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

NCT03500094 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: AT1001-0202017-000146-21
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 8

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.

Conditions

Fabry Disease

Keywords

Lysosomal storage disease; migalastat; AT1001; Galafold

Outcome Measures

Primary Outcomes (3)

• Number Of Participants Who Experienced Treatment-related Treatment-emergent Adverse Events (TEAEs)

  TEAEs included adverse events that began on or after the first dose of study drug until 30 days after the last dose. Treatment-related TEAEs were defined as TEAEs that had an investigator-defined relationship to study drug of "Definite," "Probable," or "Possible." A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

  Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose)

• Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve Over The Dosing Interval (AUCtau) Of Migalastat

  PK sampling was performed on 1 occasion at steady-state during the first month of the study. Adolescent participants were randomized to 3 sparse PK sampling groups based on optimal sampling theory. Each blood sample could have been taken at any time within the following time point ranges. Time point ranges for all 3 sparse sampling groups are arranged here in chronological order: 1 to 1.25 hours (h), 1.5 to 2h, 2.75 to 3.25h, 3.25 to 3.75h, 3.75 to 4.25h, 5 to 5.5h, 5.25 to 5.75h, 6.5 to 7h, 8.25 to 8.75h, 8.75 to 9.25h, and 10.75 to 11.25h post-dose. The combined sampling scheme resulted in rich data over an approximate 12-hour time course for AUC estimation. Additional trough samples were taken at Months 6 and 12. These trough samples (48h) assisted in estimating the terminal elimination phase for the AUC. Simulations were conducted to predict steady-state PK profiles and parameters for adolescent age subgroups 12 to \<16 years, 16 to \<18 years, and overall, 12 to \<18 years.

  0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12

• PK: Maximum Observed Plasma Concentration (Cmax) Of Migalastat

  PK sampling was performed on 1 occasion at steady-state during the first month of the study. Adolescent participants were randomized to 3 sparse PK sampling groups based on optimal sampling theory. Each blood sample could have been taken at any time within the following time point ranges. Time point ranges for all 3 sparse sampling groups are arranged here in chronological order: 1 to 1.25h, 1.5 to 2h, 2.75 to 3.25h, 3.25 to 3.75h, 3.75 to 4.25h, 5 to 5.5h, 5.25 to 5.75h, 6.5 to 7h, 8.25 to 8.75h, 8.75 to 9.25h, and 10.75 to 11.25h post-dose. The combined sampling scheme resulted in rich data over an approximate 12-hour time course for AUC and Cmax estimation. Additional trough samples were taken at Months 6 and 12. These trough samples (48h) assisted in estimating the terminal elimination phase for the AUC. Simulations were conducted to predict steady-state PK profiles and parameters for adolescent age subgroups 12 to \<16 years, 16 to \<18 years, and overall, 12 to \<18 years.

  0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12

Secondary Outcomes (10)

• Change In eGFR From Baseline To Month 12

  Baseline, Month 12 and last observation (up to Month 12)

• Annualized Rate Of Change From Baseline

  Baseline up to Month 12

• Change From Baseline In Total Urine Protein And Urine Albumin Levels At Month 12

  Baseline, Month 12 and last observation (up to Month 12)

• Change From Baseline In Left Ventricular Mass Index (LVMi)

  Baseline, Month 12 and last observation (up to Month 12)

• Change In Plasma Levels Of Globotriaosylsphingosine (Lyso-Gb3)

  Baseline, Month 12 and last observation (up to Month 12)

Study Arms (1)

migalastat HCl 150 mg

EXPERIMENTAL

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.

Drug: Migalastat HCl 150 mg

Interventions

Migalastat HCl 150 mg DRUG

migalastat HCl 150 mg capsule

Also known as: AT1001, Galafold

migalastat HCl 150 mg

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (8)

Clinical Study Site

Tampa, Florida, 33606, United States

Location

Clinical Study Site

Atlanta, Georgia, 30322, United States

Location

Clinical Study Site

Minneapolis, Minnesota, 55454, United States

Location

Clinical Study Site

Columbia, Missouri, 65212, United States

Location

Clinical Study Site

Cincinnati, Ohio, 45229, United States

Location

Clinical Study Site

Pittsburgh, Pennsylvania, 15224, United States

Location

Clinical Study Site

Fairfax, Virginia, 22030, United States

Location

Clinical Study Site

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Fabry Disease; Lysosomal Storage Diseases

Interventions

migalastat; larazotide acetate

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Medical Affairs
• Organization: Amicus Therapeutics

MedInfoUSA@amicusrx.com

+1-877-426-4287 (877-4-AMICUS)

Study Officials

• Medical Monitor Clinical Research

  Amicus Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 9, 2018
• First Posted: April 17, 2018
• Study Start: September 27, 2018
• Primary Completion: February 2, 2021
• Study Completion: February 6, 2021
• Last Updated: November 30, 2021
• Results First Posted: November 30, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (7)