Autosomal Dominant Polycystic Kidney DiseasePhase 2NCT04578548
A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
A Phase 2 study testing GLPG2737 in people with Autosomal Dominant Polycystic Kidney Disease, run by Lakefront Biotherapeutics NV at 20 sites in 7 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Autosomal Dominant Polycystic Kidney Disease
- What is being tested?
- GLPG2737
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 10 Nov 2020to 4 Apr 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.).
Who cannot join
- 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.
Trial locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
Italy4 sites
IRCSS Ospedale San Raffaele
Milan, 20132
Azienda Ospedaliera Universitaria Federico II
Naples, 80131
Uni Campania L. Vanvitelli
Naples, 80131
Fondazione Salvatore Maugeri IRCCS
Pavia, 27100
Spain4 sites
Fundacion Puigvert
Barcelona, 08025
Hospital Universitari de Bellvitge
Barcelona, 08907
Nefrologia Clinica C.P.
Madrid, 28041
Hospital Universitario Dr. Peset
Valencia, 46017
Czechia3 sites
Fakultni nemocnice u sv. Anny v Brne
Brno, 656 91
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Netherlands3 sites
Amsterdam UMC
Amsterdam, 1105
UMCG
Groningen, 9713
Radboud UMC
Nijmegen, 6525
Poland3 sites
Specjalistyczne Centrum Medyczne SCM Spółka z o.o.
Krakow, 31-559
Szpital Kliniczny UM w Lodzi
Lodz, 92-213
DaVita Sp. z o.o. Stacja Dializ
Warsaw, 02-758
Belgium2 sites
Cliniques Universitaires St. Luc (UCL)
Brussels, 1200
UZ Leuven
Leuven, 3000
About this study
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
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.
- Being tested
- GLPG2737, Placebo
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLPG2737Drug
Capsules administered orally
PlaceboDrug
Matching placebo capsules administered orally
| Study group | Role | What they receive |
|---|---|---|
| GLPG2737 During DB + During OLE | Experimental | 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. Receives: Drug: GLPG2737 |
| Placebo During DB + GLPG2737 During OLE | Placebo comparator | 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. Receives: Drug: GLPG2737; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: From first dose to Week 56
Secondary outcomes (3)
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).
Measured: 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.
Measured: 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.
Measured: Predose (within 30 minutes prior to dosing), 1, 1.5, 2, 3, 4, 5, 6, 7 hours post dose through Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2020
- Study start10 Nov 2020
- Primary completion14 Dec 2022
- Study completion4 Apr 2023
Why it stopped: The study was early terminated due to lack of efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autosomal Dominant Polycystic Kidney DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lakefront Biotherapeutics NV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Galapagos Study Director, Study director, Lakefront Biotherapeutics NV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04578548
- Sponsor's protocol ID
- GLPG2737-CL-203
- Other IDs
- 2019-003521-21, 2019
- Status last verified
- Mar 2024
- First submitted
- 1 Oct 2020
- Last updated
- 22 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
Chen CY, Hadla M, Khambati I, Kashyap S, Westerfield V, Fedeles S, Besse W, Hopp K, Harris PC, Patel V, Chini E, Salih M, Barry MA, Chebib FT. Emerging Therapies in Autosomal Dominant Polycystic Kidney Disease. Kidney360. 2026 Jul 1;7(7):1662-1676. doi: 10.34067/KID.0000001109. Epub 2025 Dec 12.
PubMed 41385299St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04578548
- Acronym / sponsor ID
- GLPG2737-CL-203
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was early terminated due to lack of efficacy.
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Lakefront Biotherapeutics NVIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2020 (actual)
- Primary completion
- 14 Dec 2022 (actual)
- Study completion
- 4 Apr 2023 (actual)
- First posted
- 8 Oct 2020 (actual)
- Results
- Posted 22 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GLPG2737 During DB + During OLE | Experimental | Drug: GLPG2737Participants 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. |
| Placebo During DB + GLPG2737 During OLE | Placebo comparator | Drug: GLPG2737, Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
- 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 (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GLPG2737Capsules administered orally | Drug | GLPG2737 During DB + During OLE, Placebo During DB + GLPG2737 During OLE |
| PlaceboMatching placebo capsules administered orally | Drug | Placebo During DB + GLPG2737 During OLE |
Primary outcome
DB Period: Mean Percent Change From MRI Baseline in htTKV
Time frame: MRI Baseline up to Week 52
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).
DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: From first dose to Week 56
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.
3 secondary outcomes
DB Period: Mean Change From Baseline in eGFR
Time frame: Baseline up to Week 52
DB Period: Area Under the Plasma Concentration-Time Curve During a Dosing Interval (AUCtau) of GLPG2737 and Its Metabolite
Time frame: 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
Time frame: Predose (within 30 minutes prior to dosing), 1, 1.5, 2, 3, 4, 5, 6, 7 hours post dose through Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationRon 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.
- Derived from this study: PubMed 41385299Chen CY, Hadla M, Khambati I, Kashyap S, Westerfield V, Fedeles S, Besse W, Hopp K, Harris PC, Patel V, Chini E, Salih M, Barry MA, Chebib FT. Emerging Therapies in Autosomal Dominant Polycystic Kidney Disease. Kidney360. 2026 Jul 1;7(7):1662-1676. doi: 10.34067/KID.0000001109. Epub 2025 Dec 12.
- Derived from this study: PubMed 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Galapagos Study Director study director
Lakefront Biotherapeutics NV
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GLPG2737 in people with Autosomal Dominant Polycystic Kidney Disease, run by Lakefront Biotherapeutics NV at 20 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Italy, Spain, Czechia, Netherlands, Poland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DB Period: Mean Percent Change From MRI Baseline in htTKV (time frame: MRI Baseline up to Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04578548, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2024.