NCT03711162终止3 期
A Phase 3, Randomized, Double-blind, Parallel-group, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Two Doses of GLPG1690 in Addition to Local Standard of Care for Minimum 52 Weeks in Subjects With Idiopathic Pulmonary Fibrosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Galapagos NV
- 入组人数
- 525
- 试验地点
- 132
- 主要终点
- Annual Rate of Decline in FVC up to Week 52
研究概览
简要总结
The main purpose of this study was to see how GLPG1690 works together with your current standard treatment on your lung function and IPF disease in general. The study also investigated how well GLPG1690 is tolerated (for example if you got any side effects while on study drug).
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subject aged ≥40 years on the day of signing the Informed Consent Form (ICF).
- •A diagnosis of IPF within 5 years prior to the screening visit, as per applicable American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines at the time of diagnosis.
- •Chest high-resolution computed tomography (HRCT) historically performed within 12 months prior to the screening visit and according to the minimum requirements for IPF diagnosis by central review based on subject's HRCT only (if no lung biopsy (LB) available), or based on both HRCT and LB (with application of the different criteria in either situation). If an evaluable HRCT <12 months prior to screening is not available, an HRCT can be performed at screening to determine eligibility, according to the same requirements as the historical HRCT.
- •Subjects receiving local standard of care for the treatment of IPF, defined as either pirfenidone or nintedanib at a stable dose for at least two months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason). A stable dose is defined as the highest dose tolerated by the subject during those two months.
- •The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (investigator-determined).
- •Meeting all of the following criteria during the screening period: FVC ≥45% predicted of normal, Forced expiratory volume in 1 second (FEV1)/FVC ≥0.7, diffusing capacity of the lung for carbon monoxide (DLCO) corrected for Hb ≥30% predicted of normal.
- •Estimated minimum life expectancy of at least 30 months for non IPF related disease in the opinion of the investigator.
- •Male subjects and female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures from the time of first dose of investigational medicinal product (IMP) (for the male subject) or the signing of the ICF (for the female subject), during the study, and until 90 days (male) or 30 days (female) after the last dose of IMP.
- •Able to walk at least 150 meters during the 6-Minute Walk Test (6MWT) at screening Visit 1; without having a contraindication to perform the 6MWT or without a condition putting the subject at risk of falling during the test (investigator's discretion). The use of a cane is allowed, the use of a stroller is not allowed at all for any condition. At Visit 2, for the oxygen titration test, resting oxygen saturation (SpO2) should be ≥88% with maximum 6 L O2/minute; during the walk, SpO2 should be ≥83% with 6 L O2/minute or ≥88% with 0, 2 or 4 L O2/minute.
排除标准
- •History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, prostate cancer that has been medically managed through active surveillance or watchful waiting, squamous cell carcinoma of the skin if fully resected, and Ductal Carcinoma In Situ).
- •Clinically significant abnormalities detected on ECG of either rhythm or conduction, a QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms, or a known long QT syndrome. Patients with implantable cardiovascular devices (e.g. pacemaker) affecting the QT interval time may be enrolled in the study based upon investigator judgment following cardiologist consultation if deemed necessary, and only after discussion with the medical monitor.
- •Acute IPF exacerbation within 6 months prior to screening and/or during the screening period. The definition of an acute IPF exacerbation is as follows: Previous or concurrent diagnosis of IPF; Acute worsening or development of dyspnea typically < 1 month duration; Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern and deterioration not fully explained by cardiac failure or fluid overload.
- •Lower respiratory tract infection requiring treatment within 4 weeks prior to screening and/or during the screening period.
- •Interstitial lung disease associated with known primary diseases (e.g. sarcoidosis and amyloidosis), exposures (e.g. radiation, silica, asbestos, and coal dust), or drugs (e.g. amiodarone).
- •Diagnosis of severe pulmonary hypertension (investigator- determined).
- •Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months prior to screening or during the screening period (e.g. acute coronary disease, heart failure, and stroke).
- •Had gastric perforation within 3 months prior to screening or during screening, and/or underwent major surgery within 3 months prior to screening, during screening or have major surgery planned during the study period.
- •History of nintedanib-related increase in ALT and/or AST of >5 x upper limit of the normal range (ULN) and increased susceptibility to elevated LFT; moderate to severe hepatic impairment (Child-Pugh B or C) and/or abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), and/or total bilirubin ≥1.5 x upper limit of the normal range (ULN), and/or gamma glutamyl transferase (GGT) ≥3 x ULN. Retesting is allowed once for abnormal LFT.
- •Abnormal renal function defined as estimated creatinine clearance, calculated according to Cockcroft-Gault calculation (CCr) <30 mL/min. Retesting is allowed once.
- •Use of any of the following therapies within 4 weeks prior to screening and during the screening period, or planned during the study: warfarin, imatinib, ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, methotrexate, sildenafil (except for occasional use), prednisone at steady dose >10 mg/day or equivalent.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants received GLPG1690 (ziritaxestat) matching placebo tablets for oral use once daily (mean GLPG1690 exposure was up to 353.4 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).
干预措施: Placebo (Drug)
GLPG1690 200 mg
Experimental
Participants received GLPG1690 (ziritaxestat) 200 mg as film-coated tablet for oral use once daily (mean GLPG1690 exposure was up to 356.0 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).
干预措施: GLPG1690 (Drug)
GLPG1690 600 mg
Experimental
Participants received GLPG1690 (ziritaxestat) 600 mg, film-coated tablets orally once daily (mean GLPG1690 exposure was up to 325.3 days) in addition to local standard of care. Standard of care included either pirfenidone or nintedanib at a stable dose for at least 2 months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason).
干预措施: GLPG1690 (Drug)
结局指标
主要结局
Annual Rate of Decline in FVC up to Week 52
时间窗: Baseline up to week 52
FVC (in mL) is the maximum amount of air exhaled from lungs by a participant after taking their deepest possible breath, as measured by spirometry.
次要结局
- Percentage of Participants With Disease Progression up to Week 52(Up to week 52)
- Annual Rate of Decline in FVC Until EoS(Baseline up to EoS (week 121))
- Percentage of Participants With All Cause Hospitalization Until EoS(Up to EoS (week 121))
- Percentage of Participants Hospitalized for Non-elective Lung Transplant Until EoS(Up to EoS (week 121))
- Percentage of Participants With All Cause Mortality or Hospitalization for Non-elective Lung Transplant Until EoS(Up to EoS (week 121))
- Percentage of Participants With Respiratory-Related Hospitalization Until End of Study (EoS)(Up to EoS (week 121))
- Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 52(Baseline, week 52)
- Percentage of Participants With Disease Progression Until EoS(Up to EoS (week 121))
- Percentage of Participants With Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation Until EoS(Up to EoS (week 121))
- Change From Baseline in St.George's Respiratory Questionnaire (SGRQ) Total Score at Week 100(Baseline, week 100)
- FVC at Week 112(Week 112)
- Percentage of Participants With Respiratory Related Mortality Until EoS(Up to EoS (week 121))
- Percentage of Participants With All-Cause Mortality or Hospitalization That Meets >=10% Absolute Decline in %FVC or Respiratory-Related Hospitalization Until EoS(Up to EoS (week 121))
- Percentage of Participants With All-Cause Mortality or Respiratory-Related Hospitalizations Until EoS(Up to EoS (week 121))
- FVC at Week 52(Week 52)
- Changes From Baseline Leicester Cough Questionnaire (LCQ) Total Score and Individual Domain Score at Week 52 and Week 100(Baseline, week 52, week 100)
- Change From Baseline in Total Distance Walked in Six-minute Walk Test (6MWT) at Week 52 and Week 100(Baseline, week 52, week 100)
- Percentage of Participants With All Cause Mortality, Hospitalization for Non-elective Lung Transplant or Hospitalization for Qualifying for Lung Transplant Until EoS(Up to EoS (week 121))
- Change From Baseline in FVC at Week 112(Baseline, week 112)
- Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤10(Baseline, week 52)
- Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤10(Baseline, week 112)
- Change From Baseline in Visual Analogue Score (VAS): Urge to Cough at Week 52 and Week 100(Baseline, week 52, week 100)
- Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) at Week 52 and Week 100(Baseline, week 52, week 100)
- Change From Baseline in FVC at Week 52(Baseline, week 52)
- Percent Change From Baseline in FVC at Week 52(Baseline, week 52)
- Percent Change From Baseline in FVC at Week 112(Baseline, week 112)
- Change From Baseline in Visual Analogue Score (VAS): Cough at Week 52 and Week 100(Baseline, week 52, week 100)
- Change From Baseline in European Quality Of Life (EQ) VAS at Week 52 and Week 100(Baseline, week 52, week 100)
- Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 52: FVC Change Within ≤5(Baseline, week 52)
- Percentage of Participants With Absolute Categorical Change From Baseline in Percent FVC at Week 112: FVC Change Within ≤5(Baseline, week 112)
- Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs(Baseline up to 30 days after the last dose (up to week 121))
- Change From Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) (Corrected for Hemoglobin [Hb]) at Week 52 and Week 100(Baseline, week 52, week 100)
- Area Under The Concentration Time Curve (AUC) of Ziritaxtestat(Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose)
- Maximum Observed Plasma Concentration (Cmax) of Ziritaxtestat(Sparse samples collected on day 1 pre-dose, day 85 post-dose, day 237 post-dose, day 183 pre-dose, day 365 pre-dose)
研究者
研究点 (132)
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