Clinical trial NCT03737214: A Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease
Official title: A Multi-center, Open-label, Uncontrolled, Single-arm, Extension Study to Determine the Long-term Safety and Tolerability of Oral Lucerastat in Adult Subjects With Fabry Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Fabry Disease
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-11-09
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multi-center, open-label, uncontrolled, single-arm, extension study
Primary purpose: TREATMENT

Brief summary: A study to determine the long-term safety and tolerability of oral lucerastat in adult subjects with Fabry disease. This study includes a sub-study evaluating kidney Gb3 inclusions (and other histologic lesions) in male participants with classic Fabry disease who have been treated for at least 2 years with lucerastat monotherapy in study ID-069A302.

Detailed description: Study ID-069A302 will continue at each site until lucerastat is commercially available in the respective country or until all subjects have reached Month 24 (for subjects participating only in Stage 1) or Month 48 (for subjects participating in Stages 1 and 2) or Month 72 (for subjects participating in Stages 1, 2 and 3), whichever is earliest.

Eligibility criteria: Inclusion Criteria:

* Signed ICF prior to any study-mandated procedure;
* Subject completed the 6-month, double-blind treatment period in study ID 069A301
* Woman of childbearing potential only if agreement 1) to follow a specified contraception scheme, 2) to undertake monthly urine pregnancy tests.
* Fertile male only if agreement 1) to use a condom, 2) to not father a child.

Exclusion Criteria:

* Pregnant / planning to be become pregnant or lactating subject;
* Subject considered to be at high risk of developing clinical signs of organ involvement within the time period of the study, as per investigator judgment;
* Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results as per investigator judgment.

In addition, the subject must not be enrolled in study ID-069A302 if at any time during study ID-069A301, one of the following criteria was met:

* Subject's eGFR per the Chronic Kidney Disease Epidemiology Collaboration creatinine equation \< 15 mL/min/1.73 m2;
* Subject experienced an event of acute kidney injury Common Terminology Criteria for Adverse Event (CTCAE) grade 2 or above;
* Subject experienced an event of stroke CTCAE grade 3 or above;
* Subject experienced an event of heart failure leading to in-patient hospitalization or prolongation of ongoing hospitalization.

Primary outcomes:
measure: Treatment-emergent adverse events (AEs)
timeFrame: From enrollment to Follow-up 1 (FU1) visit; duration: for up to 73 months (72 months OL treatment period plus 1 month Follow-up)
Secondary outcomes:
Other outcomes:
measure: Treatment-emergent serious adverse events (SAEs)
timeFrame: From enrollment to Follow-up 1 (FU1) visit; duration: for up to 73 months (72 months OL treatment period plus 1 month Follow-up)
measure: Subject estimated glomerular filtration rate (eGFR) slope
timeFrame: From baseline to Month 24, Month 48 and Month 72 (duration: up to 6 years)
measure: Change in left ventricular mass index (LVMI)
timeFrame: From baseline to Month 24, Month 48 and Month 72 (duration: up to 6 years)
measure: Change in plasma globotriaosylceramide (Gb3)
timeFrame: From baseline to Month 24, Month 48 and Month 72 (duration: up to 6 years)
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Nephrology Research Clinic
state: Alabama
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Gainesville
country: United States
facility: University of Florida Clinical and Translational Science Institute, UF Clinical Research Center
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center - Dept of Pediatrics
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Stead Family Children's Hospital - Division of Medical Genetics
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Infusion Associates
state: Michigan
city: Philadelphia
country: United States
facility: University of Pennsylvania - Dept of Medicine
state: Pennsylvania
city: Greenville
country: United States
facility: Greenwood Genetics Center
state: South Carolina
city: Dallas
country: United States
facility: Renal Disease Research Institute LLC
state: Texas
city: Dallas
country: United States
facility: Baylore University Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Division of Medical Genetics, Clinical Genetics Research
state: Utah
city: Fairfax
country: United States
facility: Lysosomal and Rare Disorders Research and Treatment Center, Inc.
state: Virginia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital - Department of Nephrology
city: Perth
country: Australia
facility: Royal Perth Hospital, Department of Nephrology
city: Vienna
country: Austria
facility: Medizinische Universität Wien, Universitätsklinik für Innere Medizin III, Klinische Abteilung für Nephrologie und Dialyse
city: Ghent
country: Belgium
facility: University Hospital Ghent (UZ Ghent)
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg, Leuven (UZ Leuven)
city: Calgary
country: Canada
facility: University of Calgary - Heritage Medical Research Clinic
city: London
country: Canada
facility: London Health Sciences CTR, Victoria Hospital
city: Montréal
country: Canada
facility: Research Center, Hôpital du Sacré-Coeur de Montréal
city: Vancouver
country: Canada
facility: Vancouver General Hospital - Adult Metabolic Diseases Clinic
city: Winnipeg
country: Canada
facility: Children's Hospital Research Institute of Manitoba
city: Garches
country: France
facility: Raymond Poincaré Hosp - Med Genetics Dept
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin - Charité Campus Mitte
city: Hochheim
country: Germany
facility: SphinCS GmbH
city: Müllheim
country: Germany
facility: Nephrologicum Markgräflerland MVZ GmbH
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Amsterdam
country: Netherlands
facility: Hospital Academisch Medisch Centrum - Department of Internal Medicine, Div. Endrocrinology and Metabolism
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Kraków
country: Poland
facility: Clinic of Immunological Diseases and Blood Coagulability Cracow University Hospital
city: Warsaw
country: Poland
facility: Narodowy Instytut Kardiologii Stefana kardynała Wyszyńskiego - Państwowy Instytut Badawczy
city: Warsaw
country: Poland
facility: The Children's Memorial Health Institute, Department of Pediatric, Nutrition and Metabolic Diseases
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital - Unit of Inherited Metabolic Disorders and Rare Diseases
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge / Nephrology Dpt
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal. Servicio de Medicina Interna
city: Zaragoza
country: Spain
facility: Hospital Quironsalud Zaragoza
city: Zürich
country: Switzerland
facility: Psychiatrische Universitätsklinik Zürich
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust Lysosomal Storage Disorder Unit; Department of Hematology
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery
city: Manchester
country: United Kingdom
facility: Salford Hospital
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wanner C, Kimonis V, Politei J, Warnock DG, Uceyler N, Frey A, Cornelisse P, Hughes D. Understanding and modifying Fabry disease: Rationale and design of a pivotal Phase 3 study and results from a patient-reported outcome validation study. Mol Genet Metab Rep. 2022 Mar 26;31:100862. doi: 10.1016/j.ymgmr.2022.100862. eCollection 2022 Jun.