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Trial record 1 of 1 for:    AT1001-020
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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
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

Tracking Information
First Submitted Date  ICMJE April 9, 2018
First Posted Date  ICMJE April 17, 2018
Last Update Posted Date June 27, 2019
Actual Study Start Date  ICMJE October 11, 2018
Estimated Primary Completion Date September 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
  • 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 percentile [ 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 ]
  • 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 1-15 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 1-15, Months 6 and 12/ET ]
    maximum observed plasma concentration
  • popPK: Cmin [ Time Frame: Day 1-15, Months 6 and 12/ET ]
    minimum observed plasma concentration
  • popPK: tmax [ Time Frame: Day 1-15, Months 6 and 12/ET ]
    time to reach Cmax
  • popPK: AUC0-T [ Time Frame: Day 1-15, 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 1-15, Months 6 and 12/ET ]
    terminal elimination half-life
  • popPK: CLss/F [ Time Frame: Day 1-15, Months 6 and 12/ET ]
    apparent oral clearance at steady-state concentration
  • popPK: Vss/F concentration [ Time Frame: Day 1-15, Months 6 and 12/ET ]
    apparent oral volume of distribution at steady-state
Change History Complete list of historical versions of study NCT03500094 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2018)
  • 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) [ Time Frame: baseline to Month 12/ET ]
  • mean PGI-C values [ Time Frame: Months 2, 6 and 12/ET ]
  • change in FPHPQ scores [ Time Frame: baseline to Month 12/ET ]
  • change in PedsQL scores [ Time Frame: baseline to Month 12/ET ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged 12 to <18 Years)
Official Title  ICMJE 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
Brief Summary This is an open-label study to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of migalastat treatment in pediatric subjects 12 to <18 years of age with Fabry disease and amenable GLA variants.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Fabry Disease
Intervention  ICMJE Drug: migalastat HCl 150 mg
migalastat HCl 150 mg capsule
Other Names:
  • migalastat
  • AT1001
Study Arms  ICMJE 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.
Intervention: Drug: migalastat HCl 150 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 14, 2018)
20
Original Estimated Enrollment  ICMJE
 (submitted: April 9, 2018)
7
Estimated Study Completion Date  ICMJE September 1, 2020
Estimated Primary Completion Date September 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Willing and able to provide written consent or assent (subject and parent/legal guardian, as applicable)
  • Male or female between 12 and <18 years of age diagnosed with Fabry disease
  • Confirmed GLA variant that has shown to be responsive to AT1001 in vivo
  • Subject weighs at least 45 kg (99 pounds) at screening
  • Subject has never been treated with ERT or has not received ERT for 14 days prior to screening
  • Subject has at least one complication (ie, laboratory abnormality and/or sign/symptom) of Fabry disease
  • Subject is able to swallow study medication whole
  • Women/girls who can become pregnant and all males agree to be sexually abstinent or use medically accepted methods of birth control during the study and for 30 days after study completion

Exclusion Criteria

  • Has moderate or severe renal impairment (eGFR <60 ml/min/1.73 m2 at screening)
  • Has advanced kidney disease requiring dialysis or kidney transplantation
  • History of allergy or sensitivity to study medication (including excipients) or other iminosugars (eg, miglustat, miglitol)
  • Has received any gene therapy at any time or anticipates starting gene therapy during the study period
  • Requires treatment with Glyset (miglitol), Zavesca (miglustat) within 6 months before screening or throughout the study
  • Requires treatment with Replagal (agalsidase alfa), or Fabrazyme (agalsidase beta) within 14 days before screening or throughout the study
  • Subject is treated or has 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 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 breast-feeding
  • Otherwise unsuitable for the study in the opinion of the investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amicus Therapeutics Patient Advocacy 609-662-2000 clinicaltrials@amicusrx.com
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03500094
Other Study ID Numbers  ICMJE AT1001-020
2017-000146-21 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Amicus Therapeutics
Study Sponsor  ICMJE Amicus Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Research Amicus Therapeutics
PRS Account Amicus Therapeutics
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP