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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 : February 20, 2019
Sponsor:
Information provided by (Responsible Party):
Amicus Therapeutics

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.

Condition or disease Intervention/treatment Phase
Fabry Disease Drug: migalastat HCl 150 mg Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Other Names:
  • migalastat
  • AT1001




Primary Outcome Measures :
  1. incidence of TEAEs, SAEs, and AEs leading to discontinuation of study drug [ Time Frame: Month 12 ]
  2. changes in clinical laboratory test results [ Time Frame: baseline over time; up to 12 months ]
  3. changes in vital signs [ Time Frame: baseline over time; up to 12 months ]
  4. changes in physical examination findings [ Time Frame: baseline over time; up to 12 months ]
  5. change in body weight and height [ Time Frame: baseline over time; up to 12 months ]
  6. changes in ECG results [ Time Frame: baseline over time; up to 12 months ]
  7. 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.

  8. change in Tanner stage [ Time Frame: baseline to Month 12/ET ]
  9. use of concomitant medications [ Time Frame: baseline to Month 12/ET ]
  10. 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.

  11. popPK: Cmax [ Time Frame: Day 15-30, Months 6 and 12/ET ]
    maximum observed plasma concentration

  12. popPK: Cmin [ Time Frame: Day 15-30, Months 6 and 12/ET ]
    minimum observed plasma concentration

  13. popPK: tmax [ Time Frame: Day 15-30, Months 6 and 12/ET ]
    time to reach Cmax

  14. 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)

  15. popPK: t½ [ Time Frame: Day 15-30, Months 6 and 12/ET ]
    terminal elimination half-life

  16. popPK: CLss/F [ Time Frame: Day 15-30, Months 6 and 12/ET ]
    apparent oral clearance at steady-state concentration

  17. popPK: Vss/F concentration [ Time Frame: Day 15-30, Months 6 and 12/ET ]
    apparent oral volume of distribution at steady-state


Secondary Outcome Measures :
  1. change in plasma levels of lyso-Gb3 [ Time Frame: baseline to Months 3, 6, and 12/ET ]
  2. change in eGFR [ Time Frame: baseline to Months 1, 3, 6, and 12/ET ]
  3. change in urine protein and albumin levels [ Time Frame: baseline to Months 3, 6, and 12/ET ]
  4. change in LVMi and other echocardiogram parameters [ Time Frame: baseline to Month 12/ET ]
  5. 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.

  6. 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.

  7. 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.

  8. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Contacts
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Contact: Amicus Therapeutics Patient Advocacy 609-662-2000 clinicaltrials@amicusrx.com

Locations
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United States, Florida
University of South Florida Recruiting
Tampa, Florida, United States, 33606
United States, Georgia
Emory University Division of Medical Genetics Recruiting
Decatur, Georgia, United States, 30033
United States, Missouri
University of Missouri Recruiting
Columbia, Missouri, United States, 65201
United States, Ohio
Cincinnati Children's Hospital Recruiting
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
United States, Virginia
Lysosomal & Rare Disorders Research & Treatment Center Recruiting
Fairfax, Virginia, United States, 22030
Sponsors and Collaborators
Amicus Therapeutics
Investigators
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Study Director: Clinical Research Amicus Therapeutics

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Responsible Party: Amicus Therapeutics
ClinicalTrials.gov Identifier: NCT03500094     History of Changes
Other Study ID Numbers: AT1001-020
2017-000146-21 ( EudraCT Number )
First Posted: April 17, 2018    Key Record Dates
Last Update Posted: February 20, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amicus Therapeutics:
Lysosomal storage disease
migalastat
AT1001

Additional relevant MeSH terms:
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Fabry Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
1-Deoxynojirimycin
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action