A study to evaluate the effect of venglustat tablets on neuropathic and abdominal pain in male and female adult participants with Fabry disease

JRCT ID: jRCT2021220001

Registered date:13/04/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Fabry Disease
• Date of first enrollment: 14/11/2022
• Target sample size: 114
• Countries of recruitment: United States,Japan,Argentina,Japan,Austria,Japan,Brazil,Japan,Canada,Japan,China,Japan,Denmark,Japan,Finland,Japan,Germany,Japan,Greece,Japan,Italy,Japan,Mexico,Japan,Norway,Japan,Poland,Japan,Romania,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

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

Outcome(s)

Primary Outcome

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, and abdominal pain) [ Time Frame: From baseline to 6 months ]

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, and abdominal pain) [ Time Frame: From baseline to 12 months ]

Secondary Outcome

1. Percent change in plasma globotriaosylsphingosine (lyso-GL-3) [ Time Frame: From baseline to 6 month and 12 months ]

2. Frequency of rescue pain medication use [ Time Frame: From baseline to 6 months and 12 months ]
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.

3. Change in the percentage of days with at least 1 stool reflecting diarrhea (Bristol Stool Form Scale [BSFS] Type 6 or 7) [ Time Frame: From baseline to 6 month and 12 months ]

4. Percent change in tiredness component of FD-PRO [ Time Frame: From baseline to 6 month and 12 months ]

5. Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO [ Time Frame: At 6 months and 12 months ]
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

6. Number of participants with adverse event (AE) and serious adverse event (SAE) [ Time Frame: From baseline to 6 month and 12 months ]

7. Change in the lens clarity (new or worsening lens opacities) by ophthalmological examination (by slit lamp exam at Visit 2 and Visit 6) [ Time Frame: From baseline to 12 months ]

8. Change in Beck Depression Inventory-II (BDI-II) score [ Time Frame: From baseline to 6 month and 12 months ]

9. Plasma venglustat concentrations at prespecified visits over the study duration [ Time Frame: From baseline to 6 month and 12 months ]

10. Maximum venglustat plasma concentration (Cmax) [ Time Frame: From baseline to 6 month and 12 months ]

11. Time to maximum venglustat plasma concentration (tmax) [ Time Frame: From baseline to 6 month and 12 months ]

12. Area under the venglustat plasma concentration versus time curve from time 0 to 24 hours (AUC0-24) [ Time Frame: From baseline to 6 month and 12 months ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Male and female adult patients 18 year of age or older with a confirmed diagnosis of Fabry disease.
- Patients who are treatment-naive 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.
- A signed informed consent must be provided prior to any study-related procedures.

Exclude 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/1.73m^2.
- 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 Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05206773,2021-002350-90