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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

8 Dec 2022 → ongoing

Decision date (initial)

2024-07-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-514381-39-00

EudraCT number

2021-005402-10

WHO UTN

U1111-1265-6930

ClinicalTrials.gov

NCT05222906

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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)

Secondary objectives 7

1. Assess maintenance of spleen volume stability with venglustat compared to Cerezyme
2. Assess maintenance of liver volume stability with venglustat compared to Cerezyme
3. Assess maintenance of hemoglobin level stability with venglustat compared to Cerezyme
4. Assess maintenance of platelet count stability with venglustat compared to Cerezyme
5. Evaluate the change in cerebrospinal (CSF) GL-1 and lyso-GL-1 biomarkers with venglustat compared to Cerezyme.
6. Evaluate the change in plasma GL-1 and lyso-GL-1 biomarkers with venglustat compared to Cerezyme
7. Evaluate the safety and tolerability of venglustat compared to Cerezyme

Conditions and MedDRA coding

Gaucher's disease type III

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001716-PIP07-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 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
2. Adult participant is ≥18 years of age
3. Pediatric participant is ≥12 years <18 years of age
4. The participant has a clinical diagnosis of GD3 and a documented deficiency of acid beta-glucosidase activity confirming this diagnosis.
5. The participant has a modified SARA score of 1 or above.
6. The presence of gaze palsy, predominantly horizontal, with slow or absent saccades.
7. 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.
8. Participants ≥ 30 kg of weight
9. Contraception for sexually active male or female participants; not pregnant or breastfeeding; no sperm donating for male participant
10. Signed written informed assent/consent

Exclusion criteria 19

1. The participant is blood transfusion-dependent.
2. 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.
3. 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.
4. The participant has renal insufficiency, as defined by an estimated glomerular filtration rate <30 mL/min/1.73m2 at the screening visit.
5. The participant has a history of cancer, except for basal cell carcinoma.
6. The participant has progressive myoclonic epilepsy.
7. The participant is pregnant (has a positive serum beta-human chronic gonadotropin [β-hCG]) or lactating.
8. The participant requires use of invasive ventilatory support.
9. The participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily.
10. The participant is scheduled for in-patient hospitalization including elective surgery, during the study.
11. The participant has had a major organ transplant (eg, bone marrow or liver).
12. A history of drug and/or alcohol abuse within the past year prior to the screening visit.
13. Chaperone therapy within 6 months, substrate reduction therapy other than venglustat within 6 months or venglustat substrate reduction therapy prior to enrollment.
14. Exposure to any investigational drug within the last 30 days or 5 half-lives from screening, whichever is longer
15. 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.
16. 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).
17. 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.
18. 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.
19. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change in Scale for Assessment and Rating of Ataxia (SARA) modified total score
2. Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score

Secondary endpoints 9

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)

Investigational products

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

Test 2

Comparator 3

Placebo 3

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

3 EU/EEA countries · 5 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 69 files

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

Application history

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