venglustat for Gaucher disease type 3

Inclusion criteria

• {"criterion_text":"- The participant has received ERT (Cerezyme or other ERT; as deemed appropriate by local regulations) for at least 3 years prior to enrollment, on a stable dose for at least 6 months, is deemed clinically stable for at least 1 year by the Investigator and is within the therapeutic goals as all of the following: - Hemoglobin level of ≥11.0 g/dL for females and ≥12.0 g/dL for males - Platelet count ≥100 000/mm3 - Spleen volume <10 multiples of normal (MN) - Liver volume <1.5 MN - No bone crisis and free of symptomatic bone disease such as bone pain attributable to osteonecrosis and/or pathological fractures within 3 months prior to screening"}
• {"criterion_text":"- Signed written informed assent/consent"}
• {"criterion_text":"- Adult participant is ≥18 years of age"}
• {"criterion_text":"- Pediatric participant is ≥12 years <18 years of age"}
• {"criterion_text":"- The participant has a clinical diagnosis of GD3 and a documented deficiency of acid beta-glucosidase activity confirming this diagnosis."}
• {"criterion_text":"- The participant has a modified SARA score of 1 or above."}
• {"criterion_text":"- The presence of gaze palsy, predominantly horizontal, with slow or absent saccades."}
• {"criterion_text":"- If the participant has a history of seizures, they are well controlled under appropriate medication not identified as a strong or moderate inducer or inhibitor of CYP3A."}
• {"criterion_text":"- Participants ≥ 30 kg of weight"}
• {"criterion_text":"- Contraception for sexually active male or female participants; not pregnant or breastfeeding; no sperm donating for male participant"}

Exclusion criteria

• {"criterion_text":"- The participant is blood transfusion-dependent."}
• {"criterion_text":"- The participant is scheduled for in-patient hospitalization including elective surgery, during the study."}
• {"criterion_text":"- The participant has had a major organ transplant (eg, bone marrow or liver)."}
• {"criterion_text":"- A history of drug and/or alcohol abuse within the past year prior to the screening visit."}
• {"criterion_text":"- Chaperone therapy within 6 months, substrate reduction therapy other than venglustat within 6 months or venglustat substrate reduction therapy prior to enrollment."}
• {"criterion_text":"- Exposure to any investigational drug within the last 30 days or 5 half-lives from screening, whichever is longer"}
• {"criterion_text":"- The participant has received strong or moderate inducers or inhibitors of CYP3A within 14 days or 5 half-lives from screening, whichever is longer, prior to screening. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting venglustat. The participant is unwilling to abstain from consumption of grapefruit, grapefruit juice, or grapefruit containing products for the duration of the treatment period."}
• {"criterion_text":"- The participant, in the opinion of the investigator, is unable to adhere to the requirements of the study or unable to undergo study assessments (eg, contraindication for MRI)."}
• {"criterion_text":"- Type of participant and disease characteristic: the participant has had a total splenectomy prior to enrollment. The patient had a partial splenectomy within 3 years prior to randomization."}
• {"criterion_text":"- Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures."}
• {"criterion_text":"- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study"}
• {"criterion_text":"- Prior esophageal varices or liver infarction or current liver enzymes (alanine aminotransferase [ALT]/ aspartate aminotransferase [AST]) or total bilirubin >2 times the upper limit of normal, unless the participant has a diagnosis of Gilbert Syndrome."}
• {"criterion_text":"- The participant has any clinically significant disease, other than GD, including cardiovascular (congenital cardiac defect, coronary artery disease, valve disease or left sided heart failure; clinically significant arrhythmias or conduction defect), hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (eg, hypokalemia, hypomagnesemia) or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may preclude participation in the opinion of the Investigator."}
• {"criterion_text":"- The participant has renal insufficiency, as defined by an estimated glomerular filtration rate <30 mL/min/1.73m2 at the screening visit."}
• {"criterion_text":"- The participant has a history of cancer, except for basal cell carcinoma."}
• {"criterion_text":"- The participant has progressive myoclonic epilepsy."}
• {"criterion_text":"- The participant is pregnant (has a positive serum beta-human chronic gonadotropin [β-hCG]) or lactating."}
• {"criterion_text":"- The participant requires use of invasive ventilatory support."}
• {"criterion_text":"- The participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily."}

Primary endpoints

• {"endpoint_text":"- Change in Scale for Assessment and Rating of Ataxia (SARA) modified total score","definition_or_measurement_approach":"Change from baseline in the modified total SARA score (Scale for Assessment and Rating of Ataxia)."}
• {"endpoint_text":"- Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score","definition_or_measurement_approach":"Change from baseline in RBANS total scale index score (Repeatable Battery for the Assessment of Neuropsychological Status)."}

Secondary endpoints

• {"endpoint_text":"- Percent change in spleen volume","definition_or_measurement_approach":"Percent change from baseline in spleen volume."}
• {"endpoint_text":"- Percent change in liver volume","definition_or_measurement_approach":"Percent change from baseline in liver volume."}
• {"endpoint_text":"- Change in hemoglobin level","definition_or_measurement_approach":"Change from baseline in hemoglobin concentration."}
• {"endpoint_text":"- Percent change in platelet count","definition_or_measurement_approach":"Percent change from baseline in platelet count."}
• {"endpoint_text":"- Percent change in CSF GL-1 and lyso-GL-1 levels","definition_or_measurement_approach":"Percent change from baseline in cerebrospinal fluid GL-1 and lyso-GL-1 biomarker levels."}
• {"endpoint_text":"- Percent change in plasma GL-1 and lyso-GL-1 levels","definition_or_measurement_approach":"Percent change from baseline in plasma GL-1 and lyso-GL-1 biomarker levels."}
• {"endpoint_text":"- Number of patients with treatment emergent adverse events (TEAEs)/ serious adverse events (SAEs)/ adverse events of special interest (AESIs)","definition_or_measurement_approach":"Count and incidence of TEAEs, SAEs and AESIs occurring during the treatment-emergent period."}
• {"endpoint_text":"- Change in score of Beck Depression Inventory II (BDI-II) during the treatment-emergent period (for participants 13 years of age and above at baseline)","definition_or_measurement_approach":"Change from baseline in BDI-II score during the treatment-emergent period (applicable to participants ≥13 years at baseline)."}
• {"endpoint_text":"- Change in Patient Health Questionnaire 9 (PHQ-9) during the treatment-emergent period (for participants 12 years of age at baseline)","definition_or_measurement_approach":"Change from baseline in PHQ-9 score during the treatment-emergent period (applicable to participants ≥12 years at baseline)."}

France

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

654

Number Of Sites

2

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

656

Number Of Sites

1

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

656

Number Of Sites

2

Number Of Participants

5

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties codes: 1 (contact email: CTIS-Biotech@iconplc.com)

Name

Marken LLP

Responsibilities

Direct to Patient (IMP) Transportation

Name

Labcorp Central Laboratory Services LP

Responsibilities

Central laboratory services (sponsorDuties code: 4)

Name

Eresearchtechnology Inc.

Responsibilities

Clinical Outcomes Assessment Instrument

Name

Bioclinica Inc.

Responsibilities

Central medical Reading / Imaging Reading

Name

ESMS Global Limited

Responsibilities

Centralized 24-Hour Emergency System

Name

Endpoint Clinical Inc.

Responsibilities

sponsorDuties code: 3

Name

Clario

Responsibilities

Cardiac Safety

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Marken LLP","duties_or_roles":"Direct to Patient (IMP) Transportation (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Clinical Outcomes Assessment Instrument (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central medical Reading / Imaging Reading (sponsorDuties code: 15)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"Centralized 24-Hour Emergency System (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clario","duties_or_roles":"Cardiac Safety (sponsorDuties code: 15)","organisation_type":"Health care"}