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Completed

NCT Number: NCT03119649

A Study to Evaluate Multiple Doses of GLPG2222 in Adult Subjects With Cystic Fibrosis

This is a Phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 4 different doses of GLPG2222 administered for 4 weeks to adult subjects with a confirmed diagnosis of CF and homozygous for the F508del Cystic Fibrosis Transmembrane conductance Regulator (CFTR) mutation.

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

UZ Antwerpen, Antwerp, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF).
  • A confirmed clinical diagnosis of CF and homozygous for the F508del CFTR mutation
  • Weight ≥ 40 kg.
  • Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline
  • Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening

Exclusion criteria

  • 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.
  • Unstable pulmonary status or respiratory tract infection 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.
  • Use of CFTR modulator therapy (e.g. lumacaftor or ivacaftor) within 4 weeks prior to the first study drug administration.
  • History of hepatic cirrhosis with portal hypertension.
  • 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) ≥ 3x the upper limit of normal (ULN); and/or total bilirubin (>1.5 times ULN)
  • Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula at screening.

Treatment and study plan

GLPG2222 50 mg

Drug

Oral tablet(s) containing GLPG2222

GLPG2222 100 mg

Drug

Oral tablet(s) containing GLPG2222

Placebo

Drug

Matching oral tablet(s) containing placebo

GLPG2222 200 mg

Drug

Oral tablet(s) containing GLPG2222

GLPG2222 400 mg

Drug

Oral tablet(s) containing GLPG2222

Primary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events

    Time frame: First administration (Day 1) through Follow-up (Day 43)

    Number of participants with any treatment-emergent adverse events (TEAEs) and serious or treatment-related TEAEs, as well as number of patients with TEAEs by worst intensity reported (mild, moderate, or severe).

Secondary outcomes

  1. Mean Change From Baseline in Sweat Chloride Concentration at Day 29

    Time frame: Prior to dosing on Days 1 and 29, or at early discontinuation

    Two sweat collections, one from each arm, were obtained. Mean sweat chloride concentration was determined from both arms and measured as millimoles per liter (mmol/L). Baseline was defined as the predose value on Day 1 (or the last non-missing predose measurement).

  2. Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29

    Time frame: Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation

    Percent predicted FEV1 for age, gender, and height was determined from standardized spirometry assessments and estimated using the 2012 Global Lungs Initiative equation. Baseline was defined as the last non-missing predose assessment on Day 1.

  3. Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29

    Time frame: Prior to dosing on Days 1 and 29, or at early discontinuation

    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. The respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), derived from Questions 40, 41, 42, 45, and 46 if at least 50% of the questions had non-missing data. The scale score ranged from 0-100; higher scores indicated fewer symptoms and better health-related quality of life with a negative change indicating a worsening of symptoms. A change of 4 is considered clinically relevant.

  4. Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222

    Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29

    Maximum concentration of GLPG2222 after multiple dosing (ng/ML), obtained directly from the observed concentration versus time data. All pharmacokinetic (PK) parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.

  5. Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)

    Time frame: Days 15 and 29 (predose)

    Plasma concentration of GLPG2222 observed at pre-dose (ng/mL), obtained directly from the observed concentration versus time data. Ctrough was calculated using both Day 15 and Day 29 PK data.

  6. Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])

    Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29

    Time of occurrence of maximum concentration of GLPG2222 after multiple dosing (h), obtained directly from the observed concentration versus time data. All PK parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.

  7. Mean Area Under the Concentration-Time Curve From Time 0 up to 24 Hours Following Multiple Dosing (AUC[0-t]; ng.h/mL) of GLPG2222

    Time frame: Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29

    Area under the concentration-time curve from time 0 up to 24 hours following multiple dosing (ng.h/mL), calculated by linear up/log down trapezoidal summation. All PK parameters were determined from Day 15; Day 29 data were determined if the participant was not available for full PK profiling on Day 15.

Sponsors and collaborators

Lead sponsor

Lakefront Biotherapeutics NV

Industry

Registry information

Official study title

A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate Multiple Doses of GLPG2222 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation

Important dates

Study start
2017
Primary completion
2017
Study completion
2017
First posted
Apr 18, 2017
Registry last updated
Nov 16, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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