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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amicus Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2025-12-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Amicus Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Pharmacodynamic

to characterize the pharmacokinetics (PK) and to confirm pediatric dose regimens predicted to provide plasma migalastat exposure levels similar to adolescents and adults in pediatric subjects aged 6 to < 12 years old and 2 to < 6 years old with Fabry disease and who have the gene encoding α-galactosidase A (α-Gal A) (GLA) variants amenable to treatment with migalastat
to evaluate the safety of migalastat treatment in pediatric subjects diagnosed with Fabry disease and who have GLA variants amenable to treatment with migalastat

Conditions and MedDRA coding

Fabry disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001194-PIP01-11

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. 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)
2. 2. 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.
3. 3. Subject has a GLA variant documented in his/her medical record that is amenable to migalastat prior to Visit 2. • For subjects without a known GLA variant, an amenable GLA genotyping result from the local laboratory must be received prior to Visit 2.
4. 4. Subject has not received ERT (eg, Replagal® [agalsidase alfa] or Fabrazyme® [agalsidase beta]) for at least 14 days prior to Baseline visit.
5. 5. Subject has at least 1 documented complication (ie, historical or current laboratory abnormality or sign/symptom) of Fabry disease, including but not limited to: a. corneal whorls b. neuropathic pain and/or acroparesthesia and/or acute crises persisting or recurring at least twice over the previous 3 months or longer, or requiring management with analgesia c. Fabry disease-related gastrointestinal signs and symptoms (eg, diarrhea, abdominal pain) persisting or recurring at least twice over the previous 3 months or longer d. hypohidrosis (present for at least 3 months) e. left ventricular mass index (LVMi) above the normal range for age and sex f. rhythm and/or conduction disturbances, for example: − episode of tachycardia or bradycardia, − arrhythmia, or; − abnormal PR, QRS, or QT interval g. reduced estimated glomerular filtration rate (eGFR) (using the Schwartz formula) for age and sex, or hyperfiltration (> 135 mL/min/1.73 m2) h. proteinuria or albuminuria in a spot urine (early morning preferable) or as determined by the investigator i. elevated plasma globotriaosylsphingosine (lyso-Gb3) j. hearing impairment and/or tinnitus k. transient ischemic attack/stroke
6. 6. 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 9

1. 1. Subject has moderate or severe renal impairment (eGFR < 60 mL/min/1.73 m2 at Visit 1 [screening]).
2. 2. Subject has advanced kidney disease requiring dialysis or kidney transplantation.
3. 3. Subject has a history of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol).
4. 4. Subject 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).
5. 5. Subject has received any gene therapy at any time or anticipates starting gene therapy during the study period.
6. 6. Subject requires treatment with Glyset® (miglitol) or Zavesca® (miglustat), within 6 months before Visit 1 (screening) or throughout the study.
7. 7. Subject 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.
8. 8. Female subject is pregnant or breastfeeding or is planning to become pregnant during the study period.
9. 9. In the opinion of the investigator, the subject and/or parent or legally-authorized representative is unlikely or unable to comply with the study requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Pharmacokinetics: Derived pharmacokinetic parameters for dosing confirmation will be estimated based on concentrations of migalastat in plasma.
2. Safety: incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug; change from baseline over time in clinical laboratory test results; change from baseline over time in vital signs;change from baseline over time in physical examination findings
3. change from baseline over time in body weight and height; change from baseline over time in ECG results; change from baseline to Month 12/ET in echocardiogram parameters; change from baseline to Month 12/ET in Tanner stage (for female subjects aged ≥ 8 years and male subjects aged ≥ 9 years)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amicus Therapeutics Inc.

Sponsor organisation

Amicus Therapeutics Inc.

Address

47 Hulfish Street

City

Princeton

Postcode

08542-3713

Country

United States

Scientific contact point

Organisation

Amicus Therapeutics Inc.

Contact name

Tiffany Patrick

Public contact point

Organisation

Amicus Therapeutics Inc.

Contact name

Tiffany Patrick

Third parties 8

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications