Phase 2, Randomized, Controlled, Open Label Multi-center Study to Assess Efficacy and Safety of DFV890 for the Treatment of SARS-CoV-2 Infected Patients With COVID-19 Pneumonia and Impaired Respiratory Function
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 143
- 试验地点
- 1
- 主要终点
- APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)
研究概览
简要总结
This clinical study was designed to assess the efficacy and safety of DFV890 for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infected patients with coronavirus disease 2019 (COVID-19) pneumonia and impaired respiratory function.
详细描述
This was a Phase II, randomized, controlled, open label multi-center study to assess the efficacy and safety of DFV890 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function.
The study consisted of four distinct study periods:
Screening / Baseline visit (Day -1 to 1): lasted up to a maximum of 24 hours and comprised a screening / baseline assessment. This visit was used to confirm that the study inclusion and exclusion criteria were met and served as baseline assessment prior to randomization.
Treatment period (Day 1-15): Participants were randomized as soon as possible, but within a maximum of 24 hours after screening in a 1:1 ratio receiving either DFV890 in addition to standard of care (SoC) or SoC alone. Participants in the investigational treatment arm received DFV890 administered for a total of 14 days in addition to SoC. Participants in the control arm received SoC alone. Study assessments were conducted every 2 days for hospitalized participants.
The End of Treatment (EOT) visit took place on Day 15. If participants were discharged from the hospital prior to Day 15, assessments on the day of discharge were performed according to the schedule listed under Day 15; participants continued to take the investigational treatment at home to complete the 14-day treatment period and the participants returned to the site for the Day 15/EOT assessment. If a hospital visit was not possible at Day 15, then home nursing services were used to support the last visit.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients aged 18-80 years inclusive at screening.
- •Clinically diagnosed with the SARS-CoV-2 virus by polymerase chain reaction (PCR) or by other approved diagnostic methodology within 7 days prior to randomization.
- •Hospitalized with COVID-19-induced pneumonia evidenced by chest X-ray, computed tomography scan (CT scan) or magnetic resonance scan (MR scan), taken within 5 days prior to randomization (within 24 hours in patients in the Netherlands).
- •Impaired respiratory function, defined as peripheral oxygen saturation (SpO2) ≤93% on room air or partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) <300 millimeter of mercury (mmHg) at screening. For cities located at altitudes greater than 2500 m above sea level, these will be substituted with SpO2 <90% and PaO2/FiO2 <250 mmHg.
- •APACHE II score of ≥10 at screening.
- •C-reactive protein (CRP) ≥20 mg/L and/or ferritin level ≥600 μg/L at screening.
- •Body mass index of ≥18 to <40kg/m2 at screening.
排除标准
- •Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection (besides SARS-CoV-2).
- •In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment.
- •Intubated prior to randomization.
- •Previous treatment with anti-rejection and immunomodulatory drugs within the past 2 weeks, or within the past 30 days or 5 half-lives (whichever is the longer) for immunomodulatory therapeutic antibodies or prohibited drugs, with the exception of hydroxychloroquine, chloroquine or corticosteroids:
- •For COVID-19 infection, ongoing corticosteroid treatment is permitted at doses as per local SoC.For non-COVID-19 disorders, ongoing corticosteroid treatment is permitted at doses up to and including prednisolone 10 mg daily or equivalent.
- •In patients in the Netherlands only, the use of hydroxychloroquine and/or chloroquine in the past 2 weeks are exclusionary.
- •Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit of normal detected within 24 hours at screening or at baseline (according to local laboratory reference ranges) or other evidence if severe hepatic impairment (Child-Pugh Class C).
- •Absolute peripheral blood neutrophil count of ≤1000/mm
- •Estimated GFR (eGFR) ≤30 mL/min/1.73m2 (based on CKD-EPI formula).
- •Patients currently being treated with drugs known to be strong or moderate inducers of isoenzyme CYP2C9 and/or strong inhibitors of CYP2C9 and/or strong inducers of cytochrome P450, family 3, subfamily A (CYP3A) and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment.
- •Patients with innate or acquired immunodeficiencies.
- •Patients who have undergone solid organ or stem cell transplantation.
研究组 & 干预措施
DFV890 + SoC
DFV890 50 mg was administered orally or nasogastrically twice per day (b.i.d) approximately 12 hours apart (morning and evening) for 14 days in addition to SoC.
干预措施: DFV890 (Drug)
DFV890 + SoC
DFV890 50 mg was administered orally or nasogastrically twice per day (b.i.d) approximately 12 hours apart (morning and evening) for 14 days in addition to SoC.
干预措施: Standard of Care (SoC) (Drug)
Standard of Care (SoC)
SoC was used as an active comparator arm.
干预措施: Standard of Care (SoC) (Drug)
结局指标
主要结局
APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)
时间窗: up to Day 15
The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. In practice, it is rare for any participant to accumulate more than 55 points. APACHE II score was measured on Day 15 or on the day of discharge (whichever was earlier). Participants who died on Day 15 or earlier were assigned the highest observed APACHE II score of any of the participants at any time during the trial (worst case imputation for deaths). Missing data values of the parameters required for the derivation of the APACHE II score were replaced by the last available assessment.
次要结局
- Number of Participants With at Least One-point Improvement From Baseline in Clinical Status(Baseline, Day 15 and Day 29)
- Serum C-reactive Protein (CRP) Levels(Days 2, 4, 6, 8, 10, 12, 14 and 15)
- Clinical Status Over Time(Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27 and 29)
- Number of Participants Not Requiring Mechanical Ventilation for Survival(Until Day 15 (Assessments on Days 2, 4, 6, 8, 10, 12, 14 and 15) and until Day 29 (Assessments on Days 17, 19, 21, 23, 25, 27 and 29))