PERIDOT: A Study to Evaluate the Effect of Venglustat Tablets on Neuropathic and Abdominal Pain in Male and Female Adult Participants With Fabry Disease
Study Details
Study Description
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 adult participants with Fabry disease who are treatment-naïve or untreated for at least 6 months.
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Study visits will take place approximately every 3 months.
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 13 months (12 month of treatment and 1 month of follow-up period)
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Venglustat Participant will receive venglustat dose once daily up to 12 months |
Drug: Venglustat (GZ402671)
Pharmaceutical form: Tablet Route of administration: Oral
|
| Placebo Comparator: Placebo Participants will receive placebo once daily up to 12 months |
Drug: Placebo
Pharmaceutical form: Tablet Route of administration: Oral
|
Outcome Measures
Primary Outcome Measures
- 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]
- 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 Outcome Measures
- Percent change in plasma globotriaosylsphingosine (lyso-GL-3) [From baseline to 6 month and 12 months]
- Frequency of rescue pain medication use [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.
- 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]
- Percent change in tiredness component of FD-PRO [From baseline to 6 month and 12 months]
- Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO [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
- Number of participants with adverse event (AE) and serious adverse event (SAE) [From baseline to 6 month and 12 months]
- Change in Beck Depression Inventory-II (BDI-II) score [From baseline to 6 month and 12 months]
- Plasma venglustat concentrations at prespecified visits over the study duration [From baseline to 6 month and 12 months]
- Maximum venglustat plasma concentration (Cmax) [From baseline to 6 month and 12 months]
- Time to maximum venglustat plasma concentration (tmax) [From baseline to 6 month and 12 months]
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male and female adult patients 18 year of age or older, who have had a previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease
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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.
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Elevated plasma globotriaosylsphingosine (lysoGL3) at screening, or a previous biopsy of any organ that shows deposition of GL3.
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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.
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Contraception (with double contraception methods) for male and female participants; not pregnant or breastfeeding for female participants; no sperm donation for male participants.
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A signed informed consent must be provided prior to any study-related procedures.
Exclusion Criteria:
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Any manifestations of Fabry disease that preclude placebo administration.
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History of transient ischemic attack, stroke, myocardial infarction, heart failure, major cardiovascular surgery, or kidney transplantation.
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History of ongoing clinically significant cardiac arrhythmia or prior or ongoing treatment for the above.
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Patients with hepatitis C, HIV, or hepatitis B infection.
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Neuropathic pain in upper or lower extremities, or abdominal pain not related to Fabry disease.
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History of seizures currently requiring treatment.
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Uncontrolled hypertension over the past 12 months prior to screening.
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Estimated glomerular filtration rate <60 mL/min/1.73m².
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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.
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Positive SARS-CoV-2 virus test within 2 weeks of enrollment, or COVID 19 requiring hospitalization within 6 months of enrollment.
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Moderate to severe hepatic impairment.
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History of drug and/or alcohol abuse.
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History of or active hepatobiliary disease.
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Liver enzymes (alanine aminotransferase (ALT)/aspartate aminotransferase (AST)) or total bilirubin >2 times the upper limit of normal (ULN).
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Initiation of chronic treatment for pain, or change in pain medication regimen, within 3 months prior to randomization.
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Strong or moderate inducers or inhibitors of cytochrome P450 CYP3A per FDA classification within 14 days or 5 halflives, 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lysosomal and Rare Disorders Research and Treatment Center_3702 Pender Drive, Suite 170_Investigational site number 8400004 | Fairfax | Virginia | United States | 22030 |
| 2 | Fundacion Cori para la Investigación y Prevención del Cancer, Dorrego 269_Investigational site number 0320002 | La Rioja | Argentina | F5300 | |
| 3 | Instituto de Nefrologia Pergamino, Av. de Mayo 1115 3rd floor, Pergamino, Provincia de Buenos Aires_Investigational site number 0320001 | Pergamino | Argentina | B2700CPM |
Sponsors and Collaborators
- Genzyme, a Sanofi Company
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EFC17045
- 2021-002350-90
- U1111-1256-9310