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

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

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 Subjects With Autosomal Dominant Polycystic Kidney Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04578548
• Other study ID #: GLPG2737-CL-203
• Secondary ID: 2019-003521-21
• Status: Terminated
• Phase: Phase 2
• Start date: November 10, 2020
• Est. completion date: April 4, 2023

Study information

• Verified date: April 2023
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 subjects with rapidly progressing ADPKD.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 66
• Est. completion date: April 4, 2023
• Est. primary completion date: December 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthrogryposis
• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Placebo
Matching placebo capsules administered orally with food
• GLPG2737
Capsules administered orally with food

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St. Luc (UCL)	Brussels
Belgium	UZ Leuven	Leuven
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	Vseobecna fakultni nemocnice v Praze	Praha
Germany	Uniklinikum Dresden	Dresden
Italy	IRCSS Ospedale San Raffaele	Milan
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Uni Campania L. Vanvitelli	Napoli
Italy	Fondazione Salvatore Maugeri IRCCS	Pavia
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	UMCG	Groningen
Netherlands	Radboud UMC	Nijmegen
Poland	Specjalistyczne Centrum Medyczne SCM Spólka z o.o.	Kraków
Poland	Szpital Kliniczny UM w Lodzi	Lódz
Poland	DaVita Sp. z o.o. Stacja Dializ	Warsaw
Spain	Fundacion Puigvert	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Nefrologia Clinica C.P.	Madrid
Spain	Hospital Universitario Dr. Peset	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

Belgium,  Czechia,  Germany,  Italy,  Netherlands,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Percent Change From Baseline of Height-Adjusted Total Kidney Volume (htTKV)		From baseline until 52 weeks
Primary	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)		From Day 1 until 56 weeks
Primary	Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)		From Day 1 until 56 weeks
Primary	Percentage of Participants With TEAEs According to Severity		From Day 1 until 56 weeks
Primary	Percentage of Participants With TEAEs Leading to Treatment Discontinuation		From Day 1 until 52 weeks
Secondary	Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)		From baseline until 52 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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