A study to evaluate the effects of GLPG2737 in subjects with autosomal dominant polycystic kidney disease

• Register: EUCTR
• Last refreshed on: 18 October 2021
• Main ID: EUCTR2019-003521-21-BE
• Date of registration: 24/10/2019
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: A study to evaluate the effects of GLPG2737 in subjects with autosomal dominant polycystic kidney disease
• Scientific 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
• Date of first enrolment: 20/01/2020
• Target sample size: 60
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-003521-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Germany, Italy, Netherlands, Spain

Contacts

• Name: Galapagos Medical Information
• Affiliation: Galapagos NV

• Name: Galapagos Medical Information
• Affiliation: Galapagos NV

Key inclusion & exclusion criteria

Inclusion criteria:
Main inclusion criteria for the double-blind period of the study:
1. Male and female subject aged 18 to 50 years, inclusive.
2. Documented diagnosis of typical ADPKD, using the Ravine criteria.
3. Rapidly progressive disease, defined as presence of all of the following:
-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 (i.e. echography, magnetic resonance imaging [MRI]).
-Mayo ADPKD Classification Classes 1C to 1E.
4. eGFR at screening between 30-90 mL/min/1.73 m2 for subjects aged 18 to 40 years (inclusive), and between 30-60 mL/min/1.73 m2 for subjects aged 40 to 50 years.
5. Blood pressure = 150/90 mmHg. In case the subject is treated for hypertension, he/she 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.


Main inclusion criteria for the open-label extension period of the study:
1. Male and female subjects who completed the 52-week double-blind treatment period on IP.
2. Subject, according to the investigator's judgement, may benefit from long-term treatment with GLPG2737.

Reference is made to the protocol for a complete overview of the inclusion criteria.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Main exclusion criteria for the double-blind period of the study:
1. Congenital absence of 1 kidney, or subject had a previous nephrectomy or has a transplanted kidney or a transplantation is planned in the foreseeable future.
2. Administration of polycystic kidney disease-modifying agents (e.g. 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.
3. Any condition or circumstances that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures and requirements (e.g. unable to undergo MRI. For example subject's weight exceeds weight capacity of the MRI, ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, etc.).

Main exclusion criterion for the open-label extension period of the study:
1. Clinically significant abnormalities detected on 12-lead ECG of either rhythm or conduction, QTcF > 450 ms, or long QT syndrome.

Reference is made to the protocol for a complete overview of the exclusion criteria.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Autosomal dominant polycystic kidney disease
MedDRA version: 20.0 Level: LLT Classification code 10036046 Term: Polycystic kidney, autosomal dominant System Organ Class: 100000004850

Intervention(s)

Product Name: GLPG2737
Product Code: G1117337
Pharmaceutical Form: Capsule
INN or Proposed INN: Not applicable
Current Sponsor code: G1117337
Other descriptive name: GLPG2737
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: - To characterize the effect of GLPG2737 on growth in total kidney volume (TKV) compared to placebo.
- To evaluate the safety and tolerability of oral doses of GLPG2737 compared to placebo.

Primary end point(s): - Mean percent change from baseline of height-adjusted TKV (htTKV).
- Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious AEs (SAEs), and TEAEs leading to treatment discontinuation.

Secondary Objective: - To characterize the effect of GLPG2737 on renal function (estimated glomerular filtration rate; eGFR) compared to placebo.
- To characterize the pharmacokinetics (PK) of oral doses of GLPG2737 and its major metabolite G1125498 (M4) using population PK analyses.

Timepoint(s) of evaluation of this end point: Various timepoints throughout the trial from baseline until the end of the double-blind period as specified in the protocol.

Secondary Outcome(s)

Secondary end point(s): - Mean change from baseline estimated GFR (eGFR).
- Estimated exposure (area under the curve [AUC], maximum plasma concentration [Cmax]), based on population PK analyses of GLPG2737 and its major metabolite M4.

Timepoint(s) of evaluation of this end point: Various timepoints throughout the trial from baseline until the end of the double-blind period as specified in the protocol.

Secondary ID(s)

GLPG2737-CL-203

Source(s) of Monetary Support

Galapagos NV

Ethics review

Status: Approved
Approval date: 20/01/2020
Contact: