Clinical trial NCT05206773: A Study to Evaluate the Effect of Venglustat Tablets on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age With Fabry Disease
Official title: A Randomized, Double-blind, Placebo-controlled, 12-month Phase 3 Study to Evaluate the Effect of Venglustat on Neuropathic and Abdominal Pain in Male and Female Participants ≥16 Years of Age With Fabry Disease Who Are Treatment-naïve or Untreated for at Least 6 Months
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Fabry Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-01-25
Enrollment: 122
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 12-month, parallel treatment, Phase 3, double-blind, randomized, placebo controlled study to evaluate the effect of venglustat on neuropathic and abdominal pain symptoms of Fabry disease in participants ≥16 years of age with Fabry disease who are treatment-naïve or untreated for at least 6 months.

* Study visits will take place approximately every 3 months.
* The double-blind period will be followed by an open-label extension (OLE) during which participants who have completed the double-blind period will be treated with venglustat for up to an additional 12 months.

Detailed description: Double blind period: the total duration will be up to approximately of 14 months (1 month of screening 12 month of treatment period, and a possible follow-up period of 1 month if no participation in the open label extension period)

Open-label extension period: the total duration will be approximately of 46 months (12 month of OLE treatment, additional OLE treatment until a common study end of treatment date (CSEOTD, approximately 33 months), and 1 month of follow-up period)

Eligibility criteria: Inclusion Criteria:

* Male and female adult patients 16 year of age or older, who have had a previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease
* 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.
* 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.
* Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
* Weight ≥30 Kg
* A signed informed consent must be provided prior to any study-related procedures.

Exclusion Criteria:

* Any manifestations of Fabry disease that preclude placebo administration.
* 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.
* 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.
* Patients with hepatitis C, HIV, or hepatitis B infection.
* Neuropathic pain in upper or lower extremities, or abdominal pain not related to Fabry disease.
* History of seizures currently requiring treatment.
* Uncontrolled hypertension over the past 12 months prior to screening, or systolic BP \>=150 or diastolic BP \>=100 at screening.
* Estimated glomerular filtration rate \<60 mL/min/1.73m².
* Urine protein to creatinine ratio \>= 1 g/g at screening.
* 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.
* Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID 19 requiring hospitalization within 6 months of enrollment.
* Moderate to severe hepatic impairment.
* History of drug and/or alcohol abuse.
* History of or active hepatobiliary disease.
* Liver enzymes (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)) or total bilirubin \>2 times the upper limit of normal (ULN).
* Initiation of chronic treatment for pain, or change in pain medication regimen, within 3 months prior to randomization.
* Strong or moderate inducers or inhibitors of cytochrome P450 3A within 14 days or 5 half-lives, whichever is longer, prior to randomization.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Primary outcomes:
measure: 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, and abdominal pain)
timeFrame: From baseline to 6 months
measure: 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, and abdominal pain)
timeFrame: From baseline to 12 months
Secondary outcomes:
measure: Percent change in plasma globotriaosylsphingosine (lyso-GL-3)
timeFrame: From baseline to 6 month and 12 months
measure: Frequency of rescue pain medication use
timeFrame: From baseline to 6 months and 12 months
measure: Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7)
timeFrame: From baseline to 6 month and 12 months
measure: Percent change in tiredness component of FD-PRO
timeFrame: From baseline to 6 month and 12 months
measure: Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO
timeFrame: At 6 months and 12 months
measure: Number of participants with adverse event (AE) and serious adverse event (SAE)
timeFrame: From baseline to 6 month and 12 months
measure: Change in the lens clarity (new or worsening lens opacities) by ophthalmological examination (by slit lamp exam at Visit 2 and Visit 6)
timeFrame: From baseline to 12 months
measure: Change in Beck Depression Inventory-II (BDI-II) score
timeFrame: From baseline to 6 month and 12 months
measure: Plasma venglustat concentrations at prespecified visits over the study duration
timeFrame: From baseline to 6 month and 12 months
measure: Maximum venglustat plasma concentration (Cmax)
timeFrame: From baseline to 6 month and 12 months
measure: Time to maximum venglustat plasma concentration (tmax)
timeFrame: From baseline to 6 month and 12 months
measure: Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24)
timeFrame: From baseline to 6 month and 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Nephrology Clinic at Kirklin Clinic of UAB Hospital_Investigational Site Number: 8400011
state: Alabama
city: Los Angeles
country: United States
facility: UCLA Medical Center_Investigational Site Number: 8400006
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center- Site Number : 8400019
state: California
city: Orlando
country: United States
facility: Advent Health Orlando_Investigational Site Number: 8400008
state: Florida
city: Atlanta
country: United States
facility: Emory Genetics- Site Number : 8400010
state: Georgia
city: Hawthorne
country: United States
facility: Westchester Medical Center Healthcare Corporation- Site Number : 8400001
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center - PIN- Site Number : 8400013
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Site Number : 8400016
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital Of Pittsburgh- Site Number : 8400009
state: Pennsylvania
city: Dallas
country: United States
facility: Renal Disease Research Institute, An affiliate of: Dallas Nephrology Associates_Investigational Site Number: 8400012
state: Texas
city: Salt Lake City
country: United States
facility: University Of Utah Health Sciences Center- Site Number : 8400005
state: Utah
city: Fairfax
country: United States
facility: Lysosomal and Rare Disorders Research and Treatment Center_Investigational Site Number: 8400004
state: Virginia
city: La Rioja
country: Argentina
facility: Fundacion Cori para la Investigación y Prevención del Cancer_Investigational Site Number: 0320002
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clínicas Quilmes (IICQ) SRL_Investigational Site Number: 0320003
city: Parkville
country: Australia
facility: Investigational Site Number : 0360001
state: Victoria
city: Vienna
country: Austria
facility: Investigational Site Number: 0400001
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre_Investigational Site Number: 0760001
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Instituto de Genética e Erros Inatos do Metabolismo - IGEIM- Site Number : 0760002
city: Calgary
country: Canada
facility: M.A.G.I.C Calgary LTD_Investigational Site Number: 1240003
state: Alberta
city: Halifax
country: Canada
facility: Medicine Dalhousie University_Investigational Site Number : 1240001
state: Nova Scotia
city: Toronto
country: Canada
facility: University Health Network_Investigational Site Number : 1240005
state: Ontario
city: Beijing
country: China
facility: No.8, Xishiku Street, Xicheng District_Site Number: 1560001
city: Shanghai
country: China
facility: No.197,2nd Ruijin road, Huangpu district_Site Number: 1560003
city: Taiyuan
country: China
facility: No.85 South Jiefang road, Yingze District_Site Number: 1560004
city: Zhengzhou
country: China
facility: Investigational Site Number : 1560006
city: Copenhagen
country: Denmark
facility: Investigational Site Number: 2080001
city: Turku
country: Finland
facility: Investigational Site Number: 2460001
city: Garches
country: France
facility: Investigational Site Number : 2500001
city: Hochheim Am Main
country: Germany
facility: ISphinCS GmbH_Investigational Site Number: 2760004
city: Mainz
country: Germany
facility: Investigational Site Number : 2760005
city: München
country: Germany
facility: Investigational Site Number: 2760003
city: Wurzburg
country: Germany
facility: Investigational Site Number: 2760001
city: Athens
country: Greece
facility: Investigational Site Number : 3000003
city: Heraklion
country: Greece
facility: University Hospital of Heraklion_Investigational Site Number: 3000001
city: Ioannina
country: Greece
facility: University Hospital of Ioannina_Investigational Site Number: 3000002
city: Bologna
country: Italy
facility: IRCCS Policlinico di Sant'Orsola_Investigational Site Number : 3800005
city: Monza
country: Italy
facility: Fondazione IRCCS San Gerardo dei Tintori, S.C. Nefrologia - Clinica Nefrologica_Investigational Site Number: 3800002
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II", U.O. di Nefrologia- Diparimento di Sanità Pubblica_Investigational Site Number: 3800001
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria_Investigational Site Number: 3800003
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario_Investigational Site Number: 3800004
city: Kawasaki
country: Japan
facility: Investigational Site Number : 3920005
state: Kanagawa
city: Fukuoka-shi, Fukuoka
country: Japan
facility: Fukuoka University Hospital_Investigational Site Number: 3920004
city: Minato-ku, Tokyo
country: Japan
facility: The Jikei University Hospital_Investigational Site Number: 3920003
city: Sendai-shi, Miyagi
country: Japan
facility: Tohoku University Hospital_Investigational Site Number: 3920001
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. José Eleuterio González" Departamento de Genética Centro Universitario contra el cáncer_Investigational Site Number: 4840001
state: Nuevo León
city: Ciudad de Mexico
country: Mexico
facility: Odette del Carmen DIAZ-AVENDAÑO Clinstile, S.A. de C.V. Durango_Investigational Site Number: 4840002
city: Bergen
country: Norway
facility: Investigational Site Number: 5780001
city: Poznan
country: Poland
facility: Investigational Site Number : 6160002
state: Wielkopolskie
city: Rzeszow
country: Poland
facility: Investigational Site Number : 6160004
city: Wroclaw
country: Poland
facility: Investigational Site Number: 6160003
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni_Investigational Site Number: 6420001
city: Zürich
country: Switzerland
facility: Investigational Site Number : 7560001
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920001
city: Izmit
country: Turkey
facility: Investigational Site Number : 7920002
city: Malatya
country: Turkey
facility: Investigational Site Number : 7920004
city: Cambridge
country: United Kingdom
facility: Investigational Site Number: 8260001
state: Cambridgeshire
city: London
country: United Kingdom
facility: Investigational Site Number: 8260002
state: London, City Of
city: Salford
country: United Kingdom
facility: Investigational Site Number : 8260003
state: Manchester
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: