Evaluation of Activity and Safety of Two Regimens of Low Dose Oral Selinexor in Participants With Moderate or Severe COVID-19
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Selinexor 40mg 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
20 mg selinexor oral tablet.
Other Names:
|
| Experimental: Selinexor 20mg 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
20 mg selinexor oral tablet.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants with at Least a 2 Point Improvement in the Ordinal Scale [Baseline to Day 14]
Secondary Outcome Measures
- 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)]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Confirmed laboratory diagnosis of SARS-CoV2 by standard approved reverse transcription polymerase chain reaction (RT-PCR) assay or equivalent approved testing (by local labs).
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Currently hospitalized and consented within the first 48 hours of hospitalization.
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Informed consent provided as above (patients must be dosed with study drug within 12 hours of consent).
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Has symptoms of moderate or severe COVID-19 as demonstrated by:
Moderate COVID-19:
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Currently hospitalized and requiring medical care for COVID-19, and
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Peripheral capillary oxygen saturation (SpO2, pulse oximetry) > 94% on room air at screening, and
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Radiographic evidence of pulmonary infiltrates
Severe COVID-19:
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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
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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)
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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.
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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)
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Septic shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg)
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Multiple organ dysfunction/failure
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In the opinion of the investigator, unlikely to survive for at least 48 hours from screening or anticipate mechanical ventilation within 48 hours
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Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) are not permitted.
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Inadequate hematologic parameters as indicated by the following labs:
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Patients with severe neutropenia (ANC <1,000 x 10^9/liter [L]) or
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Thrombocytopenia (e.g., platelets <100,000 per microliter of blood)
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Inadequate renal function as indicated by creatinine clearance (CrCl) <20 milliliter per minute (mL/min) using the formula of Cockcroft and Gault.
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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.
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Hyponatremia defined as sodium < 135 milliequivalents per liter (mEq/L).
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In the opinion of the Investigator, patients who are below their ideal body weight and would be unduly impacted by changes in their weight.
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Unable to take oral medication when informed consent is obtained.
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Patients with a legal guardian or who are incarcerated.
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Pregnant and breastfeeding women.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Karyopharm Therapeutics Inc
Investigators
- Study Director: Dayana Michel, Karyopharm Therapeutics Inc
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XPORT-CoV-1002