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GLPG2737-CL-105 Assessment of multiple oral doses of GLPG2451/GLPG2222

Details

Therapeutic category
the type of treatment or therapy being studied. A therapy could range from a medication addressing a particular characteristic of CF to a device or activity e.g. exercise

Restore CFTR Function

Trial status

Closed to recruitment - in follow up

Participating Centres
Phase
the different stages involved in the development of a new medication. Phase I focuses on initial safety in people. Phase 2 evaluates safety, correct dose and early signs of whether the medication works. Phase 3 is the stage before medication licensing and looks at safety and medication effectiveness. Phase 4 evaluates longer term use of a medication after it has been licensed for use

Phase I

Full title

Assessment of safety, tolerability, pharmacokinetics and pharmacodynamics of multiple oral doses of the combination of GLPG2451 and GLPG2222, with or without GLPG2737, in adult subjects with cystic fibrosis

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a cAMP-regulated anion channel expressed primarily at the apical plasma membrane of secretory epithelia. Over 2,000 mutations in the CFTR gene have been identified, which are grouped into 6 classes (class I-VI). The F508del mutation is by far the most common CFTR mutation globally, especially in the Caucasian population. Approximately 80 to 90% of CF patients in the United States and Europe have at least one copy of this mutation on one allele, with almost half of them being F508del homozygous (i.e., the mutation is present on both alleles). The F508del mutation impairs CFTR folding, stability at the endoplasmic reticulum and plasma membrane, and chloride gating. Thus, the F508del mutation results in very little to no CFTR protein in the apical membrane. CFTR dysfunction results in increased chloride concentration in sweat and viscous secretions that are difficult to clear, affecting most exocrine glands, notably the pancreas, intestine, liver, and bile duct. However, most morbidity and mortality results from dehydration of the airway surface liquid and impaired airway mucociliary clearance, which leads to cycles of bacterial infection, chronic inflammation, bronchiectasis and progressive decline in pulmonary function. There is a high unmet medical need for subjects with CF, especially for subjects that are either homozygous or heterozygous for the F508del mutation (with a potentiator non-responsive mutation on the second allele). GLPG2451, GLPG2222 and GLPG2737 are in clinical development for the oral treatment of CF, and represent the components of a potentiator/correctors triple combination therapy targeting the F508del CF subject population.

Trial Reference Number

104923

Trial type

Medication

Intervention
the name of the treatment or therapy being researched

GLPG2451 dose regimen A GLPG2451 dose regimen B GLPG2222 GLPG2737

Recruitment target
the number of participants who need to be recruited for the trial in the UK

24

Last edited date

20 December 2017

CF sponsor

Galapagos

CF sponsor type

Commercial

Who can take part?

Age

18+

Top inclusion criteria
  • Sweat chloride concentration ≥60 mmol/L at screening.
  • A body weight of ≥40 kg at screening.
  • table concomitant medication for pulmonary health for CF for at least 4 weeks prior to the first study drug administration and planned continuation of the same concomitant medication for the duration of the dosing period of the study. Subjects with diabetes mellitus and/or pancreatic insufficiency are eligible for the study provided they are on stable treatment (e.g. medication, diet, pancreatic enzyme replacement therapy) for at least 4 weeks prior to the first study drug administration in the opinion of the investigator.
Top exclusion criteria
  • Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks prior to the first study drug administration.
  • History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices).
  • Need for supplemental oxygen during the day, and >2 L/minute while sleeping.

CF centres running this trial

Closed

Central Manchester University Hospitals NHS Foundation Trust

Address

Trust Headquarters Cobbett House Manchester Royal Infirmary Oxford Road Manchester Greater Manchester M13 9WL

Recruitment ends

August 2018

Contact

,

Get in touch

Closed

Heart of England NHS Foundation Trust

Address

Birmingham Heartlands Hospital Bordesley Green East Birmingham West Midlands B9 5SS

Recruitment ends

June 2018

Contact

Whitehouse, Joanna

Get in touch

Closed

Queen Elizabeth University Hospital

Address

1345 Govan Road G51 4TF

Recruitment starts

July 2018

Contact

MacGregor, Gordon

Get in touch