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.

NCT03540524 | Completed Phase 1 DMC

• 2 other identifiers: GLPG2737-CL-1052017-001067-20
• Study Type: interventional
• Target: 10
• Locations: 7 countries
• Sites: 19

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

Outcome Measures

Primary Outcomes (8)

• Number of subjects with adverse events.

  To assess safety and tolerability of doses of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I and Part II).

  Up to 24 weeks after the last dose

• Maximum observed plasma concentration (Cmax).

  To characterize the pharmacokinetics (PK) of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).

  Day 14

• Maximum observed plasma concentration (Cmax).

  To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).

  Day 28

• Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h).

  To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).

  Day 14

• Area under the plasma concentration-time curve from time zero until 24 hours (AUC0-24h).

  To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I).

  Day 28

• Trough plasma concentration observed at the end of the dosing interval (24 hours post-dose) (Ctrough).

  To characterize the PK of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part I and Part II).

  Between Day 2 and Day 28

• Change from baseline in sweat chloride concentration.

  To assess changes in sweat chloride concentration after administration of the combination of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part II).

  Between Day 1 pre-dose and Day 28

• Change from baseline in percent predicted FEV1.

  To assess changes in percent predicted FEV1 after administration of the combination of GLPG2451 and GLPG2222 with or without GLPG2737 (Study Part II).

  Between Day 1 pre-dose and Day 28

Secondary Outcomes (2)

• Change from baseline in sweat chloride concentration.

  Between Day 1 pre-dose and Day 28

• Change from baseline in percent predicted FEV1.

  Between Day 1 pre-dose and Day 28

Study Arms (3)

Cohort A - F508del homozygous

EXPERIMENTAL

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)

Drug: GLPG2451 dose regimen A; Drug: GLPG2222; Drug: GLPG2737

Cohort B - F508del heterozygous/potentiator nonresponsive

EXPERIMENTAL

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)

Drug: GLPG2451 dose regimen B; Drug: GLPG2222; Drug: GLPG2737

Cohort C - F508del homozygous

EXPERIMENTAL

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)

Drug: GLPG2451 dose regimen B; Drug: GLPG2222; Drug: GLPG2737

Interventions

GLPG2451 dose regimen A DRUG

GLPG2451 oral suspension, daily.

Cohort A - F508del homozygous

GLPG2451 dose regimen B DRUG

GLPG2451 oral suspension, daily.

Cohort B - F508del heterozygous/potentiator nonresponsive; Cohort C - F508del homozygous

GLPG2222 DRUG

GLPG2222 tablet for oral use, daily.

Cohort A - F508del homozygous; Cohort B - F508del heterozygous/potentiator nonresponsive; Cohort C - F508del homozygous

GLPG2737 DRUG

GLPG2737 capsules for oral use, daily.

Cohort A - F508del homozygous; Cohort B - F508del heterozygous/potentiator nonresponsive; Cohort C - F508del homozygous

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (20)

Study Site BEL004

Antwerp, Belgium

Location

Study Site BEL003

Brussels, Belgium

Location

Study Site BEL002

Ghent, Belgium

Location

Study Site BEL001

Leuven, Belgium

Location

Study Site BGR001

Sofia, Bulgaria

Location

Study Site DEU001

Berlin, Germany

Location

Study Site DEU002

Essen, Germany

Location

Study Site GRC001

Thessaloniki, Greece

Location

Study Site NLD002

Amsterdam, Netherlands

Location

Study Site NLD001

Utrecht, Netherlands

Location

Study Site SRB001

Belgrade, Serbia

Location

Study Site SWE001

Gothenburg, Sweden

Location

Study Site SWE002

Stockholm, Sweden

Location

Study Site GBR003

Birmingham, United Kingdom

Location

Study Site GBR004

Glasgow, United Kingdom

Location

Study Site GBR005

Liverpool, United Kingdom

Location

Study Site GBR007

London, SW3 6NP, United Kingdom

Location

Study Site GBR006

Newcastle, United Kingdom

Location

Study Site GBR001

Papworth Everard, United Kingdom

Location

Study Site GBR002

Wythenshawe, United Kingdom

Location

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 de Steen, MD MBA

  Galapagos NV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2018
• First Posted: May 30, 2018
• Study Start: May 31, 2018
• Primary Completion: March 11, 2019
• Study Completion: March 11, 2019
• Last Updated: April 8, 2019

Record last verified: 2018-04

Locations

BE (4); BU (1); DE (2); SE (2); GR (1); NL (2); GB (7)