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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

Tracking Information
First Submitted Date  ICMJE October 6, 2010
First Posted Date  ICMJE October 11, 2010
Results First Submitted Date  ICMJE August 10, 2018
Results First Posted Date  ICMJE November 1, 2018
Last Update Posted Date November 1, 2018
Actual Study Start Date  ICMJE September 8, 2011
Actual Primary Completion Date May 27, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2010)
renal function assessed by iohexol Glomerular Filtration Rate (GFR) [ Time Frame: 18 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2010)
  • renal function (assessed by estimated GFR and 24-hour urine protein) [ Time Frame: 18 months ]
  • composite clinical outcome (assessed by time to occurrence of renal, cardiac, cerebrovascular events or death) [ Time Frame: 18 months ]
  • cardiac function (assessed by echocardiography) [ Time Frame: 18 months ]
  • patient reported outcomes (pain and quality of life) [ Time Frame: 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fabry Disease
Intervention  ICMJE
  • Drug: migalastat hydrochloride
    150-mg capsule administered orally QOD
    Other Names:
    • AT1001
    • Migalastat
    • Galafold
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: migalastat hydrochloride
  • 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.
    Intervention: Biological: agalsidase
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: October 1, 2018)
68
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2010)
60
Actual Study Completion Date  ICMJE May 28, 2015
Actual Primary Completion Date May 27, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 74 Years   (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 Australia,   Austria,   Belgium,   Brazil,   Denmark,   France,   Italy,   Japan,   United Kingdom,   United States
Removed Location Countries Argentina,   Germany,   Greece,   Poland,   Switzerland,   Taiwan,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT01218659
Other Study ID Numbers  ICMJE AT1001-012
ATTRACT ( Other Identifier: Amicus Therapeutics )
2010-022636-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Amicus Therapeutics
Study Sponsor  ICMJE Amicus Therapeutics
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