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

Fabry Disease Clinical Trial

— PERIDOT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05206773
• Other study ID #: EFC17045
• Secondary ID: U1111-1256-93102
• Status: Recruiting
• Phase: Phase 3
• Start date: March 11, 2022
• Est. completion date: October 6, 2025

Study information

• Verified date: June 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 31 months (12 month of OLE treatment, additional OLE treatment until a common study end of treatment date (CSEOTD, approximately 18 months), and 1 month of follow-up period)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: October 6, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Abdominal Pain
• Fabry Disease

Intervention

Drug:
• Venglustat (GZ402671)
Pharmaceutical form: Tablet Route of administration: Oral
• Placebo
Pharmaceutical form: Tablet Route of administration: Oral

Locations

Country	Name	City	State
Argentina	Fundacion Cori para la Investigación y Prevención del Cancer_Investigational Site Number: 0320002	La Rioja
Argentina	Instituto de Nefrologia Pergamino_Investigational Site Number: 0320001	Pergamino
Argentina	Instituto de Investigaciones Clínicas Quilmes (IICQ) SRL_Investigational Site Number: 0320003	Quilmes
Australia	Investigational Site Number : 0360001	Parkville	Victoria
Austria	Investigational Site Number: 0400001	Wien
Brazil	Hospital de Clínicas de Porto Alegre_Investigational Site Number: 0760001	Porto Alegre	Rio Grande Do Sul
Canada	M.A.G.I.C Calgary LTD_Investigational Site Number: 1240003	Calgary	Alberta
Canada	Medicine Dalhousie University_Investigational Site Number : 1240001	Halifax	Nova Scotia
Canada	University Health Network_Investigational Site Number : 1240005	Toronto	Ontario
China	No.8, Xishiku Street, Xicheng District_Site Number: 1560001	Beijing
China	No.197,2nd Ruijin road, Huangpu district_Site Number: 1560003	Shanghai
China	No.85 South Jiefang road, Yingze District_Site Number: 1560004	Taiyuan
China	Investigational Site Number : 1560006	Zhengzhou
Denmark	Investigational Site Number: 2080001	Copenhagen
Finland	Investigational Site Number: 2460001	Turku
France	Investigational Site Number : 2500001	Garches
Germany	ISphinCS GmbH_Investigational Site Number: 2760004	Hochheim Am Main
Germany	Investigational Site Number : 2760005	Mainz
Germany	Investigational Site Number: 2760003	München
Germany	Investigational Site Number: 2760001	Wurzburg
Greece	University Hospital of Heraklion_Investigational Site Number: 3000001	Heraklion
Greece	University Hospital of Ioannina_Investigational Site Number: 3000002	Ioannina
Italy	Investigational Site Number : 3800005	Bologna
Italy	Fondazione IRCCS San Gerardo dei Tintori, S.C. Nefrologia - Clinica Nefrologica_Investigational Site Number: 3800002	Monza
Italy	Azienda Ospedaliera Universitaria "Federico II", U.O. di Nefrologia- Diparimento di Sanità Pubblica_Investigational Site Number: 3800001	Napoli
Italy	Azienda Ospedaliera Universitaria_Investigational Site Number: 3800003	Palermo
Italy	Fondazione Policlinico Universitario_Investigational Site Number: 3800004	Roma
Japan	Fukuoka University Hospital_Investigational Site Number: 3920004	Fukuoka-shi, Fukuoka
Japan	Investigational Site Number : 3920005	Kawasaki-shi	Kanagawa
Japan	The Jikei University Hospital_Investigational Site Number: 3920003	Minato-ku, Tokyo
Japan	Tohoku University Hospital_Investigational Site Number: 3920001	Sendai-shi, Miyagi
Mexico	Odette del Carmen DIAZ-AVENDAÑO Clinstile, S.A. de C.V. Durango_Investigational Site Number: 4840002	Ciudad de Mexico
Mexico	Hospital Universitario "Dr. José Eleuterio González" Departamento de Genética Centro Universitario contra el cáncer_Investigational Site Number: 4840001	Monterrey	Nuevo León
Norway	Investigational Site Number: 5780001	Bergen
Poland	Investigational Site Number: 6160001	Lodz
Poland	Investigational Site Number : 6160002	Poznan	Wielkopolskie
Poland	Investigational Site Number: 6160003	Wroclaw
Romania	Institutul Clinic Fundeni_Investigational Site Number: 6420001	Bucuresti
Switzerland	Investigational Site Number : 7560001	Zürich
Turkey	Investigational Site Number : 7920001	Ankara
Turkey	Investigational Site Number : 7920002	Kocaeli
Turkey	Investigational Site Number : 7920004	Malatya
United Kingdom	Investigational Site Number: 8260001	Cambridge
United Kingdom	Investigational Site Number: 8260002	London
United States	Emory Genetics Site Number : 8400010	Atlanta	Georgia
United States	Nephrology Clinic at Kirklin Clinic of UAB Hospital_Investigational Site Number: 8400011	Birmingham	Alabama
United States	Cincinnati Children's Hospital Medical Center - PIN Site Number : 8400013	Cincinnati	Ohio
United States	Renal Disease Research Institute, An affiliate of: Dallas Nephrology Associates_Investigational Site Number: 8400012	Dallas	Texas
United States	Lysosomal and Rare Disorders Research and Treatment Center_Investigational Site Number: 8400004	Fairfax	Virginia
United States	Westchester Medical Center Healthcare Corporation Site Number : 8400001	Hawthorne	New York
United States	UCLA Medical Center_Investigational Site Number: 8400006	Los Angeles	California
United States	University of California Irvine Medical Center Site Number : 8400019	Orange	California
United States	Advent Health Orlando_Investigational Site Number: 8400008	Orlando	Florida
United States	Children's Hospital Of Pittsburgh Site Number : 8400009	Pittsburgh	Pennsylvania
United States	University Of Utah Health Sciences Center Site Number : 8400005	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  China,  Denmark,  Finland,  France,  Germany,  Greece,  Italy,  Japan,  Mexico,  Norway,  Poland,  Romania,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		From baseline to 6 months
Primary	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)		From baseline to 12 months
Secondary	Percent change in plasma globotriaosylsphingosine (lyso-GL-3)		From baseline to 6 month and 12 months
Secondary	Frequency of rescue pain medication use	Number of days with use of rescue pain medications during the 6-month treatment period, divided by duration of the 6-month treatment period and multiplied by 100. The same definition will be used for the 12-month period.	From baseline to 6 months and 12 months
Secondary	Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7)		From baseline to 6 month and 12 months
Secondary	Percent change in tiredness component of FD-PRO		From baseline to 6 month and 12 months
Secondary	Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO	Response is defined as at least a 30% decrease from baseline in the most bothersome of 3 FD-PRO items between neuropathic pain in upper extremities, neuropathic pain in lower extremities, and abdominal pain	At 6 months and 12 months
Secondary	Number of participants with adverse event (AE) and serious adverse event (SAE)		From baseline to 6 month and 12 months
Secondary	Change in the lens clarity (new or worsening lens opacities) by ophthalmological examination (by slit lamp exam at Visit 2 and Visit 6)		From baseline to 12 months
Secondary	Change in Beck Depression Inventory-II (BDI-II) score		From baseline to 6 month and 12 months
Secondary	Plasma venglustat concentrations at prespecified visits over the study duration		From baseline to 6 month and 12 months
Secondary	Maximum venglustat plasma concentration (Cmax)		From baseline to 6 month and 12 months
Secondary	Time to maximum venglustat plasma concentration (tmax)		From baseline to 6 month and 12 months
Secondary	Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24)		From baseline to 6 month and 12 months