LEAP
Research type
Research Study
Full title
A 52-week two-part, open-label, multicentre, multinational study of the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of GZ/SAR402671 in combination with Cerezyme in adult patients with Gaucher disease type3.
IRAS ID
161921
Contact name
Derralynn Hughes
Contact email
Sponsor organisation
Sanofi
Eudract number
2014-002550-39
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
U1111-1156-4278, Universal Trial Number
Duration of Study in the UK
6 years, 0 months, 1 days
Research summary
Gaucher disease is an autosomal recessive inherited lysosomal storage disease that results from a deficiency of acid β-glucosidase [also known as glucocerebrosidase (GCase)], which leads to accumulation of glycosphingolipids in the reticuloendothelial system, particularly macrophages in the spleen, liver, bone marrow, and lung. Manifestations most frequently related to this accumulation include splenomegaly, hepatomegaly, thrombocytopenia, anemia, and skeletal pathology. Clinically, 3 major forms of Gaucher disease (GD1, GD2 & GD3)continue to be distinguished, based upon the presence or absence and rate of progression of the classically described constellation of neurological manifestations.
Genzyme is investigating GZ/SAR402671 as a possible oral therapeutic for the treatment of GD3. This compound is a second generation glucosylceramide synthase (GCS) inhibitor that blocks the conversion of ceramide to GL-1. As GL-1 serves as the central building block for more complex glycosphingolipids such as globotriaosylceramide (GL-3), monosialodihexosylganglioside(GM3)and GM2 anglioside, substrate reduction therapy (SRT) with GCS inhibitors is expected to have broad therapeutic applicability across a number of lysosomal storage diseases.
The objective of this study in Part 1 is to evaluate CNS biomarkers in GD3 patients that distinguish GD3 from GD1 and in Part 2 is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of GZ/SAR402671 in combination with Cerezyme in GD3 patients.
REC name
London - London Bridge Research Ethics Committee
REC reference
16/LO/1304
Date of REC Opinion
15 Sep 2016
REC opinion
Further Information Favourable Opinion