A Study Looking at the Safety, Tolerability and Efficacy of the Combination of the Study Drugs GLPG2451 and GLPG2222 With or Without GLPG2737 in Patients With Cystic Fibrosis.

NCT ID: NCT03540524

Last Updated: 2019-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-31
• Study Completion Date: 2019-03-11

Brief Summary

This is a Phase Ib, multi-center, open-label, nonrandomized multiple cohorts study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of a combination treatment of GLPG2451 and GLPG2222, with and without GLPG2737, in adult subjects with Cystic Fibrosis.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A - F508del homozygous

Dual combination (GLPG2451 and GLPG2222) will be administered for 14 days, followed by the triple combination (GLPG2451, GLPG2222 and GLPG2737) for 14 days, without washout in between the sequential treatment periods.( Study Part I)

Group Type: EXPERIMENTAL

GLPG2451 dose regimen A

Intervention Type: DRUG

GLPG2451 oral suspension, daily.

GLPG2222

Intervention Type: DRUG

GLPG2222 tablet for oral use, daily.

GLPG2737

Intervention Type: DRUG

GLPG2737 capsules for oral use, daily.

Cohort B - F508del heterozygous/potentiator nonresponsive

Dual combination (GLPG2451 and GLPG2222) will be administered for 14 days, followed by the triple combination (GLPG2451, GLPG2222 and GLPG2737) for 14 days, without washout in between the sequential treatment periods. (study Part II)

Group Type: EXPERIMENTAL

GLPG2451 dose regimen B

Intervention Type: DRUG

GLPG2451 oral suspension, daily.

GLPG2222

Intervention Type: DRUG

GLPG2222 tablet for oral use, daily.

GLPG2737

Intervention Type: DRUG

GLPG2737 capsules for oral use, daily.

Cohort C - F508del homozygous

Dual combination (GLPG2451 and GLPG2222) will be administered for 14 days, followed by the triple combination (GLPG2451, GLPG2222 and GLPG2737) for 14 days, without washout in between the sequential treatment periods. (Study Part II)

Group Type: EXPERIMENTAL

GLPG2451 dose regimen B

Intervention Type: DRUG

GLPG2451 oral suspension, daily.

GLPG2222

Intervention Type: DRUG

GLPG2222 tablet for oral use, daily.

GLPG2737

Intervention Type: DRUG

GLPG2737 capsules for oral use, daily.

Interventions

GLPG2451 dose regimen A

GLPG2451 oral suspension, daily.

Intervention Type: DRUG

GLPG2451 dose regimen B

GLPG2451 oral suspension, daily.

Intervention Type: DRUG

GLPG2222

GLPG2222 tablet for oral use, daily.

Intervention Type: DRUG

GLPG2737

GLPG2737 capsules for oral use, daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female or male subject ≥18 years of age, on the day of signing the Informed Consent Form (ICF)
• Confirmed clinical diagnosis of cystic fibrosis (CF) (documented in the subject's medical record).
• Eligible cystic fibrosis transmembrane conductance regulator (CFTR) genotype at screening:

• Cohort A: Homozygous for the F508del CFTR mutation
• Cohort B: Heterozygous for the F508del CFTR mutation with a potentiator non-responsive mutation on the second allele
• Cohort C: Homozygous for the F508del CFTR mutation
• A body weight of ≥40 kg at screening.
• Stable 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.
• Forced expiratory volume in 1 second (FEV1): 40% ≤ FEV1 ≤ 90% of predicted normal for age, sex, and height at screening (pre- or post bronchodilator) at screening.
• Sweat chloride concentration ≥60 mmol/L at screening.
• Non-smoker and non-user of any nicotine and or cannabis containing products. A non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to the screening. A non-user is defined as an individual who has abstained from any nicotine containing products for at least 1 year prior to the screening.

Exclusion Criteria

• History of or ongoing allergic bronchopulmonary aspergillosis.
• Medical history of cataract (or lens opacity) and/or glaucoma.
• Cataract (or lens opacity) and/or glaucoma determined by an ophthalmologist during the screening period.
• 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 clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator.
• Need for supplemental oxygen during the day, and >2 L/minute while sleeping.
• History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices).
• History of malignancy within the past 5 years (except for basal cell carcinoma of the skin with no evidence of recurrence and/or carcinoma in situ of the cervix that has been treated with no evidence of recurrence).
• Use of any moderate and strong inhibitor(s) or inducer(s) of CYP3A4 within 4 weeks prior to the first study drug administration (e.g., clarithromycin, itraconazole, ketoconazole, telithromycin, rifampin, carbamazepine).
• Use of CFTR modulator therapy (e.g., lumacaftor and/or ivacaftor) within 4 weeks prior to the first study drug administration.
• Use of any oral corticosteroid within 3 months of screening; or history of oral corticosteroid use for ≥30 days (cumulative) within 2 years of screening.
• 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) ≥3× the upper limit of normal (ULN); and/or total bilirubin ≥1.5× the ULN.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Galapagos NV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olivier Van de Steen, MD MBA

Role: STUDY_DIRECTOR

Galapagos NV

Locations

Study Site BEL004

Antwerp, , Belgium

Study Site BEL003

Brussels, , Belgium

Study Site BEL002

Ghent, , Belgium

Study Site BEL001

Leuven, , Belgium

Study Site BGR001

Sofia, , Bulgaria

Study Site DEU001

Berlin, , Germany

Study Site DEU002

Essen, , Germany

Study Site GRC001

Thessaloniki, , Greece

Study Site NLD002

Amsterdam, , Netherlands

Study Site NLD001

Utrecht, , Netherlands

Study Site SRB001

Belgrade, , Serbia

Study Site SWE001

Gothenburg, , Sweden

Study Site SWE002

Stockholm, , Sweden

Study Site GBR003

Birmingham, , United Kingdom

Study Site GBR004

Glasgow, , United Kingdom

Study Site GBR005

Liverpool, , United Kingdom

Study Site GBR007

London, , United Kingdom

Study Site GBR006

Newcastle, , United Kingdom

Study Site GBR001

Papworth Everard, , United Kingdom

Study Site GBR002

Wythenshawe, , United Kingdom

Countries

Belgium; Bulgaria; Germany; Greece; Netherlands; Serbia; Sweden; United Kingdom

Other Identifiers

2017-001067-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GLPG2737-CL-105

Identifier Type: -

Identifier Source: org_study_id