A Study to Evaluate GLPG2222 in Ivacaftor-treated Subjects With Cystic Fibrosis

NCT03045523 | Completed Phase 2

• 1 other identifier: GLPG2222-CL-201
• Study Type: interventional
• Target: 37
• Locations: 6 countries
• Sites: 22

Brief Summary

This clinical study is a phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel group study to evaluate two doses of orally administered GLPG2222 in adult subjects with a confirmed diagnosis of CF harbouring one F508del CFTR mutation and a second gating (class III) mutation and on stable treatment with ivacaftor. Up to 35 evaluable subjects are planned to be included in the study. Eligible subjects must be on stable treatment with physician prescribed ivacaftor (Kalydeco®) for at least 28 days at the baseline visit. They will be randomized in a 2:2:1 ratio to receive one of two active doses of GLPG2222 (150 mg q.d. or 300 mg q.d.) or placebo q.d. administered for 29 days. Subjects will be in the study for a minimum of 6 weeks and a maximum of 10 weeks, from screening until the follow-up visit.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (3)

• Changes in adverse events

  To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of adverse events

  at screening and at each study visit up to day 43 which is the final FU visit

• Changes in abnormal laboratory

  To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of laboratory

  at screening and at each study visit up to day 43 which is the final FU visit

• Changes in abnormal vital signs, ECG or physical examination

  To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of vital signs, ECG or physical examination

  at screening and at each study visit up to day 43 which is the final FU visit

Secondary Outcomes (3)

• Change from baseline of Sweat chloride concentration

  at screening and at each study visit up to day 43 which is the final FU visit

• Change from baseline of FEV1 (L) and percent predicted FEV1 for age, gender and height as assessed by spirometry

  at screening and at each study visit up to day 43 which is the final FU visit

• Change from baseline on the respiratory domain of Revised Cystic Fibrosis Questionnaire (CFQ-R)

  at screening and at each study visit up to day 43 which is the final FU visit

Study Arms (3)

GLPG2222 Dose 1

EXPERIMENTAL

Drug: GLPG2222 150 mg q.d.

GLPG2222 Dose 2

EXPERIMENTAL

Drug: GLPG2222 300 mg q.d.

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

GLPG2222 150 mg q.d. DRUG

GLPG2222 150 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days

GLPG2222 Dose 1

GLPG2222 300 mg q.d. DRUG

GLPG2222 300 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days

GLPG2222 Dose 2

Placebo DRUG

Placebo administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days

Placebo

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.
• One F508del mutation on one allele in the CFTR gene, a gating (class III) mutation (one of the following: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R) on the 2nd allele in the CFTR gene (documented in the subject's medical record or CF registry).
• Weight ≥ 40 kg.
• Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline (including physician prescribed ivacaftor (Kalydeco®) 150 mg b.i.d.).
• Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).

You may not qualify if:

• Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) 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.
• History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices, etc).
• Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or total bilirubin (\>1.5 times ULN (CTCAE Grade 2) and/or gamma-glutamyl transferase (GGT) ≥ 3x the upper limit of normal (ULN), and/or total bilirubin (\>1.5 times ULN (CTCAE Grade 2).
• Estimated creatinine clearance \< 60mL/min using the Cockroft-Gault formula at screening.

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (22)

The Prince Charles Hospital

Chermside, Australia

Location

The Alfred

Melbourne, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Australia

Location

Westmead Hospital

Westmead, Australia

Location

UZ Brussel

Brussels, Belgium

Location

UZ Gent

Ghent, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Fakultni nemocnice v Motole

Prague, Czechia

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Germany

Location

University Children´s Hospital

Tübingen, Germany

Location

Cork University Hospital

Cork, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

St Vincents University Hospital

Dublin, Ireland

Location

Birmingham Heartlands

Birmingham, United Kingdom

Location

Royal Devon and Exeter

Exeter, United Kingdom

Location

St James's University

Leeds, United Kingdom

Location

Liverpool Heart and Chest Hospital

Liverpool, United Kingdom

Location

Royal Brompton Hospital

London, United Kingdom

Location

University Hospital of South Manchester

Manchester, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (3)

• Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

  PMID: 37983082 DERIVED

• Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.

  PMID: 33331662 DERIVED

• 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

Study Officials

• Olivier Van Steen, MD, MBA

  Galapagos NV

  STUDY DIRECTOR

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: January 26, 2017
• First Posted: February 7, 2017
• Study Start: January 1, 2017
• Primary Completion: August 11, 2017
• Study Completion: August 11, 2017
• Last Updated: November 21, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); CZ (1); GB (8); IE (3); AU (4); DE (3)