Severe COVID-19 Infection MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Karyopharm Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if they meet all the following criteria: 1.Age =18 years 2.Confirmed laboratory diagnosis of SARS-CoV2 by standard - approved RT-PCR assay (local labs) within 7 days of enrollment 3.Currently hospitalized 4.Informed consent 5.Has symptoms of severe COVID-19 as demonstrated by: a.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 AND b. Clinical signs indicative of lower respiratory infection with COVID-19, with at least one of the following: SaO2 2 x ULN 7.Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) are permitted. If in the physician’s judgement, it is in the best interest of the patient to use anti-viral or anti-inflammatory treatments, these treatments are to be documented in the patient’s chart and entered in the electronic case report form. Note: Patients who may have received plasma convalescent therapy > 48 hours prior to enrollment with no clinical improvement and who still meet criteria for severe COVID-19 may enroll. On study plasma convalescent therapy is not permitted. Patient who receive plasma convalescent therapy within 48 hours may be permitted to enroll based on discussion with sponsor. 8.Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment. Highly effective methods of contraception are listed in Section 8.3.1 of the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: 1.Evidence of critical COVID-19 based on: a.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) b.Septic shock (defined by investigator assessment or requiring vasopressors) c.Multiple organ dysfunction/failure 2.In the opinion of the investigator, unlikely to survive for at least 48 hours from screening 3.Inadequate hematologic parameters as indicated by the following labs: a.Patients with severe neutropenia (ANC 5x the upper limit of normal 5.Unable to take oral medication when inform consent is obtained. 6.Patients with a legal guardian or who are incarcerated. 7.Pregnant and breastfeeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Day 14 Ordinal Scale Improvement (OSI);Secondary Objective: Key secondary objectives: -To evaluate improvement in clinical measures across the 2 treatment arms Additional secondary objectives: -To evaluate improvement in additional clinical measures across the 2 treatment arms -To determine the anti-inflammatory and immune effect of selinexor -To assess safety and tolerability of selinexor [time frame: up to 28 days];Timepoint(s) of evaluation of this end point: Throughout the study;Primary end point(s): Proportion of patients with at least a 2 point improvement (increase) in the Ordinal Scale from baseline to Day 14. The Ordinal Scale is an assessment of the clinical status at the first assessment on each day of hospitalization. 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 (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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary endpoints: •Time to recovery defined as improvement from baseline score of 3 to =4 or from a baseline score of 4 to =5 •Proportion of patients with at least a 2 point improvement (increase) in the Ordinal Scale from baseline to Day 7. •Proportion of patients with at least a 1 point improvement (increase) in the Ordinal Scale from baseline to Day 7 •Proportion of patients with at least a 1 point improvement (increase) in the Ordinal Scale from baseline to Day 14. •Time to an improvement of 2 point using WHO Ordinal Scale Improvement (TTCI-2) •Time to clinical improvement (TTCI-1): defined as the time from randomization, or lower score within 24 hours, to an improvement of 1 point on the Ordinal Scale) •Overall death rate on Day 28 •Rate of mechanical ventilation Additional secondary endpoints: •Overall Survival •Overall death rate on Day 14 •Rate of ICU admission •Length of hospitalization •Length of ICU stay •Duration of mechanical ventilation •PaO2:FiO2 and/or oxygenation index over time •Reduction of C-reactive protein (CRP) •Reduction in ferritin levels •LDH •Measure changes from baseline of blood plasma cytokines: IL-1ß, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IFN?, IP10, TNFa •Listing and documentation of frequency and severity of adverse effects ;Timepoint(s) of evaluation of this end point: Overall death rate on Day 14 and Day 28 Rest of endpoints during the course of the study | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, India, Israel, Italy, Malaysia, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Karyopharm Therapeutics Inc.
Outcome results
None listed