safety, pharmacokinetics, pharmacodynamics, and efficacy of migalastat in pediatric subjects (aged 12 to <18 years)

Conditions: Fabry Disease

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.

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

Keywords: lysosomal storage disease migalastat at1001 galafold