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

NCT04578548 | Terminated Phase 2 Results DMC

• 2 other identifiers: GLPG2737-CL-2032019-003521-21
• Study Type: interventional
• Target: 66
• Locations: 7 countries
• Sites: 20

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 participants with rapidly progressing ADPKD.

Conditions

Autosomal Dominant Polycystic Kidney Disease

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  From first dose to Week 56

Secondary Outcomes (3)

• DB Period: Mean Change From Baseline in eGFR

  Baseline up to Week 52

• DB Period: Area Under the Plasma Concentration-Time Curve During a Dosing Interval (AUCtau) of GLPG2737 and Its Metabolite

  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

  Predose (within 30 minutes prior to dosing), 1, 1.5, 2, 3, 4, 5, 6, 7 hours post dose through Week 52

Study Arms (2)

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.

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.

Drug: GLPG2737; Drug: Placebo

Interventions

GLPG2737 DRUG

Capsules administered orally

GLPG2737 During DB + During OLE; Placebo During DB + GLPG2737 During OLE

Placebo DRUG

Matching placebo capsules administered orally

Placebo During DB + GLPG2737 During OLE

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 milliliters per minute per 1.73 square meter (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 millimeters of mercury (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.
• 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.

You may not qualify if:

• 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.).
• Clinically significant abnormalities detected on 12-lead electrocardiogram (ECG) of either rhythm or conduction, QTcF \>450 ms, or long QT syndrome.

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (20)

Cliniques Universitaires St. Luc (UCL)

Brussels, 1200, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 08, Czechia

Location

Uniklinikum Dresden

Dresden, 01307, Germany

Location

IRCSS Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliera Universitaria Federico II

Napoli, 80131, Italy

Location

Uni Campania L. Vanvitelli

Napoli, 80131, Italy

Location

Fondazione Salvatore Maugeri IRCCS

Pavia, 27100, Italy

Location

Amsterdam UMC

Amsterdam, 1105, Netherlands

Location

UMCG

Groningen, 9713, Netherlands

Location

Radboud UMC

Nijmegen, 6525, Netherlands

Location

Specjalistyczne Centrum Medyczne SCM Spółka z o.o.

Krakow, 31-559, Poland

Location

Szpital Kliniczny UM w Lodzi

Lodz, 92-213, Poland

Location

DaVita Sp. z o.o. Stacja Dializ

Warsaw, 02-758, Poland

Location

Fundacion Puigvert

Barcelona, 08025, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

Location

Nefrologia Clinica C.P.

Madrid, 28041, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

Related Publications (2)

• 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.

  RESULT

• St 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.

  PMID: 39356039 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Limitations and Caveats

The early termination was decided due to the lack of efficacy of GLPG2737, making the expected benefit-risk balance negative.

Results Point of Contact

• Title: Galapagos Medical Information
• Organization: Galapagos NV

medicalinfo@glpg.com

+3215342900

Study Officials

• Galapagos Study Director

  Galapagos NV

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 8, 2020
• Study Start: November 10, 2020
• Primary Completion: December 14, 2022
• Study Completion: April 4, 2023
• Last Updated: August 22, 2024
• Results First Posted: August 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); PL (3); CZ (3); BE (2); DE (1); NL (3); ES (4)