Clinical trial • Phase III • Rare Disease|Cardiology|Nephrology
venglustat for Fabry disease
Phase III trial of venglustat for Fabry disease.
Overview
- Trial Therapeutic Area
- Rare Disease|Cardiology|Nephrology
- Trial Disease
- Fabry disease
- Trial Stage
- Phase III
- Drug Modality
- Small molecule|Peptide/protein/enzyme
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 26-04-2024
- First CTIS Authorization Date
- 20-06-2024
Trial design
Randomised, open-label, fabrazyme (agalsidase beta) iv infusion, max daily amount reported as 1 mg/kg; replagal (agalsidase alfa) iv infusion, max daily amount reported as 0.2 mg/kg; galafold (migalastat) oral capsules, 123 mg (authorized comparator). scheduling details not specified in the ctis data.-controlled Phase III trial across 22 sites in Austria, Greece, Spain and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Fabrazyme (agalsidase beta) IV infusion, max daily amount reported as 1 mg/kg; Replagal (agalsidase alfa) IV infusion, max daily amount reported as 0.2 mg/kg; Galafold (migalastat) oral capsules, 123 mg (authorized comparator). Scheduling details not specified in the CTIS data.
- Target Sample Size
- 53
- Trial Duration For Participant
- 540
Eligibility
Recruits 53 Vulnerable population is selected. A signed informed consent must be provided prior to any study-related procedures. Participants are adults (aged 18–65); no provisions for assent of minors are provided in the criteria..
- Pregnancy Exclusion
- Contraception for male or female participants: not pregnant or breastfeeding; no sperm donating for male participant.
- Vulnerable Population
- Vulnerable population is selected. A signed informed consent must be provided prior to any study-related procedures. Participants are adults (aged 18–65); no provisions for assent of minors are provided in the criteria.
Inclusion criteria
- {"criterion_text":"- Male and female participants aged 18 to 65 with previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease.\n- Participants may be receiving treatment with agalsidase alfa, agalsidase beta, or migalastat, or may be untreated.\n- Left ventricular hypertrophy.\n- Contraception for male or female participants: not pregnant or breastfeeding; no sperm donating for male participant.\n- A signed informed consent must be provided prior to any study-related procedures."}
Exclusion criteria
- {"criterion_text":"- History of transient ischemic attack, stroke, myocardial infarction, heart failure, major cardiovascular surgery or kidney transplantation.\n- Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID-19 requiring hospitalization within 6 months of enrollment.\n- History of drug and/or alcohol abuse.\n- Moderate to severe hepatic impairment.\n- History of or active hepatobiliary disease.\n- Liver enzymes (alanine aminotransferase/aspartate aminotransferase) or total bilirubin >2 times the upper limit of normal.\n- Strong or moderate inducers or inhibitors of cytochrome P450 CYP3A4 within 14 days or 5 half-lives, whichever is longer, prior to randomization.\n- Known contraindication to undergoing MRI or known hypersensitivity to gadolinium-based contrast agents.\n- History of seizures currently requiring treatment.\n- Underlying medical condition that may cause or contribute to left ventricular hypertrophy.\n- Asymmetric hypertrophy by cardiac MRI at screening if considered by central reader to be not related to Fabry disease.\n- Advanced cardiac fibrosis, defined as significant late gadolinium enhancement affecting 3 or more segments involving >50% of myocardial thickness on screening cardiac MRI.\n- History of clinically significant cardiac arrhythmia. Atrial fibrillation that is well controlled on a stable medical regimen for at least 12 months is not an exclusion if the CHA2DS2-VASc score is 0 for males or 1 for females.\n- Estimated glomerular filtration rate <45 mL/min/1.73m2.\n- Presence of severe depression as measured by Beck’s Depression Inventory (BDI)- II >28 and/or a history of an untreated, unstable major affective disorder within 1 year of the screening visit.\n- Patients with hepatitis C, HIV, or hepatitis B infection."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Slope of left ventricular mass index as measured by cardiac magnetic resonance imaging (MRI) (central reading)","definition_or_measurement_approach":"Left ventricular mass index slope measured by cardiac MRI with central reading (change over time / slope over 18 months)."}
Secondary endpoints
- {"endpoint_text":"- Slope of estimated glomerular filtration rate (eGFR) as assessed by the chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine equation","definition_or_measurement_approach":"Slope of eGFR over time calculated using the CKD-EPI creatinine equation."}
- {"endpoint_text":"- Change in T1 relaxation time, measured by cardiac MRI (central reading)","definition_or_measurement_approach":"T1 relaxation time change measured by cardiac MRI with central reading."}
- {"endpoint_text":"- Change in global longitudinal strain, measured by echocardiography (central reading)","definition_or_measurement_approach":"Change in global longitudinal strain measured by echocardiography with central reading."}
- {"endpoint_text":"- Percent Change in tiredness component of FDPRO","definition_or_measurement_approach":"Percent change from baseline in the tiredness component of the FD-PRO patient-reported outcome instrument."}
- {"endpoint_text":"- Percent Change in swelling in lower extremities component of FD-PRO","definition_or_measurement_approach":"Percent change from baseline in the lower extremity swelling component of the FD-PRO patient-reported outcome instrument."}
- {"endpoint_text":"- Number of participants with adverse event (AE) and serious adverse event (SAE)","definition_or_measurement_approach":"Count of participants experiencing AEs and SAEs during the study period."}
- {"endpoint_text":"- Change in Beck Depression Inventory-II (BDI-II) score","definition_or_measurement_approach":"Change from baseline in BDI-II score."}
- {"endpoint_text":"- Change in the lens clarity by ophthalmological examination","definition_or_measurement_approach":"Change from baseline in lens clarity assessed by ophthalmological exam."}
- {"endpoint_text":"- Plasma venglustat concentrations at prespecified visits over the study duration","definition_or_measurement_approach":"Plasma concentrations of venglustat measured at prespecified visits (PK sampling)."}
Recruitment
- Registry Or Advocacy Recruitment
- True, Fabry registry (document: L1-sis-icf-fabry-registry-cz)
- Digital Remote Recruitment
- True, use of direct-to-patient services and recruitment advertisements/materials (documents indicate direct-to-patient service and online/advertisement materials).
- Planned Sample Size
- 53
- Recruitment Window Months
- 67
- Consent Approach
- Signed informed consent required prior to any study-related procedures ("A signed informed consent must be provided prior to any study-related procedures."). Participant consent forms and related ICFs (including partner/pregnancy ICFs) are provided; translations and redacted ICFs are available for multiple countries/languages (documents show ICFs and redacted ICFs in EN, ES, FR, DE, NL, PL, EL, IT, NO, CS/CZ, DA and others). No assent process for minors is described (participants are adults 18–65).
Methods
- Country-specific recruitment materials (posters, brochures, informational leaflets) as provided in recruitment documents (examples: brochures and posters in ES, IT, DE, PL, NL, DA, EN).
- Advertisements and patient outreach letters (documented recruitment-arrangements and recruitment-material files).
- Direct-to-patient service / home health approaches (documented through sponsor third parties providing Direct to Patient Service and Home Health Care / Nursing).
- Use of patient registry linkage for recruitment in at least one country (see Fabry registry document for Czechia).
- Waiver documents for recruitment arrangements in multiple countries (K1 recruitment-arrangements-en-waiver files).
Geography
- Total Number Of Sites
- 22
- Total Number Of Participants
- 57
Austria
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 25-06-2024
- Processing Time Days
- 33
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Medical University Of Graz
- Department Name
- Universitatsklinik fur Innere Medizin Kardiologie
- Principal Investigator Name
- Nicolas Verheyen
- Principal Investigator Email
- nicolas.verheyen@medunigraz.at
- Contact Person Name
- Nicolas Verheyen
- Contact Person Email
- nicolas.verheyen@medunigraz.at
Greece
- Earliest CTIS Part Ii Submission Date
- 18-07-2024
- Latest Decision Or Authorization Date
- 22-08-2024
- Processing Time Days
- 35
- Number Of Sites
- 3
- Number Of Participants
- 5
Sites
- Site Name
- University General Hospital Of Heraklion
- Department Name
- Nephrology Dept
- Principal Investigator Name
- Konstantinos Stylianou
- Principal Investigator Email
- kstylianu@gmail.com
- Contact Person Name
- Konstantinos Stylianou
- Contact Person Email
- kstylianu@gmail.com
- Site Name
- Laiko General Hospital Of Athens
- Department Name
- Department Of Nephrology And Renal Transplantation
- Principal Investigator Name
- Ioannis Boletis
- Principal Investigator Email
- laikneph@laiko.gr
- Contact Person Name
- Ioannis Boletis
- Contact Person Email
- laikneph@laiko.gr
- Site Name
- University General Hospital Attikon
- Department Name
- 2nd Neurology Dept
- Principal Investigator Name
- Georgios Tsivgoulis
- Principal Investigator Email
- tsivgoulisgiorg@yahoo.gr
- Contact Person Name
- Georgios Tsivgoulis
- Contact Person Email
- tsivgoulisgiorg@yahoo.gr
Spain
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 21-06-2024
- Processing Time Days
- 29
- Number Of Sites
- 3
- Number Of Participants
- 5
Sites
- Site Name
- Hospital Alvaro Cunqueiro
- Department Name
- Complexo Hospitalario Universitario de Vigo. Servicio de Medicina Interna
- Principal Investigator Name
- Alberto Jose Rivera
- Principal Investigator Email
- riveraalberto0@gmail.com
- Contact Person Name
- Alberto Jose Rivera
- Contact Person Email
- riveraalberto0@gmail.com
- Site Name
- Hospital General Universitario Dr. Balmis
- Department Name
- Servicio de Cardiologia. Consultas externas, 5ª planta. Ensayos clinicos de Cardiologia
- Principal Investigator Name
- Vicente Eduardo Climent
- Principal Investigator Email
- vcliment@coma.es
- Contact Person Name
- Vicente Eduardo Climent
- Contact Person Email
- vcliment@coma.es
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Servicio de Cardiologia
- Principal Investigator Name
- Javier Bermejo
- Principal Investigator Email
- javier.bermejo@salud.madrid.org
- Contact Person Name
- Javier Bermejo
- Contact Person Email
- javier.bermejo@salud.madrid.org
Czechia
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 24-06-2024
- Processing Time Days
- 32
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Vseobecna Fakultni Nemocnice V Praze
- Department Name
- II. interni klinika
- Principal Investigator Name
- Gabriela Dostalova
- Principal Investigator Email
- gabriela.dostalova@vfn.cz
- Contact Person Name
- Gabriela Dostalova
- Contact Person Email
- gabriela.dostalova@vfn.cz
Norway
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 21-06-2024
- Processing Time Days
- 29
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Helse Bergen HF
- Department Name
- Klinisk Forskningspost Barn og Unge
- Principal Investigator Name
- Camilla Tondel
- Principal Investigator Email
- camilla.tondel@helse-bergen.no
- Contact Person Name
- Camilla Tondel
- Contact Person Email
- camilla.tondel@helse-bergen.no
Denmark
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 21-06-2024
- Processing Time Days
- 29
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Rigshospitalet
- Department Name
- Department of Medical Endocrinology
- Principal Investigator Name
- Caroline Michaela Kistorp
- Principal Investigator Email
- caroline.michaela.kistorp@region.dk
- Contact Person Name
- Caroline Michaela Kistorp
- Contact Person Email
- caroline.michaela.kistorp@region.dk
Italy
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 25-06-2024
- Processing Time Days
- 33
- Number Of Sites
- 4
- Number Of Participants
- 8
Sites
- Site Name
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Department Name
- Cardiologia
- Principal Investigator Name
- Elena Biagini
- Principal Investigator Email
- elena.biagini73@gmail.com
- Contact Person Name
- Elena Biagini
- Contact Person Email
- elena.biagini73@gmail.com
- Site Name
- Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
- Department Name
- UOS Attivita Diurne Malattie Rare Internistiche
- Principal Investigator Name
- Valeria Di Stefano
- Principal Investigator Email
- valeria.distefano@policlinico.mi.it
- Contact Person Name
- Valeria Di Stefano
- Contact Person Email
- valeria.distefano@policlinico.mi.it
- Site Name
- Azienda Ospedaliera Dei Colli
- Department Name
- Unita di malattie rare, genetiche e cardiovascolari
- Principal Investigator Name
- Giuseppe Limongelli
- Principal Investigator Email
- limongelligiuseppe@libero.it
- Contact Person Name
- Giuseppe Limongelli
- Contact Person Email
- limongelligiuseppe@libero.it
- Site Name
- Azienda Ospedaliera Universitaria Federico II Di Napoli
- Department Name
- U.O. di Nefrologia Dipartimento di Sanita Pubblica
- Principal Investigator Name
- Antonio Pisani
- Principal Investigator Email
- antonio.pisani13@gmail.com
- Contact Person Name
- Antonio Pisani
- Contact Person Email
- antonio.pisani13@gmail.com
Germany
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 24-06-2024
- Processing Time Days
- 32
- Number Of Sites
- 4
- Number Of Participants
- 10
Sites
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Nephrologie und Intensivmedizin
- Principal Investigator Name
- Sima Canaan-Kuhl
- Principal Investigator Email
- sima.canaan-kuehl@charite.de
- Contact Person Name
- Sima Canaan-Kuhl
- Contact Person Email
- sima.canaan-kuehl@charite.de
- Site Name
- SphinCS GmbH
- Department Name
- Geheimrat-Hummel-Platz 2
- Principal Investigator Name
- Eugen Mengel
- Principal Investigator Email
- eugen.mengel@sphincs.de
- Contact Person Name
- Eugen Mengel
- Contact Person Email
- eugen.mengel@sphincs.de
- Site Name
- Universitaetsklinikum Wuerzburg AöR
- Department Name
- "Zentrum Innere Medizin (ZIM) Oberdurrbacherstr. 6"
- Principal Investigator Name
- Christoph Wanner
- Principal Investigator Email
- wanner_c@ukw.de
- Contact Person Name
- Christoph Wanner
- Contact Person Email
- wanner_c@ukw.de
- Site Name
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Department Name
- Kinderklinik - Villa Metabolica
- Principal Investigator Name
- Julia Hennermann
- Principal Investigator Email
- julia.hennermann@unimedizin-mainz.de
- Contact Person Name
- Julia Hennermann
- Contact Person Email
- julia.hennermann@unimedizin-mainz.de
France
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 20-06-2024
- Processing Time Days
- 28
- Number Of Sites
- 1
- Number Of Participants
- 10
Sites
- Site Name
- Raymond Poincare Hospital
- Department Name
- Unite Fonctionnelle de Genetique Medicale
- Principal Investigator Name
- Dominique Germain
- Principal Investigator Email
- dominique.germain@uvsq.fr
- Contact Person Name
- Dominique Germain
- Contact Person Email
- dominique.germain@uvsq.fr
Poland
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 24-06-2024
- Processing Time Days
- 32
- Number Of Sites
- 2
- Number Of Participants
- 4
Sites
- Site Name
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi
- Department Name
- Klinika Elektrokardiologii
- Principal Investigator Name
- Krzysztof Kaczmarek
- Principal Investigator Email
- krzysztof.kaczmarek@umed.lodz.pl
- Contact Person Name
- Krzysztof Kaczmarek
- Contact Person Email
- krzysztof.kaczmarek@umed.lodz.pl
- Site Name
- Krakowski Szpital Specjalistyczny Im. Sw. Jana Pawla II
- Department Name
- Oddzial Kliniczny Chorob Serca i Naczyn z Pododdzialem Intensywnego Nadzoru Kardiologicznego
- Principal Investigator Name
- Piotr Podolec
- Principal Investigator Email
- p.podolec@szpitaljp2.krakow.pl
- Contact Person Name
- Piotr Podolec
- Contact Person Email
- p.podolec@szpitaljp2.krakow.pl
Netherlands
- Earliest CTIS Part Ii Submission Date
- 23-05-2024
- Latest Decision Or Authorization Date
- 21-06-2024
- Processing Time Days
- 29
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Academisch Medisch Centrum
- Department Name
- Amsterdam Universitair Medische Centra(#1)
- Principal Investigator Name
- Mirjam Langeveld
- Principal Investigator Email
- m.langeveld@amsterdamumc.nl
- Contact Person Name
- Mirjam Langeveld
- Contact Person Email
- m.langeveld@amsterdamumc.nl
Sponsor
Primary sponsor
- Full Name
- Sanofi-Aventis Recherche & Developpement
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- France
Contract research organisations
- Name
- Bioclinica Inc.
- Responsibilities
- Central Medical Reading /Imaging Reading
- Name
- Labcorp Central Laboratory Services LP
- Name
- QPS LLC
- Name
- Endpoint Clinical Inc.
- Name
- Azenta Germany GmbH
Third parties
- {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac Safety","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Marken","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central Medical Reading /Imaging Reading","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Greenwood Genetic Center Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"Centralized 24-Hour Emergency System: eSMS","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"QPS LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Marken LLP","duties_or_roles":"Direct to Patient Service","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Accellacare Limited","duties_or_roles":"Home Health Care / Nursing","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Clinical Outcomes Assessment Instrument (COA)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- venglustat GZ402671 - SAR402671
- Active Substance
- venglustat
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- Not authorised (development)
- Orphan Designation
- Yes
- Frequency
- Daily
- Maximum Dose
- 15 mg
- Investigational Product Name
- Galafold 123 mg hard capsules
- Active Substance
- migalastat
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- Authorised
- Orphan Designation
- Yes
- Frequency
- Daily
- Maximum Dose
- 123 mg
- Investigational Product Name
- Fabrazyme 35 mg powder for concentrate for solution for infusion
- Active Substance
- agalsidase beta
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- Authorised
- Maximum Dose
- 1 mg/kg
- Investigational Product Name
- Replagal 1 mg/ml concentrate for solution for infusion.
- Active Substance
- agalsidase alfa
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- Authorised
- Maximum Dose
- 0.2 mg/kg
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