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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Galapagos NV
- 入组人数
- 59
- 试验地点
- 23
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Cohort A: GLPG2222 50 mg once daily (QD)
Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.
干预措施: GLPG2222 50 mg (Drug)
Cohort A: GLPG2222 50 mg once daily (QD)
Participants received a single GLPG2222 50 mg tablet and two matching placebo tablets orally, QD for 29 days.
干预措施: Placebo (Drug)
Cohort A: GLPG2222 100 mg QD
Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.
干预措施: GLPG2222 100 mg (Drug)
Cohort A: GLPG2222 100 mg QD
Participants received a single GLPG2222 100 mg tablet and two matching placebo tablets orally, QD for 29 days.
干预措施: Placebo (Drug)
Cohort B: GLPG2222 200 mg QD
Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.
干预措施: Placebo (Drug)
Cohort B: GLPG2222 200 mg QD
Participants received two GLPG2222 100 mg tablets and one matching placebo tablet orally, QD for 29 days.
干预措施: GLPG2222 200 mg (Drug)
Cohort B: GLPG2222 400 mg QD
Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.
干预措施: Placebo (Drug)
Cohort B: GLPG2222 400 mg QD
Participants received two GLPG2222 150 mg tablets and one GLPG2222 100 mg tablet orally, QD for 29 days.
干预措施: GLPG2222 400 mg (Drug)
Cohort A Placebo
Participants received three matching placebo tablets, orally, QD for 29 days.
干预措施: Placebo (Drug)
Cohort B Placebo
Participants received three matching placebo tablets, orally, QD for 29 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events
时间窗: 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).
次要结局
- Mean Change From Baseline in Sweat Chloride Concentration at Day 29(Prior to dosing on Days 1 and 29, or at early discontinuation)
- Mean Maximum Observed Plasma Concentration (Cmax; Nanograms Per Milliliter [mg/mL]) of GLPG2222(Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29)
- Mean Change From Baseline in Percent (%) Predicted FEV1 (%FEV1) at Day 29(Predose and between 1 and 2 hours postdose on Days 1 and 29, or at early discontinuation)
- 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(Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29)
- Mean Change From Baseline in the Respiratory Domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at Day 29(Prior to dosing on Days 1 and 29, or at early discontinuation)
- Mean GLPG2222 Plasma Concentration Observed at Predose (Ctrough; ng/mL)(Days 15 and 29 (predose))
- Median Time to Occurrence of GLPG2222 Cmax (Tmax; Hours [h])(Day 15 (predose and 0.5, 1, 2, 3, 4, 6, and 8 hours postdose) and prior to dosing on Day 29)