Clinical trial NCT03500094: Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged 12 to <18 Years)
Official title: An Open-label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of 12 Month Treatment With Migalastat in Pediatric Subjects (Aged 12 to <18 Years) With Fabry Disease and Amenable GLA Variants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fabry Disease
Keywords: Lysosomal storage disease
migalastat
AT1001
Galafold
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-04-17
Enrollment: 22
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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

Key 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

Primary outcomes:
measure: Number Of Participants Who Experienced Treatment-related Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose)
measure: Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve Over The Dosing Interval (AUCtau) Of Migalastat
timeFrame: 0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12
measure: PK: Maximum Observed Plasma Concentration (Cmax) Of Migalastat
timeFrame: 0 to 12 hours postdose during the first month of study and trough samples at Months 6 and 12
Secondary outcomes:
measure: Change In eGFR From Baseline To Month 12
timeFrame: Baseline, Month 12 and last observation (up to Month 12)
measure: Annualized Rate Of Change From Baseline
timeFrame: Baseline up to Month 12
measure: Change From Baseline In Total Urine Protein And Urine Albumin Levels At Month 12
timeFrame: Baseline, Month 12 and last observation (up to Month 12)
measure: Change From Baseline In Left Ventricular Mass Index (LVMi)
timeFrame: Baseline, Month 12 and last observation (up to Month 12)
measure: Change In Plasma Levels Of Globotriaosylsphingosine (Lyso-Gb3)
timeFrame: Baseline, Month 12 and last observation (up to Month 12)
measure: FABPRO-GI And Pain Scores
timeFrame: Month 12 and last observation (up to Month 12)
measure: Patient's Global Impression Of Change (PGI-C) Scores
timeFrame: Month 12
measure: Number Of Participants Who Experienced Sudden Onset Of Pain As Assessed Using The Fabry-Specific Pediatric Health And Pain Questionnaire (FPHPQ)
timeFrame: Month 12
measure: Change From Baseline In FPHPQ Score For Pain Intensity
timeFrame: Baseline, Month 12 and last observation (up to Month 12)
measure: Change From Baseline In Pediatric Quality Of Life (PedsQL) At Month 12
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Clinical Study Site
state: Florida
city: Atlanta
country: United States
facility: Clinical Study Site
state: Georgia
city: Minneapolis
country: United States
facility: Clinical Study Site
state: Minnesota
city: Columbia
country: United States
facility: Clinical Study Site
state: Missouri
city: Cincinnati
country: United States
facility: Clinical Study Site
state: Ohio
city: Pittsburgh
country: United States
facility: Clinical Study Site
state: Pennsylvania
city: Fairfax
country: United States
facility: Clinical Study Site
state: Virginia
city: London
country: United Kingdom
facility: Clinical Study Site
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor Clinical Research
role: STUDY_DIRECTOR
References: