A Phase 2 Randomized Single-Blind Study to Evaluate the Activity and Safety of Low Dose Oral Selinexor (KPT-330) in Patients With Severe COVID-19 Infection
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 190
- 试验地点
- 32
- 主要终点
- Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale
研究概览
简要总结
The main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo. The study had 2 arms and evaluated selinexor 20 mg + standard of care (SoC) and placebo + SoC. As the treatment for COVID-19 is rapidly evolving, the SoC varied over time and across regions of the world.
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
- Single (Participant)
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
- •Confirmed laboratory diagnosis of SARS-CoV2 by standard FDA-approved reverse transcription polymerase chain reaction (RT-PCR) assay or equivalent FDA-approved testing (local labs).
- •Currently hospitalized.
- •Informed consent provided as above (it is recommended that participants are dosed with study drug within 12 hours of consent).
- •Has symptoms of severe COVID-19 as demonstrated by:
- •At least one of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath at rest or with exertion, confusion, or symptoms of severe lower respiratory symptoms including dyspnea at rest or respiratory distress.
- •Clinical signs indicative of lower respiratory infection with COVID-19, with at least one of the following: SaO2 <92% on room air in last 12 hours or requires > 4 liters per minute (LPM) oxygen by nasal canula, non-rebreather/Ventimask or high flow nasal canula in order maintain SaO2 ≥92%, PaO2/FiO2 <300 millimeter per mercury (mm/hg).
- •Elevated C-reactive protein (CRP) > 2 x upper limit of normal (ULN).
- •Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) are permitted. If in the physician's judgment, it is in the best interest of the participant to use anti-viral or anti-inflammatory treatments, these treatments are to be documented in the participant's chart and entered in the electronic case report form.
- •Female participants of childbearing potential must have a negative serum pregnancy test at Screening. Female participants of childbearing potential and fertile male participants must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
排除标准
- •Evidence of critical COVID-19 based on:
- •Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations)
- •Septic shock (defined by Systolic blood pressure [BP] < 90 mm Hg, or Diastolic BP < 60 mm Hg)
- •Multiple organ dysfunction/failure
- •In the opinion of the investigator, unlikely to survive for at least 48 hours from screening or anticipate mechanical ventilation within 48 hours.
- •Inadequate hematologic parameters as indicated by the following labs:
- •Participants with severe neutropenia (ANC <1000 x 10^9/L) or
- •Thrombocytopenia (e.g., platelets <100,000 per microliter of blood)
- •Inadequate renal and liver function as indicated by the following labs:
- •Creatinine clearance (CrCL) <20 mL/min using the formula of Cockcroft and Gault
- •Aspartate transaminase (AST) or alanine transaminase (ALT) > 5 x ULN
- •Hyponatremia defined as sodium < 135 milliequivalents per liter (mEq/L).
- •Unable to take oral medication when informed consent is obtained.
- •Participants with a legal guardian or who are incarcerated.
- •Treatment with strong CYP3A inhibitors or inducers.
- •Pregnant and breastfeeding women.
研究组 & 干预措施
Selinexor 20 mg
Participants will receive 20 milligram (mg) of selinexor oral tablet on Days 1, 3, and 5 of each week for up to 2 weeks (14 days). If the participant is tolerating therapy and clinically benefitting, dosing can continue for an additional 2 weeks (28 days).
干预措施: Selinexor (Drug)
Placebo
Participants will receive 20 mg of placebo matched to selinexor oral tablet on Days 1, 3, and 5 of each week for up to 2 weeks (14 days). If the participant is tolerating therapy and clinically benefitting, dosing can continue for an additional 2 weeks (28 days).
干预措施: Placebo (Other)
结局指标
主要结局
Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale
时间窗: Baseline up to Day 14
Ordinal Scale 2-Point improvement was defined as percentage of participants with at least a 2-points improvement (increase from baseline) by Day 14. Baseline score was defined as the last score measured before first dosing. The 8-point ordinal scale ranges from 1 to 8: where 1= death, 2= hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3= hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus disease 2019 \[COVID-19\] related or otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7= not hospitalized, limitation on activities and/or requiring home oxygen; 8= not hospitalized, no limitations on activities.
次要结局
- Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7(Baseline up to Day 7)
- Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2)(Baseline up to Day 28)
- Overall Death Rate(Baseline up to Day 28)
- Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale(Baseline up to Day 7 and 14)
- Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6)(Baseline, Day 3, 5, 8, 12, 15, 22 and 26)
- Rate of Mechanical Ventilation (RMV)(Baseline up to Day 28)
- Rate of Intensive Care Unit (ICU) Admission(Baseline up to Day 28)
- Length of Hospitalization(Baseline up to Day 67)
- Change From Baseline in C-reactive Protein (CRP) Levels(Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26)
- Change From Baseline in Ferritin Levels(Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26)
- Change From Baseline in Lactate Dehydrogenase (LDH) Levels(Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs(From start of study drug administration up to Day 58)