An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Itacitinib in Participants With Bronchiolitis Obliterans Syndrome Following Lung Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 9
- 主要终点
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of itacitinib in participants with post-lung transplant bronchiolitis obliterans syndrome (BOS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Double lung transplantation ≥ 1 year before informed consent. Confirmed BOS progression to Grade 1, 2, or 3 diagnosed within 1 year of screening
- •*Confirmed BOS progression to Grade 1, 2, or 3 diagnosed within 2 years of screening AND:
- •A ≥ 200 mL decrease in FEV1 in the previous 12 months
- •*A ≥ 50 mL decrease in FEV1 in the last 2 measurements.
- •Willingness to avoid pregnancy or fathering children.
排除标准
- •History of a single lung transplant
- •FEV1 decline attributable to cause(s) other than BOS.
- •Participants who have had any significant change (eg, addition of new agents) in an immunosuppressive regimen in the 4 weeks before screening.
- •Untreated and/or symptomatic gastroesophageal reflux disease.
- •Significant infectious comorbidities including invasive fungal disease, B. Cepacia, non TB mycobacteria, or TB.
- •Receipt of JAK inhibitor therapy after lung transplant for any indication. Treatment with a JAK inhibitor before lung transplant is permitted.
- •Laboratory values at screening outside the protocol-defined ranges.
- •Active HBV or HCV infection that requires treatment, or at risk for HBV reactivation (ie, positive HBsAg).
- •Known HIV infection.
- •History of active malignancy within 3 years of screening.
- •Women who are pregnant or breastfeeding.
- •Treatment with an investigational agent, procedure, or device within 30 days of enrollment, or within 5 half-lives of the investigational product, whichever is longer.
研究组 & 干预措施
Itacitinib 300 mg
Phase 1: Itacitinib 300 mg twice daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.
干预措施: Itacitinib (Drug)
Itacitinib 400 mg
Phase 1: Itacitinib 400 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration.
干预措施: Itacitinib (Drug)
Itacitinib 600 mg
Phase 1: Itacitinib 600 mg once daily. There can be required dose adjustments in the protocol for concurrent CYP3A administration
干预措施: Itacitinib (Drug)
Itacitinib
Phase 2: Itacitinib administered orally at the recommended dose from Phase 1.
干预措施: Itacitinib (Drug)
结局指标
主要结局
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
时间窗: up to approximately 162 weeks
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as either an AE reported for the first time or the worsening of a pre-existing condition after the first dose of itacitinib until 30 days after the last dose of itacitinib.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 12
时间窗: Baseline; Week 12
FEV1 was defined as the volume of air exhaled in 1 second. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Phase 2: FEV1 Response Rate
时间窗: Baseline through Week 12
FEV1 response rate was defined as the percentage of participants demonstrating a ≥10% absolute increase in FEV1 compared with Baseline, confirmed by 2 consecutive spirometric assessments ≥1 week apart.
Number of Participants With Any Grade 3 or Higher TEAE
时间窗: up to approximately 162 weeks
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as either an AE reported for the first time or the worsening of a pre-existing condition after the first dose of itacitinib until 30 days after the last dose of itacitinib. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events v5.0. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
次要结局
- Phase 1: Duration of FEV1 Response(up to 34.9 months)
- Phase 2: Duration of FEV1 Response(up to 24 months)
- Phase 1: Time to Progression(up to 36.4 months)
- Phase 2: Time to Progression(up to 24 months)
- Phase 1: Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score(Baseline; up to 158.4 weeks)
- Phase 2: Change From Baseline in the SGRQ Total Score(up to 24 months)
- Phase 1: Change From Baseline in the Quality of Life-Short Form-12 (QOL-SF-12) Questionnaire Scores(Baseline; up to 158.4 weeks)
- Phase 2: Change From Baseline in QOL-SF-12 Questionnaire Scores(up to 24 months)
- Phase 1: Number of Participants With the Indicated Responses on the EQ-5D-3L Questionnaire Regarding Their Health State(Baseline; up to 158.4 weeks)
- Phase 2: Number of Participants With the Indicated Responses on the EQ-5D-3L Questionnaire Regarding Their Health State(up to 24 months)
- Phase 1: Cmax of Itacitanib(pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4)
- Phase 2: Cmax of Itacitanib(pre-dose and 1, 2, and 5 hours post-dose at Week 4)
- Phase 1: AUC0-24h of Itacitanib(pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4)
- Phase 2: AUC0-24h of Itacitanib(pre-dose and 1, 2, and 5 hours post-dose at Week 4)
- Phase 1: Tmax of Itacitanib(pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4)
- Phase 2: Tmax of Itacitanib(pre-dose and 1, 2, and 5 hours post-dose at Week 4)
- Phase 1: Ctau of Itacitanib(pre-dose and 1, 2, and 5 hours post-dose on Day 1 (Baseline) and at Week 4)
- Phase 2: Ctau of Itacitanib(pre-dose and 1, 2, and 5 hours post-dose at Week 4)
- Phase 2: Time to Retransplantation or Death(up to 24 months)