A Phase 2 Randomized, Double-blind, Placebo-controlled, Multicenter Study of Pacritinib Plus Standard of Care Versus Placebo and Standard of Care in Hospitalized Patients With Severe COVID-19 With or Without Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 200
- 试验地点
- 21
- 主要终点
- Percentage of Participants With Progression to IMV and/or ECMO or Death
研究概览
简要总结
This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or without cancer.
详细描述
This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or without cancer. Severe COVID-19 is defined as confirmed disease in patients who are hospitalized with hypoxia (blood oxygen saturation [SpO2] ≤93% on room air at sea level), respiratory rate >30, arterial oxygen partial pressure [PaO2]/ fraction of inspired oxygen [FiO2] <300, or lung infiltrates >50% but do not require IMV.
Patients will be randomized 1:1 to receive pacritinib (400 mg once daily [QD] on Day 1, then 200 mg twice daily [BID] from Day 2 to Day 14) + SOC or placebo + SOC.
Assigned treatment will continue for up to Day 14 or until the patient experiences intolerable adverse events (AEs), withdraws consent, or initiates another investigational therapy or until the study is terminated. Assigned therapy may be given for an additional 7 days (for a total of 21 days) with the approval of the Medical Monitor if, in the opinion of the investigator, the patient's clinical signs and symptoms are improving and the potential benefit outweighs the potential risk.In the event of hospital discharge, patients will complete treatment with the assigned therapy as an outpatient.
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)
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 or will be hospitalized prior to randomization for the treatment of severe COVID-19 with SARS-CoV-2 infection confirmed by either a) a positive reverse transcriptase polymerase chain reaction (RT PCR) or b) an antigen-based test from any respiratory, nasopharyngeal, saliva, blood, or stool specimen at Screening or documented within 1 week prior to the start of Screening (Severe COVID-19 is defined as confirmed disease in patients who are hospitalized with hypoxia [SpO2 ≤93% on room air], respiratory rate >30, PaO2/FiO2 <300, but do not require IMV).
- •Age ≥ 18 years
- •Platelet count ≥ 50,000/µL
- •If fertile, willing to use effective birth control methods during the study
- •Provision of informed consent within 96 hours after hospitalization
排除标准
- •In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
- •Currently intubated or intubated between screening and randomization
- •Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID 19)
- •Prior allogenic hematopoietic stem cell transplantation
- •Active lung cancer or history of lung cancer within the past 12 months
- •Any active grade 2 or higher hemorrhage
- •Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
- •Uncontrolled intercurrent illness that, in the judgment of the treating physician, would limit compliance with study requirements
- •Known seropositivity for human immunodeficiency virus with cluster of differentiation 4 (CD4) count < 200/mm3 within 3 months prior to randomization
- •Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
- •Concurrent enrollment in another interventional trial (investigational COVID-19 antiviral studies are permitted)
- •Serum creatinine > 2.5 mg/dL
- •Total bilirubin > 4× the upper limit of normal
- •QT corrected by the Fridericia method (QTcF) prolongation > 480 msec
- •Known history of New York Heart Association Class II, III, or IV congestive heart failure prior to hospital admission
- •Known allergic reaction to any Janus kinase 2 (JAK2) inhibitor
- •Exposure to any JAK2 inhibitor within 28 days
- •Currently receiving a strong CYP3A4 inhibitor or strong P450 inducer (Appendix 1 and Appendix 2, respectively) and unable to stop the medication prior to the first dose of study drug and throughout the duration of study drug administration
- •Treatment with cytoreductive chemotherapy administered within 14 days prior to randomization
- •Administration of an IL 1 or IL 6 blocking immunomodulatory agent (such as tocilizumab, canakinumab, sarilumab, anakinra) within 48 hours prior to randomization
- •Currently receiving therapeutic anticoagulation or anti platelet medication and unable to stop the medication prior to randomization. Prophylactic anticoagulation therapy or aspirin (≤ 100mg) are permitted.
- •Unable to ingest capsules or tablets at randomization
研究组 & 干预措施
Pacritinib and SOC
Pacritinib 400 mg once daily [QD] on Day 1, then 200 mg twice daily [BID] from Day 2 to Day 14) + SOC
干预措施: Pacritinib (Drug)
Placebo and SOC
4 capsules once daily [QD] on Day 1, then 2 capsules twice daily [BID] from Day 2 to Day 14) + SOC
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Progression to IMV and/or ECMO or Death
时间窗: Baseline to Day 28
The percentage is calculated as the number of patients who progress to IMV/ECMO or death divided by the total number of patients in the ITT population (n/N \* 100).
次要结局
- The Mortality Rate at Day 15(Baseline to Day 15)
- The Number of Ventilator-Free Days(Baseline to Day 28)
- The Mortality Rate at Day 28(Baseline to Day 28)
- The Clinical Status as Assessed by the 7-point Ordinal Scale of Clinical Status at Days 8, 15, 22, and 28(Baseline, Day 8, 15, 22, 28)
- The Time to Improvement by at Least 2 Points Relative to Baseline on the 7-point Ordinal Scale of Clinical Status(Baseline, Day 8, 15, 22, and 28.)
- The Rate of Use of Immunomodulatory Agents as Treatment for COVID-19(Baseline to Day 28)