A Phase IIa, Randomized, Double-blind, Placebo-controlled Study to Evaluate GLPG2222 in Ivacaftor-treated Subjects With Cystic Fibrosis Harbouring One F508del CFTR Mutation and a Second Gating (Class III) Mutation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Galapagos NV
- 入组人数
- 37
- 试验地点
- 22
- 主要终点
- Changes in adverse events
研究概览
简要总结
This clinical study is a phase IIa, multi-center, randomized, double-blind, placebo-controlled, parallel group study to evaluate two doses of orally administered GLPG2222 in adult subjects with a confirmed diagnosis of CF harbouring one F508del CFTR mutation and a second gating (class III) mutation and on stable treatment with ivacaftor.
Up to 35 evaluable subjects are planned to be included in the study. Eligible subjects must be on stable treatment with physician prescribed ivacaftor (Kalydeco®) for at least 28 days at the baseline visit. They will be randomized in a 2:2:1 ratio to receive one of two active doses of GLPG2222 (150 mg q.d. or 300 mg q.d.) or placebo q.d. administered for 29 days. Subjects will be in the study for a minimum of 6 weeks and a maximum of 10 weeks, from screening until the follow-up visit.
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.
- •One F508del mutation on one allele in the CFTR gene, a gating (class III) mutation (one of the following: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R) on the 2nd allele in the CFTR gene (documented in the subject's medical record or CF registry).
- •Weight ≥ 40 kg.
- •Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline (including physician prescribed ivacaftor (Kalydeco®) 150 mg b.i.d.).
- •Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).
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 (including rhinosinusitis) 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.
- •History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices, etc).
- •Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or total bilirubin (>1.5 times ULN (CTCAE Grade 2) and/or gamma-glutamyl transferase (GGT) ≥ 3x the upper limit of normal (ULN), and/or total bilirubin (>1.5 times ULN (CTCAE Grade 2).
- •Estimated creatinine clearance < 60mL/min using the Cockroft-Gault formula at screening.
研究组 & 干预措施
GLPG2222 Dose 1
干预措施: GLPG2222 150 mg q.d. (Drug)
GLPG2222 Dose 2
干预措施: GLPG2222 300 mg q.d. (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Changes in adverse events
时间窗: at screening and at each study visit up to day 43 which is the final FU visit
To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of adverse events
Changes in abnormal laboratory
时间窗: at screening and at each study visit up to day 43 which is the final FU visit
To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of laboratory
Changes in abnormal vital signs, ECG or physical examination
时间窗: at screening and at each study visit up to day 43 which is the final FU visit
To evaluate the safety and tolerability of GLPG2222 as compared to placebo in terms of vital signs, ECG or physical examination
次要结局
- Change from baseline of Sweat chloride concentration(at screening and at each study visit up to day 43 which is the final FU visit)
- Change from baseline of FEV1 (L) and percent predicted FEV1 for age, gender and height as assessed by spirometry(at screening and at each study visit up to day 43 which is the final FU visit)
- Change from baseline on the respiratory domain of Revised Cystic Fibrosis Questionnaire (CFQ-R)(at screening and at each study visit up to day 43 which is the final FU visit)