Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Venglustat in Combination With Cerezyme in Adult Patients With Gaucher Disease Type 3 (LEAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02843035
Recruitment Status : Active, not recruiting
First Posted : July 25, 2016
Last Update Posted : August 27, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Brief Summary:

Primary Objectives:

Part 1: Biomarker evaluation/screening phase

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

Parts 2 and 3: Treatment phases

  • 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-GL-1]) from adult GD3 patients receiving venglustat in combination with Cerezyme (Part 2 only)

Secondary Objectives:

  • Evaluate the pharmacokinetics (PK) of venglustat in adult GD3 patients
  • Explore the efficacy of venglustat in combination with Cerezyme in infiltrative lung disease (ILD) in adult GD3 patients (Part 2 only)
  • Explore the efficacy of venglustat in combination with Cerezyme in systemic disease in adult GD3 patients
  • Explore the efficacy of venglustat in combination with Cerezyme on neurological function and on exploratory CSF biomarkers other than lyso-GL-1 and GL-1 in adult GD3 patients

Condition or disease Intervention/treatment Phase
Gaucher Disease Type 1 Gaucher Disease Type 3 Drug: venglustat (GZ402671) Drug: imiglucerase Phase 2

Detailed Description:
The total duration for GD1 participants is 45 days (Part 1), while for GD3 participants the total duration is up to 5.2 years

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 260-Week, 3-part, Open-label, Multicenter, Multinational Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamic, and Exploratory Efficacy of Venglustat in Combination With Cerezyme in Adult Patients With Gaucher Disease Type 3
Actual Study Start Date : January 4, 2017
Estimated Primary Completion Date : January 11, 2024
Estimated Study Completion Date : January 11, 2024


Arm Intervention/treatment
Experimental: Open label (OL) venglustat
Administered once a day orally for 260 weeks. Patients will continue their usual dose of Cerezyme throughout study.
Drug: venglustat (GZ402671)

Pharmaceutical form: tablet or capsule

Route of administration: oral


Drug: imiglucerase

Pharmaceutical form: sterile lyophilized product

Route of administration: intravenous

Other Name: Cerezyme




Primary Outcome Measures :
  1. Number of patients with Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From screening through Week 260 ]
  2. Assessment of pharmacodynamic (PD) parameter: Lyso-glucosylceramide (lyso-GL1) and glucosylceramide (GL-1) in cerebrospinal fluid (CSF) [ Time Frame: From screening through Week 52 ]
  3. Assessment of pharmacodynamic (PD) parameter: Lyso-glucosylceramide (lyso-GL1) and glucosylceramide (GL-1) in plasma [ Time Frame: From screening through Week 260 ]

Secondary Outcome Measures :
  1. Assessment of pharmacokinetic parameter: plasma maximum concentration (Cmax) [ Time Frame: Day 1, Week 4, Week 26, and Week 52 ]
  2. Assessment of pharmacokinetic parameter: plasma time at Cmax (Tmax) [ Time Frame: Day 1, Week 4, Week 26, and Week 52 ]
  3. Assessment of pharmacokinetic parameter: plasma area under the curve (AUC) [ Time Frame: Day 1, Week 4, Week 26, and Week 52 ]
  4. Assessment of pharmacokinetic parameter: plasma trough concentration (Ctrough) [ Time Frame: Weeks 12 and 39 (Part 2), and on Weeks 78, 104, and 156 (for Part 3) ]
  5. Assessment of pharmacokinetic parameter: CSF maximum concentration (Cmax) [ Time Frame: Day 1, Week 4, Week 26, and Week 52 ]
  6. Assessment of pharmacokinetic parameter: CSF time at Cmax (Tmax) [ Time Frame: Day 1, Week 4, Week 26, and Week 52 ]
  7. Assessment of pharmacokinetic parameter: CSF area under the curve (AUC) [ Time Frame: Day 1, Week 4, Week 26, and Week 52 ]
  8. Immunogenicity testing as needed for IAR (Cerezyme) [ Time Frame: From screening through Week 260 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

GD3 and GD1 patients must meet the following criteria to be eligible for this study:

  • GD1 participant is ≥18 and ≤40 years of age.
  • GD3 participant is ≥18 years of age.
  • Participant must provide written informed consent prior to any study-related procedures being 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 (β-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.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

  • 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, alphaadrenergic 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02843035


Locations
Layout table for location information
United States, Connecticut
Investigational Site Number :840002
New Haven, Connecticut, United States, 06520
United States, Texas
Investigational Site Number :840001
Dallas, Texas, United States, 75226
United States, Virginia
Investigational Site Number :840003
Fairfax, Virginia, United States, 22030
Germany
Investigational Site Number :276001
Mainz, Germany, 55131
Japan
Investigational Site Number :392001
Minato-ku, Tokyo, Japan, 105-8471
United Kingdom
Investigational Site Number :826003
Cambridge, Cambridgeshire, United Kingdom, CB2 OQQ
Investigational Site Number :826001
London, London, City Of, United Kingdom, NW1 2PJ
Investigational Site Number :826002
Salford, Manchester, United Kingdom, M6 8HD
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
Layout table for additonal information
Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT02843035    
Other Study ID Numbers: PDY13949
2014-002550-39 ( EudraCT Number )
U1111-1156-4278 ( Registry Identifier: ICTRP )
First Posted: July 25, 2016    Key Record Dates
Last Update Posted: August 27, 2021
Last Verified: August 23, 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Gaucher Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders