Venglustat in Combination With Cerezyme in Adult and Pediatric Patients With Gaucher Disease Type 3

  • STATUS
    Recruiting
  • participants needed
    49
  • sponsor
    Genzyme, a Sanofi Company
Send
Updated on 19 February 2024
See if I qualify

Summary

Primary Objectives:

Part 1:

Cohorts 1, 2 and 3

  • Evaluate cerebrospinal fluid (CSF) biomarkers in adult Gaucher disease (GD) Type 3 patients that distinguish GD3 from adult Gaucher disease Type 1 (GD1) patients.
  • Screen adult and pediatric GD3 patients who qualify for treatment with venglustat in Parts 2 and 3.

Parts 2 and 3:

Cohort 2

  • Evaluate short-term (Part 2) and long-term (Part 3) safety and tolerability of venglustat in combination with Cerezyme in adult GD3 patients.
  • Evaluate the change in CSF central nervous system (CNS) biomarkers (glucosylceramide [GL-1] and lyso-glucosylceramide [lyso-GL1]) from adult GD3 patients receiving venglustat in combination with Cerezyme (Part 2 only).

Cohort 3

  • Evaluate the efficacy of venglustat in combination with Cerezyme in adult and pediatric 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:

Parts 2 and 3:

Cohort 2

  • Evaluate the pharmacokinetics (PK) of venglustat in adult GD3 patients.

Cohort 3

  • Evaluate the efficacy of venglustat in combination with Cerezyme in adult and pediatric GD3 patients by assessing:
  • CSF Lyso-GL1 levels
  • Modified Friedreichs Ataxia Rating Scale - Activities of Daily Living (FARS-ADL)
  • Brain resting-state functional Magnetic Resonance Imaging (rs-fMRI) reflecting connectivity between parieto-occipital areas
  • Bone disease manifestations
  • Evaluate safety and tolerability of venglustat in combination with Cerezyme in adult and pediatric GD3 patients
  • Evaluate PK of venglustat in adult and pediatric GD3 patients.

Description

The total duration for GD1 participants is 45 days (Part 1), while for GD3 participants the total duration is up to 4.2 years for Cohort 2 and up to 3.7 years for Cohort 3.

Details
Condition Gaucher Disease Type 1-Gaucher Disease Type 3, Gaucher Disease Type 1-Gaucher Disease Type 3
Age 12-100 years
Treatment Placebo, venglustat (GZ/SAR402671), imiglucerase
Clinical Study IdentifierNCT02843035
SponsorGenzyme, a Sanofi Company
Last Modified on19 February 2024

Eligibility

 Yes No Not Sure

Inclusion Criteria

For participants 18 years of age: Participant must provide written informed consent prior to any study-related procedures being performed
For participants 12 and <18 years of age: Parent(s)/legal guardian(s) must provide written informed consent prior to any study related procedures being performed. If the patient is considered able by local regulation, assent will also be obtained before any study related procedures are performed
Participant has a clinical diagnosis of Gaucher Disease Type 1 (GD1) or Gaucher Disease Type 3 (GD3) and documented deficiency of acid beta-glucosidase activity confirming this diagnosis
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 and is within the therapeutic goals defined below, and is deemed clinically stable for at least 1 year by the Investigator
Participant has reached Gaucher disease therapeutic goals defined 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), or total splenectomy (provided the splenectomy occurred >3 years prior to randomization)
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
Participant, if female and of childbearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (-hCG)] at baseline
If participant has a history of seizures, except for myoclonic seizures, they are well controlled under appropriate medication not identified as a strong or moderate inducer or inhibitor of cytochrome P450 (CYP) 3A
Participant is willing to abstain from consumption of grapefruit, grapefruit juice, or grapefruit containing products for 72 hours prior to administration of the first dose of venglustat and for the duration of the treatment period
Oculomotor apraxia characterized by a horizontal saccade abnormality
Female participants of childbearing potential and male patients must be willing to practice true abstinence in line with their preferred and usual lifestyle, or use 2 acceptable effective methods of contraception for the duration of the study and for at least 6 weeks for females and 90 days for males following their last dose of venglustat
Cohort 1 only
GD1 participant is 18 and 40 years of age
Cohort 2 only
GD3 participant is 18 years of age
Cohort 3 only
GD3 adult participant 18 years of age
GD3 pediatric participant is 12 years of age <18 years and 30 kg of weight. For male patients 12 to <18 years of age: There is a potential risk for venglustat to impact male fertility particularly when used in patients who have not reached a certain stage of sexual maturation. If a patient has not reached Tanner Stage 3 by the screening visit, the Investigator should assess and discuss with the patient the potential benefits and risks when considering eligibility for study participation. In this benefit/risk assessment-discussion, the parent(s)/legal guardian(s), the patient (if considered able by local regulation), and the Sponsor's medical representative (if considered appropriate) shall be consulted

Exclusion Criteria

Substrate reduction therapy or chaperone therapy for GD within 6 months prior to enrollment
Participant has had a partial or total splenectomy within 3 years prior to randomization
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 patient has a diagnosis of Gilbert Syndrome
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
Participant has renal insufficiency, as defined by an estimated glomerular filtration rate <30 mL/min/1.73m2 at the screening visit
Participant has received an investigational product within 30 days prior to enrollment
Participant has a history of cancer, with the exception of basal cell carcinoma
Participant has myoclonic seizures
Participant is pregnant or lactating
Participant has, according to World Health Organization (WHO) Grading, a cortical cataract >one-quarter of the lens circumference (Grade cortical cataract-2) or a posterior subcapsular cataract >2 mm (Grade posterior subcapsular cataract-2). Patients with nuclear cataracts will not be excluded
Participant requires use of invasive ventilatory support
Participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily
Participant is unable to receive treatment with Cerezyme due to a known hypersensitivity or is unwilling to receive Cerezyme treatment to ensure maintenance of Gaucher treatment goals
Participant is currently receiving potentially cataractogenic medications (corticosteroids, psoralens used in dermatology with ultraviolet light therapy [PUVA], typical antipsychotics, and glaucoma medications) or any medication that may worsen the vision of a patient with cataract (eg, alpha-adrenergic glaucoma medications)
Participant has received strong or moderate inducers or inhibitors of CYP3A within 15 days or 5 half-lives from screening, whichever is longer, prior to enrolment in Part 2\. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting venglustat administration in Parts 2 and 3
Participant is scheduled for in-patient hospitalization including elective surgery, during the study
Participant has had a major organ transplant (e.g., bone marrow or liver)
Participant, in the opinion of the investigator, is unable to adhere to the requirements of the study or unable to undergo study assessments (e.g., contraindications for magnetic resonance imaging)
The above information is not intended to contain all considerations relevant
to a patient's potential participation in a clinical trial
Clear my responses
Read more

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name
Edit Delete

Added by • 

 • 

Private

Edit Delete

Reply by • • Private
Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note
  • abc Select a piece of text.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.