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Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection (Coronavirus)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04349098
Recruitment Status : Completed
First Posted : April 16, 2020
Last Update Posted : December 24, 2020
Sponsor:
Information provided by (Responsible Party):
Karyopharm Therapeutics Inc

Tracking Information
First Submitted Date  ICMJE April 14, 2020
First Posted Date  ICMJE April 16, 2020
Last Update Posted Date December 24, 2020
Actual Study Start Date  ICMJE April 17, 2020
Actual Primary Completion Date October 5, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 14, 2020)
Percentage of Participants with at Least a 2 Point Improvement in the Ordinal Scale [ Time Frame: Baseline to Day 14 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2020)
  • Time to Clinical Improvement (TTCI) [ Time Frame: Up to Day 28 ]
  • Overall Death Rate [ Time Frame: Day 14, Day 28 ]
  • Rate of Mechanical Ventilation [ Time Frame: Up to Day 28 ]
  • Time to Mechanical Ventilation [ Time Frame: Up to Day 28 ]
  • Overall Survival [ Time Frame: Up to Day 28 ]
  • Time to Improvement (2 points) in Clinical Measures Using the Ordinal Scale [ Time Frame: Baseline, Day 28 ]
  • Time to Intensive Care Unit (ICU) Admission [ Time Frame: Up to Day 28 ]
  • Rate of Intensive Care Unit (ICU) Admission [ Time Frame: Up to Day 28 ]
  • Length of Stay in Hospital [ Time Frame: Up to Day 28 ]
  • Percentage of Participants Discharged from Hospital [ Time Frame: Up to Day 28 ]
  • Length of Stay in Intensive Care Unit (ICU) [ Time Frame: Up to Day 28 ]
  • Duration of Oxygen Supplementation [ Time Frame: Up to Day 28 ]
  • Duration of Mechanical Ventilation [ Time Frame: Up to Day 28 ]
  • Time to Clinical Improvement in Participants ≤ 70 Years Old [ Time Frame: Up to Day 28 ]
  • Time to Clinical Improvement in Participants > 70 Years Old [ Time Frame: Up to Day 28 ]
  • Time to Clinical Improvement in Participants with Pre-existing Diseases [ Time Frame: Up to Day 28 ]
  • Change in Oxygenation Index [ Time Frame: Up to Day 28 ]
  • Time to Improvement of One Point Using WHO Ordinal Scale Improvement [ Time Frame: Up to Day 28 ]
  • Percentage of Participants Experiencing WHO Ordinal Scale Improvement of >1 point [ Time Frame: Up to Day 28 ]
  • Change from Baseline in C-reactive protein (CRP) Levels [ Time Frame: Up to Day 28 ]
  • Change from Baseline in Ferritin Levels [ Time Frame: Up to Day 28 ]
  • Change from Baseline in Lactate Dehydrogenase (LDH) Levels [ Time Frame: Up to Day 28 ]
  • Changes from Baseline in Blood Plasma Cytokines Levels [ Time Frame: Up to Day 28 ]
  • Number of Participants with Adverse Events (AE) [ Time Frame: From start of study drug administration up to Day 28 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2020)
  • Time to Clinical Improvement (TTCI) [ Time Frame: Up to Day 28 ]
  • Number of Participants with Overall Death Rate [ Time Frame: Day 14, Day 28 ]
  • Number of Participants With Rate of Mechanical Ventilation [ Time Frame: Up to Day 28 ]
  • Time to Mechanical Ventilation [ Time Frame: Up to Day 28 ]
  • Overall Survival [ Time Frame: Up to Day 28 ]
  • Time to Improvement (2 points) in Clinical Measures Using the Ordinal Scale [ Time Frame: Baseline, Day 28 ]
  • Time to Intensive Care Unit (ICU) Admission [ Time Frame: Up to Day 28 ]
  • Rate of Intensive Care Unit (ICU) Admission [ Time Frame: Up to Day 28 ]
  • Length of Stay in Hospital [ Time Frame: Up to Day 28 ]
  • Percentage of Participants Discharged from Hospital [ Time Frame: Up to Day 28 ]
  • Length of Stay in Intensive Care Unit (ICU) [ Time Frame: Up to Day 28 ]
  • Duration of Oxygen Supplementation [ Time Frame: Up to Day 28 ]
  • Duration of Mechanical Ventilation [ Time Frame: Up to Day 28 ]
  • Change in Vienna Vaccine Safety Initiative (ViVI) Disease Severity Score [ Time Frame: Up to Day 28 ]
  • Time to Clinical Improvement in Participants ≤ 70 Years Old [ Time Frame: Up to Day 28 ]
  • Time to Clinical Improvement in Participants > 70 Years Old [ Time Frame: Up to Day 28 ]
  • Time to Clinical Improvement in Participants with Pre-existing Diseases [ Time Frame: Up to Day 28 ]
  • Change in Oxygenation Index [ Time Frame: Up to Day 28 ]
  • Time to Improvement of One Point Using WHO Ordinal Scale Improvement [ Time Frame: Up to Day 28 ]
  • Percentage of Participants Experiencing WHO Ordinal Scale Improvement of >1 point [ Time Frame: Up to Day 28 ]
  • Change from Baseline in C-reactive protein (CRP) Levels [ Time Frame: Up to Day 28 ]
  • Change from Baseline in Ferritin Levels [ Time Frame: Up to Day 28 ]
  • Change from Baseline in Lactate Dehydrogenase (LDH) Levels [ Time Frame: Up to Day 28 ]
  • Changes from Baseline in Blood Plasma Cytokines Levels [ Time Frame: Up to Day 28 ]
  • Number of Participants with Adverse Events (AE) [ Time Frame: From start of study drug administration up to Day 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Coronavirus Infection
Intervention  ICMJE
  • Drug: Selinexor
    Participants will receive 20 mg of selinexor.
    Other Names:
    • KPT-330
    • XPOVIO
  • Other: Placebo
    Participants will receive 20 mg of placebo matched to selinexor.
Study Arms  ICMJE
  • Experimental: 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).
    Intervention: Drug: Selinexor
  • Placebo Comparator: 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).
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 23, 2020)
202
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2020)
230
Actual Study Completion Date  ICMJE October 5, 2020
Actual Primary Completion Date October 5, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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: respiratory rate ≥ 30 breaths/minute (min), heart rate ≥ 125/min, SaO2 <93% on room air or requires > 2 liter (L) oxygen by NC in order maintain SaO2 ≥93%, PaO2/FiO2 <300 millimeter per mercury (mm/hg).
  • 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 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.

Exclusion Criteria:

  • 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) > 2.5 x upper limit of normal (ULN)
    • Total bilirubin >1.5 x upper limit of normal (ULN)
  • Hyponatremia defined as sodium < 135 milliequivalents per litre (mEq/L).
  • Unable to take oral medication when informed consent is obtained.
  • Treatment with strong CYP3A inhibitors or inducers.
  • Pregnant and breastfeeding women.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   France,   Israel,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04349098
Other Study ID Numbers  ICMJE XPORT-CoV-1001
2020-001411-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Karyopharm Therapeutics Inc
Study Sponsor  ICMJE Karyopharm Therapeutics Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Dayana Michel Karyopharm Therapeutics Inc
PRS Account Karyopharm Therapeutics Inc
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP