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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Autosomal Dominant Polycystic Kidney Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: GLPG2737


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DB Period: GLPG2737<br>GLPG2737 will be administered orally once daily with food for 52 weeks. | Drug: GLPG2737<br>* Capsules administered orally with food<br>|
| Placebo Comparator: DB Period: Placebo<br>Matching placebo will be administered orally once daily with food for 52 weeks. | Drug: Placebo<br>* Matching placebo capsules administered orally with food<br>|
| Experimental: OLE Period: GLPG2737<br>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. | Drug: GLPG2737<br>* Capsules administered orally with food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline of Height-Adjusted Total Kidney Volume (htTKV) |  | From baseline until 52 weeks | 
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) |  | From Day 1 until 56 weeks | 
| Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) |  | From Day 1 until 56 weeks | 
| Percentage of Participants With TEAEs According to Severity |  | From Day 1 until 56 weeks | 
| Percentage of Participants With TEAEs Leading to Treatment Discontinuation |  | From Day 1 until 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) |  | From baseline until 52 weeks | 
| 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 | 
| 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 | 
| 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 | 
| 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 |