Migalastat for children aged 2 to <12 with Fabry disease and amenable GLA variants

An Open-label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of 12 Month Treatment With Migalastat in Pediatric Subjects (Aged 2 to < 12 Years) With Fabry Disease and Amenable GLA Variants

This test gives the oral drug migalastat to children aged 2 to <12 who have Fabry disease with GLA variants that respond to the drug to see if it is safe and how it acts in their bodies.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 2 Years to 11 Years
• Sex: All
• Sponsor: Amicus Therapeutics (industry)
• Locations: 11 sites (Atlanta, Georgia and 10 other locations)
• Trial ID: NCT06904261 on ClinicalTrials.gov

What this trial studies

This Phase 3b, open-label, uncontrolled, multicenter study will treat children aged 2 to <12 with Fabry disease and amenable GLA variants with oral migalastat 20 mg for 12 months divided into an approximately 3-month Stage 1 and a 9-month Stage 2 with no break between stages. Subjects must be ERT-naïve or have stopped enzyme replacement therapy at least 14 days before baseline. Participants are randomized 1:1:1 into three pharmacokinetic (PK) sampling groups with intensive PK sampling between Days 15–30 and at Month 6 and trough PK samples at Months 6 and 12. The study tracks safety, pharmacokinetics, pharmacodynamics, and efficacy measures over the treatment period, with a 30-day safety follow-up after any discontinuation.

Who should consider this trial

Good fit: Children aged 2 to <12 with a documented GLA variant shown to be amenable to migalastat, who are ERT-naïve or have stopped ERT at least 14 days prior, with parent/guardian consent and any required assent.

Not a fit: Patients whose GLA variants are not amenable to migalastat, those outside the 2 to <12 age range, or those with medical contraindications are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, this could provide an oral treatment option for young children with amenable GLA variants that may reduce disease activity and offer an alternative to regular intravenous enzyme replacement.

How similar studies have performed: Adult clinical trials of migalastat showed benefit for patients with amenable GLA variants and supported approval in adults, but pediatric data are limited and this study aims to expand evidence in children.

Eligibility criteria

Inclusion Criteria

* Male or female subjects, diagnosed with Fabry disease who are between ages 2 and \< 12 years at randomization (subjects aged 11 years must have birthdays \> 30 days after randomization)
* Subject's parent or legally authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent, if applicable.
* Subject has a GLA variant documented in his/her medical record that is amenable to migalastat prior to Visit 2.
* Subject has not received ERT (eg, Replagal® \[agalsidase alfa\] or Fabrazyme® \[agalsidase beta\]) for at least 14 days prior to Baseline visit.
* Subject has at least 1 documented complication (ie, historical or current laboratory abnormality or sign/symptom) of Fabry disease
* If of reproductive potential, both male and female subjects agree to use a medically accepted method of contraception throughout the duration of the study and for up to 30 days after their last dose of migalastat.

Exclusion Criteria

* Has moderate or severe renal impairment (eGFR \< 60 mL/min/1.73 m2 at Visit 1 \[screening\]).
* Has advanced kidney disease requiring dialysis or kidney transplantation.
* History of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol).
* Has received any investigational/experimental drug, biologic, or device within 30 days or 5 half-lives of the investigational product (whichever is longer) before Visit 1 (screening).
* Has received any gene therapy at any time or anticipates starting gene therapy during the study period.
* Requires treatment with Glyset (miglitol) or Zavesca (miglustat), within 6 months before Visit 1(screening) or throughout the study.
* Has any intercurrent illness or condition at Visit 1 (screening) or Visit 2 (baseline) that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study.
* Pregnant or breastfeeding
* Otherwise unsuitable for the study in the opinion of the investigator

Where this trial is running

Atlanta, Georgia and 10 other locations

• Emory Genetics — Atlanta, Georgia, United States (RECRUITING)
• University of Minnesota Masonic Children's Hospital — Minneapolis, Minnesota, United States (NOT_YET_RECRUITING)
• Atrium Health Levine Children's Hospital — Charlotte, North Carolina, United States (RECRUITING)
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (RECRUITING)
• UPMC Children's Hospital of Pittsburgh — Pittsburgh, Pennsylvania, United States (NOT_YET_RECRUITING)
• Lysosomal and Rare Disorders Research and Treatment Center, Inc. — Fairfax, Virginia, United States (RECRUITING)
• Universitair Ziekenhuis (UZ) Leuven — Leuven, Vlaams-Brabant, Belgium (NOT_YET_RECRUITING)
• Universitäetsklinikum Müenster (UKM) Klinik für Kinder- und Jugendmedizin - Allgemeine Paediatrie — Münster, North Rhine-Westphalia, Germany (RECRUITING)
• Hospital Universitario de la Paz — Madrid, Madrid, Spain (RECRUITING)
• Great Ormond Street Hospital for Children NHS Foundation Trust — London, United Kingdom (NOT_YET_RECRUITING)
• Manchester University NHS Foundation Trust — Manchester, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Amicus Therapeutics Patient Advocacy

Conditions: Fabry Disease, migalastat, AT1001, Galafold, lysosomal disease