A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

An Exploratory, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Orally Administered GLPG2737 for 52 Weeks, Followed by an Open-label Extension Period of 52 Weeks in Subjects With Autosomal Dominant Polycystic Kidney Disease

This is an exploratory, randomized, double-blind, placebo-controlled, parallel group, multicenter, proof of concept study (Phase 2a), evaluating orally administered GLPG2737 for a double-blind (DB) treatment period of 52 weeks and 4 weeks of follow up as well as an open-label extension (OLE) treatment period of 52 weeks and 4 weeks of follow-up, in subjects with rapidly progressing ADPKD.

Study Overview

• Status: Terminated
• Conditions: Autosomal Dominant Polycystic Kidney Disease
• Intervention / Treatment: Drug: GLPG2737; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St. Luc (UCL)
  • Leuven, Belgium, 3000
    • UZ Leuven
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni Nemocnice u sv. Anny v Brne
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Praha, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
• Germany
  • Dresden, Germany, 01307
    • Uniklinikum Dresden
• Italy
  • Milan, Italy, 20132
    • Ircss Ospedale San Raffaele
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Napoli, Italy, 80131
    • Uni Campania L. Vanvitelli
  • Pavia, Italy, 27100
    • Fondazione Salvatore Maugeri IRCCS
• Netherlands
  • Amsterdam, Netherlands, 1105
    • Amsterdam UMC
  • Groningen, Netherlands, 9713
    • UMCG
  • Nijmegen, Netherlands, 6525
    • Radboud UMC
• Poland
  • Kraków, Poland, 31-559
    • Specjalistyczne Centrum Medyczne SCM Spółka z o.o.
  • Warsaw, Poland, 02-758
    • DaVita Sp. z o.o. Stacja Dializ
  • Łódź, Poland, 92-213
    • Szpital Kliniczny UM w Lodzi
• Spain
  • Barcelona, Spain, 08025
    • Fundacion Puigvert
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Madrid, Spain, 28041
    • Nefrologia Clinica C.P.
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria for the double-blind period of the study:

• Documented diagnosis of typical ADPKD, using the Ravine criteria (Ravine, et al., 1994).

• Rapidly progressive disease, defined as presence of all of the following:

  • Total Kidney Volume (TKV) >750 mL, as determined on imaging not older than 5 years before screening. If historical imaging is not available or older than 5 years, imaging can be performed during the screening period according to local clinical practice (that is, echography, magnetic resonance imaging [MRI])
  • Mayo ADPKD Classification Classes 1C to 1E.
• eGFR at screening between 30 to 90 mL/min/1.73 m^2 for participants aged 18 to 40 years (inclusive), and between 30 to 60 mL/min/1.73 m^2 for participants aged 40 to 50 years.
• Blood pressure ≤ 150/90 mmHg. In case a participant is treated for hypertension, she/he should be on a stable treatment regimen of antihypertensive therapy for at least 8 weeks prior to the screening visit, and during the screening period.

Key Inclusion Criteria for the OLE period of the study:

• Male and female subjects who completed the 52-week double-blind treatment period on investigational product (IP).
• Subject, according to the investigator's judgment, may benefit from long-term treatment with GLPG2737.

Key Exclusion Criteria for the double-blind period of the study:

• Congenital absence of 1 kidney, or participant had a previous nephrectomy or has a transplanted kidney or a transplantation is planned in the foreseeable future.
• Administration of polycystic kidney disease-modifying agents (for example, tolvaptan, somatostatin analogues) or interventions (such as cyst aspiration or cyst fenestration) within 12 weeks prior to the screening visit and during the screening period. In case tolvaptan is not being administered, this should be because of e.g. non-availability, intolerance, or physician's clinical judgment.
• Any condition or circumstances that, in the opinion of the investigator, may make a participant unlikely or unable to complete the study or comply with study procedures and requirements (for example, unable to undergo MRI due to participant's weight exceeds the weight capacity of the MRI, ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, etc.).

Key exclusion criteria for the OLE period of the study:

• Clinically significant abnormalities detected on 12-lead ECG of either rhythm or conduction, QTcF >450 ms, or long QT syndrome.

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DB Period: GLPG2737; GLPG2737 will be administered orally once daily with food for 52 weeks.	Drug: GLPG2737; Capsules administered orally with food
Placebo Comparator: DB Period: Placebo; Matching placebo will be administered orally once daily with food for 52 weeks.	Drug: Placebo; Matching placebo capsules administered orally with food
Experimental: OLE Period: GLPG2737; Participants completing the DB period (GLPG2737 and placebo arm) will enter an OLE period of 52 weeks where GLPG2737 will be administered orally once daily.	Drug: GLPG2737; Capsules administered orally with food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Percent Change From Baseline of Height-Adjusted Total Kidney Volume (htTKV)	From baseline until 52 weeks
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	From Day 1 until 56 weeks
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	From Day 1 until 56 weeks
Percentage of Participants With TEAEs According to Severity	From Day 1 until 56 weeks
Percentage of Participants With TEAEs Leading to Treatment Discontinuation	From Day 1 until 52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)	From baseline until 52 weeks
Area Under the Plasma Concentration-Time Curve During a Dosing Interval (AUCtau) of GLPG2737, estimated based on population pharmacokinetics (PK) modelling	predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 5-7, 8-9 hours postdose on Week 4
AUCtau of G1125498 (Major Active Metabolite of GLPG2737), estimated based on population PK modelling	predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 5-7, 8-9 hours postdose on Week 4
Maximum Observed Plasma Concentration (Cmax) of GLPG2737, estimated based on population PK modelling	predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 5-7, 8-9 hours postdose on Week 4
Cmax of G1125498 (Major Active Metabolite of GLPG2737), estimated based on population PK modelling	predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 5-7, 8-9 hours postdose on Week 4

Collaborators and Investigators

• Sponsor: Galapagos NV
• Investigators: Study Director: Ann Fieuw, MD, MSc, Galapagos NV

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Actual): December 14, 2022
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: October 1, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Arthrogryposis
• Other Study ID Numbers: GLPG2737-CL-203; 2019-003521-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes