NCT06317285终止2 期
A Phase 2, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study (TRANSFORM) to Evaluate the Efficacy and Safety of GSK3915393 in Participants With Idiopathic Pulmonary Fibrosis (IPF)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 158
- 试验地点
- 59
- 主要终点
- Absolute Change From Baseline in Forced Vital Capacity (FVC) at Week 26
研究概览
简要总结
Idiopathic Pulmonary Fibrosis is a chronic lung disease which causes scarring of the lungs and difficulty in breathing. GSK3915393 is a new medicine, which is being tested in participants with IPF for the first time. The study will assess the safety and effectiveness of GSK3915393 in IPF participants.
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)
盲法说明
This will be a double-blind study with respect to allocation of GSK3915393 or placebo to participants.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with IPF diagnosed within 5 years prior to screening based on the applicable American Thoracic Society (ATS)/ European Respiratory Society (ERS)/ Japanese Respiratory Society (JRS)/ Latin American Thoracic Society (ALAT) Guideline at the time of diagnosis.
- •Centrally read chest High Resolution Computed Tomography (HRCT) obtained at screening or historical HRCT obtained within 12 months of screening that is consistent with Usual interstitial pneumonia (UIP) or probable UIP (if indeterminate HRCT finding, IPF may be confirmed locally by historical biopsy).
- •FVC greater than or equal to (>=) 45 percent (%) of predicted normal.
- •Diffusing Capacity (of Lung) for Carbon Monoxide (DLCO) >=25% of predicted normal corrected for hemoglobin (Hb).
- •Prebronchodilator Forced Expiratory Volume in 1 second (FEV1)/FVC >=0.
- •If receiving antifibrotics must be on stable dose of nintedanib or pirfenidone for at least 12 weeks prior to screening.
- •If not receiving approved antifibrotics (pirfenidone or nintedanib) there should be a valid reason for this, such as previous failure, contraindications, failure to meet national or regional eligibility criteria for anti-fibrotic treatment, or participant choice.
- •If not currently receiving pirfenidone or nintedanib, participant must have stopped pirfenidone or nintedanib for at least 4 weeks prior to screening.
- •Body weight >=40 kilogram (kg) and body mass index within the range 18.5-35 kilogram per meter square (kg/m^2) (inclusive).
- •A female participant is eligible to participate if a woman of nonchildbearing potential (WONCBP)
- •Capable of giving signed informed consent
排除标准
- •Participants with Interstitial Lung Disease (ILD) associated with other known causes.
- •Diagnosis of sarcoidosis or any systemic autoimmune disease (including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus and rheumatoid arthritis).
- •Acute IPF exacerbation within 6 months prior to screening and/or during the screening period (investigator-determined).
- •Clinically significant non-parenchymal lung disease (e.g., asthma, chronic obstructive pulmonary disease, cavitary or pleural diseases) at screening.
- •Diagnosis of severe pulmonary hypertension (investigator-determined)
- •Extent of emphysema is greater than the extent of fibrosis according to reported results from the most recent HRCT.
- •History of previous lung transplant or recent major surgery (investigator-determined) within 12 weeks prior to screening or planned during the trial period. Registration on a transplant waiting list is allowed.
- •Clinically significant respiratory tract infection (e.g., active tuberculosis, infectious pneumonia, Corona virus disease 2019 [COVID-19]) requiring treatment within 4 weeks prior to and/or during the screening period.
- •Cigarette smoking (including e-cigarettes) either current or within 3 months before screening.
- •Current or chronic liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP) greater than (>) 2x Upper Limit of Normal (ULN) and bilirubin >1.5x ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than (<) 35% at screening).
- •Clinically significant abnormalities detected on ECG of either rhythm or conduction, a Corrected QT interval (QTc) >450 millisecond (msec) or QTc > 480msec for participants with a bundle branch block and/or a pacemaker who are actively ventricularly pacing during the screening ECG.
- •Participants with pacemakers who are not pacing at the time of the screening ECG should have a non-paced QTc <450 msec.
- •Prior/Concomitant Therapy-
- •Simultaneous use of pirfenidone and nintedanib at screening.
- •Received systemic corticosteroids equivalent to prednisone >10 milligrams/day or equivalent within 2 weeks of screening period.
- •Use of any of the following therapies within 4 weeks prior to screening and during the screening period or planned during the study:
- •Immunomodulatory therapies, including but not limited to azathioprine, mycophenolate mofetil, methotrexate, tacrolimus, cyclophosphamide, imatinib, Tumour Necrosis Factor -Alpha (TNF- α) inhibitors.
- •Medications that are under investigation for the treatment of IPF including inhaled treprostinil and Phosphodiesterase-4 (PDE-4) inhibitors. Symptomatic cough therapies are allowed.
- •Current use of systemic strong and moderate inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) that cannot be safely discontinued or switched to an alternative agent at least 14 days before randomization.
- •Current use of systemic CYP3A4 substrates that have a narrow therapeutic index that cannot be safely discontinued or switched to an alternative agent at least 14 days before randomization.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants received matching placebo, orally, twice daily for 26 weeks.
干预措施: Placebo (Drug)
GSK3915393
Experimental
Participants received GSK3915393 80 milligrams (mg), orally, twice daily for 26 weeks.
干预措施: GSK3915393 (Drug)
结局指标
主要结局
Absolute Change From Baseline in Forced Vital Capacity (FVC) at Week 26
时间窗: Baseline (Day 1) and Week 26
Forced vital capacity (FVC) is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. The maximum of triplicate FVC for each participant was used for calculations. Baseline was defined as the last non-missing value/assessment prior to the first dose of study treatment on Day 1. Change from Baseline (CFB) in FVC at Week 26 was calculated for each participant using the FVC Week 26 result minus the Baseline FVC result. Posterior median CFB and the 95% highest posterior density (HPD) interval were derived using a Bayesian repeated measures model. The data presented as "Median" refers to the 'posterior median' and "95% confidence interval" to '95% HPD interval'.
Absolute Change from Baseline in Forced Vital Capacity (FVC) (milliliters [mL]) at Week 26
时间窗: Baseline and at Week 26
次要结局
- Number of Participants with Clinically Important Findings in Electrocardiogram (ECG)(Baseline and up to Week 26)
- Number of Participants with Clinically Important Findings in Hepatobiliary Parameters(Baseline and up to Week 26)
- Absolute Change from Baseline in Percent Predicted Forced Vital Capacity (%) at Weeks 4, 8, 12, 18 and 26(Baseline and at Week 4, Week 8, Week 12, Week 18 and Week 26)
- Absolute Change from Baseline in Forced Vital Capacity (mL) at Weeks 4, 8, 12 and 18(Baseline and at Week 4, Week 8, Week 12 and Week 18)
- Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Week 26)
- Absolute Change From Baseline in Forced Vital Capacity at Weeks 4, 8, 12 and 18(Baseline (Day 1) and Weeks 4, 8, 12 and 18)
- Absolute Change From Baseline in FVC (Percentage [%] Predicted) at Weeks 4, 8, 12, 18 and 26(Baseline (Day 1) and Weeks 4, 8, 12, 18 and 26)
- Proportion of Participants Who Achieved Relative Decline of Less Than or Equal to (<=) 5% in FVC From Baseline at Week 26(Baseline (Day 1) and Week 26)
- Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Week 29)
- Number of Participants With Vital Signs Results by Potential Clinical Importance (PCI) Criteria(Up to Week 29)
- Number of Participants With Electrocardiogram (ECG) Results by PCI Criteria(Up to Week 29)
- Number of Participants With Hematology Laboratory Results by PCI Criteria(Up to week 29)
- Number of Participants With Hepatobiliary Laboratory Results by PCI Criteria(Up to week 29)
- Number of Participants With Clinical Chemistry Laboratory Results by PCI Criteria(Up to Week 29)
- Maximum Observed Plasma Concentration (Cmax) of GSK3915393(Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2)
- Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to 4 Hours (AUC [0-4]) of GSK3915393(Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2)
- Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to Infinity (AUC [0-inf]) of GSK3915393(Pre-dose, 0.5, 1, 1.5, 2, 3, and 4 hours post-dose at Week 2)
- Number of Participants with Clinically Important Findings in Hematology(Baseline and up to Week 26)
- Number of Participants with Clinically Important Findings in Clinical Chemistry(Baseline up to Week 26)
- Maximum observed concentration (Cmax) of GSK3915393 in IPF Participants(At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour post-dose))
- Area under the time-concentration curve (AUC) from Zero (pre-dose) to 4 hours post-dose sample (AUC0-4 hour) of GSK3915393(At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour post-dose))
- Number of Participants with Clinically Important Findings in Vital Signs(Baseline and up to Week 26)
- Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC-inf) of GSK3915393(At Week 2 (pre-dose, and 0.5, 1, 1.5, 2, 3 and 4 hour post-dose))
- Number of Participants Achieving Relative Decline from Baseline in FVC (mL) Less than or Equal to (≤) 5 Percent (%) at Week 26(Baseline and at Week 26)
研究者
研究点 (59)
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