A Phase Ib, Open-label, Randomized, Dose-finding, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of GDC-8264 in Combination With Standard of Care in the Treatment of Acute Graft-versus-Host Disease in Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 4
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
The primary purpose of the study is to assess the safety and pharmacokinetics (PK) of GDC-8264 in participants with acute graft-versus-host disease (aGVHD).
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
- 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
- •Diagnosis of post-allogeneic hematopoietic stem cell transplantation (HSCT) aGVHD at screening
- •Evidence of engraftment post-transplant
- •Diagnosis of high-risk aGVHD, per refined Minnesota high-risk aGVHD criteria during screening
- •Initiation of treatment with systemic corticosteroids for aGVHD at a dose of prednisone ≥2 milligrams per kilograms per day (mg/kg/day) by orally (PO) or methylprednisolone ≥2 mg/kg/day intravenously (or equivalent) in divided doses at diagnosis and up to 3 days prior to or on the same day as initiation of GDC-8264 (Day 1), with no taper planned prior to Day 3
排除标准
- •Evidence of relapsed, progressing, or persistent malignancy, or treatment for relapse after transplant, or requirement for rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse
- •Prior receipt of more than one allogeneic HSCT
- •Prior receipt of solid organ transplantation that are target organs for aGVHD (e.g., liver transplant)
- •Prior systemic treatment for aGVHD, except for the standard of care corticosteroid treatment initiated as part of this trial
- •Diagnosis of chronic GVHD or overlap syndrome
- •Uncontrolled active infection (i.e., progressive symptoms related to infection despite treatment, or persistently positive blood cultures despite treatment, or any other evidence of severe sepsis)
- •Severe organ dysfunction (e.g., acute liver failure, renal failure requiring dialysis, ventilator support, or vasopressor therapy)
- •Initiation or planned use of a marketed small molecule (excluding corticosteroids) or biologic therapy as treatment for aGVHD from the start of screening through the treatment period
研究组 & 干预措施
GDC-8264, 35 mg
Participants will receive oral GDC-8264, 35 milligrams (mg), once daily (QD) for 28 days.
干预措施: GDC-8264 (Drug)
GDC-8264, 75 mg
Participants will receive oral GDC-8264, 75 mg, PO, QD for 28 days.
干预措施: GDC-8264 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: From signing informed consent form until 28 days after the final dose of GDC-8264 (up to 9 months)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Plasma Concentration of GDC-8264
时间窗: Predose, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose on Days 1 and 4; Predose on Days 8, 15, 22, 29
Plasma concentration of GDC-8264 at specified timepoints was determined.
Maximum Plasma Concentration (Cmax) of GDC-8264
时间窗: Day 1 and SS visit (any time between Day 4 to Day 28)
Steady-state (SS) PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Time to Reach Maximum Plasma Concentration (Tmax) of GDC-8264
时间窗: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of GDC-8264
时间窗: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Terminal Half-life (T1/2) of GDC-8264
时间窗: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Apparent Clearance (CL/F) of GDC-8264
时间窗: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Apparent Volume of Distribution (Vz/F) of GDC-8264
时间窗: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
次要结局
- Overall Response Rate (ORR) on Day 29(Up to Day 29)
- Duration of Response (DOR)(From Day 29 up to end of study (up to 9 months))
- Percentage of Participants With aGVHD Flares by Day 56(Baseline up to Day 56)
- Percentage of Participants With Non-relapse Mortality (NRM) by Day 180(Baseline up to Day 180)