Clinical trial • Phase III • Rare Disease
venglustat for Fabry disease
Phase III trial of venglustat for Fabry disease.
Overview
- Trial Therapeutic Area
- Rare Disease
- Trial Disease
- Fabry disease
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 15-05-2024
- First CTIS Authorization Date
- 19-06-2024
Trial design
Randomised, venglustat oral tablets (investigational product) at the study dose levels (product records show max daily amounts 12 mg and 15 mg) versus matching placebo (placebo 6mg tablets and placebo 15mg tablets). exact dosing schedule beyond daily dosing is not specified in the provided registration data.-controlled Phase III trial in Romania, Norway, Italy and others.
- Randomised
- Yes
- Comparator
- Venglustat oral tablets (investigational product) at the study dose levels (product records show max daily amounts 12 mg and 15 mg) versus matching placebo (Placebo 6mg tablets and Placebo 15mg Tablets). Exact dosing schedule beyond daily dosing is not specified in the provided registration data.
- Target Sample Size
- 76
- Trial Duration For Participant
- 365
Eligibility
Recruits 76 paediatric patients.
- Pregnancy Exclusion
- Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
- Vulnerable Population
- Vulnerable population selected. Adolescents aged ≥16 (i.e. participants under 18 are eligible). A signed informed consent is required prior to any study-related procedures. Country- and age-specific informed consent, parent/guardian information and adolescent assent documents are provided (multiple L1/L1-redacted ICF and assent documents present in the submission), indicating assent/parent consent handling for minors.
Inclusion criteria
- {"criterion_text":"- Male and female adult patients 16 year of age or older with a confirmed diagnosis of Fabry disease"}
- {"criterion_text":"- Patients who are treatment-naïve or without prior treatment with an approved or experimental therapy for Fabry disease within at least 6 months prior to screening."}
- {"criterion_text":"- Average score of ≥3 (0=no symptom, 10=symptom as bad as you can imagine) on the participant-defined most-bothersome symptom (among neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain), as measured by the Fabry Disease Patient-Reported Outcome (FD PRO) at screening."}
- {"criterion_text":"- Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants."}
- {"criterion_text":"- Weight ≥30 Kg"}
- {"criterion_text":"- A signed informed consent must be provided prior to any study-related procedures."}
- {"criterion_text":"- A signed informed consent must be provided prior to any study-related procedures."}
Exclusion criteria
- {"criterion_text":"- Any manifestations of Fabry disease that preclude placebo administration."}
- {"criterion_text":"- 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."}
- {"criterion_text":"- Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID 19 requiring hospitalization within 6 months of enrollment."}
- {"criterion_text":"- Moderate to severe hepatic impairment."}
- {"criterion_text":"- History of drug and/or alcohol abuse."}
- {"criterion_text":"- History of or active hepatobiliary disease."}
- {"criterion_text":"- Liver enzymes (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)) or total bilirubin >2 times the upper limit of normal (ULN)."}
- {"criterion_text":"- Initiation of chronic treatment for pain, or change in pain medication regimen, within 3 months prior to randomization."}
- {"criterion_text":"- Strong or moderate inducers or inhibitors of cytochrome P450 3A within 14 days or 5 half lives, whichever is longer, prior to randomization."}
- {"criterion_text":"- History of transient ischemic attack, stroke, myocardial infarction, heart failure, evidence of left ventricular hypertrophy and/or cardiac fibrosis, major cardiovascular surgery, or kidney transplantation."}
- {"criterion_text":"- 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."}
- {"criterion_text":"- Patients with hepatitis C, HIV, or hepatitis B infection."}
- {"criterion_text":"- Neuropathic pain in upper or lower extremities, or abdominal pain not related to Fabry disease."}
- {"criterion_text":"- History of seizures currently requiring treatment."}
- {"criterion_text":"- Uncontrolled hypertension over the past 12 months prior to screening, or systolic BP >=150 or diastolic BP >=100 at screening."}
- {"criterion_text":"- Estimated glomerular filtration rate <60 mL/min/1.73m²."}
- {"criterion_text":"- Urine protein to creatinine ratio >= 1 g/g at screening."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Percent change from baseline at 6 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain)","definition_or_measurement_approach":"Percent change from baseline at 6 months measured using the Fabry Disease Patient-Reported Outcome (FD-PRO) most-bothersome symptom item (one of: neuropathic pain upper extremities, neuropathic pain lower extremities, or abdominal pain)."}
- {"endpoint_text":"- Percent change from baseline at 12 months in the most bothersome symptom of 3 Fabry Disease Patient-Reported Outcome (FD-PRO) items (neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain)","definition_or_measurement_approach":"Percent change from baseline at 12 months measured using the Fabry Disease Patient-Reported Outcome (FD-PRO) most-bothersome symptom item (one of: neuropathic pain upper extremities, neuropathic pain lower extremities, or abdominal pain)."}
Secondary endpoints
- {"endpoint_text":"- Percent change in plasma globotriaosylsphingosine (lyso-GL-3)","definition_or_measurement_approach":"Percent change in plasma lyso-GL-3 levels (measured in plasma)."}
- {"endpoint_text":"- Frequency of rescue pain medication use","definition_or_measurement_approach":"Assessment of frequency of use of rescue pain medication (count/frequency measures over study period)."}
- {"endpoint_text":"- Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7)","definition_or_measurement_approach":"Change in percent of days with at least one stool classified as BSFS Type 6 or 7 (diarrhea) compared to baseline."}
- {"endpoint_text":"- Change in tiredness component of FD-PRO","definition_or_measurement_approach":"Change from baseline in the fatigue/tiredness component score of the FD-PRO instrument."}
- {"endpoint_text":"- Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO","definition_or_measurement_approach":"Proportion of participants meeting responder criteria for neuropathic or abdominal pain per FD-PRO assessments."}
- {"endpoint_text":"- Number of participants with adverse event (AE) and serious adverse event (SAE)","definition_or_measurement_approach":"Counts and incidence of AEs and SAEs as reported during the study."}
- {"endpoint_text":"- Change in the lens clarity (new or worsening lens opacities) by ophthalmological examination (by slit lamp exam at Visit 2 and Visit 6)","definition_or_measurement_approach":"Ophthalmological slit-lamp examinations at specified visits to detect new or worsening lens opacities (lens clarity changes)."}
- {"endpoint_text":"- Change in Beck Depression Inventory-II (BDI-II) score","definition_or_measurement_approach":"Change from baseline in BDI-II total score."}
- {"endpoint_text":"- Plasma venglustat concentrations at prespecified visits over the study duration","definition_or_measurement_approach":"Measured plasma concentrations of venglustat at prespecified pharmacokinetic sampling visits."}
- {"endpoint_text":"- Maximum venglustat plasma concentration (Cmax)","definition_or_measurement_approach":"Measured Cmax from plasma concentration-time data."}
- {"endpoint_text":"- Time to maximum venglustat plasma concentration (tmax)","definition_or_measurement_approach":"Measured tmax from plasma concentration-time profile."}
- {"endpoint_text":"- Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24)","definition_or_measurement_approach":"Calculated AUC0-24 from plasma concentration-time data."}
Recruitment
- Registry Or Advocacy Recruitment
- True, Fabry registry (Finland)
- Planned Sample Size
- 76
- Recruitment Window Months
- 54
- Consent Approach
- A signed informed consent must be provided prior to any study-related procedures. Age-specific informed consent and assent procedures are in place: adolescent assent and parent/guardian information/ICF documents are included (L1-redacted-sis-icf-assent, L1-redacted-sis-icf-parent, L1-redacted-sis-icf-adolescents etc.). Multiple country/language-specific ICF and assent documents are provided (documents available in English, Polish, German (Austria/Germany), Romanian, Greek, French, Norwegian, Italian, Finnish, Danish and others per submitted L1 documents).
Methods
- Use of recruitment materials (brochures and posters) - documents present in submission include K2 recruitment-material-brochure and recruitment-material-poster files for multiple countries.
- Site-based recruitment at participating hospitals and clinics (trial sites listed per country in Part II submissions).
- Use of Fabry disease registry resources in Finland (document L1-sis-icf-fabry-registry-fi present) as part of recruitment/subject information.
Geography
- Total Number Of Sites
- 16
- Total Number Of Participants
- 48
Romania
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 26-06-2024
- Processing Time Days
- 23
- Number Of Sites
- 1
- Number Of Participants
- 5
Sites
- Site Name
- Institutul Clinic Fundeni
- Department Name
- Nefrologie
- Principal Investigator Name
- Elena Emanuela Rusu
- Principal Investigator Email
- ela.rusu@gmail.com
- Contact Person Name
- Elena Emanuela Rusu
- Contact Person Email
- ela.rusu@gmail.com
- Number Of Participants
- 5
Norway
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 20-06-2024
- Processing Time Days
- 17
- Number Of Sites
- 1
- Number Of Participants
- 1
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
- Number Of Participants
- 1
Italy
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 01-07-2024
- Processing Time Days
- 28
- Number Of Sites
- 2
- Number Of Participants
- 8
Sites
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Dipartimento di Scienze dell'invecchiamento,neurologiche, ortopediche e della testa-collo
- Principal Investigator Name
- Elena Verrecchia
- Principal Investigator Email
- elena.verrecchia@policlinicogemelli.it
- Contact Person Name
- Elena Verrecchia
- Contact Person Email
- elena.verrecchia@policlinicogemelli.it
- Site Name
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Department Name
- UO Nefrologia, Dialisi e trapianto
- Principal Investigator Name
- Gaetano La Manna
- Principal Investigator Email
- gaetano.lamanna@unibo.it
- Contact Person Name
- Gaetano La Manna
- Contact Person Email
- gaetano.lamanna@unibo.it
Finland
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 20-06-2024
- Processing Time Days
- 17
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Varsinais-Suomen hyvinvointialue
- Department Name
- Medisiininen toimialue, Kliininen tutkimuskeskus
- Principal Investigator Name
- Ilkka Kantola
- Principal Investigator Email
- ilkka.kantola@varha.fi
- Contact Person Name
- Ilkka Kantola
- Contact Person Email
- ilkka.kantola@varha.fi
- Number Of Participants
- 3
Greece
- Earliest CTIS Part Ii Submission Date
- 02-08-2024
- Latest Decision Or Authorization Date
- 09-09-2024
- Processing Time Days
- 38
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- University General Hospital Of Ioannina
- Department Name
- Nephrology department
- Principal Investigator Name
- Evangelia Ntounousi
- Principal Investigator Email
- edounous@uoi.gr
- Contact Person Name
- Evangelia Ntounousi
- Contact Person Email
- edounous@uoi.gr
- Site Name
- Eginitio Hospital
- Department Name
- 1st Department of Neurology
- Principal Investigator Name
- Panagiotis Kokotis
- Principal Investigator Email
- pkokotis@hotmail.com
- Contact Person Name
- Panagiotis Kokotis
- Contact Person Email
- pkokotis@hotmail.com
Austria
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 24-06-2024
- Processing Time Days
- 21
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- Universitätsklinik für Neurologie
- Principal Investigator Name
- Paulus Rommer
- Principal Investigator Email
- paulus.rommer@meduniwien.ac.at
- Contact Person Name
- Paulus Rommer
- Contact Person Email
- paulus.rommer@meduniwien.ac.at
- Number Of Participants
- 4
Denmark
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 19-06-2024
- Processing Time Days
- 16
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Rigshospitalet
- Department Name
- Department of Medical Endocrinology
- Principal Investigator Name
- Caroline Kistorp
- Principal Investigator Email
- caroline.michaela.kistorp@region.dk
- Contact Person Name
- Caroline Kistorp
- Contact Person Email
- caroline.michaela.kistorp@region.dk
- Number Of Participants
- 1
Poland
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 26-07-2024
- Processing Time Days
- 53
- Number Of Sites
- 2
- Number Of Participants
- 8
Sites
- Site Name
- Uniwersytecki Szpital Kliniczny W Poznaniu
- Department Name
- Oddzial Kliniczny Nefrologii, Transplantologii i Chorob Wewnetrznych
- Principal Investigator Name
- Krzysztof Pawlaczyk
- Principal Investigator Email
- kpawlac@ump.edu.pl
- Contact Person Name
- Krzysztof Pawlaczyk
- Contact Person Email
- kpawlac@ump.edu.pl
- Site Name
- Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
- Department Name
- Klinika Nefrologii i Medycyny Transplantacyjnej
- Principal Investigator Name
- Mariusz Kusztal
- Principal Investigator Email
- mariusz.kusztal@umed.wroc.pl
- Contact Person Name
- Mariusz Kusztal
- Contact Person Email
- mariusz.kusztal@umed.wroc.pl
Germany
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 20-06-2024
- Processing Time Days
- 17
- Number Of Sites
- 4
- Number Of Participants
- 9
Sites
- Site Name
- Universitaetsklinikum Wuerzburg AöR
- Department Name
- Medizinische Klinik und Poliklinik I, Abteilung Nephrologie
- 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
- Center For Pediatric And Adolescent Medicine Of The Johannes Gutenberg University Mainz
- Department Name
- Zentrum für Kinder und Jugendmedizin, 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
- Site Name
- SphinCS GmbH
- Department Name
- (private clinic)
- 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
- Friedrich Baur Institute An Der Neurologischen Klinik Und Poliklinik
- Department Name
- Neurologische Klinik, Friedrich-Baur Institut
- Principal Investigator Name
- Stephan Wenninger
- Principal Investigator Email
- stephan.wenninger@med.uni-muenchen.de
- Contact Person Name
- Stephan Wenninger
- Contact Person Email
- stephan.wenninger@med.uni-muenchen.de
France
- Earliest CTIS Part Ii Submission Date
- 03-06-2024
- Latest Decision Or Authorization Date
- 20-06-2024
- Processing Time Days
- 17
- Number Of Sites
- 1
- Number Of Participants
- 6
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
- Number Of Participants
- 6
Sponsor
Primary sponsor
- Full Name
- Sanofi-Aventis Recherche & Developpement
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- France
Contract research organisations
- Name
- QPS LLC
- Responsibilities
- code:4
- Name
- Icon Clinical Research Limited
- Responsibilities
- code:7
- Name
- Endpoint Clinical Inc.
- Responsibilities
- code:3
- Name
- Eresearchtechnology Inc.
- Responsibilities
- Clinical Outcomes Assessment Instrument; Cardiac Safety (code:15)
Third parties
- {"country":"United States","full_name":"Greenwood Genetic Center Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"Centralized 24-Hour Emergency System (code:15)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"QPS LLC","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code:3","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code:7","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Clinical Outcomes Assessment Instrument (code:15)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac Safety (code:15)","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 USE
- Authorisation Status
- prodAuthStatus:1
- Orphan Designation
- Yes
- Dose Levels
- 15 mg (maxDailyDoseAmount:15)
- Maximum Dose
- 15 mg
- Investigational Product Name
- venglustat GZ402671 - SAR402671
- Active Substance
- venglustat
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL USE
- Authorisation Status
- prodAuthStatus:1
- Orphan Designation
- Yes
- Dose Levels
- 12 mg (maxDailyDoseAmount:12)
- Maximum Dose
- 12 mg
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