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 Participants 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 participants 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
    • Fundaciòn 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 milliliters per minute per 1.73 square meter (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 millimeters of mercury (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 participants who completed the 52-week double-blind treatment period on investigational product (IP).
• Participant, 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 magnetic resonance imaging (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 electrocardiogram (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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLPG2737 During DB + During OLE; Participants received 150 milligrams (mg) GLPG2737 capsules orally once daily for 52 weeks in the double-blind (DB) treatment period. Eligible participants were rolled over to an open-label extension (OLE) period to receive 150 mg GLPG2737 orally once daily for 52 weeks.	Drug: GLPG2737; Capsules administered orally
Placebo Comparator: Placebo During DB + GLPG2737 During OLE; Participants received placebo matched to GLPG2737 capsules orally once daily for 52 weeks in the DB treatment period. Eligible participants were rolled over to an OLE period to receive 150 mg GLPG2737 orally once daily for 52 weeks.	Drug: GLPG2737; Capsules administered orally; Drug: Placebo; Matching placebo capsules administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Mean Percent Change From MRI Baseline in htTKV	htTKV is used in participants with ADPKD disease to predict the onset of renal insufficiency. htTKV was calculated using TKV (in mL) obtained from MRI divided by height (in m). MRI Baseline: For MRI assessments, all non-missing values before the first study drug administration in the study +14 days (included) was considered as the primary baseline definition. Results were derived by mean of the individual slopes (i.e. using all MRI performed between baseline and Week 52).	MRI Baseline up to Week 52
DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug, whether or not considered related to it. A serious adverse event (SAE) is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results a congenital anomaly/birth defect or other medically important event. A TEAE was defined as an AE observed after starting administration of the study drug until 30 days after last DB dose or 1 day before OLE dose, whichever occurred first.	From first dose to Week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Mean Change From Baseline in eGFR	The eGFR is a test that measures level of kidney function and determines the stage of kidney disease. eGFR was based on CKD-EPI formula (2009) calculated from serum creatinine concentrations. Results were derived by mean of the individual slopes (i.e. using data between baseline and Week 52).	Baseline up to Week 52
DB Period: Area Under the Plasma Concentration-Time Curve During a Dosing Interval (AUCtau) of GLPG2737 and Its Metabolite	AUC0-tau described the area under the curve limited to the end of a dosing interval. The metabolite of GLPG2737 is M4.	Predose (within 30 minutes prior to dosing), 1, 1.5, 2, 3, 4, 5, 6, 7 hours post dose through Week 52
DB Period: Maximum Observed Plasma Concentration (Cmax) of GLPG2737 and Its Metabolite	Cmax is the maximum observed plasma concentration of the drug. The metabolite of GLPG2737 is M4.	Predose (within 30 minutes prior to dosing), 1, 1.5, 2, 3, 4, 5, 6, 7 hours post dose through Week 52

Collaborators and Investigators

• Sponsor: Galapagos NV
• Investigators: Study Director: Galapagos Study Director, Galapagos NV

Publications and helpful links

General Publications

• Ron T. Gansevoort et al., 2022. The MANGROVE Phase 2 Trial: Study Design and Baseline Characteristics of Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD). Abstract (385) presented at the Annual Congress of the American Society of Nephrology, 3-Nov-2022 to 6-Nov-2022.

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): August 22, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

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; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; 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