A Phase 3, Multicenter, Prospective, Randomized, Open-label Efficacy and Safety Study of Intravenous Brincidofovir Versus Intravenous Cidofovir for Treatment of Adenovirus Infection in Pediatric and Adult Subjects After Allogeneic Hematopoietic Cell Transplantation (Allo-HCT)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 84
- 主要终点
- To assess efficacy of intravenous (IV) brincidofovir (BCV), compared with IV cidofovir (CDV), in subjects after allo-HCT with adenovirus (AdV) viremia.
研究概览
简要总结
This randomized, open-label, parallel group, two-arm, multi-center assessment will compare IV BCV with IV CDV in adult and pediatric allogeneic HCT recipients with AdV viremia. A virologic response-driven approach to duration of treatment will be evaluated, in which randomized subjects are treated with either BCV or CDV until AdV viremia is confirmed as undetectable or until a maximum of 12 weeks of therapy, whichever occurs first. All subjects will be followed for a total of 24 weeks post-randomization, regardless of treatment assignment. Subjects will be assessed on a weekly basis through the end of treatment visit (EOT). Additional assessments will be performed at the test of cure (TOC) visit, which is 4 weeks after the last dose of study drug and at Weeks 12 and 24 post W1D1.
详细描述
This Phase 3 multi-center, randomized, open-label study will assess efficacy of IV BCV, compared to IV CDV, in allo-HCT subjects with AdV viremia. Randomized subjects will be treated for up to a maximum of 12 weeks of therapy for both arms. Primary efficacy assessment will be performed at W5D1. Consistent with ECIL guidelines for high-risk patients, AdV viremia will be assessed weekly. Subjects randomized to receive BCV or CDV are treated until AdV DNA is confirmed to be undetectable in plasma for two consecutive tests 7 days apart, or until Week 12 post W1D1, whichever occurs first. Subjects will continue BCV or CDV as long as AdV viremia is detectable, contingent on tolerability, until viremia clears, or the subject reaches a maximum duration of 12 weeks of study drug treatment.
Subjects will receive assigned randomized therapy until time of AdV virological success plus 2 weeks, for up to a maximum of 12 weeks. All subjects will be followed through 24 weeks. All study visits and follow-up assessments must be completed regardless of the study drug treatment duration. All subjects are considered on study through the Week 24 follow-up visit.
For subjects who achieve virological success from their initial randomized study drug treatment and experience an AdV viremia recurrence, repeat treatment with their randomized study drug is allowed. There is no cross-over study drug treatment allowed in this study and subjects can only receive retreatment with their randomized study drug.
Subjects who stop study drug therapy due to confirmed undetectable AdV viremia may re-initiate study drug treatment if AdV viremia is subsequently confirmed at ≥ 1000 IU/mL by the designated central virology laboratory (recurrence). For the purposes of re-initiating study drug therapy, "confirmed viremia ≥ 1000 IU/mL" is defined as two consecutive results ≥ 1000 IU/mL from the designated central laboratory, with the second sample drawn at least 48 hours after the first sample.
Subjects who permanently discontinue study drug therapy for toxicity reasons are not eligible to re-initiate study drug dosing. Study procedures are to be followed during these Retreatment visits as applicable for BCV and CDV outlined in the schedule of assessments (SOA).
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 2 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female, post-allo HCT within last 180 days, aged 2 months and older at time of signing informed consent form.
- •Subject/Guardian willing and able to understand and provide written informed consent to participate in the study.
- •In the investigator's judgement, the subject's clinical condition justifies treatment with IV BCV or IV CDV for AdV infection.
- •Has adenoviremia, based on any of:
- •AdV viremia DNA ≥10,000 IU/mL, OR
- •Two consecutive and rising AdV viremia DNA results of ≥1,000 IU/mL at screening, OR
- •AdV viremia DNA of ≥1,000 IU/mL, AND
- •1. Lymphocyte count <180/mm3, OR
- •Received T cell depletion, cord blood, or haploidentical transplant, OR
- •prior alemtuzumab, OR
- •anti-thymocyte globulin (ATG)
排除标准
- •Subject received an allo-HCT with a matched sibling donor
- •Subject received more than 5 mg/kg of CDV for any reason in the 21 days prior to first dose of study drug.
- •Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components.
- •Subject received anti-AdV-specific cell-based therapy within 3 weeks prior to W1D1 or an anti-AdV vaccine at any time.
- •Subject has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the informed consent form (ICF), is currently participating in another interventional treatment trial with an investigational agent or is using an investigational device at the time of Screening.
研究组 & 干预措施
IV BCV
干预措施: Brincidofovir (Drug)
IV CDV
干预措施: cidofovir (Drug)
结局指标
主要结局
To assess efficacy of intravenous (IV) brincidofovir (BCV), compared with IV cidofovir (CDV), in subjects after allo-HCT with adenovirus (AdV) viremia.
时间窗: Week (W) 5 Day (D) 1.
The primary efficacy endpoint is defined as AdV virological success at W5D1. -Proportion of subjects with AdV virological success
次要结局
- To assess the efficacy and safety of IV BCV, and IV CDV, in subjects after allo-HCT with AdV viremia.(Test Of Cure (Last Dose + 30 days))
- To assess the efficacy and safety of IV BCV, and IV CDV, in subjects after allo-HCT with AdV viremia.(Week 1 Day 1 Through End Of Study (Week 24).)
- To assess the efficacy and safety of IV BCV, and IV CDV, in subjects after allo-HCT with AdV viremia.(Week 5 Day 1, Last Dose + 4 Days, Last Dose + 30 days, Week 12, and Week 24.)
- BCV Plasma Concentrations will be collected, measured and reported(Plasma samples will be collected at Week 1 Day 1, and Week 5 Day 1)