Assessing Safety, Hospitalization and Efficacy of rNAPc2 in COVID-19 (ASPEN-COVID-19)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 24
- 主要终点
- Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b)
研究概览
简要总结
Sequential randomized, multicenter, active comparator study to evaluate the hypothesis that rNAPc2 (AB201), a novel, potent and highly selective tissue factor inhibitor with anticoagulant, anti-inflammatory and potential antiviral properties, shortens time to recovery compared to heparin in hospitalized patients with COVID-19 and elevated D-dimer levels.
详细描述
Sequential randomized, multicenter, active comparator study to evaluate the hypothesis that rNAPc2, a novel, potent and highly selective tissue factor inhibitor with anticoagulant, anti-inflammatory and potential antiviral properties, shortens time to recovery compared to heparin in hospitalized patients with COVID-19 and elevated D-dimer levels. Study participants and Clinical Endpoint Committee (CEC) members assessing the clinical endpoints will be blinded to treatment assignment. The protocol comprises sequential Phase 2b and Phase 3 studies. Analysis of Phase 2b data could lead to study discontinuation, adjustment of eligibility criteria or sample size, and will inform the rNAPc2 dose level to be studied in Phase 3.
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, Outcomes Assessor)
盲法说明
Participant, clinical events committee members will be blind to treatment assignment. Investigator assessing outcomes will be blinded wherever possible.
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years and ≤ 90 years at the Screening assessment
- •Weight ≥ 50 kg at randomization
- •Hospitalized with a diagnosis of COVID-19 and in need of inpatient medical care
- •Positive for SARS-CoV-2 on nasopharyngeal, oropharyngeal or other tissue/body fluid samples by PCR or validated other test of ongoing infection (not an antibody test for prior exposure), within seven (7) days of hospitalization or screening assessment
- •D-dimer level > upper limit of normal at screening
- •Provided electronic or written informed consent, either personally or through a legally authorized representative (LAR)
- •Must agree not to participate in a concurrent interventional study involving anticoagulation or anti-platelet therapy
- •Female patients of reproductive or child-bearing potential must be willing to use an effective method of contraception for the duration of the study, and male patients must be willing to use an effective method of contraception to avoid partner pregnancy and abstain from sperm donation for at least 90 days after last dose
排除标准
- •High bleeding risk, e.g. major surgery within prior 1 month, history of a major bleed while receiving anticoagulation, recent hemorrhagic stroke, current or planned (during current hospitalization) dual anti-platelet therapy, platelet count <25,000/uL, current therapeutic anticoagulation for a medical indication other than COVID-19, e.g. atrial fibrillation, known thrombosis, hereditary or acquired coagulopathy treated with therapeutic anticoagulation. Patients receiving prophylactic anticoagulation are eligible if they are willing to discontinue current anticoagulation.
- •Sustained systolic blood pressure < 90 mmHg considered to be clinically significant
- •Persistent eGFR <20 ml/min/1.73m2
- •Known severe liver disease (e.g. bilirubin >3.5 mg/dL (60 umol/L))
- •Life expectancy estimated to be < 72 hours based on current clinical condition
- •Anticipated hospital discharge or transfer within 5 days based on current clinical condition
- •Known anti-phospholipid syndrome
- •Unable to receive heparin, e.g. history of heparin-induced thrombocytopenia and thrombosis (HITT)
- •Participation in any interventional clinical study with an investigational product within seven (7) days of the Screening assessment or within 5 half-lives of the investigational agent, whichever is longer
研究组 & 干预措施
rNAPc2 Higher Dose
loading dose of 7.5 μg/kg SC on Day 1 followed by 5 μg/kg SC on Days 3 and 5
干预措施: rNAPc2 (Drug)
rNAPc2 Lower Dose
loading dose of 5 ug/kg SC on Day 1 followed by 3 ug/kg SC on Days 3 and 5
干预措施: rNAPc2 (Drug)
Heparin
heparin at either prophylactic or therapeutic doses per Standard of Care at Institution
干预措施: Heparin (Drug)
结局指标
主要结局
Proportional Change in D-dimer Level From Baseline to Day 8, or Day of Discharge if Prior to Day 8 (Phase 2b)
时间窗: 8 days
Proportional change is represented as percent change, and is defined as: 100 × (D-Dimer level at Day 8 or early discharge - D-Dimer level at baseline) / D-Dimer level at baseline. Baseline and post-baseline D-Dimer results are tested in the same laboratory, i.e. both from central laboratory, or local laboratory paired samples if the central laboratory values are not available.
次要结局
- Change in Tissue Factor Laboratory Values From Baseline Through Day 8 (Phase 2b)(8 days)
- Number of Major or Non-major Clinically Relevant Bleeding Events Within Eight (8) Days of Randomization as Compared to Heparin (Phase 2b)(8 days)
- Proportional Change in D-dimer Level From Baseline to 24 Hours Post-dose (Day 2) and Day 3 (Phase 2b)(2 days and 3 days)
- Number of Major or Non-major Clinically Relevant Bleeding Events With rNAPc2 vs. Heparin Through Day 30 (Phase 2b)(30 days)
- Change in Interleukin-6 Laboratory Values From Baseline Through Day 8 (Phase 2b)(8 days)
- Change in Antiphospholipid Antibodies Laboratory Values From Baseline Through Day 8 (Anti-Beta 2 Glycoprotein IgG) (Phase 2b)(8 days)
- Change in High Sensitivity C-reactive Protein Laboratory Values From Baseline Through Day 8 (Phase 2b)(8 days)