Phase II, Open-label, Randomized, Multiple Ascending Dose Confirmation of the Safety and Tolerability of Brincidofovir in Subjects With BK Virus Infection (Viremia) After Kidney Transplantation (BASTION)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a Phase II, multicenter, open-label, randomized, standard of care (SOC) controlled, multiple ascending dose study to assess the safety and tolerability of IV Brincidofovir (BCV) in subjects with BKV infection after kidney transplantation. The study will be conducted at multiple study sites in several countries including Australia and Japan. Subjects who meet eligibility criteria will be enrolled in the study and will be randomized and assigned to BCV or SOC (defined as use of the same immunosuppressant administered during prescreening) before receipt of the first dose of study drug in both the Dose Escalation Phase and the Expansion Phase.
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
- •Male or female, at least 18 years of age at the time of signing the informed consent at screening.
- •Kidney transplant recipient. "BK viral load increase and ≥ 3.6 log IU/mL" at 2 weeks post immunosuppression reduction or "BK viral load does not decrease by ≥ 0.3 log IU/mL" at 4 weeks post immunosuppression reduction during prescreening.
- •(Note: Immunosuppressant reduction needs to be continued during the screening period).
- •eGFR ≥ 30 mL/min.
- •Subjects under immunosuppression with tacrolimus, MMF/Myfortic, and/or corticosteroid.
排除标准
- •Subjects who weigh ≥ 120 kg.
- •National Institutes of Health/NCI CTCAE Grade 2 or higher diarrhea (ie, increase of ≥ 4 stools per day over usual pretransplant stool output) within 7 days before Day
- •Poor clinical prognosis, including active malignancy or use of vasopressors other than low dose (eg, ≤ 5 μg/kg/min) dopamine for renal perfusion within 7 days before Day
- •Use of renal replacement therapy within 7 days before Day
- •History of intolerance to cidofovir or related compounds (ie, other nucleotide derivatives [adefovir or tenofovir])
研究组 & 干预措施
Dose Escalation Phase: Cohort 1: BCV 0.3 mg/kg BIW
BCV: 0.3 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for 8 weeks (up to a maximum of 14 weeks).
干预措施: Brincidofovir (Drug)
Dose Escalation Phase: Cohort 2: BCV 0.4 mg/kg BIW
BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours on Day1 and Day4 for 8 weeks (up to a maximum of 14 weeks).
干预措施: Brincidofovir (Drug)
Expansion Phase: BCV Recommended dosage regimen in the Dose Escalation Phase
BCV: Recommended dosage administered as a continuous IV infusion over 2 hours on Day1 and Day4 for 8 weeks (up to a maximum of 14 weeks).
干预措施: Brincidofovir (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: from the time of administration of the first dose of study drug through the follow-up visit(up to 14 weeks (treatment period) and 30 days (follow-up period))
* Incidence of TEAEs of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 severity and serious adverse events * Incidence of treatment-related TEAEs * Incidence of adverse events (AEs) requiring permanent discontinuation of BCV * Absolute and changes over time in safety laboratory parameters (ie, hematology, blood chemistry, and urinalysis)
Antiviral Effects
时间窗: From baseline to follow-up visit(up to 14 weeks (treatment period) and 30 days (follow-up period))
Change from baseline in BK viral load in plasma measured through follow-up for each subject. Change from baseline in BK viral load in urine measured through follow-up for each subject. Peak BK viral load in plasma from Week 2 Day 1 through follow-up for each subject. Time-averaged area under the viremia-time curve for BK viral load in plasma from baseline through follow-up for each subject.
次要结局
未报告次要终点