A Multicenter, Randomized, Open-label Parallel Group Pilot Study to Evaluate Safety and Efficacy of High Dose Intravenous Immune Globulin (IVIG) Plus Standard Medical Treatment (SMT) Versus SMT Alone in Subjects With COVID-19 Requiring Admission to the Intensive Care Unit
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 18
- 主要终点
- All-Cause Mortality Rate Through Day 29
研究概览
简要总结
The purpose of the study is to determine if a high dose of Intravenous Immune Globulin (IVIG) plus Standard Medical Treatment (SMT) can reduce all-cause mortality versus SMT alone in hospitalized participants with COVID-19 requiring admission to the ICU through Day 29.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospitalized male or female subjects of ≥ 18 years of age at time of Screening who are being treated in the ICU for COVID-19 for not longer than 48 hours or for whom a decision has been made that COVID-19 disease severity warrants ICU admission.
- •Has laboratory-confirmed novel coronavirus {SARS-CoV-2} infection as determined by qualitative polymerase chain reaction (PCR) (reverse transcriptase [RT]-PCR), or other United States Food and Drug Administration (FDA)-approved diagnostic assay for COVID-19 in any specimen during the current hospital admission prior to randomization.
- •Illness (symptoms of COVID-19 of any duration requiring ICU level care), and the following:
- •Radiographic infiltrates by imaging (chest X-Ray, computerized tomography (CT) scan, etc.), and
- •Requiring mechanical ventilation and/or supplemental oxygen.
- •Any one of the following related to COVID-19: i. Ferritin > 400 nanogram per milliliter (ng/mL), ii. Lactate dehydrogenase (LDH) > 300 units per liter (U/L), iii. D-Dimers > reference range, or iv. C-reactive protein (CRP) > 40 milligram per liter (mg/L).
- •Subject provides informed consent prior to initiation of any study procedures.
排除标准
- •Clinical evidence of any significant acute or chronic disease or pathophysiologic manifestations (eg, complications of COVID-19 standard medical treatments) that, in the opinion of the investigator, may place the subject at undue medical risk.
- •The subject has had a known (documented) serious anaphylactic reaction to blood, any blood-derived or plasma product or a past history of any hypersensitivity reactions to commercial immunoglobulin.
- •A medical condition in which the infusion of additional fluid is contraindicated.
- •Shock that is unresponsive to fluid challenge and/or multiple vasopressors and accompanied by multiorgan failure considered by the Principal Investigator not able to be reversed.
- •Subjects with known (documented) thrombotic complications to polyclonal IVIG therapy in the past.
- •Subjects with current or prior myocardial infarction, stroke, deep vein thrombosis, or thromboembolic event (within the past 12 months) or who have a history of thromboembolic events of unknown etiology.
- •Subjects with limitations of therapeutic effort.
- •Female subjects who are pregnant or of child-bearing potential with a positive test for pregnancy blood or urine human chorionic gonadotropin (HCG)-based assay at Screening/Baseline.
- •Subjects participating in another interventional clinical trial with investigational medical product or device.
- •Known history of prothrombin gene mutation 20210, homozygous Factor V Leiden mutations, antithrombin III deficiency, protein C deficiency, protein S deficiency or antiphospholipid syndrome.
- •Presence of malignancy (either new diagnosis of malignancy or known residual disease) within the past 12 months.
- •Creatinine at Screening is ≥ 4 mg/dL (or subject is dependent on dialysis/renal replacement therapy).
- •Known Immunoglobulin A (IgA) deficiency with anti-IgA serum antibodies.
- •Uncontrolled hypertension at the time of Screening (systolic blood pressure > 200 mm Hg) or refractory severe hypotension with sustained systolic blood pressure < 90 mm Hg unresponsive to vasopressors.
研究组 & 干预措施
GAMUNEX-C + Standard Medical Treatment
Participants received 2 grams per kilogram (g/kg) of GAMUNEX-C, which was capped to a maximum of 160 g infusion intravenously (IV) for participants weighing more than 80 kg on Day 1. The 2 g/kg net total dose was divided either into infusions of 500 mg/kg body weight over 4 days or 400 mg/kg body weight over 5 days as per investigator's decision. Participants received standard of care interventions as per Principal Investigator's discretion from Day 1 up to Day 29.
干预措施: GAMUNEX-C (Biological)
GAMUNEX-C + Standard Medical Treatment
Participants received 2 grams per kilogram (g/kg) of GAMUNEX-C, which was capped to a maximum of 160 g infusion intravenously (IV) for participants weighing more than 80 kg on Day 1. The 2 g/kg net total dose was divided either into infusions of 500 mg/kg body weight over 4 days or 400 mg/kg body weight over 5 days as per investigator's decision. Participants received standard of care interventions as per Principal Investigator's discretion from Day 1 up to Day 29.
干预措施: Standard Medical Treatment (Drug)
Standard Medical Treatment
Participants received all standard of care interventions required as per Principal Investigator's discretion throughout the participant's hospitalization, from Day 1 to Day 29.
干预措施: Standard Medical Treatment (Drug)
结局指标
主要结局
All-Cause Mortality Rate Through Day 29
时间窗: Up to Day 29
All-cause mortality rate is percentage of participants in each treatment group who experienced mortality up to Day 29.
次要结局
- Percentage of Participants With Actual Intensive Care Unit (ICU) Discharge Time(Up to Day 29)
- Duration of Any Oxygen Use From Day 1 Through Day 29(Up to Day 29)
- Change From Baseline in National Early Warning Score (NEWS)(Baseline and Day 29)
- Duration of Mechanical Ventilation(Up to Day 29)
- Absolute Change From Baseline in Ordinal Scale at Day 29(Baseline, Day 29)
- Percentage of Participants in Each Severity Category of the 7-Point Ordinal Scale(Days 15 and 29)
- Percentage of Participants Who Develop Acute Respiratory Distress Syndrome (ARDS)(Days 1, 5, 15 and 29)
- Percentage of Participants With Actual Hospital Discharge Time(Up to Day 29)
- Percentage of Participants Achieving Clinical Response: NEWS ≤ 2 Maintained for 24 Hours(Day 29)
- Mean Change From Baseline in Ordinal Scale(Baseline up to Day 29)
- Percentage of Participants Who Develop ARDS Distributed by Severity(Days 1, 5, 15 and 29)
- Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 5, Day 15, and Day 29(Days 5, 15, and 29)