Venglustat in Combination With Cerezyme in Adult Patients With Gaucher Disease Type 3 With Venglustat Monotherapy Extension

NCT02843035 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: PDY13949U1111-1156-42782023-508646-182014-002550-39
• Study Type: interventional
• Target: 12
• Locations: 4 countries
• Sites: 7

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

Conditions

Gaucher Disease Type 1; Gaucher Disease Type 3

Outcome Measures

Primary Outcomes (2)

• Number of participants with Treatment Emergent Adverse Events (TEAEs)

  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)

  From screening through Week 52

Secondary Outcomes (16)

• 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)

Study Arms (1)

Open label (OL) venglustat

EXPERIMENTAL

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.

Drug: venglustat (GZ402671); Drug: imiglucerase

Interventions

venglustat (GZ402671) DRUG

Pharmaceutical form: capsule or tablet Route of administration: oral

Open label (OL) venglustat

imiglucerase DRUG

Pharmaceutical form: sterile lyophilized product Route of administration: intravenous

Also known as: Cerezyme

Open label (OL) venglustat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/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 has maintained GD therapeutic goals defined as all of the following to be eligible for entering Part 4 of this study:
• Hemoglobin level of ≥11.0 g/dL for females and ≥12.0 g/dL for males
• Platelet count ≥100 000/mm3

You may not qualify if:

• 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.
• 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). Participants 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (7)

Yale University School of Medicine Site Number : 840002

New Haven, Connecticut, 06520, United States

Location

Baylor Institute of Metabolic Diseases Site Number : 840001

Dallas, Texas, 75226, United States

Location

Lysosomal and Rare Disorders Research and Treatment Center, Inc Site Number : 840003

Fairfax, Virginia, 22030, United States

Location

Investigational Site Number : 276001

Mainz, 55131, Germany

Location

Investigational Site Number : 392001

Minato-ku, Tokyo, 105-8471, Japan

Location

Investigational Site Number : 826003

Cambridge, Cambridgeshire, CB2 OQQ, United Kingdom

Location

Investigational Site Number : 826002

Salford, Manchester, M6 8HD, United Kingdom

Location

Related Publications (1)

• Schiffmann R, Mengel E, Wallace M, Rochmann C, Turnbull J, Krupnick R, Gwaltney C, Pulikottil-Jacob R, Batsu I, Zheng R, Hamed A. Qualitative Study of the Patient Experience with Venglustat for Gaucher Disease Type 3 in a Phase 2 Open-Label, Multicenter, Multinational Study (LEAP). Adv Ther. 2024 Jul;41(7):2907-2923. doi: 10.1007/s12325-024-02881-2. Epub 2024 May 27.

  PMID: 38802634 DERIVED

MeSH Terms

Conditions

Gaucher Disease

Interventions

venglustat; imiglucerase

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2016
• First Posted: July 25, 2016
• Study Start: January 4, 2017
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (3); JP (1); GB (2); DE (1)