Adaptive Dengue Antiviral Platform Trial (ADAPT): a Phase 2 Randomized, Adaptive, Open Label Trial for Antiviral Screening in Patients With Early Symptomatic Dengue
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Viral clearance rate
研究概览
简要总结
This is a randomized, open-label adaptive platform trial aiming to screen the antiviral effectiveness of the experimental drug(s) in early dengue infection
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Primary objectives:
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To determine the antiviral effectiveness of the experimental drug(s) in early dengue infection
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To assess the safety and tolerability of the experimental drug(s) in dengue patients
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Secondary objective:
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To assess the effect of the experimental drug(s) in dengue patients on physiological, clinical and virological parameters
详细描述
This is a randomized, open-label adaptive platform trial investigating the antiviral effectiveness of various intervention arms in patients with lab-confirmed dengue and less than 48 hours of fever. The antiviral candidates in this trial will include the repurposed antiviral drugs, novel small molecule drugs and dengue monoclonal antibody. Patients will be randomly allocated between available treatment arms and compared to standard of care ("no study drug": no placebos will be made for this trial).
The current sites include Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Other sites and countries may be added in due course.
This is a continually running adaptive platform trial, which begins with two initial candidate drugs (a total of 3 arms): molnupiravir and VIS513 (a dengue monoclonal antibody). New therapies may be added and poorly performing arms or interventions meeting pre-specific thresholds for in vivo antiviral efficacy will be removed.
The sample size is adaptive with multiple planned interim analyses. The number of patients recruited depends on the results. For each intervention studied the sample size will be adaptive and determined by pre-specified stopping rules for futility and efficacy. Patients are invited to participate in the trial if they present at the healthcare settings with early symptomatic dengue virus infection (less than 48 hours since the onset of fever and positive NS1 antigen test) and can be able to return for follow up visits at 30 and 60 days after randomization.
The randomization ratios will be uniform for all available and eligible arms (1:1:1...).
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
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male patients with a clinical diagnosis of dengue virus infection and less than 48 hours of fever
- •Positive NS1 rapid diagnostic test
- •>= 10 years or ≥ 18 years of age (depending on license of therapeutic being evaluated)
- •Patient is able to give written informed consent or assent for full participation in the study.
- •Agreement to stay in hospital for duration of the intervention (most will be 5 days) and follow-up visits at day 30 and 60 post enrolment.
排除标准
- •Meets criteria for severe dengue at baseline (severe plasma leakage leading to dengue shock syndrome, fluid accumulation with respiratory distress, severe bleeding, severe organ involvement - AST/ALT>1000 U/L, impaired consciousness, multiple organ dysfunction)
- •Pregnancy (either clinically confirmed or by urine dipstick for human chorionic gonadotrophin hormone)
- •Breastfeeding women
- •Localising features suggesting an alternative/additional diagnosis, e.g. pneumonia, sepsis
- •Renal failure (baseline eGFR < 30ml/min)
- •History or presence of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, autoimmune, dermatologic or immunosuppressive disorders
- •History of allergic disease, allergic reactions or known hypersensitivity to any component of the study product (Mild non-medication allergies allowed)
- •Any condition that, in the opinion of the investigator, would complicate or compromise the study or well-being of the participant
- •Participation or planned participation in a study involving the administration of an investigational compound within the past one month.
研究组 & 干预措施
Molnupiravir (arm B)
Patients, who are randomly allocated into arm B, will receive 800mg po bid of Molnupiravir for 5 days
干预措施: Molnupiravir 400 mg (Drug)
Monoclonal antibody (arm C)
Patients, who are randomly allocated into arm C, will receive a single dose of 6mg/Kg of the dengue monoclonal antibody via an intravenous line over 2 hours.
干预措施: VIS513 (a monoclonal antibody) (Drug)
结局指标
主要结局
Viral clearance rate
时间窗: From randomization until day 5 of study
Rate of viral clearance estimated under a hierarchical log-linear model fit to the serial viral load measurements over 5 days after enrolment. The viremia kinetics will be measured using the qRT-PCR assay, which will be performed on samples taken twice a day from day 1 to day 3 of study and then once a day on days 4 and 5 of study (total 9 samples per patient).
Number of AEs (grade 3, 4 and 5)
时间窗: Until day 30 post-enrolment
All patients will be followed up daily until discharge and then at around days 30 after randomization to collect information on clinical progress of dengue illness and any adverse events occurring during the study course. All AEs and SAEs will be recorded.
次要结局
- Viral log reduction(up to 48 hours of study)
- Number of patients requiring for ICU admission(From enrolment until discharge, assessed up to 30 days)
- Area under the viremia curve(From randomisation until day 5 of study)
- NS1 clearance time(up to day 5)
- Number of patients progress to severe dengue (WHO 2009 criteria)(From enrolment until discharge, assessed up to 30 days)
- Change in haematocrit(Until day 30 post-enrolment)
- Fever clearance time(From enrolment until discharge, assessed up to 30 days)
- Platelet nadir(Until day 30 post-enrolment)
- Maximum AST/ALT(Until day 30 post-enrolment)