Evaluation of Activity and Safety of Two Regimens of Low Dose Oral Selinexor in Participants With Moderate or Severe COVID-19

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the activity, safety and reduction in mortality of two regimens of low dose selinexor (KPT-330) in patients with moderate or severe COVID-19.

Official Title
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A Phase 2 Randomized, Open-Label, Multicenter Study to Evaluate the Activity and Safety of Two Regimens of Low Dose Oral Selinexor in Patients With Moderate or Severe COVID-19

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Drug: Selinexor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed laboratory diagnosis of SARS-CoV2 by standard approved reverse transcription polymerase chain reaction (RT-PCR) assay or equivalent approved testing (by local labs). Currently hospitalized and consented within the first 48 hours of hospitalization. Informed consent provided as above (patients must be dosed with study drug within 12 hours of consent). Has symptoms of moderate or severe COVID-19 as demonstrated by: Moderate COVID-19: Currently hospitalized and requiring medical care for COVID-19, and Peripheral capillary oxygen saturation (SpO2, pulse oximetry) > 94% on room air at screening, and Radiographic evidence of pulmonary infiltrates Severe COVID-19: 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 Clinical signs indicative of lower respiratory infection with COVID-19, with at least one of the following: respiratory rate ≥ 30 breaths/minute (min), heart rate ≥ 125/min, Oxygen saturation (SpO2) <93% on room air or requires > 2L/minute oxygen by NC in order to maintain SaO2 ≥93%, PaO2/FiO2 <300 millimeter per mercury (mm/hg) Female patients of childbearing potential must have a negative serum pregnancy test at Screening and must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment. Males who are sexually active must commit to use a highly effective method of contraception while receiving selinexor and for 3 months after the last selinexor dose, or consent to total sexual abstinence (abstinence must occur from enrollment and continue for 3 months after the last selinexor dose). Exclusion Criteria: Evidence of critical COVID-19 based on: Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations) Septic shock (defined by SBP < 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 Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) are not permitted. Inadequate hematologic parameters as indicated by the following labs: Patients with severe neutropenia (ANC <1,000 x 10^9/liter [L]) or Thrombocytopenia (e.g., platelets <100,000 per microliter of blood) Inadequate renal function as indicated by creatinine clearance (CrCl) <20 milliliter per minute (mL/min) using the formula of Cockcroft and Gault. Inadequate hepatic function defined as AST or ALT > 5x the upper limit of normal OR serum direct bilirubin > 2.5x the upper limit of normal. Hyponatremia defined as sodium < 135 milliequivalents per liter (mEq/L). In the opinion of the Investigator, patients who are below their ideal body weight and would be unduly impacted by changes in their weight. Unable to take oral medication when informed consent is obtained. Patients with a legal guardian or who are incarcerated. Pregnant and breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selinexor 40mg<br>Participants will receive 40 milligram (mg) of selinexor as oral tablets on Days 1 and 3 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). | Drug: Selinexor<br>* 20 mg selinexor oral tablet.<br>* Other names: XPOVIO;|
| Experimental: Selinexor 20mg<br>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). | Drug: Selinexor<br>* 20 mg selinexor oral tablet.<br>* Other names: XPOVIO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with at Least a 2 Point Improvement in the Ordinal Scale |  | Baseline to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Clinical Improvement (TTCI) |  | Up to Day 28 | 
| Overall Death Rate |  | Day 14, Day 28 | 
| Rate of Mechanical Ventilation |  | Up to Day 28 | 
| Time to Mechanical Ventilation |  | Up to Day 28 | 
| Overall Survival |  | Up to Day 28 | 
| Time to Improvement (2 points) in Clinical Measures Using the Ordinal Scale |  | Up to Day 28 | 
| Time to Intensive Care Unit (ICU) Admission |  | Up to Day 28 | 
| Rate of Intensive Care Unit (ICU) Admission |  | Up to Day 28 | 
| Length of Stay in Hospital |  | Up to Day 28 | 
| Percentage of Participants Discharged From Hospital |  | Up to Day 28 | 
| Length of Stay in Intensive Care Unit (ICU) |  | Up to Day 28 | 
| Duration of Oxygen Supplementation |  | Up to Day 28 | 
| Duration of Mechanical Ventilation |  | Up to Day 28 | 
| Time to Clinical Improvement in Participants ≤ 70 Years Old |  | Up to Day 28 | 
| Time to Clinical Improvement in Participants > 70 Years Old |  | Up to Day 28 | 
| Time to Clinical Improvement in Participants with Pre-existing Diseases |  | Up to Day 28 | 
| Change in Oxygenation Index |  | Up to Day 28 | 
| Time to Improvement of One Point Using WHO Ordinal Scale Improvement |  | Up to Day 28 | 
| Percentage of Participants Experiencing WHO Ordinal Scale Improvement of >1 point |  | Up to Day 28 | 
| Change from Baseline in C-reactive protein (CRP) Levels |  | Up to Day 28 | 
| Change from Baseline in Ferritin Levels |  | Up to Day 28 | 
| Change from Baseline in Lactate Dehydrogenase (LDH) Levels |  | Up to Day 28 | 
| Number of Participants with Adverse Events (AE) |  | From start of study drug administration up to follow-up (Day 30) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2