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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fabry Disease	Drug: migalastat HCl 150 mg	Phase 3

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Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in Subjects With Fabry Disease
• Actual Study Start Date: March 14, 2015
• Actual Primary Completion Date: October 23, 2019
• Actual Study Completion Date: October 23, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Migalastat HCl 150 mg; Migalastat HCl 150 milligram (mg).	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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Georgia

Clinical Study Site

Atlanta, Georgia, United States, 30322

United States, Kansas

Clinical Study Site

Kansas City, Kansas, United States, 66160

United States, Michigan

Clinical Study Site

Grand Rapids, Michigan, United States, 49525

United States, New York

Clinical Study Site

New York, New York, United States, 10016

United States, Oregon

Clinical Study Site

Portland, Oregon, United States, 97239

United States, Texas

Clinical Study Site

Dallas, Texas, United States, 75226

United States, Virginia

Clinical Study Site

Fairfax, Virginia, United States, 22030

Argentina

Clinical Study Site

Pilar, Argentina, B1629ODT

Australia

Clinical Study Site

Adelaide, Australia, 5000

Clinical Study Site

Parkville, Australia, 3050

Austria

Clinical Study Site

Wien, Austria, 1090

Belgium

Clinical Study Site

Edegem, Belgium, 2650

Brazil

Clinical Study Site

Porto Alegre, Brazil, 90035-903

Canada, Quebec

Clinical Study Site

Montreal, Quebec, Canada, H4J 1C5

Denmark

Clinical Study Site

Copenhagen, Denmark, 2100

Egypt

Clinical Study Site

Cairo, Egypt, 11451

France

Clinical Study Site

Garches, France, 92380

Clinical Study Site

Lille, France, 59037

Italy

Clinical Study Site

Firenze, Italy, 50134

Clinical Study Site

Roma, Italy, 00168

Japan

Clinical Study Site

Suita, Osaka, Japan, 565-0871

Clinical Study Site

Niigata, Japan, 951-8520

Clinical Study Site

Osaka-shi, Japan, 545-8586

Clinical Study Site

Tokyo, Japan, 105-8471

Spain

Clinical Study Site

Barcelona, Spain, 08025

Turkey

Clinical Study Site

Ankara, Turkey, 06500

United Kingdom

Clinical Study Site

London, United Kingdom, NW3 2QG

Clinical Study Site

London, United Kingdom, WC1N3BG

Sponsors and Collaborators

Amicus Therapeutics

Investigators

• Study Director: Medical Monitor Clinical Research; Amicus Therapeutics

  Study Documents (Full-Text)

Documents provided by Amicus Therapeutics:

Study Protocol  [PDF] October 21, 2015

Statistical Analysis Plan  [PDF] August 21, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Amicus Therapeutics
• ClinicalTrials.gov Identifier: NCT02194985
• Other Study ID Numbers: AT1001-042; 2014-002701-38 ( EudraCT Number )
• First Posted: July 21, 2014
• Results First Posted: December 21, 2020
• Last Update Posted: December 21, 2020
• Last Verified: November 2020

Keywords provided by Amicus Therapeutics:

Amicus Therapeutics; Galafold; Migalastat; AT1001

Additional relevant MeSH terms:

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