Study to evaluate the efficacy and safety of venglustat in adult and pediatric patients with Gaucher disease Type 3

• Register: EUCTR
• Last refreshed on: 5 August 2024
• Main ID: EUCTR2021-005402-10-DE
• Date of registration: 05/01/2022
• Prospective Registration: Yes
• Primary sponsor: Sanofi-aventis recherche & développement
• Public title: Study to evaluate the efficacy and safety of venglustat in adult and pediatric patients with Gaucher disease Type 3
• Scientific title: A phase 3, multicenter, multinational, randomized, double-blind, double-dummy, active-comparator study to evaluate the efficacy and safety of venglustat in adult and pediatric patients with Gaucher disease Type 3 (GD3) who have reached therapeutic goals with Enzyme Replacement Therapy (ERT) - LEAP2MONO
• Date of first enrolment: 23/03/2022
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-005402-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Canada, China, Egypt, France, Germany, Hungary, Italy, Japan, Taiwan, Türkiye, United Kingdom, United States

Contacts

• Affiliation: Sanofi-Aventis Deutschland GmbH

• Affiliation: Sanofi-Aventis Deutschland GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- 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

- Adult participant is =18 years of age

- Pediatric participant is =12 years <18 years of age

- The participant has a clinical diagnosis of GD3 and a documented deficiency of acid beta-glucosidase activity confirming this diagnosis.

- The participant has a modified SARA score of 1 or above.

- The presence of gaze palsy, predominantly horizontal, with slow or absent saccades.

- 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.

- Participants = 30 kg of weight

- Contraception for sexually active male participants or female participants; not pregnant or breastfeeding; no sperm donating for male participant
- Signed written informed assent/consent

Are the trial subjects under 18? yes
Number of subjects for this age range: 16
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Participants are excluded from the study if any of the following criteria apply:
- The participant is blood transfusion-dependent.
- 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.
- 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.
- The participant has renal insufficiency, as defined by an estimated glomerular filtration rate <30 mL/min/1.73m2 at the screening visit.
- The participant has a history of cancer, except for basal cell carcinoma.
- The participant has progressive myoclonic epilepsy.
- The participant is pregnant (has a positive serum beta-human chronic gonadotropin [ß-hCG]) or lactating.
- The participant requires use of invasive ventilatory support.
- The participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily.
- The participant is scheduled for in-patient hospitalization including elective surgery, during the study.
- The participant has had a major organ transplant (eg, bone marrow or liver).
- A history of drug and/or alcohol abuse within the past year prior to the screening visit.
- Chaperone therapy within 6 months, substrate reduction therapy other than venglustat within 6 months or venglustat substrate reduction therapy prior to enrollment.
- Exposure to any investigational drug (including venglustat) within the last 30 days or 5 half-lives from screening, whichever is longer.
- 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.
- 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).
- 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.
- 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
- 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Gaucher's disease type III
MedDRA version: 24.1 Level: PT Classification code 10075699 Term: Gaucher's disease type III System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: venglustat
Product Code: SAR402671, GZ402671 or GZ / SAR402671
Pharmaceutical Form: Tablet
INN or Proposed INN: Venglustat malate
CAS Number: 1629063-78-0
Current Sponsor code: GZ402671
Other descriptive name: GZ/SAR402671
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: venglustat
Product Code: SAR402671, GZ402671 or GZ / SAR402671
Pharmaceutical Form: Tablet
INN or Proposed INN: Venglustat malate
CAS Number: 1629063-78-0
Current Sponsor code: GZ402671
Other descriptive name: GZ/SAR402671
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Cerezyme 400 Units Powder for concentrate for solution for infusion
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Imiglucerase
CAS Number: 154248-97-2
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): - Change in Scale for Assessment and Rating of Ataxia (SARA) modified total score
- Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score

Secondary Objective: • Assess maintenance of spleen volume stability with venglustat compared to Cerezyme
• Assess maintenance of liver volume stability with venglustat compared to Cerezyme
• Assess maintenance of hemoglobin level stability with venglustat compared to Cerezyme
• Assess maintenance of platelet count stability with venglustat compared to Cerezyme
• Evaluate the change in cerebrospinal (CSF) GL-1 and lyso GL-1
biomarkers with venglustat compared to Cerezyme.
• Evaluate the change in plasma GL-1 and lyso GL-1 biomarkers with venglustat compared to Cerezyme
• Evaluate the safety and tolerability of venglustat compared to Cerezyme

Main Objective: Evaluate the efficacy of venglustat compared to Cerezyme in adult and pediatric (12-18 years) GD3 patients by assessing:
• Ataxia using the Scale for the Assessment and Rating of Ataxia (SARA)
• Cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

Timepoint(s) of evaluation of this end point: From baseline to Week 52

Secondary Outcome(s)

Secondary end point(s): 1/ Percent change in spleen volume

2/ Percent change in liver volume

3/ Change in hemoglobin level

4/ Percent change in platelet count

5/ Percent change in CSF GL-1 and lyso GL-1 levels

6/ Percent change in plasma GL-1 and lyso GL-1 levels

7/Number of patients with treatment emergent adverse events
(TEAEs)/ serious adverse events (SAEs)/ adverse events of special
interest (AESIs)

8/ 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)

9/ Change in Patient Health Questionnaire 9 (PHQ-9) during the treatment-emergent period (for participants 12 years of age at baseline)

Timepoint(s) of evaluation of this end point: From 1/ to 6/ and from 8/ to 9/: From baseline to Week 52

7/: From baseline to max of 3.5 years

Secondary ID(s)

EFC17215

Source(s) of Monetary Support

Sanofi-aventis recherche & développement

Ethics review

Status: Approved
Approval date: 23/03/2022
Contact: