A Study to Evaluate Multiple Doses of GLPG2222 in Adult Subjects With Cystic Fibrosis

NCT03119649 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GLPG2222-CL-202
• Study Type: interventional
• Target: 59
• Locations: 6 countries
• Sites: 23

Brief Summary

This is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 4 different doses of GLPG2222 administered for 4 weeks to adult subjects with a confirmed diagnosis of CF and homozygous for the F508del Cystic Fibrosis Transmembrane conductance Regulator (CFTR) mutation.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events

  Number of participants with any treatment-emergent adverse events (TEAEs) and serious or treatment-related TEAEs, as well as number of patients with TEAEs by worst intensity reported (mild, moderate, or severe).

  First administration (Day 1) through Follow-up (Day 43)

Secondary Outcomes (7)

• Mean Change From Baseline in Sweat Chloride Concentration at Day 29

  Prior to dosing on Days 1 and 29, or at early discontinuation

• Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29

  Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation

• Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29

  Prior to dosing on Days 1 and 29, or at early discontinuation

• Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222

  Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29

• Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)

  Days 15 and 29 (predose)

Study Arms (6)

Cohort A: GLPG2222 50 mg once daily (QD)

EXPERIMENTAL

Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.

Drug: GLPG2222 50 mg; Drug: Placebo

Cohort A: GLPG2222 100 mg QD

EXPERIMENTAL

Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.

Drug: GLPG2222 100 mg; Drug: Placebo

Cohort B: GLPG2222 200 mg QD

EXPERIMENTAL

Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.

Drug: Placebo; Drug: GLPG2222 200 mg

Cohort B: GLPG2222 400 mg QD

EXPERIMENTAL

Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.

Drug: Placebo; Drug: GLPG2222 400 mg

Cohort A Placebo

PLACEBO COMPARATOR

Participants received three matching placebo tablets, orally, QD for 29 days.

Drug: Placebo

Cohort B Placebo

PLACEBO COMPARATOR

Participants received three matching placebo tablets, orally, QD for 29 days.

Drug: Placebo

Interventions

GLPG2222 50 mg DRUG

Oral tablet(s) containing GLPG2222

Cohort A: GLPG2222 50 mg once daily (QD)

GLPG2222 100 mg DRUG

Oral tablet(s) containing GLPG2222

Cohort A: GLPG2222 100 mg QD

Placebo DRUG

Matching oral tablet(s) containing placebo

Cohort A Placebo; Cohort A: GLPG2222 100 mg QD; Cohort A: GLPG2222 50 mg once daily (QD); Cohort B Placebo; Cohort B: GLPG2222 200 mg QD; Cohort B: GLPG2222 400 mg QD

GLPG2222 200 mg DRUG

Oral tablet(s) containing GLPG2222

Cohort B: GLPG2222 200 mg QD

GLPG2222 400 mg DRUG

Oral tablet(s) containing GLPG2222

Cohort B: GLPG2222 400 mg QD

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF).
• A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation
• Weight ≥ 40 kg.
• Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline
• Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening

You may not qualify if:

• Unstable pulmonary status or respiratory tract infection requiring a change in therapy within 4 weeks of baseline.
• Need for supplemental oxygen during the day, and \>2 liters per minute (LPM) while sleeping.
• Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration.
• History of hepatic cirrhosis with portal hypertension.
• Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/ or alkaline phosphatase and/or gamma-glutamyl transferase (GGT) ≥ 3x the upper limit of normal (ULN); and/or total bilirubin (\>1.5 times ULN)
• Estimated creatinine clearance \< 60 mL/min using the Cockcroft-Gault formula at screening.

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (23)

Child Health Research Unit at UAB

Chatom, Alabama, 35233, United States

Location

University of Arkansas for medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Central Florida Pulmonary Group

Orlando, Florida, 32803, United States

Location

Cystic Fibrosis Center of Chicago

Glenview, Illinois, 60026, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

John Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

UZ Antwerpen

Antwerp, Belgium

Location

UZ Brussel

Brussels, Belgium

Location

UZ Gent

Ghent, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

AMC Amsterdam

Amsterdam, Netherlands

Location

Erasmus medisch centrum

Rotterdam, Netherlands

Location

Haga Ziekenhuis

The Hague, Netherlands

Location

UMC Utrecht

Utrecht, Netherlands

Location

Mother and child health institute of Serbia

New Belgrade, Serbia

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitarii Plitecnic La Fe

Valencia, Spain

Location

Papworth Hospital

Cambridge, United Kingdom

Location

St James University Hospital

Leeds, United Kingdom

Location

Liverpool Heart and Chest Hospital

Liverpool, United Kingdom

Location

Southampton general Hospital

Southampton, United Kingdom

Location

Related Publications (1)

• Bell SC, Barry PJ, De Boeck K, Drevinek P, Elborn JS, Plant BJ, Minic P, Van Braeckel E, Verhulst S, Muller K, Kanters D, Bellaire S, de Kock H, Geller DE, Conrath K, Van de Steen O, van der Ent K. CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials. J Cyst Fibros. 2019 Sep;18(5):700-707. doi: 10.1016/j.jcf.2019.04.014. Epub 2019 May 3.

  PMID: 31056441 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

GLPG2222

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

None reported

Results Point of Contact

• Title: Evelyn Fox
• Organization: Galapagos NV

evelyn.fox@glpg.com

0032 15 34 29 00

Study Officials

• Olivier Van Steen, MD, MBA

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 18, 2017
• Study Start: March 18, 2017
• Primary Completion: October 19, 2017
• Study Completion: October 19, 2017
• Last Updated: November 16, 2018
• Results First Posted: November 16, 2018

Record last verified: 2018-10

Locations

BE (4); US (7); GB (4); NL (4); SE (1); ES (3)