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Fabry DiseasePhase 3NCT03500094

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

A Phase 3 study testing Migalastat HCl 150 mg in people with Fabry Disease, run by Amicus Therapeutics at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 to 17 years
Conditions the study is for
Fabry Disease
What is being tested?
Migalastat HCl 150 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
8 sitesin 2 countries
Study dates
27 Sep 2018to 6 Feb 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

United States7 sites
  • Clinical Study Site

    Atlanta, Georgia, 30322

  • Clinical Study Site

    Cincinnati, Ohio, 45229

  • Clinical Study Site

    Columbia, Missouri, 65212

  • Clinical Study Site

    Fairfax, Virginia, 22030

  • Clinical Study Site

    Minneapolis, Minnesota, 55454

  • Clinical Study Site

    Pittsburgh, Pennsylvania, 15224

  • Clinical Study Site

    Tampa, Florida, 33606

Other trials in United States

United Kingdom1 site
  • Clinical Study Site

    London, NW3 2QG

Other trials in United Kingdom

About this study

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

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.

Read the 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
Being tested
Migalastat HCl 150 mg
Keywords
Lysosomal storage disease, migalastat, AT1001, Galafold
Medical subject headings
Fabry Disease, Lysosomal Storage Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Migalastat HCl 150 mgDrug

    Also called AT1001, Galafold

    migalastat HCl 150 mg capsule

Study groups in NCT03500094
Study groupRoleWhat they receive
migalastat HCl 150 mgExperimentalOne 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.
Receives: Drug: Migalastat HCl 150 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

Secondary outcomes (10)
  1. Change In eGFR From Baseline To Month 12

    eGFR was calculated using the modified Schwartz formula for creatinine clearance.

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

  2. Annualized Rate Of Change From Baseline

    Annualized rate of change from baseline of eGFR was defined as change from baseline to last visit divided by the duration from baseline to the last visit (Last assessment date - First dose date +1) and multiplied by 365.25. Baseline was defined as the last non-missing assessment prior to the first dose of study drug.

    Measured: Baseline up to Month 12

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

    Renal function was assessed by urine protein and urine albumin levels. Urine samples were collected as part of urinalysis to measure protein and albumin levels.

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

  4. Change From Baseline In Left Ventricular Mass Index (LVMi)

    LVMi was assessed as a measure of cardiac impairment in the study participants. LVMi values for both M Mode and 2D views are presented.

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

  5. Change In Plasma Levels Of Globotriaosylsphingosine (Lyso-Gb3)

    Blood samples were collected for measurement of lyso-Gb3 levels in plasma. Plasma levels of lyso-Gb3 were measured using a validated liquid chromatography-mass spectrometry assay.

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

  6. FABPRO-GI And Pain Scores

    The Fabry Disease Patient-Reported Outcome - Gastrointestinal Signs And Symptoms (FABPRO-GI) And Pain Questionnaire For Clinical Trials (24-hr Version) consists of questions regarding gastrointestinal signs and symptoms and pain relative to the past 24 hours. Participants rated the severity of their symptoms and pain from 0 (none) to 10 (worst possible). The monthly average score at Month 12 and at last observation are presented. A higher score indicated higher levels of symptoms and pain.

    Measured: Month 12 and last observation (up to Month 12)

  7. Patient's Global Impression Of Change (PGI-C) Scores

    The PGI-C consists of 4 questions regarding diarrhea, abdominal pain, overall pain, and daily living. Participants rated their status based on improvement, worsening, or the same. Improved status includes "Much better", "Better" and "A little better"; worsened status includes "A little worse", "Worse" and "Much worse".

    Measured: Month 12

  8. Number Of Participants Who Experienced Sudden Onset Of Pain As Assessed Using The Fabry-Specific Pediatric Health And Pain Questionnaire (FPHPQ)

    The assessment of "In the last 3 months how many times did you experience sudden onset of pain?" using the FPHPQ for ages 13 to 18 is presented.

    Measured: Month 12

  9. Change From Baseline In FPHPQ Score For Pain Intensity

    The assessment of "How bad is your pain today?" using the FPHPQ for ages 13 to 18 is presented. Pain intensity was measured on a 10-point scale, 0 (no pain) to 10 (pain as bad as you can imagine). A decrease from baseline indicates an improvement in the condition.

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

  10. Change From Baseline In Pediatric Quality Of Life (PedsQL) At Month 12

    The PedsQL is a modular approach to measuring health-related quality of life in healthy children and adolescents and those with acute and chronic health conditions. The psychosocial score for the PedsQL encompassed 15 questions relating to the participants' feelings, social interaction with others, and school. The physical score was derived from answers to 8 questions about the participants' ease of managing physical activity.

    All components of the PedsQL were scored based on a scale of 0 (never) to 4 (almost always) and linearly transformed to a 0-100 scale as follows: 0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0. Both categories were combined for a total score. Total scores for the child report ages 13 to 18 years old and parent report are presented at Month 12.

    Measured: Baseline, Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2018
  2. Study start27 Sep 2018
  3. Primary completion2 Feb 2021
  4. Study completion6 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03500094
Sponsor's protocol ID
AT1001-020
Other IDs
2017-000146-21, 2017
Status last verified
Nov 2021
First submitted
9 Apr 2018
Last updated
30 Nov 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Migalastat HCl 150 mg in people with Fabry Disease, run by Amicus Therapeutics at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number Of Participants Who Experienced Treatment-related Treatment-emergent Adverse Events (TEAEs) (time frame: Day 1 (after dosing) through Month 12 and follow-up (30 days after last dose)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2021.

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