Clinical trial NCT05222906: Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients With Gaucher Disease Type 3
Official 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Gaucher's Disease Type III
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-02-03
Enrollment: 43
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double Dummy
Primary purpose: TREATMENT

Brief summary: This is a parallel arm, Phase 3, double-blind, double-dummy, active-comparator, 2 arm study to evaluate the efficacy and safety of daily oral venglustat versus intravenous Cerezyme infusions every two weeks for improvement or stabilization of the neurological manifestations and maintenance of systemic disease stability in participants aged ≥12 and \<18 years and adult patients with Gaucher disease Type 3 (GD3) who have been treated with Enzyme Replacement Therapy (ERT) for at least 3 years.

Detailed description: Screening period: 45 days

Double blind, double-dummy, primary analysis treatment period: 52 weeks

Open label extended treatment period: minimum of 52 weeks due to a common study end of treatment date

Follow up phone call: 30-37 days after end of treatment

Eligibility 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 or female participants; not pregnant or breastfeeding; no sperm donating for male participant
* Signed written informed assent/consent

Exclusion Criteria:

* 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 \[β-hCG\]) 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 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

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Primary outcomes:
measure: Change in Scale for Assessment and Rating of Ataxia (SARA) modified total score
timeFrame: From baseline to Week 52
measure: Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score
timeFrame: From baseline to Week 52
Secondary outcomes:
measure: Percent change in spleen volume
timeFrame: From baseline to Week 52
measure: Percent change in liver volume
timeFrame: From baseline to Week 52
measure: Change in hemoglobin level
timeFrame: From baseline to Week 52
measure: Percent change in platelet count
timeFrame: From baseline to Week 52
measure: Percent change in CSF GL-1 and lyso-GL-1 levels
timeFrame: From baseline to Week 52
measure: Percent change in plasma GL-1 and lyso-GL-1 levels
timeFrame: From baseline to Week 52
measure: Number of patients with treatment emergent adverse events (TEAEs)/ serious adverse events (SAEs)/ adverse events of special interest (AESIs)
timeFrame: From baseline to max of 4.5 years
measure: 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)
timeFrame: From baseline to Week 52
measure: Change in Patient Health Questionnaire 9 (PHQ-9) during the treatment-emergent period (for participants 12 years of age at baseline)
timeFrame: From baseline to Week 52
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University School of Medicine - Investigational Site Number: 8400003
state: Connecticut
city: Iowa City
country: United States
facility: University of Iowa - Investigational Site Number: 8400002
state: Iowa
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas Site Number : 8400008
state: Texas
city: Fairfax
country: United States
facility: Lysosomal & Rare Disorders Research & Treatment Center, Inc - Investigational Site Number: 8400001
state: Virginia
city: Buenos Aires
country: Argentina
facility: Hospital de Ninos - Investigational Site Number: 320001
city: Winnipeg
country: Canada
facility: Children's Hospital Research Institute of Manitoba - Investigational Site Number: 1240001
state: Manitoba
city: Taipei
country: China
facility: National Taiwan University Hospital-Investigational Site Number: 1580001
state: Taiwan
city: Beijing
country: China
facility: Peking Union Medical College Hospital - Investigational Site Number: 1560001
city: Guangzhou
country: China
facility: The First Affiliated Hospital - Investigational Site Number: 1560002
city: Shanghai
country: China
facility: Xinhua Hospital - Investigational Site Number: 1560004
city: Paris
country: France
facility: 47-87, boulevard de l'hôpital - Investigational Site Number: 2500003
city: Paris
country: France
facility: Hopital Necker - Investigational Site Number: 2500001
city: Hochheim am Main
country: Germany
facility: SphinCS GmbH - Investigational Site Number: 2760001
city: Debrecen
country: Hungary
facility: Debreceni Egyetem, Klinikai Központ, Reumatológiai Klinika - Investigational Site Number: 3480001
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Investigational Site Number : 3800003
state: Lombardia
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria (AOU) "Federico II" - Investigational Site Number: 3800002
city: Odawara
country: Japan
facility: Odawara Municipal Hospital-Investigational Site Number : 3920002
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku University School of Medicine - Investigational Site Number: 3920001
city: Adana
country: Turkey
facility: Cukurova University Medical School Hospital-Investigational Site Number : 7920001
city: Ankara
country: Turkey
facility: Gazi University Medical Hospital-Investigational Site Number : 7920002
city: Istanbul
country: Turkey
facility: Istanbul University Medical Faculty Hospital-Investigational Site Number : 7920004
city: London
country: United Kingdom
facility: Investigational Site Number : 8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: