Open-Label Extension Study of the Long-Term Effects of Migalastat HCL in Patients With Fabry Disease

• ClinicalTrials.gov Identifier: NCT02194985
• Recruitment Status: Completed
• First Posted: July 21, 2014
• Results First Posted: December 21, 2020
• Last Update Posted: December 21, 2020
• Sponsor: Amicus Therapeutics
• Information provided by (Responsible Party): Amicus Therapeutics

Tracking Information

• First Submitted Date: July 17, 2014
• First Posted Date: July 21, 2014
• Results First Submitted Date: October 21, 2020
• Results First Posted Date: December 21, 2020
• Last Update Posted Date: December 21, 2020
• Actual Study Start Date: March 14, 2015
• Actual Primary Completion Date: October 23, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 25, 2020)

Number Of Participants Experiencing Adverse Events (AEs) [ Time Frame: Day 1 after first dose to approximately 30 days after last treatment, median duration of 3.1 years ]

An 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 time of reporting; visits typically occurred every 6 months. Serious AEs were life threatening or resulted in death, resulted in disability/incapacity, hospitalization or prolonged hospitalization, or a congenital anomaly. The criteria for AE severity were: Mild: awareness of sign or symptom, does not interfere with normal everyday activities; Moderate: discomforting, interferes with normal everyday activities, but able to function; Severe: incapacitating, prevents normal everyday activities or significantly affects clinical status and requires medical intervention. 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 (submitted: July 17, 2014)

• Incidence of adverse events (AEs) [ Time Frame: up to 5 years ]
  non-serious AEs, serious AEs, possible suicidality related AEs
• Withdrawal due to AEs [ Time Frame: up to 5 years ]
  including non-serious and serious AEs
• Vital signs and body weight - change in baseline in vital signs and body weight [ Time Frame: up to 5 years ]
  blood pressure and heart rate
• Change from baseline in laboratory parameters [ Time Frame: up to 5 years ]
  hematology, chemistry, and urinalysis
• Change from baseline in electrocardiogram (ECG) [ Time Frame: up to 5 years ]
  12-lead ECG
• Change from baseline in echocardiography [ Time Frame: up to 5 years ]
  echocardiography ultrasound

Current Secondary Outcome Measures (submitted: November 25, 2020)

• Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline to approximately 30 days after last treatment, median duration of 3.1 years ]
  The annualized rate of change in 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 × (1/Serum Creatinine in mg/deciliter^1.154) × (1/Age in years^0.203) × 0.742 [if female] × 1.212 [if black] × 0.808 [if Japanese]; eGFR [CKD-EPI] = 141 × min(Serum creatinine [Scr]/k, 1)α × max(Scr/k, 1) - 1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black], where Scr is serum creatinine, k 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 Scr/k or 1, and max indicates the maximum of Scr/k or 1. Participants with at least a Baseline and a post-Baseline value are presented.
• Change From Baseline In eGFR At End Of Study [ Time Frame: Baseline to approximately 30 days after last treatment, median duration of 3.1 years ]
  The change from baseline in eGFR was calculated using eGFR[CKD-EPI] and eGFR[MDRD] equations. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis.
• Change From Baseline In Plasma Globotriaosylsphingosine (Lyso-Gb3) To End Of Study [ Time Frame: Baseline to approximately 30 days after last treatment, median duration of 3.1 years ]
  Concentrations of lyso-Gb3 were measured in plasma using a qualified assay. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis.
• Change From Baseline In White Blood Cell α-Gal A Activity To End Of Study [ Time Frame: Baseline to approximately 30 days after last treatment, median duration of 3.1 years ]
  The activity of the α-galactosidase A (α-Gal A) enzyme was measured in leukocyte lysate by a validated fluorometric assay method, using 4-methylumbelliferone as a reference. The activity values obtained were normalized to protein (measured using a colorimetric assay). Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Results for male participants are reported. Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis.
• Change From Baseline In 24-hour Urine Protein To End Of Study [ Time Frame: Baseline to approximately 30 days after last treatment, median duration of 3.1 years ]
  A 24-hour urine sample was collected to measure 24-hour urine protein. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis.
• Change From Baseline In Left Ventricular Mass (LVM) To End Of Study [ Time Frame: Baseline to approximately 30 days after last treatment, median duration of 3.1 years ]
  LVM was measured by echocardiography. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis.
• Change From Baseline In Left Ventricular Mass Index (LVMi) To End Of Study [ Time Frame: Baseline to approximately 30 days after last treatment, median duration of 3.1 years ]
  LVMi was measured by echocardiography. Baseline was defined as the data collected at Month 0, if not available, it was the last visit of the previous (feeder) study if done within 6 months. End of Study was the last recorded observation for each participant (approximately 30 days after last treatment). Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis.
• Change From Baseline In Patient Reported Quality Of Life To End Of Study, As Assessed By The Short Form-36 (SF-36) Questionnaire [ Time Frame: Baseline to approximately 30 days after last treatment, median duration of 3.1 years ]
  The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health). Scores on each item are summed and averaged (range: 0=worst to 100=best). Scores were normed to the US population. Higher score indicates less disability. A positive change from baseline indicates improvement. Baseline was defined as the data collected in the last visit of the previous (feeder) study. Only participants with both a Baseline value and an End of Study value were included in the change from baseline analysis.

Original Secondary Outcome Measures (submitted: July 17, 2014)

• Estimated glomerular filtration rate (eGFR) [ Time Frame: up to 5 years ]
  based on the Modification of Diet in Renal Disease (MDRD) equation
• Evaluation of left ventricular mass index (LVMi) [ Time Frame: up to 5 years ]
  as measured by echocardiography
• Ejection fraction [ Time Frame: up to 5 years ]
  as measured by echocardiography
• Fractional shortening [ Time Frame: up to 5 years ]
  as assessed by echocardiography
• Measurement of LV internal dimension (LVIDd and LVIDs) and wall thickness [ Time Frame: up to 5 years ]
  as assessed by echocardiography
• Evaluation of white blood cell (WBC) α-Gal A activity [ Time Frame: up to 5 years ]
  enzyme responsible for breaking down GL-3
• Evaluation of subject reported Quality of Life [ Time Frame: up to 5 years ]
  as assessed by the Short Form - 36 Survey (SF-36)
• Measurement of 24-hour urine protein [ Time Frame: up to 5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Open-Label Extension Study of the Long-Term Effects of Migalastat HCL in Patients With Fabry Disease
• Official Title: 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 is an open-label extension study intended to provide continued treatment with migalastat hydrochloride (HCl) for participants with Fabry disease who completed treatment of a previous migalastat HCl study. The study assessed the long-term safety and effectiveness of migalastat HCl.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Fabry Disease

Intervention

Drug: migalastat HCl 150 mg

Migalastat HCl 150 mg (equivalent to 123 mg migalastat) was provided as capsules in blister packs. One capsule was taken orally every other day.

Other Names:

• AT1001
• Galafold

Study Arms

Experimental: Migalastat HCl 150 mg

Migalastat HCl 150 milligram (mg).

Intervention: Drug: migalastat HCl 150 mg

• Publications *: Narita I, Ohashi T, Sakai N, Hamazaki T, Skuban N, Castelli JP, Lagast H, Barth JA. Efficacy and safety of migalastat in a Japanese population: a subgroup analysis of the ATTRACT study. Clin Exp Nephrol. 2020 Feb;24(2):157-166. doi: 10.1007/s10157-019-01810-w. Epub 2019 Dec 30.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 25, 2020): 84
• Original Estimated Enrollment (submitted: July 17, 2014): 100
• Actual Study Completion Date: October 23, 2019
• Actual Primary Completion Date: October 23, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant had completed treatment in a previous study of migalastat HCl given as a monotherapy
• Male and female participant agreed to use protocol-identified acceptable contraception
• Participant was willing to provide written informed consent and authorization for use and disclosure of Personal Health Information (PHI)

Exclusion Criteria:

• Participant's last available estimated glomerular filtration rate (eGFR) in the previous study was <30 milliliter (mL)/minute (min)/1.73 meters squared (m^2); unless there was measured GFR available within 3 months of Baseline Visit, which was >30 mL/min/1.73 m^2
• Participant had undergone, or was scheduled to undergo kidney transplantation or was currently on dialysis
• Participant had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 3 months before Baseline Visit
• Participant had 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 class III or IV congestive heart failure)
• Participant had a history of allergy or sensitivity to AT1001 (including excipients) or other iminosugars (for example, miglustat, miglitol)
• Participant required treatment with Glyset® (miglitol) or Zavesca® (miglustat)
• Participants with severe or unsuitable concomitant medical condition
• Participants with clinically significant abnormal laboratory value(s) and/or clinically significant electrocardiogram (ECG) findings

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Denmark, Egypt, France, Italy, Japan, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT02194985
• Other Study ID Numbers: AT1001-042; 2014-002701-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amicus Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Amicus Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor Clinical Research; Amicus Therapeutics

• PRS Account: Amicus Therapeutics
• Verification Date: November 2020