NCT04324021终止2 期
A Phase 2/3, Randomized, Open-label, Parallel Group, 3-arm, Multicenter Study Investigating the Efficacy and Safety of Intravenous Administrations of Emapalumab, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, and Anakinra, an Interleukin-1(IL-1) Receptor Antagonist, Versus Standard of Care, in Reducing Hyper-inflammation and Respiratory Distress in Patients With SARS-CoV-2 Infection.
Swedish Orphan Biovitrum17 个研究点 分布在 2 个国家目标入组 16 人开始时间: 2020年4月2日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 16
- 试验地点
- 17
- 主要终点
- Number of Participants With Treatment Success
研究概览
简要总结
Hyper-inflammation, caused by a cytokine storm resulting from an exaggerated response of the immune system in the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered to represent one of the most important negative prognostic factors in patients infected with sSARS-CoV-2. The objective of this study is to investigate new treatment options to reduce the number of patients requiring mechanical ventilation. This is intended to address the most urgent need to preserve the access to intensive care unit support to the lowest possible number of patients and may potentially reduce mortality.
详细描述
This is an open label, controlled, parallel group, 3-arm, multicenter study to assess the efficacy and safety of Emapalumab or Anakinra, versus standard of care (SoC). Patients between 30 and 80 years will be eligible to participate in the study. The study is planned to consist of three groups, each comprising 18 patients. Treatment will be randomized to either Emapalumab+SoC, Anakinra+SoC or only SoC for two weeks. Follow-up visit or phone calls will be made 4 and 8 weeks after end of treatment period.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent provided by the patient, or by the patient's legally authorized representative(s), as applicable.
- •Documented presence of SARS-CoV-2 infection as per hospital routine.
- •Age > 18 to < 85 years at the time of screening.
- •Presence of respiratory distress, defined as:
- •PaO2/FiO2 < 300 mm Hg and >200 mm Hg or
- •Respiratory Rate (RR) ≥30 breaths/min or
- •SpO2 < 93 percent in air at rest. Note: Patients given continous positive airway pressure (CPAP) ventilator support are eligible for inclusion.
- •Presence of hyperinflammation defined as:
- •Lymphocyte counts:
- •< 1000 cells/µL, in patients who have not received systemic glucocorticoids for at least 2 days prior to the assessment of the lymphocyte count
- •< 1200 cells/µL, in patients who have received systemic glucocorticoids for at least 2 days prior to the assessment of the lymphocyte count
- •One of the following three criteria:
- •i. Ferritin > 500ng/mL
- •ii. LDH > 300 U/L
- •iii. D-Dimers > 1000 ng/mL
排除标准
- •Patients in mechanical ventilation or with modified early warning score (MEWS) >4 with evidence of moderate or above ARDS (Berlin definition, namely with PaO2/FiO2 >100, but <200 mm Hg) or severe respiratory insufficiency or evidence of rapid worsening (respiratory distress requiring mechanical ventilation or presence of shock or presence of concomitant organ failure requiring ICU admission). Note: For the evaluation of patient eligibility, temperature will not be considered in the calculation of the total MEWS score since presence of fever is a hallmark of SARS-CoV-2 infection
- •Impairment of cardiac function defined as poorly controlled heart diseases, such as New York heart association (NYHA) class II (mild) and above, cardiac insufficiency, unstable angina pectoris, myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia need treatment or intervention.
- •Severe renal dysfunction (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
- •Uncontrolled hypertension (seated systolic blood pressure >180 mmHg, or diastolic blood pressure >110mmHg) .
- •Administration of plasma from convalescent patients who recovered from SARS-CoV-2 infection.
- •Clinical suspicion of latent tuberculosis.
- •History of hypersensitivity or allergy to any component of the study drug.
- •Pregnant women.
- •Existence of any life-threatening co-morbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion.
- •Enrollment in another concurrent clinical interventional study, or intake of an investigational drug within three months or 5 half-lives prior to inclusion in this study, if considered interfering with this study objectives as assessed by the Investigator.
- •Foreseeable inability to cooperate with given instructions or study procedures.
- •Clinical suspicion of active mycobacteria, histoplasma capsulatum, herpes zoster, salmonella, and shigella Infections.
- •Patients with liver dysfunction defined as AST or ALT > 5 × ULN
结局指标
主要结局
Number of Participants With Treatment Success
时间窗: Up to Day 15
Defined as the number of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)
次要结局
- Number of Participants Requiring Mechanical Ventilation(Date of randomization to date of mechanical ventilation, up to 15 Days)
- Change From Baseline in Modified Early Warning System Score(Baseline, Day 15)
- Change From Baseline in Ferritin(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2)(Baseline, Day 15)
- Overall Survival(Weeks 6 and 10)
- Change of Carbon Dioxide Tension (pCO2) in Hemogasanalysis From Baseline(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Lactate Dehydrogenase (LDH)(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in D-dimers(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Resting Peripheral Capillary Oxygen Saturation (SpO2)(Baseline, 3 assessments every Days 4, 7, 10, 13 and 15)
- Number of Participants With Changes in High-resolution Computed Tomography (CT) Scan of the Chest(Screening, Day 15)
- Number of Patients With Hospital Discharge(Until discharge up to Week 10)
- Change of Oxygen Tension (pO2) in Hemogasanalysis From Baseline(Baseline, Days 4, 7, 10, 13 and 15)
- Change of Chloride in Hemogasanalysis From Baseline(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in White Blood Cells With Differential Counts(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Red Blood Counts(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Total Bilirubin Levels(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in C-Reactive Protein(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Oxygen Supplementation(Baseline, Days 4, 7, 10, 13 and 15.)
- Change From Baseline in Prothrombin Time(Baseline, Days 4, 7, 10, 13 and 15)
- Change of Potassium in Hemogasanalysis From Baseline(Baseline, Days 4, 7, 10, 13 and 15)
- Change of Sodium in Hemogasanalysis From Baseline(Baseline, Days 4, 7, 10, 13 and 15)
- Change of Lactic Acid in Hemogasanalysis From Baseline(Baseline, Days 4, 7, 10, 13 and 15)
- Change of Hemoglobin in Hemogasanalysis From Baseline(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Hemoglobin(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Creatinine(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Platelet Count(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Fibrinogen(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Complement Factors C3/C4(Day 15)
- Change From Baseline in Aspartate Aminotransferase (AST)(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Alanine Aminotransferase (ALT)(Baseline, Days 4, 7, 10, 13 and 15)
- Change From Baseline in Cardiac Troponin(Baseline, Days 4, 7, 10, 13 and 15)
研究者
研究点 (17)
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