Back to resultsA Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Primary Purpose
Autosomal Dominant Polycystic Kidney Disease
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
GLPG2737
Sponsored by
About this trial
This is an interventional treatment trial for Autosomal Dominant Polycystic Kidney Disease
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 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.
Sites / Locations
- Cliniques Universitaires St. Luc (UCL)
- UZ Leuven
- Fakultni nemocnice u sv. Anny v Brne
- Fakultni nemocnice Hradec Kralove
- Vseobecna fakultni nemocnice v Praze
- Uniklinikum Dresden
- IRCSS Ospedale San Raffaele
- Azienda Ospedaliera Universitaria Federico II
- Uni Campania L. Vanvitelli
- Fondazione Salvatore Maugeri IRCCS
- Amsterdam UMC
- UMCG
- Radboud UMC
- Specjalistyczne Centrum Medyczne SCM Spółka z o.o.
- DaVita Sp. z o.o. Stacja Dializ
- Szpital Kliniczny UM w Lodzi
- Fundacion Puigvert
- Hospital Universitari de Bellvitge
- Nefrologia Clinica C.P.
- Hospital Universitario Dr. Peset
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
DB Period: GLPG2737
DB Period: Placebo
OLE Period: GLPG2737
Arm Description
GLPG2737 will be administered orally once daily with food for 52 weeks.
Matching placebo will be administered orally once daily with food for 52 weeks.
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.
Outcomes
Primary Outcome Measures
Mean Percent Change From Baseline of Height-Adjusted Total Kidney Volume (htTKV)
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Percentage of Participants With TEAEs According to Severity
Percentage of Participants With TEAEs Leading to Treatment Discontinuation
Secondary Outcome Measures
Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Area Under the Plasma Concentration-Time Curve During a Dosing Interval (AUCtau) of GLPG2737, estimated based on population pharmacokinetics (PK) modelling
AUCtau of G1125498 (Major Active Metabolite of GLPG2737), estimated based on population PK modelling
Maximum Observed Plasma Concentration (Cmax) of GLPG2737, estimated based on population PK modelling
Cmax of G1125498 (Major Active Metabolite of GLPG2737), estimated based on population PK modelling
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04578548
Brief Title
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 Subjects With Autosomal Dominant Polycystic Kidney Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Terminated
Why Stopped
The study was early terminated due to lack of efficacy.
Study Start Date
November 10, 2020 (Actual)
Primary Completion Date
December 14, 2022 (Actual)
Study Completion Date
April 4, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Galapagos NV
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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 subjects with rapidly progressing ADPKD.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autosomal Dominant Polycystic Kidney Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DB Period: GLPG2737
Arm Type
Experimental
Arm Description
GLPG2737 will be administered orally once daily with food for 52 weeks.
Arm Title
DB Period: Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo will be administered orally once daily with food for 52 weeks.
Arm Title
OLE Period: GLPG2737
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo capsules administered orally with food
Intervention Type
Drug
Intervention Name(s)
GLPG2737
Intervention Description
Capsules administered orally with food
Primary Outcome Measure Information:
Title
Mean Percent Change From Baseline of Height-Adjusted Total Kidney Volume (htTKV)
Time Frame
From baseline until 52 weeks
Title
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame
From Day 1 until 56 weeks
Title
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Time Frame
From Day 1 until 56 weeks
Title
Percentage of Participants With TEAEs According to Severity
Time Frame
From Day 1 until 56 weeks
Title
Percentage of Participants With TEAEs Leading to Treatment Discontinuation
Time Frame
From Day 1 until 52 weeks
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Time Frame
From baseline until 52 weeks
Title
Area Under the Plasma Concentration-Time Curve During a Dosing Interval (AUCtau) of GLPG2737, estimated based on population pharmacokinetics (PK) modelling
Time Frame
predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 5-7, 8-9 hours postdose on Week 4
Title
AUCtau of G1125498 (Major Active Metabolite of GLPG2737), estimated based on population PK modelling
Time Frame
predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 5-7, 8-9 hours postdose on Week 4
Title
Maximum Observed Plasma Concentration (Cmax) of GLPG2737, estimated based on population PK modelling
Time Frame
predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 5-7, 8-9 hours postdose on Week 4
Title
Cmax of G1125498 (Major Active Metabolite of GLPG2737), estimated based on population PK modelling
Time Frame
predose (within 30 minutes prior to dosing) and 1, 2, 3, 4, 5-7, 8-9 hours postdose on Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann Fieuw, MD, MSc
Organizational Affiliation
Galapagos NV
Official's Role
Study Director
Facility Information:
Facility Name
Cliniques Universitaires St. Luc (UCL)
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Fakultni nemocnice u sv. Anny v Brne
City
Brno
ZIP/Postal Code
656 91
Country
Czechia
Facility Name
Fakultni nemocnice Hradec Kralove
City
Hradec Králové
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Praha
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Uniklinikum Dresden
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
IRCSS Ospedale San Raffaele
City
Milan
ZIP/Postal Code
20132
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Federico II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Uni Campania L. Vanvitelli
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Fondazione Salvatore Maugeri IRCCS
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Amsterdam UMC
City
Amsterdam
ZIP/Postal Code
1105
Country
Netherlands
Facility Name
UMCG
City
Groningen
ZIP/Postal Code
9713
Country
Netherlands
Facility Name
Radboud UMC
City
Nijmegen
ZIP/Postal Code
6525
Country
Netherlands
Facility Name
Specjalistyczne Centrum Medyczne SCM Spółka z o.o.
City
Kraków
ZIP/Postal Code
31-559
Country
Poland
Facility Name
DaVita Sp. z o.o. Stacja Dializ
City
Warsaw
ZIP/Postal Code
02-758
Country
Poland
Facility Name
Szpital Kliniczny UM w Lodzi
City
Łódź
ZIP/Postal Code
92-213
Country
Poland
Facility Name
Fundacion Puigvert
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Universitari de Bellvitge
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Nefrologia Clinica C.P.
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario Dr. Peset
City
Valencia
ZIP/Postal Code
46017
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
We'll reach out to this number within 24 hrs