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

A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate GLPG2222 in Ivacaftor-treated Subjects With Cystic Fibrosis Harbouring One F508del CFTR Mutation and a Second Gating (Class III) Mutation

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: GLPG2222 150 mg q.d.; Drug: GLPG2222 300 mg q.d.; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Chermside, Australia
    • The Prince Charles Hospital
  • Melbourne, Australia
    • The Alfred
  • Nedlands, Australia
    • Sir Charles Gairdner Hospital
  • Westmead, Australia
    • Westmead Hospital
• Belgium
  • Brussels, Belgium
    • UZ Brussel
  • Ghent, Belgium
    • UZ Gent
  • Leuven, Belgium
    • UZ Leuven
• Czechia
  • Praha, Czechia
    • Fakultni nemocnice v Motole
• Germany
  • Dresden, Germany
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Erlangen, Germany
    • Universitätsklinikum Erlangen
  • Tübingen, Germany
    • University children´s hospital
• Ireland
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland
    • Beaumont Hospital
  • Dublin, Ireland
    • St Vincents University Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Heartlands
  • Exeter, United Kingdom
    • Royal Devon and Exeter
  • Leeds, United Kingdom
    • St James's University
  • Liverpool, United Kingdom
    • Liverpool Heart and Chest Hospital
  • London, United Kingdom
    • Royal Brompton Hospital
  • Manchester, United Kingdom
    • University Hospital of South Manchester
  • Newcastle, United Kingdom
    • Royal Victoria Infirmary
  • Southampton, United Kingdom
    • Southampton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF).
2. A confirmed clinical diagnosis of CF.
3. 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).
4. Weight ≥ 40 kg.
5. Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline (including physician prescribed ivacaftor (Kalydeco®) 150 mg b.i.d.).
6. Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).

Exclusion Criteria:

1. History of clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator.
2. Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks of baseline.
3. Need for supplemental oxygen during the day, and >2 liters per minute (LPM) while sleeping.
4. History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices, etc).
5. 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).
6. Estimated creatinine clearance < 60mL/min using the Cockroft-Gault formula at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days
EXPERIMENTAL: GLPG2222 Dose 1	Drug: GLPG2222 150 mg q.d.; GLPG2222 150 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days
EXPERIMENTAL: GLPG2222 Dose 2	Drug: GLPG2222 300 mg q.d.; GLPG2222 300 mg administered as a ready-to-use oral suspension, once daily (q.d.) for 29 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Galapagos NV

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (ACTUAL): August 11, 2017
• Study Completion (ACTUAL): August 11, 2017

Study Registration Dates

• First Submitted: January 26, 2017
• First Submitted That Met QC Criteria: February 3, 2017
• First Posted (ESTIMATE): February 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 20, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: GLPG2222-CL-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO