A Randomized, Controlled, Open-Label, Multiple Ascending Dose Study of Intravenous Brincidofovir in Adult Allogeneic Hematopoietic Cell Transplant Recipients With Adenovirus Viremia
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Chimerix
- 试验地点
- 8
- 主要终点
- Plasma Cmax of BCV
研究概览
简要总结
This is a randomized, controlled, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetic (PK), and adenovirus (AdV) antiviral activity of multiple ascending doses of IV brincidofovir (BCV). Approximately 30 eligible subjects will be sequentially enrolled into 1 of 3 planned cohorts. Within each cohort, subjects will be randomized in a 4:1 ratio to receive IV BCV dosed twice weekly (BIW) (on Days 1, 4, 8, and 11) or to receive investigator-assigned standard of care (SoC).
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be ≥ 18-years-old (or per local law or regulations on legal age of consent).
- •Have received an allogeneic hematopoietic cell transplant (HCT) within the previous 100 days.
- •Have plasma AdV DNA viremia ≥ 1,000 copies/mL (via quantitative polymerase chain reaction assay; local results must be confirmed by the designated central virology laboratory).
排除标准
- •Diarrhea meeting the US National Institutes of Health (NIH)/National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater
- •Acute graft versus host disease (GVHD)
- •NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea > 1,000 mL/day, or severe abdominal pain with or without ileus) or liver (i.e., bilirubin > 3 mg/dL : > 51 μmol/L) within 7 days prior to Day 1
- •Any NIH Stage 3 or Stage 4 acute GVHD within 7 days prior to Day 1
- •Concurrent human immunodeficiency virus or active hepatitis B or C infection
- •An estimated creatinine clearance of < 30 mL/min, and/or use of renal replacement therapy within 7 days prior to Day
- •Poor clinical prognosis, including active malignancy, irreversible organ failure, use of vasopressors, requirement for mechanical ventilation, resting oxygen saturation < 88%, or Pulmonary Arterial oxygen (PaO2) ≤ 55 mm Hg without supplemental oxygen at any time within 7 days prior to Day
- •Receiving or anticipated to start systemic cyclosporine immunosuppressant treatment during study participation.
- •Received treatment with CDV within 14 days prior to Day
- •Previous receipt of cell-based anti-AdV therapy within 6 weeks prior to Day 1 or prior receipt of an anti-AdV vaccine at any time.
- •Consumed food products containing sesame seeds, sesame oil, or dietary supplements containing sesamin within 3 days prior to Day
- •Received any investigational drug within 28 days prior to Day 1 or currently participating in another interventional study.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Brincidofovir (BCV)
- Cohort 1: BCV 10 mg twice weekly via IV infusion over 2 hours
- Cohort 2: BCV 15 mg twice weekly via IV infusion over 2 hours
- Cohort 3: BCV In Cohort 3, the actual dose may be higher or lower than doses administered in previous cohorts; the maximum dose of IV BCV will be ≤ 25 mg.
干预措施: Brincidofovir (Drug)
Standard of Care (SoC)
Subjects randomized to the SoC in each cohort will be managed per local institutional guidelines and investigator judgement. SoC treatment options may include, but are not limited to, taking a "watch and-wait" approach, with or without decreased immunosuppression (i.e., no active treatment), or treatment with IV Cidofovir (CDV), ganciclovir, or ribavirin.
干预措施: Standard of Care (Drug)
结局指标
主要结局
Plasma Cmax of BCV
时间窗: 15 days
BCV Cmax will be determined by analysis of BCV plasma concentrations at the following time points after the start of Dose 1 and Dose 4: 30 minutes, and 2.5, 3, 4, 8, 10, 12, 36, and 72 hours
Incidence (number and percentage of subjects) of treatment-emergent adverse events
时间窗: 22 days
Plasma area under the curve (AUC) of BCV
时间窗: 15 days
BCV AUC will be determined by analysis of BCV plasma concentrations at the following time points after the start of Dose 1 and Dose 4: 30 minutes, and 2.5, 3, 4, 8, 10, 12, 36, and 72 hours
次要结局
未报告次要终点