A Pragmatic Adaptive Randomized, Controlled Phase II/III Multicenter Study of IFX-1 in Patients With Severe COVID-19 Pneumonia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- InflaRx GmbH
- 入组人数
- 399
- 试验地点
- 48
- 主要终点
- Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position at Day 5 (FAS)
研究概览
简要总结
Phase II & Phase III:
This is a pragmatic, adaptive, randomized, multicenter phase II/III study evaluating IFX-1 for the treatment of COVID-19 related severe pneumonia. The study consists of two parts: Phase II, an open-label, randomized, 2-arm phase evaluating best supportive care (BSC) + IFX-1 (Arm A) and BSC alone (Arm B); and Phase III, a double-blind, placebo-controlled, randomized phase comparing standard of care (SOC) + IFX-1 (Arm A) versus SOC + placebo-to-match (Arm B)
详细描述
The phase II and Phase III portions enrolled patients subsequently.
1st patient was enrolled in the phase III portion on 1st October 2020.
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
- Double (Participant, Investigator)
盲法说明
Phase II: Open label study (30 patients), Phase III: Double- blind (360 patients)
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
- •At least 18 years of age or older
- •Clinically evident or otherwise confirmed severe pneumonia
- •SARS-CoV-2 infection confirmation (tested positive in last 14 days before randomization with locally available test system)
排除标准
- •Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months
- •Patient moribund or expected to die in next 24h according to the judgment of the investigator
- •Known severe congestive heart failure (New York Heart Association [NYHA] Class III- IV)
- •Received organ or bone marrow transplantation in past 3 months
- •Known cardio-pulmonary mechanical resuscitation in past 14 days
- •Inclusion Criteria:
- •At least 18 years of age or older
- •Patient on invasive mechanical ventilation (but not more than 48h post intubation at time point of first IMP administration)
- •Patients with a PaO2 / FiO2 ratio of < 200 and > 60 at randomization (one representative measurement within 6h before randomization)
- •SARS-CoV-2 infection confirmation (tested positive in last 14 days before randomization with locally available test system)
- •Exclusion Criteria:
- •Intubated > 48 h at time point of first IMP administration
- •Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator
- •Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization
- •Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months
- •Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.)
- •At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.)
- •Received cytokine adsorption therapy in past 3 days
- •Known severe congestive heart failure (corresponding to e.g. NYHA Class III-IV, left ventricular ejection fraction <40%)
- •Known history of chronic liver disease (Child-Pugh B or C)
研究组 & 干预措施
Phase II: IFX-1 + BSC
Phase II study part: IFX-1: 800mg intravenously administered, BSC: Best supportive care
干预措施: IFX-1 + BSC (Drug)
Phase II: BSC
Phase II study part: BSC: Best supportive care
干预措施: BSC (Drug)
Phase III: IFX-1 + SOC
Phase III study part: IFX-1: 800mg intravenously administered, SOC: Standard of care
干预措施: IFX-1 + SOC (Drug)
Phase III: Placebo + SOC
Phase III study part: Placebo: placebo infusion intravenously administered, SOC: Standard of care
干预措施: Placebo + SOC (Drug)
结局指标
主要结局
Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position at Day 5 (FAS)
时间窗: Baseline and Day 5
Relative change (%) from baseline in Oxygenation Index (OI; partial pressure of oxygen in the arterial blood (PaO2) / fractional inspired oxygen (FiO2)) in supine position for ≥2 hours at day 5 (FAS)
Phase III: 28-day All-cause Mortality (FAS)
时间窗: Day 28
Number and percentage of deaths (all-cause) until Day 28 (FAS)
次要结局
- Phase III: Percentage of Patients Free of Any Renal Replacement Therapy Within 28 Days Upon Randomization (FAS)(Day 28)
- Phase III: Percentage of Patients Developing Acute Kidney Failure Until Day 28 (FAS)(Day 28)
- Phase II: All-cause 28-day Mortality (FAS)(Day 28)
- Phase III: 60-day All-cause Mortality (FAS)(Day 60)
- Phase II: Early Response at Day 7 After Enrollment(Day 7)
- Phase II: Late Response Until Day 28 After Enrollment(Baseline until Day 28)
- Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position (FAS)(Baseline, Day 3, Day 7, Day 9, Day 11, Day 15)
- Phase III: Percentage of Patients With an Improvement in the 8-point Ordinal Scale (FAS)(Day 15, Day 28)