other Identifier: Amicus Therapeutics )
2010-022636-37 ( EudraCT Number )
First Posted: October 11, 2010    Key Record Dates
Results First Posted: November 1, 2018
Last Update Posted: November 1, 2018
Last Verified: October 2018
Keywords provided by Amicus Therapeutics:
Amicus Therapeutics
Galafold
AT1001
Migalastat
Additional relevant MeSH terms:
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Fabry Disease
Sphingolipidoses
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
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders