Clinical Trials/NCT02843035

NCT02843035

Active, Not Recruiting

Phase 2

A 4-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 With Venglustat Monotherapy Extension

Genzyme, a Sanofi Company7 sites in 4 countries12 target enrollmentJanuary 4, 2017

ConditionsGaucher Disease Type 1 Gaucher Disease Type 3

Interventionsvenglustat (GZ402671)imiglucerase

Overview

Phase: Phase 2
Intervention: venglustat (GZ402671)
Conditions: Gaucher Disease Type 1
Sponsor: Genzyme, a Sanofi Company
Enrollment: 12
Locations: 7
Primary Endpoint: Number of participants with Treatment Emergent Adverse Events (TEAEs)
Status: Active, Not Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Part 1: Biomarker evaluation/screening phase

Primary Objectives:

Evaluate cerebrospinal fluid (CSF) biomarkers in adult Gaucher disease Type 3 (GD3) participants that distinguish GD3 from adult Gaucher disease Type 1 (GD1) participants
Screen adult GD3 participants who qualify for treatment with venglustat in Parts 2, Part 3, and Part 4 Parts 2 and 3: Combination treatment phases

Primary objectives:

Evaluate short-term (Part 2) and long-term (Part 3) safety and tolerability of venglustat in combination with Cerezyme in adult GD3 participants
Evaluate the change in CSF central nervous system (CNS) biomarkers (glucosylceramide [GL-1] and lyso-glucosylceramide [lyso-GL-1]) from adult GD3 participants receiving venglustat in combination with Cerezyme (Part 2 only) Part 4: Extended treatment phase with monotherapy

Primary objectives:

• Evaluate safety and tolerability of venglustat monotherapy in adult GD3 participants who have remained systemically stable on venglustat in combination with Cerezyme Parts 2 and 3: Combination treatment phases

Secondary Objectives:

Evaluate the pharmacokinetics (PK) of venglustat in adult GD3 participants
Evaluate the efficacy of venglustat in combination with Cerezyme in systemic disease in adult GD3 participants by assessing spleen volume, liver volume, hemoglobin level and platelet count
Evaluate the efficacy of venglustat in combination with Cerezyme on neurological function in adult GD3 participants by assessing Ataxia using the Scale for the Assessment and Rating of Ataxia (SARA)
Evaluate plasma biomarkers (lyso-GL-1 and GL-1) in adult GD3 participants Part 4: Extended treatment phase with monotherapy

Secondary objectives:

Evaluate the efficacy of venglustat in systemic disease in adult GD3 participants by assessing spleen volume, liver volume, hemoglobin level and platelet count
Evaluate the efficacy of venglustat on neurological function in adult GD3 participants by assessing Ataxia using the Scale for the Assessment and Rating of Ataxia (SARA)
Evaluate plasma biomarkers (lyso-GL-1 and GL-1) in adult GD3 participants

Detailed Description

The total duration for GD1 participants is 45 days (Part 1), while for GD3 participants the total duration is up to approximately 10 years

Registry

clinicaltrials.gov

Start Date

January 4, 2017

End Date

October 30, 2026

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Genzyme, a Sanofi Company

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•GD3 and GD1 participants 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 to be eligible for this study:
•Hemoglobin level of ≥11.0 g/dL for females and ≥12.0 g/dL for males.
•Platelet count ≥100,000/mm
•Spleen volume \<10 multiples of normal (MN), or total splenectomy (provided the splenectomy occurred \>3 years prior to randomization).

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 participant 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.

Arms & Interventions

Open label (OL) venglustat

Administered once a day orally for up to approximately 10 years. Participants will continue their usual dose of Cerezyme during Part 1, Part 2 and Part 3. There is no administration of Cerezyme in Part 4 unless administrated as rescue treatment.

Intervention: venglustat (GZ402671)

Open label (OL) venglustat

Intervention: imiglucerase

Outcomes

Primary Outcomes

Number of participants with Treatment Emergent Adverse Events (TEAEs)

Time Frame: From screening up to end of study, up to approximately 10 years

Assessment of pharmacodynamic (PD) parameter: Lyso-glucosylceramide (lyso-GL1) and glucosylceramide (GL-1) in cerebrospinal fluid (CSF)

Time Frame: From screening through Week 52

Secondary Outcomes

Assessment of pharmacodynamic (PD) parameter: Lyso-glucosylceramide (lyso-GL1) and glucosylceramide (GL-1) in plasma(From screening up to end of study, up to approximately 10 years)
Assessment of plasma pharmacokinetic parameter: Cmax (Part 2)(Day 1)
Assessment of plasma pharmacokinetic parameter: Tmax (Part 2)(Day 1)
Assessment of plasma pharmacokinetic parameter: AUC0-24h (Part 2)(Day 1)
Assessment of plasma pharmacokinetic parameter: Ctrough(Weeks 12 and 39 (Part 2), and on Weeks 78, 104, and 156 (for Part 3))
Assessment of CSF pharmacokinetic parameter: Cmax(Week 4, Week 26, and Week 52)
Assessment of spleen volume(From screening up to end of study, up to approximately 10 years)
Assessment of spleen volume (Part 4)(From Week 260 up to end of study, up to approximately 10 years)
Assessment of liver volume(From screening up to end of study, up to approximately 10 years)
Assessment of liver volume (Part 4)(From Week 260 up to end of study, up to approximately 10 years)
Assessment of hemoglobin level(From screening up to end of study, up to approximately 10 years)
Assessment of hemoglobin level (Part 4)(From Week 260 up to end of study, up to approximately 10 years)
Assessment of platelet level(From screening up to end of study, up to approximately 10 years)
Assessment of platelet level (Part 4)(From Week 260 up to end of study, up to approximately 10 years)
Assessment of Ataxia(From screening up to end of study, up to approximately 10 years)
Assessment of Ataxia (Part 4)(From Week 260 up to end of study, up to approximately 10 years)