Kidney Week

Abstract: TH-PO385

The MANGROVE Phase 2 Trial: Study Design and Baseline Characteristics of Patients With Autosomal Dominant Polycystic Kidney Disease

Session Information

• Genetic Diseases of the Kidneys: Cystic - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1101 Genetic Diseases of the Kidneys: Cystic

Authors

• Gansevoort, Ron T., Department of Nephrology, University Medical Centre Groningen, University Hospital Groningen, Groningen, Netherlands

Ron T. Gansevoort,

• Pisani, Antonio, Department of Nephrology, University of Naples Federico II, Naples, Italy

Antonio Pisani,

• Hueso, Miguel, Department of Nephrology, Bellvitge University Hospital, Barcelona, Spain

Miguel Hueso,

• Van den Bergh, Davinia, Galapagos, NV, Mechelen, Belgium

Davinia Van den Bergh,

• Hettema, Willem, Galapagos, NV, Leiden, Belgium

Willem Hettema,

• Muller, Karine, Galapagos, NV, Mechelen, Belgium

Karine Muller,

• Fieuw, Ann, Galapagos, NV, Mechelen, Belgium

Ann Fieuw,

• Sulowicz, Wladyslaw, Department of Nephrology, Jagiellonian University, Kraków, Poland

Wladyslaw Sulowicz,

Background

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst development, mainly driven by chloride secretion that is mediated by the cystic fibrosis transmembrane conductance regulator (CFTR) channel.¹ Although the underlying molecular mechanism is not fully known, CFTR inhibitors have been shown to reduce cyst growth in vitro and in vivo.¹ With only one approved treatment, there is an unmet need for novel ADPKD therapies. MANGROVE is an ongoing phase 2a, proof-of-concept trial, evaluating the efficacy and safety of the CFTR inhibitor GLPG2737 in patients with ADPKD.

Methods

MANGROVE (NCT04578548; 2019-003521-21) comprises a randomized, double-blind, placebo-controlled treatment period and an open-label extension (OLE) treatment period (each 52 weeks with 4 weeks follow up). Adults (18–50 years) with rapidly progressing ADPKD (total kidney volume [TKV] >750 mL, Mayo class 1C–1E) and age-dependent estimated glomerular filtration rate (eGFR) (18–40 years: 30–90 mL/min/1.73 m²; >40–50 years: 30–60 mL/min/1.73 m²) were randomized 2:1 to receive GLPG2737 or matching placebo once daily for 52 weeks at baseline. Patients who completed double-blind treatment could enter the OLE. MANGROVE assessed treatment differences between GLPG2737 and placebo. Primary outcomes included change in height-adjusted TKV and frequency and severity of adverse events. Secondary outcomes included change in eGFR and estimated exposure to GLPG2737.

Results

The study enrolled 66 patients with ADPKD with a mean±SD age of 40.3±6.3 years, most of whom (92.4%) had arterial hypertension. Key disease characteristics and concomitant medication are reported in the table.

Conclusion

Study inclusion criteria were designed to enrich for patients with a high chance of rapid disease progression and were successful in doing so, as shown by the baseline patient characteristics.

1. Jouret F, Devuyst O. Cell Signal 2020;73:109703.

Funding

• Commercial Support – Galapagos NV and AbbVie Inc.