Finding Treatments for COVID-19: A Phase 2 Multi-centre Adaptive Platform Trial to Assess Antiviral Pharmacodynamics in Early Symptomatic COVID-19 (PLATCOV)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 3,800
- 试验地点
- 9
- 主要终点
- Rate of viral clearance for interventions relative to the no study arm (This is a superiority comparison)
研究概览
简要总结
The trial will develop and validate a platform for quantitative assessment of antiviral effects in low-risk patients with high viral burdens and uncomplicated COVID-19 to determine in-vivo antiviral activity. In this randomized open label, controlled, group sequential adaptive platform trial, we will assess the performance of three distinct types of intervention relative to control (no treatment):
A: Small molecule drugs; B: Monoclonal antibodies; C: Dose finding for the constituent parts of nirmatrelvir/ritonavir
PLATCOV study is supported by the Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator.
详细描述
The platform trial will assess drugs with potential SARS-CoV-2 antiviral activity of three general types:
A. Small molecule drugs: currently nitazoxanide, nirmatrelvir/ritonavir, hydroxychloroquine, atilotrelvir/ritonavir and metformin.
B. Monoclonal antibodies: Sotrovimab and any other monoclonal antibodies that become available. Monoclonal antibodies are vulnerable to viral escape mutations. Tracking their performance over time is important to characterise the impact and inform the therapeutics of mutant SARS-CoV-2 strains. This will also be important for other antivirals. Monoclonal antibodies are expensive and cannot be produced at large scale currently, but this may change in the near future. These drugs will be included if there is local availability and regulatory approval.
C. : Dose finding for the constituent parts of nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir has shown clinical efficacy in phase III studies, however, there are disadvantages to using it (drug-drug interactions, side effects, cost). In the urgent context of the pandemic, a higher dose of ritonavir was chosen to guarantee maximum boosting effect. We do not know if the maximal boosting effect could have been achieved with less, or even without ritonavir. It will be investigated whether reducing the doses of the constituent parts can still retain the effectiveness.
Randomization to the no antiviral treatment control arm (no intervention) will be fixed at a minimum of 20% throughout the study. The randomization ratios will be uniform for all available interventions.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient understands the procedures and requirements and is willing and able to give informed consent for full participation in the study.
- •Previously healthy adults, male or female, aged 18 to 60 years at time of consent with early symptomatic COVID-19
- •SARS-CoV-2 positive by lateral flow antigen test OR a positive PCR test for SARS-CoV-2 within the last 24hrs with a Ct value of less than 25 (all viral targets)
- •Symptoms of COVID-19 (including fever, or history of fever) for less than 4 days (96 hours).
- •Oxygen saturation ≥96% measured by pulse-oximetry at time of screening.
- •Able to walk unaided and unimpeded in ADLs
- •Agrees and is able to adhere to all study procedures, including availability and contact information for follow-up visits
排除标准
- •The patient may not enter the study if ANY of the following apply:
- •Taking any concomitant medications or drugs (see appendix 4)†
- •Presence of any chronic illness/ condition requiring long term treatment, or other significant comorbidity (e.g. diabetes, obesity but see appendix 4 for the full list)
- •Laboratory abnormalities discovered at screening (see appendix 4)
- •For females: pregnancy, actively trying to become pregnant, or lactation
- •Contraindication to taking, or known hypersensitivity reaction to any of the proposed therapeutics (see appendix 4)
- •Currently participating in another COVID-19 therapeutic or vaccine trial
- •Evidence of pneumonia (although imaging is NOT required)
- •healthy women on the oral contraceptive pill are eligible to join the study
研究组 & 干预措施
Sotrovimab [Pending addition]
干预措施: Sotrovimab (Drug)
Positive control: Nirmatrelvir/ritonavir (e.g. PAXLOVID™)
干预措施: Nirmatrelvir/ritonavir (e.g. PAXLOVID™) (Drug)
Nitazoxanide
干预措施: Nitazoxanide (Drug)
Molnupiravir and Nirmatrelvir/ritonavir (e.g. PAXLOVID™) [This arm is now closed to recruitment]
干预措施: Molnupiravir and nirmatrelvir/ritonavir (e.g. PAXLOVID™) (Drug)
Hydroxychloroquine
干预措施: Hydroxychloroquine (Drug)
Negative control group
干预措施: No treatment (Other)
AZD7442 (EVUSHELD™) [This arm is now closed to recruitment]
干预措施: Monoclonal antibodies (Drug)
Fluoxetine [This arm is now closed to recruitment]
干预措施: Fluoxetine (Drug)
Molnupiravir [This arm is now closed to recruitment]
干预措施: Molnupiravir (Drug)
Ensitrelvir [This arm is now closed to recruitment]
干预措施: Ensitrelvir (Drug)
Positive control (REGN-COV2) [This arm is now closed to recruitment]
干预措施: Monoclonal antibodies (Drug)
Favipiravir [This arm is now closed to recruitment]
干预措施: Favipiravir (Drug)
Ivermectin [This arm is now closed to recruitment]
干预措施: Ivermectin (Drug)
Remdesivir [This arm is now closed to recruitment]
干预措施: Remdesivir (Drug)
Atilotrelvir/ritonavir [Pending addition]
干预措施: Atilotrelvir/ritonavir (Drug)
Metformin (modified release) [Pending addition]
干预措施: Metformin (Drug)
Nirmatrelvir/ritonavir - 300/50 - dose finding [Pending addition]
干预措施: Nirmatrelvir/ritonavir (Drug)
Nirmatrelvir/ritonavir - 150/50 - dose finding [Pending addition]
干预措施: Nirmatrelvir/ritonavir (Drug)
Nirmatrelvir - dose finding [Pending addition]
干预措施: Nirmatrelvir (Drug)
结局指标
主要结局
Rate of viral clearance for interventions relative to the no study arm (This is a superiority comparison)
时间窗: Days 0-5
Rate of viral clearance- estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/ saliva taken daily from baseline (day 0) to day 5 for each intervention compared with the no antiviral treatment control i.e., those not receiving study drug
Rate of viral clearance for interventions relative to the positive control arm (This is a non-inferiority or superiority comparison).
时间窗: Days 0-5
Rate of viral clearance- estimated from the log10 viral density derived from qPCR of standardised duplicate oropharyngeal swabs/ saliva taken daily from baseline (day 0) to day 5 for interventions compared with the current best antiviral treatment option (accelerated viral clearance relative to the positive control arm)
次要结局
- Viral kinetic levels in early COVID-19 disease(Days 0-5)
- Optimal dosing regimens through pharmacometric assessment for antiviral drugs with evidence of efficacy in the literature or from the trial data (e.g., Nirmatrelvir/ritonavir, Ensitrelvir etc).(Days 0-5)
- Viral rebound of studied treatment arms in comparison to contemporaneous controls (e.g. no study drug arm, positive control)(Days 6-14)
- Rates of fever clearance and symptom resolution with respect to no treatment(Days 0-14)