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

An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in Subjects With Fabry Disease

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02194985

Enrollment

Registered

2014-07-21

Start date

2015-03-14

Completion date

2019-10-23

Last updated

2020-12-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fabry Disease

Keywords

Amicus Therapeutics, Galafold, Migalastat, AT1001

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.

Interventions

DRUGmigalastat 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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number Of Participants Experiencing Adverse Events (AEs)	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

Measure	Time frame	Description
Change From Baseline In eGFR At End Of Study	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	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	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.
Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR)	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 Left Ventricular Mass (LVM) To End Of Study	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	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	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.
Change From Baseline In 24-hour Urine Protein To End Of Study	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.

Countries

Argentina, Australia, Austria, Belgium, Brazil, Canada, Denmark, Egypt, France, Italy, Japan, Spain, Turkey (Türkiye), United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Migalastat HCl 150 mg Migalastat HCl 150 mg was administered orally once every other day for a median duration of 3.1 years (ranged from approximately 1 month to 4.3 years).	84
Total	84

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Lost to Follow-up	1
Overall Study	Met Protocol Defined Stopping Criteria	3
Overall Study	Physician Decision	4
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	Migalastat HCl 150 mg
Age, Continuous	51.9 years STANDARD_DEVIATION 12.27
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	38 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	6 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	78 Participants
Sex: Female, Male Female	50 Participants
Sex: Female, Male Male	34 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 84
other Total, other adverse events	74 / 84
serious Total, serious adverse events	26 / 84

Outcome results

Primary

Number Of Participants Experiencing Adverse Events (AEs)

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.

Time frame: Day 1 after first dose to approximately 30 days after last treatment, median duration of 3.1 years

Population: Safety Population: All participants who received at least 1 dose of study drug after they enrolled into this open-label extension study.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants with at least 1 serious AE	26 Participants
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants discontinued due to AEs	1 Participants
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants with AEs related to study drug	24 Participants
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants with AEs unrelated to study drug	56 Participants
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants with at least 1 AE	80 Participants
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants with AEs leading to death	0 Participants
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants with at least 1 mild AE	19 Participants
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants with at least 1 moderate AE	46 Participants
Migalastat HCl 150 mg	Number Of Participants Experiencing Adverse Events (AEs)	Participants with at least 1 severe AE	15 Participants

Secondary

Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR)

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.