An Open-Label, Single-Arm, Phase 1/2 Study Evaluating the Safety and Efficacy of Itacitinib in Combination With Corticosteroids for the Treatment of Steroid-Naive Acute Graft-Versus-Host Disease in Pediatric Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 36
- 主要终点
- Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate itacitinib in combination with corticosteroids for the treatment of Grades II to IV acute graft-versus-host disease (aGVHD) in steroid-naive pediatric participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 28 Days 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants: 12 to < 18 years old (Cohort 1), 6 to < 12 years old (Cohort 2), 2 to < 6 years old (Cohort 3), Weighing > 8 kg to < 2 years old (Cohort 4), and 28 days old to weighing ≤ 8 kg (Cohort 5).
- •Undergone 1 allogeneic hematopoietic stem cell transplantation (allo-HSCT) from any donor and source for hematological malignancies or disorders. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
- •Clinically suspected Grade II to IV aGVHD as per Mount Sinai Acute GVHD International Consortium (MAGIC) criteria, occurring after allo-HSCT and any GVHD prophylactic medication.
- •Evidence of myeloid engraftment.
排除标准
- •More than 1 allo-HSCT.
- •Received more than 2 days of systemic corticosteroids for aGVHD before the first study drug administration.
- •Presence of GVHD overlap syndrome.
- •Presence of an active uncontrolled infection.
- •Known HIV infection.
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment or at risk for HBV reactivation.
- •Evidence of relapsed primary disease or have been treated for relapse after the allo-HSCT was performed.
- •Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg once daily of methylprednisolone (or equivalent) within 7 days of the first study drug administration.
- •Receipt of live (including attenuated) vaccines or anticipation of need for such vaccines during the study.
- •Receipt of JAK inhibitor therapy after allo-HSCT for any indication.
- •Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment.
研究组 & 干预措施
Itacitinib + Corticosteroids
干预措施: Itacitinib (Drug)
Itacitinib + Corticosteroids
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: up to 45 days
A TEAE was defined as an AE that began or worsened from Baseline after the first administration of study drug.
Phase 1: Cmax of Itacitinib When Administered With Corticosteroids
时间窗: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
Cmax was defined as the maximum observed plasma concentration.
Phase 1: Cmin of Itacitinib When Administered With Corticosteroids
时间窗: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
Cmin was defined as the minimum observed plasma concentration.
Phase 1: Tmax of Itacitinib When Administered With Corticosteroids
时间窗: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
Tmax was defined as the time to the maximum concentration.
Phase 1: AUC of Itacitinib When Administered With Corticosteroids
时间窗: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
AUC was defined as the area under the plasma concentration-time curve.
Phase 1: Cl/F of Itacitinib When Administered With Corticosteroids
时间窗: Day 1: 1, 2, 4, and 6 hours post-dose. Day 7: predose; 1, 2, 4, and 6 hours post-dose
Cl/F was defined as the apparent oral dose clearance.
Phase 2: Overall Response Rate up to Day 28
时间窗: up to Day 28
Overall response rate was defined as the number of participants demonstrating a complete response (CR), a very good partial response (VGPR), or a partial response (PR).
次要结局
- Phase 2: Relapse Rate of Malignant and Nonmalignant Disorders(up to approximately 12 months)
- Phase 2: Malignant and Nonmalignant Disorders Relapse-related Mortality Rate(up to approximately 12 months)
- Phase 2: Failure-free Survival(up to 6 months)
- Phase 2: Overall Survival(up to approximately 12 months)
- Phase 2: Incidence Rate of Secondary Graft Failure(up to approximately 12 months)
- Phase 2: Average Corticosteroid Use(up to 180 days)
- Phase 2: Number of Participants With TEAEs(up to 12 months)
- Phase 2: Cmax of Itacitinib When Administered With Corticosteroids(Day 7: predose; 1, 2, and 4 hours post-dose)
- Phase 2: Cmin of Itacitinib When Administered With Corticosteroids(Day 7: predose; 1, 2, and 4 hours post-dose)
- Phase 2: Tmax of Itacitinib When Administered With Corticosteroids(Day 7: predose; 1, 2, and 4 hours post-dose)
- Phase 2: AUC of Itacitinib When Administered With Corticosteroids(Day 7: predose; 1, 2, and 4 hours post-dose)
- Phase 2: Cl/F of Itacitinib When Administered With Corticosteroids(Day 7: predose; 1, 2, and 4 hours post-dose)
- Phase 2: Overall Response Rate up to 100 Days(up to 100 days)
- Phase 1: Overall Response Rate(up to Day 28)
- Phase 2: Non Relapse Mortality(up to 24 months)
- Phase 2: Number of Participants With Chronic Graft-versus-host Disease (cGVHD)(up to 365 days)
- Phase 2: Duration of Response(up to approximately 12 months)
- Phase 2: Time to Response(up to approximately 12 months)
- Phase 2: Cumulative Corticosteroid Dose(up to 180 days)
- Phase 2: Number of Participants Who Discontinued Corticosteroids(up to 100 days)
- Phase 2: Number of Participants Who Discontinued Immunosuppressive Medication(up to 100 days)
- Phase 2: Number of Participants With aGVHD Flares(up to 100 Days)