Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease (MODIFY)

A Multicenter, dOuble-blind, ranDomized, Placebo-controlled, Parallel-group Study to Determine the effIcacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With FabrY Disease

This study aimed to determine the efficacy and safety of lucerastat oral monotherapy in adult subjects with Fabry disease.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Lucerastat; Drug: Placebo

Detailed Description

The primary objective of this prospective, multicenter, double-blind, randomized, placebo-controlled, parallel group, Phase 3 study is to determine the effect of oral lucerastat monotherapy on neuropathic pain in subjects with Fabry disease (FD) through daily collection of patient-reported outcomes with an electronic diary.

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia, 3050
    • Royal Melbourne Hospital - Department of Nephrology
  • Perth, Australia, 6000
    • Royal Perth Hospital, Department of Nephrology
• Austria
  • Vienna, Austria, 1090
    • Allgemeines Krankenhaus der Stadt Wien - Universitätsklinik für Innere Medizin III - Klinische Abteilung für Nephrologie und Dialyse
• Belgium
  • Ghent, Belgium, 9000
    • University Hospital Ghent
  • Leuven, Belgium, 3000
    • University Hospital Leuven
• Canada
  • Calgary, Canada, T2M 0L6
    • M.A.G.I.C Clinic Ltd
  • Halifax, Canada, B3H 3A7
    • Queen Elizabeth II Health Sciences Center - Halifax Infirmary - Division of Nephrology
  • Montréal, Canada, H4J 1C5
    • Research Center, Hôpital du Sacré-Coeur de Montréal
  • Vancouver, Canada, V5Z 1M9
    • Vancouver Hospital & Health Sciences - Vancouver General Hospital
  • Winnipeg, Canada, R3A 1S1
    • Health Sciences Center Winnipeg
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre - Victoria Hospital
• Germany
  • Berlin, Germany, 13353
    • Charite Campus Virchow-Klinikum - Nephrologie und Internistische Intensivmedizin
  • Hochheim, Germany, 65239
    • SphinCS GmbH
  • Mühlheim, Germany, 79379
    • Fachinternistische Gemeinschaftspraxis Markgräferland
  • Würzburg, Germany, 97080
    • Medizinische Klinik und Poliklinik I der Universität - Schwerpunkt Nephrologie
• Ireland
  • Dublin, Ireland, DD7 R2WY
    • Hosp Alma Mater Studiorum
• Italy
  • Monza, Italy, 20900
    • ASST Monza, Hospital San Gerardo, Nephrology
  • Naples, Italy, 80131
    • University of Naples Federico II (Nephrology)
• Netherlands
  • Amsterdam, Netherlands, 22660
    • Hospital Academisch Medisch Centrum - Department of Internal Medicine Div. Endrocrinology and Metabolism
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital Helse Bergen HF
• Poland
  • Krakow, Poland, 31-066
    • University Hospital in Cracow - Dep. of of Allergies and Immunology
  • Warsaw, Poland, 04-628
    • Cardinal Wyszynski Institute of Cardiology
  • Warsaw, Poland, 04-730
    • Department of Pediatric Nutrition and Metabolic Diseases; The Children's Memorial Health Institute
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge; Hospitalet de Llobregat
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal. Servicio de Medicina Interna
  • Zaragoza, Spain, 50012
    • Hospital Quironsalud Zaragoza
• Switzerland
  • Zurich, Switzerland, 8032
    • Universität Zürich Psychiatrische Universitätsklinik
• United Kingdom
  • Birmingham, United Kingdom, B15 2WB
    • University Hospital Birmingham NHS Foundation Trust - Center for Rare Diseases
  • London, United Kingdom, NW3 2QG
    • The Royal Free Hospital, Department of Haematology Royal Free London NHS Foundation Trust
  • London, United Kingdom, WC1N3BG
    • National Hospital For Neurology and Neurosurgery
  • Salford, United Kingdom, M6 8HD
    • Salford Royal (Hope) Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham - Nephrology Research Clinic
  • California
    • Irvine, California, United States, 92696
      • University of California Irvine
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine - Division of Nephrology, Hypertension & Renal Transplantation
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine; Department of Human Genetics
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Stead Family Children's Hospital - Division of Medical Genetics
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • Infusion Associates
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh (UPMC)
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenwood Genetic Center
  • Texas
    • Dallas, Texas, United States, 75226
      • Research Baylor Institute of Metabolic Disease
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah - Division of Medical Genetics
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal and Rare Disorders Research and Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed and dated ICF prior to any study-mandated procedure;
2. Male or female adult subjects;
3. FD diagnosis confirmed with local genetic test results;
4. Fabry-associated neuropathic pain, as defined by the subject, in the last 3 months prior to screening;

5. Enzyme replacement therapy (ERT) status:

   1. Subject never treated with ERT; or
   2. Subject has not received ERT for at least 6 months prior to screening; or
   3. Subject treated with ERT since at least 12 months at the time of the screening visit, and agreeing to stop ERT for approximately 8 months.
6. A woman of childbearing potential is eligible only under certain conditions, e.g. taking contraceptive measures.
7. Subjects with moderate or severe neuropathic pain during the screening period.

Exclusion Criteria:

1. Pregnant, planning to be become pregnant, or lactating subject.
2. Severe renal insufficiency (eGFR < 30 mL/min/1.73 m2) at screening.
3. Subject on regular dialysis for the treatment of chronic kidney disease.
4. Known and documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within 6 months prior to screening.
5. Clinically significant unstable cardiac disease (e.g. uncontrolled symptomatic arrhythmia, congestive heart failure NYHA class III or IV).
6. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo capsules are identical in appearance to the lucerastat capsules, and contain inactive excipients; 4 capsules b.i.d.; dose adjusted for renal function.
Experimental: Lucerastat	Drug: Lucerastat; Hard gelatin capsules containing 250 mg of lucerastat and inactive excipients; 1000 mg (4 capsules) twice daily (b.i.d.); dose adjusted for renal function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline to Month 6 in the "modified" Brief Pain Inventory-Short Form 3 (BPI-SF3) score of "neuropathic pain at its worst in the last 24 hours"	From baseline to Month 6 (duration: 6 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline to Month 6 in the 11-point Numerical Rating Scale (NRS-11) score of "abdominal pain at its worst in the last 24 hours" in subjects with GI symptoms at baseline.	From baseline to Month 6 (duration: 6 months)
Change from baseline to Month 6 in the number of days with at least one stool of a Bristol Stool Scale (BSS) consistency Type 6 or 7 in subjects with GI symptoms at baseline.	From baseline to Month 6 (duration: 6 months)
Change from baseline to Month 6 in plasma globotriaosylceramide (Gb3).	From baseline to Month 6 (duration: 6 months)

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2018
• Primary Completion (Actual): August 17, 2021
• Study Completion (Actual): September 2, 2021

Study Registration Dates

• First Submitted: January 16, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 7, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 5, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: ID-069A301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No