Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged 12 to <18 Years)
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|ClinicalTrials.gov Identifier: NCT03500094|
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : June 27, 2019
|Condition or disease||Intervention/treatment||Phase|
|Fabry Disease||Drug: migalastat HCl 150 mg||Phase 3|
This is a Phase 3b, 2-stage, open-label, uncontrolled, multicenter study to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of migalastat treatment in pediatric subjects 12 to <18 years of age and weighing ≥ 45 kg (99 pounds) with Fabry disease and with amenable GLA variants. Subjects must be either naïve to enzyme replacement therapy (ERT) or have stopped ERT at least 14 days at the time of screening.
Stage 1 will be a treatment period of approximately 1 month (4 weeks); Stage 2 will be a treatment period of 11 months and a 30-day (untreated) safety follow-up period. There will be no break in treatment between Stages 1 and 2. Prior to Stage 1, there will be a screening period lasting at least 14 days and up to 30 days (or more, if GLA genotyping is required). Stage 1 and 2 together will consist of a 12-month treatment period, and a 30-day safety follow-up period, for a total of approximately 13 months. Subjects may have the option to enroll in a long-term extension study conducted under a separate protocol.
Subjects will be randomly assigned 1:1:1 to 1 of 3 PK sampling groups using interactive response technology (IRT). Four blood samples for determination of migalastat concentrations in plasma will be collected on any one 24 hour period between Day 15 and Day 30 of study drug administration and again at Months 6 and 12.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||October 11, 2018|
|Estimated Primary Completion Date :||September 1, 2020|
|Estimated Study Completion Date :||September 1, 2020|
Experimental: migalastat HCl 150 mg
One migalastat 123 mg capsule equivalent to 150 mg migalastat HCl (herein referred to as "migalastat") will be administered with water every other day for 12 months.
Drug: migalastat HCl 150 mg
migalastat HCl 150 mg capsule
- incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug [ Time Frame: Month 12 ]
- changes in clinical laboratory test results [ Time Frame: baseline over time; up to 12 months ]
- changes in vital signs [ Time Frame: baseline over time; up to 12 months ]
- changes in physical examination findings [ Time Frame: baseline over time; up to 12 months ]
- change in body weight and height [ Time Frame: baseline over time; up to 12 months ]
- changes in ECG results [ Time Frame: baseline over time; up to 12 months ]
- changes in echocardiogram parameters [ Time Frame: baseline to Month 12/ET ]Systolic and diastolic heart function and structure is assessed by ultrasound of the heart.
- change in Tanner stage [ Time Frame: baseline to Month 12/ET ]
- use of concomitant medications [ Time Frame: baseline to Month 12/ET ]
- population pharmacokinetics (popPK) model that describes the relationship between weight and age and migalastat pharmacokinetics in pediatric subjects [ Time Frame: baseline to Month 12/ET ]Four blood samples will be collected on any 1 day during Day 15-30 according to random 1:1:1 assignment to 1 of 3 PK sampling groups: Group 1: 1hr, 1.5hr, 5hr, 6.5hr; Group 2: 1hr, 2.75hr, 5.25hr, 10.75hr; Group 3: 3.25hr, 3.75hr, 8.25hr, 8.75hr; and for all groups: one sample at Month 6 and at Month 12.
- popPK: Cmax [ Time Frame: Day 15-30, Months 6 and 12/ET ]maximum observed plasma concentration
- popPK: Cmin [ Time Frame: Day 15-30, Months 6 and 12/ET ]minimum observed plasma concentration
- popPK: tmax [ Time Frame: Day 15-30, Months 6 and 12/ET ]time to reach Cmax
- popPK: AUC0-T [ Time Frame: Day 15-30, Months 6 and 12/ET ]area under the plasma concentration-time curve from time 0 over the dosing interval (ie, 48 hours)
- popPK: t½ [ Time Frame: Day 15-30, Months 6 and 12/ET ]terminal elimination half-life
- popPK: CLss/F [ Time Frame: Day 15-30, Months 6 and 12/ET ]apparent oral clearance at steady-state concentration
- popPK: Vss/F concentration [ Time Frame: Day 15-30, Months 6 and 12/ET ]apparent oral volume of distribution at steady-state
- change in plasma levels of lyso-Gb3 [ Time Frame: baseline to Months 3, 6, and 12/ET ]
- change in eGFR [ Time Frame: baseline to Months 1, 3, 6, and 12/ET ]
- change in urine protein and albumin levels [ Time Frame: baseline to Months 3, 6, and 12/ET ]
- change in LVMi and other echocardiogram parameters [ Time Frame: baseline to Month 12/ET ]
- change in gastrointestinal signs and symptoms and pain, as measured by e-diary responses (FABPRO-GI and Pain Questionnaire for Clinical Trials [24-hour version]) [ Time Frame: baseline to Month 12/ET ]The FABPRO-GI and Pain Questionnaire for Clinical Trials (24-hour version) consists of 4 questions regarding gastrointestinal signs and symptoms and 2 questions regarding pain relative to the past 24 hours. Subjects will record the frequency and consistency of stools using the Bristol Stool Scale, a pictorial chart and descriptive text for 7 types of stool, ranging from Type 1 (separate hard lumps, like nuts - hard to pass) through Type 7 (watery, no solid pieces - entirely liquid). Subjects will also rate the severity of their worst occurrence of diarrhea, constipation, tummy pain, and overall pain from 0 (none) to 10 (worst possible); for tummy pain, subjects will indicate the location of any tummy pain using a diagram.
- mean Patient Global Impression of Change (PGI-C) values [ Time Frame: Months 3, 6 and 12/ET ]The PGI-C consists of 4 questions regarding diarrhea, abdominal pain, overall pain, and daily living to be answered using a 7-point scale. Subjects rate their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." Subjects will complete the questions by themselves without assistance from their parents or legal guardians.
- change in FPHPQ scores [ Time Frame: baseline to Month 12/ET ]The FPHPQ includes questions about Fabry disease-specific symptoms (eg, sweating, pain, dizziness and tiredness, heat and cold intolerance, swollen eyelids, gastrointestinal symptoms, feeling thirsty, difficulty hearing, ringing or buzzing noise in the ears, and ability and enjoyment to participate in sports). The frequency of these symptoms will be rated using a 5-point Likert scale (always (worse), often, sometimes, seldom, never (better)). Pain intensity is measured on a 10-point scale, numeric responses are given for onset of pain and school days missed, and yes/no questions are posed about difficulty hearing and other problems not specifically mentioned. There are 2 age-specific self-report versions for children 8 to 12 years and 13 to 18 years, respectively.
- change in PedsQL scores [ Time Frame: baseline to Month 12/ET ]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. It consists of 23 items and includes questions about physical functioning, emotional functioning, social functioning, and school functioning relative to the prior 7 days, using a 5-point scale (never (better), almost never, sometimes, often and almost always (worse)). Both parents or legally-authorized representatives and subjects complete the appropriate version of the PedsQL independently of one another. Parents or legally-authorized representatives and subjects may self-administer the questions after introductory instructions are given by study site personnel.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500094
|Contact: Amicus Therapeutics Patient Advocacyemail@example.com|
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|Tampa, Florida, United States, 33606|
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|Philadelphia, Pennsylvania, United States, 19104|
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|Barcelona, Spain, 08035|
|Study Director:||Clinical Research||Amicus Therapeutics|