A Randomized, Double-blind, Placebo-controlled, Multinational, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 698
- 试验地点
- 306
- 主要终点
- Change in Absolute FVC from Baseline to Week 52
研究概览
简要总结
Study RIN-PF-305 is designed to evaluate the safety and efficacy of inhaled treprostinil in subjects with progressive pulmonary fibrosis (PPF) over a 52-week period.
详细描述
Study RIN-PF-305 is a Phase 3, multinational, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of inhaled treprostinil in subjects with PPF over a 52-week period. Subjects will be randomly allocated 1:1 to receive inhaled treprostinil or placebo. All subjects will initiate inhaled treprostinil or placebo at a dose of 3 breaths administered 4 times daily (QID) and will titrate to a target dosing regimen of 12 breaths QID. Study drug doses may be titrated up as tolerated, until the target dose or maximum clinically tolerated dose is achieved. Once eligible, 6 Treatment Period visits to the clinic will be required at Weeks 4, 8, 16, 28, 40, and 52.
Efficacy assessments include spirometry (forced vital capacity [FVC]), time to clinical worsening, time to first acute exacerbation of interstitial lung disease (ILD), overall survival, King's Brief Interstitial Lung Disease (K-BILD) questionnaire, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, supplemental oxygen use, and lung diffusion capacity (DLCO). Safety assessments include the development of adverse events (AEs)/serious adverse events (SAEs), vital signs, clinical laboratory parameters, and electrocardiogram (ECG) parameters.
Subjects who complete the Week 52 Visit may be offered the opportunity to enter an open-label extension (OLE) study after completing the final study 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject gives voluntary informed consent to participate in the study.
- •Subject is ≥18 years of age, inclusive, at the time of signing informed consent.
- •Subject has radiological evidence of pulmonary fibrosis of >10% extent on an HRCT scan in the previous 12 months (confirmed by central review).
- •Subject has a diagnosis of PPF (other than IPF) that fulfills at least 1 of the following criteria for progression within 24 months of screening despite standard treatment of ILD, as assessed by the Investigator:
- •Clinically significant decline in % predicted FVC based on ≥10% relative decline
- •Marginal decline in % predicted FVC based on ≥5% to <10% relative decline combined with worsening of respiratory symptoms
- •Marginal decline in % predicted FVC based on ≥5% to <10% relative decline combined with increasing extent of fibrotic changes on chest imaging
- •Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging
- •FVC ≥45% predicted at Screening (confirmed by central review).
- •Subjects must be on 1 of the following:
- •On nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator's opinion, are planning to continue treatment through the study
- •Not on treatment with nintedanib or pirfenidone for ≥90 days prior to Baseline and in the Investigator's opinion, not planning to initiate either treatment during the study.
- •Concomitant use of both nintedanib and pirfenidone is not permitted.
- •Subjects treated with immunosuppressive agents (eg, mycophenolate, methotrexate, azathioprine, oral corticosteroids, rituximab) need to be on treatment for at least 120 days prior to Baseline and, in the Investigator's clinical opinion, must be refractory to treatment.
- •Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will agree to do 1 of the following:
- •Abstain from intercourse (when it is in line with their preferred and usual lifestyle)
- •Use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug.
- •i. Medically acceptable, highly effective forms of contraception can include approved hormonal contraceptives (oral, injectable, and implantable) and barrier methods (such as a condom or diaphragm) when used with a spermicide.
- •Women who are successfully sterilized (including hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal (defined as amenorrhea for at least 12 consecutive months) are not considered to be of reproductive potential.
- •Males with a partner of childbearing potential must agree to use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug.
- •In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.
排除标准
- •Subject is pregnant or lactating.
- •Subject has primary obstructive airway physiology (forced expiratory volume in 1 second/FVC <0.70 at Screening) or greater extent of emphysema than fibrosis on HRCT (confirmed by central review).
- •Subject has a diagnosis of IPF.
- •Subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy.
- •Subject has received any PAH-approved therapy, including prostacyclin therapy (epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), IP receptor agonists (selexipag), endothelin receptor antagonists, phosphodiesterase type 5 inhibitors (PDE5-Is), soluble guanylate cyclase stimulators, or activin signaling inhibitors (sotatercept) within 60 days prior to Baseline. As needed use of a PDE5-I for erectile dysfunction is permitted, provided no doses are taken within 48 hours prior to any study-related efficacy assessments.
- •Subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline.
- •Exacerbation of ILD or active pulmonary or upper respiratory infection within 30 days prior to Baseline. Subjects must have completed any antibiotic or steroid regimens for treatment of the infection or acute exacerbation more than 30 days prior to Baseline to be eligible. If hospitalized for an acute exacerbation of ILD or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible.
- •Subject has uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline.
- •Use of any other investigational drug/device or participation in any investigational study in which the subject received a medical intervention (ie, procedure, device, medication/supplement) within 30 days prior to Screening. Subjects participating in non-interventional, observational, or registry studies are eligible.
- •Acute pulmonary embolism within 90 days prior to Baseline.
- •In the opinion of the Investigator, the subject has any condition that would interfere with the interpretation of study assessments or would impair study participation or cooperation.
- •In the opinion of the Investigator, life expectancy <12 months due to ILD or a concomitant illness.
- •Subject has received nerandomilast within 60 days prior to Baseline.
研究组 & 干预措施
Inhaled Treprostinil
Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled QID and titrated up to a target of 12 breaths QID or until the subject reaches their maximum clinically tolerated dose.
干预措施: Inhaled Treprostinil (Drug)
Placebo
Matching placebo inhaled using an ultrasonic nebulizer QID
干预措施: Placebo (Drug)
Inhaled Treprostinil
Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled QID and titrated up to a target of 12 breaths QID or until the subject reaches their maximum clinically tolerated dose.
干预措施: Treprostinil Ultrasonic Nebulizer (Device)
Placebo
Matching placebo inhaled using an ultrasonic nebulizer QID
干预措施: Treprostinil Ultrasonic Nebulizer (Device)
结局指标
主要结局
Change in Absolute FVC from Baseline to Week 52
时间窗: Baseline to Week 52
The FVC measurement indicates the amount of air a person can forcefully and quickly exhale after taking a deep breath.
次要结局
- Time to First Clinical Worsening(Baseline to Week 52)
- Change in K-BILD Questionnaire Score from Baseline to Week 52(Baseline to Week 52)
- Time to First Acute Exacerbation of ILD(Baseline to Week 52)
- Overall Survival at Week 52(Week 52)
- Change in % Predicted FVC from Baseline to Week 52(Baseline to Week 52)
- Change in DLCO from Baseline to Week 52(Baseline to Week 52)