Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged 12 to <18 Years)

NCT ID: NCT03500094

Last Updated: 2021-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-27
• Study Completion Date: 2021-02-06

Brief Summary

This was an open-label study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of migalastat treatment in pediatric participants 12 to <18 years of age with Fabry disease and amenable gene encoding α-galactosidase A (GLA) variants.

Detailed Description

This was a Phase 3b, 2-stage, open-label, uncontrolled, multicenter study to evaluate the safety, PK, PD, and efficacy of migalastat treatment in pediatric participants 12 to <18 years of age and weighing ≥ 45 kilograms (99 pounds) with Fabry disease and amenable GLA variants. Participants must have been naïve to enzyme replacement therapy (ERT) or have stopped ERT at least 14 days at the time of screening.

Stage 1 was a treatment period of approximately 1 month (4 weeks); Stage 2 was a treatment period of 11 months and a 30-day (untreated) safety follow-up period. There was no break in treatment between Stages 1 and 2. Prior to Stage 1, there was a screening period lasting at least 14 days and up to 30 days (or more, if GLA genotyping was required). Stages 1 and 2 together consisted of a 12-month treatment period, and a 30-day safety follow-up period, for a total of approximately 13 months. Upon study completion, participants had the option to enroll in a long-term extension study conducted under a separate protocol (NCT04049760).

Participants were randomly assigned 1:1:1 to 1 of 3 PK sampling groups using interactive response technology (IRT). Four blood samples for the determination of migalastat concentrations in plasma were collected during Stage 1 study drug administration, and 1 PK (trough) sample was collected at Month 6 and again at Month 12.

Conditions

Fabry Disease

Keywords

Lysosomal storage disease; migalastat; AT1001; Galafold

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

migalastat HCl 150 mg

One migalastat 123 milligrams (mg) capsule equivalent to 150 mg migalastat hydrochloride (HCl) (herein referred to as "migalastat") was administered every other day for 12 months.

Group Type: EXPERIMENTAL

Migalastat HCl 150 mg

Intervention Type: DRUG

migalastat HCl 150 mg capsule

Interventions

Migalastat HCl 150 mg

migalastat HCl 150 mg capsule

Intervention Type: DRUG

Other Intervention Names

AT1001; Galafold

Eligibility Criteria

Inclusion Criteria

• Willing and able to provide written consent or assent (participant and parent/legal guardian, as applicable)
• Male or female between 12 and <18 years of age diagnosed with Fabry disease
• Confirmed, amenable GLA variant
• Participant weighed at least 45 kg (99 pounds) at screening
• Participant had never been treated with ERT or had not received ERT for 14 days prior to screening
• Participant had at least 1 complication (such as, laboratory abnormality and/or sign/symptom) of Fabry disease
• Participant was able to swallow study medication whole

Exclusion Criteria

• Had moderate or severe renal impairment (estimated glomerular filtration rate (eGFR) <60 milliliter/minute/1.73 meter squared (m^2) at screening)
• Had advanced kidney disease requiring dialysis or kidney transplantation
• History of allergy or sensitivity to study medication (including excipients) or other iminosugars (for example, miglustat, miglitol)
• Had received any gene therapy at any time or anticipated starting gene therapy during the study period
• Required treatment with Glyset (miglitol) and/or Zavesca (miglustat) within 6 months before screening or throughout the study
• Required treatment with Replagal (agalsidase alfa), or Fabrazyme (agalsidase beta) within 14 days before screening or throughout the study
• Participant was treated or had been treated with any investigational/experimental drug, biologic or device within 30 days before screening
• Any intercurrent illness or condition or concomitant medication use considered to be a contraindication at screening or baseline or that may have precluded the participant from fulfilling the protocol requirements or suggested to the investigator that the potential participant may have had an unacceptable risk by participating in this study
• Pregnant or breast-feeding or planned to become pregnant during the study period
• Otherwise unsuitable for the study in the opinion of the investigator

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amicus Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor Clinical Research

Role: STUDY_DIRECTOR

Amicus Therapeutics

Locations

Clinical Study Site

Tampa, Florida, United States

Clinical Study Site

Atlanta, Georgia, United States

Clinical Study Site

Minneapolis, Minnesota, United States

Clinical Study Site

Columbia, Missouri, United States

Clinical Study Site

Cincinnati, Ohio, United States

Clinical Study Site

Pittsburgh, Pennsylvania, United States

Clinical Study Site

Fairfax, Virginia, United States

Clinical Study Site

London, , United Kingdom

Countries

Spain; United States; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000146-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AT1001-020

Identifier Type: -

Identifier Source: org_study_id