STAGED-PKD

  • Research type

    Research Study

  • Full title

    Multicenter, randomized, double-blind, placebo-controlled two stage study to characterize the efficacy, safety, tolerability and pharmacokinetics of GZ/SAR402671 in patients at risk of rapidly progressive Autosomal Dominant Polycystic Kidney Disease (ADPKD)

  • IRAS ID

    245567

  • Contact name

    Albert Chee Meng Ong

  • Contact email

    a.ong@sheffield.ac.uk

  • Sponsor organisation

    Genzyme Corporation

  • Eudract number

    2017-004084-12

  • ISRCTN Number

    ISRCTN00000000

  • Clinicaltrials.gov Identifier

    NCT03523728

  • Clinicaltrials.gov Identifier

    U1111-1202-0775, WHO universal trial number

  • Duration of Study in the UK

    4 years, 2 months, 17 days

  • Research summary

    Summary of Research

    Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening genetic disease caused by mutations in PKD1 and PKD2 genes characterized by the formation of multiple kidney cysts that enlarge with disease progression to result in end-stage renal disease and dialysis in ~50% of patients.

    GZ/SAR402671 is a glucosylceramide synthase (GCS) inhibitor that decreases the synthesis of glucosylceramide (GL-1), a central building block for more complex glycosphingolipids (GSLs).

    Human and murine ADPKD is associated with increased GCS activity, leading to a pathogenic accumulation of GSLs such as GL-1, lactosylceramide (GL-2)and GM3. Several structurally distinct GCS inhibitors have significantly reduced cyst growth and preserved renal function in 3 different preclinical ADPKD models.

    This is a multicentre, randomized, double-blind, placebo-controlled two stage study to characterize the efficacy, safety, tolerability and pharmacokinetics of GZ/SAR402671 in patients at risk of rapidly progressive ADPKD.

    Primary objective is to determine the effect of GZ/SAR402671 on the rate of total kidney volume (TKV) growth in patients at risk of rapidly progressive ADPKD and to determine the effect of GZ/SAR402671 on rate of renal function (eGFR) decline as compared to placebo in patients at risk of rapidly progressive ADPKD.

  • REC name

    North West - Greater Manchester Central Research Ethics Committee

  • REC reference

    18/NW/0792

  • Date of REC Opinion

    28 Jan 2019

  • REC opinion

    Further Information Favourable Opinion