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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

28 Jun 2022 → ongoing

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-511990-31-00

EudraCT number

2021-002350-90

WHO UTN

U1111-1256-9310

ClinicalTrials.gov

NCT05206773

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To assess the effect of venglustat on neuropathic or abdominal pain in participants ≥16 years of age with Fabry disease who are treatment-naïve or untreated for at least 6 months prior to screening

Secondary objectives 5

1. To assess the effect of venglustat on plasma globotriaosylsphingosine (lyso-GL-3) levels
2. To assess the effect of venglustat on rescue pain medication use
3. To evaluate the effect of venglustat on symptoms of Fabry disease
4. To assess the safety and tolerability of venglustat in patients with Fabry disease
5. To evaluate the pharmacokinetics (PK) of venglustat in patients with Fabry disease

Conditions and MedDRA coding

Fabry Disease

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001716-PIP08-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male and female adult patients 16 year of age or older with a confirmed diagnosis of Fabry disease
2. 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.
3. 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.
4. Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
5. Weight ≥30 Kg
6. A signed informed consent must be provided prior to any study-related procedures.

Exclusion criteria 17

1. Any manifestations of Fabry disease that preclude placebo administration.
2. 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.
3. 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.
4. Patients with hepatitis C, HIV, or hepatitis B infection.
5. Neuropathic pain in upper or lower extremities, or abdominal pain not related to Fabry disease.
6. History of seizures currently requiring treatment.
7. Uncontrolled hypertension over the past 12 months prior to screening, or systolic BP >=150 or diastolic BP >=100 at screening.
8. Estimated glomerular filtration rate <60 mL/min/1.73m².
9. Urine protein to creatinine ratio >= 1 g/g at screening.
10. 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.
11. Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID 19 requiring hospitalization within 6 months of enrollment.
12. Moderate to severe hepatic impairment.
13. History of drug and/or alcohol abuse.
14. History of or active hepatobiliary disease.
15. Liver enzymes (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)) or total bilirubin >2 times the upper limit of normal (ULN).
16. Initiation of chronic treatment for pain, or change in pain medication regimen, within 3 months prior to randomization.
17. Strong or moderate inducers or inhibitors of cytochrome P450 3A within 14 days or 5 half lives, whichever is longer, prior to randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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)
2. 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)

Secondary endpoints 12

1. Percent change in plasma globotriaosylsphingosine (lyso-GL-3)
2. Frequency of rescue pain medication use
3. Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7)
4. Change in tiredness component of FD-PRO
5. Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO
6. Number of participants with adverse event (AE) and serious adverse event (SAE)
7. Change in the lens clarity (new or worsening lens opacities) by ophthalmological examination (by slit lamp exam at Visit 2 and Visit 6)
8. Change in Beck Depression Inventory-II (BDI-II) score
9. Plasma venglustat concentrations at prespecified visits over the study duration
10. Maximum venglustat plasma concentration (Cmax)
11. Time to maximum venglustat plasma concentration (tmax)
12. Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 8

Locations

10 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 125 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications