NCT02843035: LEAP

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

Active, enrolled Phase 2 Last updated 26 March 2025

What this trial tests

Phase 2 trial testing venglustat (GZ402671) in Gaucher Disease Type 1 in 12 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

4 January 2017

Primary endpoint
30 October 2026

30 October 2026

Quick facts

Lead sponsor	Genzyme, a Sanofi Company
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	12
Start date	4 January 2017
Primary completion	30 October 2026
Estimated completion	30 October 2026
Sites	7 locations across United Kingdom, Japan, United States, Germany

Drugs / interventions tested

• venglustat (GZ402671)
• imiglucerase (IMIGLUCERASE) — full drug profile →

Conditions studied

• Gaucher Disease Type 1 — all drugs for Gaucher Disease Type 1 →
• Gaucher Disease Type 3 — all drugs for Gaucher Disease Type 3 →

Sponsor

Genzyme, a Sanofi Company — full company profile →

Who can join

18 and older, any sex, with Gaucher Disease Type 1 or Gaucher Disease Type 3. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Diagnosing neuronopathic Gaucher disease: New considerations and challenges in assigning Gaucher phenotypes.
   Daykin EC, Ryan E, Sidransky E. · · 2021 · cited 51× · PMID 33483255 · DOI 10.1016/j.ymgme.2021.01.002
2. Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients with Parkinson's Disease and a GBA Mutation: Results from Part 1 of the Randomized, Double-Blinded, Placebo-Controlled MOVES-PD Trial.
   Peterschmitt MJ, Saiki H, Hatano T, Gasser T, et al · · 2022 · cited 48× · PMID 34897099 · DOI 10.3233/jpd-212714
3. Lipids as Emerging Biomarkers in Neurodegenerative Diseases.
   Wei J, Wong LC, Boland S. · · 2023 · cited 46× · PMID 38203300 · DOI 10.3390/ijms25010131
4. The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment.
   Toro C, Zainab M, Tifft CJ. · · 2021 · cited 46× · PMID 34450229 · DOI 10.1016/j.neulet.2021.136195
5. Therapeutic Approaches in Lysosomal Storage Diseases.
   Fernández-Pereira C, San Millán-Tejado B, Gallardo-Gómez M, Pérez-Márquez T, et al · · 2021 · cited 43× · PMID 34944420 · DOI 10.3390/biom11121775
6. The heat shock protein amplifier arimoclomol improves refolding, maturation and lysosomal activity of glucocerebrosidase.
   Fog CK, Zago P, Malini E, Solanko LM, et al · · 2018 · cited 41× · PMID 30497978 · DOI 10.1016/j.ebiom.2018.11.037
7. Venglustat combined with imiglucerase for neurological disease in adults with Gaucher disease type 3: the LEAP trial.
   Schiffmann R, Cox TM, Dedieu JF, Gaemers SJM, et al · · 2023 · cited 34× · PMID 36256599 · DOI 10.1093/brain/awac379
8. Elevated glucosylsphingosine in Gaucher disease induced pluripotent stem cell neurons deregulates lysosomal compartment through mammalian target of rapamycin complex 1.
   Srikanth MP, Jones JW, Kane M, Awad O, et al · · 2021 · cited 34× · PMID 33656802 · DOI 10.1002/sctm.20-0386