Clinical trial NCT04578548: A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Autosomal Dominant Polycystic Kidney Disease
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2020-10-08
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: DB Period: Mean Percent Change From MRI Baseline in htTKV
timeFrame: MRI Baseline up to Week 52
measure: DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From first dose to Week 56
Secondary outcomes:
measure: DB Period: Mean Change From Baseline in eGFR
timeFrame: Baseline up to Week 52
measure: DB Period: Area Under the Plasma Concentration-Time Curve During a Dosing Interval (AUCtau) of GLPG2737 and Its Metabolite
timeFrame: Predose (within 30 minutes prior to dosing), 1, 1.5, 2, 3, 4, 5, 6, 7 hours post dose through Week 52
measure: DB Period: Maximum Observed Plasma Concentration (Cmax) of GLPG2737 and Its Metabolite
timeFrame: Predose (within 30 minutes prior to dosing), 1, 1.5, 2, 3, 4, 5, 6, 7 hours post dose through Week 52
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires St. Luc (UCL)
city: Leuven
country: Belgium
facility: UZ Leuven
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Dresden
country: Germany
facility: Uniklinikum Dresden
city: Milan
country: Italy
facility: IRCSS Ospedale San Raffaele
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Napoli
country: Italy
facility: Uni Campania L. Vanvitelli
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri IRCCS
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Groningen
country: Netherlands
facility: UMCG
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Kraków
country: Poland
facility: Specjalistyczne Centrum Medyczne SCM Spółka z o.o.
city: Warsaw
country: Poland
facility: DaVita Sp. z o.o. Stacja Dializ
city: Łódź
country: Poland
facility: Szpital Kliniczny UM w Lodzi
city: Barcelona
country: Spain
facility: Fundacion Puigvert
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Nefrologia Clinica C.P.
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director
role: STUDY_DIRECTOR
References:
citation: 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.