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

Coronavirus Infection Clinical Trial

— Coronavirus  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04349098
• Other study ID #: XPORT-CoV-1001
• Secondary ID: 2020-001411-25
• Status: Completed
• Phase: Phase 2
• Start date: April 17, 2020
• Est. completion date: October 5, 2020

Study information

• Verified date: January 2023
• Source: Karyopharm Therapeutics Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: October 5, 2020
• Est. primary completion date: October 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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: 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.

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) > 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.

Related Conditions & MeSH terms

• Communicable Diseases
• Coronavirus Infection
• Coronavirus Infections
• COVID-19
• Infections

Intervention

Drug:
• Selinexor
Participants will receive 20 mg of selinexor.

Other:
• Placebo
Participants will receive 20 mg of placebo matched to selinexor.

Locations

Country	Name	City	State
Austria	Hospital Hietzing, 2. Medical department - Center for Diagnosis and Therapy of Rheumatic Diseases	Vienna
France	CHU Bordeaux	Bordeaux
France	CHU Lyon	Lyon
France	CHU Nantes	Nantes
Israel	Hadassah MC	Jerusalem
Israel	Hasharon Medical Center	Petah Tiqva
Israel	Sheba Medical Center	Tel HaShomer
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca	Salamanca
United Kingdom	Princess Royal University Hospital	Kent
United Kingdom	Kings College Hospital	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	University Hospitals Plymouth NHS Trust	Plymouth
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Emory University	Atlanta	Georgia
United States	Boston Medical Center	Boston	Massachusetts
United States	Levine Cancer Institute-Atrium Health University City	Charlotte	North Carolina
United States	Baylor Scott & White Dallas	Dallas	Texas
United States	Karmanos	Detroit	Michigan
United States	Michigan Center of Medical Research	Farmington Hills	Michigan
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	UCLA	Los Angeles	California
United States	Norton Healthcare	Louisville	Kentucky
United States	Miami Cancer Institute at Baptist Health	Miami	Florida
United States	Columbia University	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Kaiser Permanente Oakland	Oakland	California
United States	Michigan Center of Medical Research	Royal Oak	Michigan
United States	Kaiser Permanente Sacramento	Sacramento	California
United States	UC Davis Health	Sacramento	California
United States	Kaiser Permanente San Francisco	San Francisco	California
United States	MultiCare Institute for Research & Innovation (Puget Sound)	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Karyopharm Therapeutics Inc

Countries where clinical trial is conducted

United States,  Austria,  France,  Israel,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale	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.	Baseline up to Day 14
Secondary	Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7	Ordinal Scale 2-points improvement was defined as percentage of participants with at least a 2-points improvement (increase from baseline) by Day 7. 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 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.	Baseline up to Day 7
Secondary	Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale	Ordinal Scale 1-point improvement was defined as percentage of participants with at least 1-point improvement (increase from baseline) by Day 7 and 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 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.	Baseline up to Day 7 and 14
Secondary	Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2)	TTCI-2 was defined as the time from randomization to an improvement of 2-points using 8-points Ordinal Scale. 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.	Baseline up to Day 28
Secondary	Overall Death Rate	Overall death rate was defined as the percentage of participants who died on or before Day 28.	Baseline up to Day 28
Secondary	Rate of Mechanical Ventilation (RMV)	The rate of RMV was defined as the percentage of participants who ever used invasive mechanical ventilation or ECMO during the hospital stay.	Baseline up to Day 28
Secondary	Rate of Intensive Care Unit (ICU) Admission	The rate of ICU admission was defined as the percentage of participants with ICU admissions.	Baseline up to Day 28
Secondary	Length of Hospitalization	Length of hospitalization (days) was defined as (first hospital discharge date - date of randomization + 1).	Baseline up to Day 67
Secondary	Change From Baseline in C-reactive Protein (CRP) Levels	The anti-inflammatory and immune effects of selinexor were assessed by CRP levels. Baseline was defined as the most recent non-missing measurement prior to the first administration of study treatment. Change from Baseline at the indicated time points was calculated as the value at the indicated time points minus the value at Baseline.	Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Secondary	Change From Baseline in Ferritin Levels	The anti-inflammatory and immune effects of selinexor were assessed by ferritin levels. Baseline was defined as the most recent non-missing measurement prior to the first administration of study treatment. Change from Baseline at the indicated time points was calculated as the value at the indicated time points minus the value at Baseline.	Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Secondary	Change From Baseline in Lactate Dehydrogenase (LDH) Levels	The anti-inflammatory and immune effects of selinexor were assessed by LDH levels. Baseline was defined as the most recent non-missing measurement prior to the first administration of study treatment. Change from Baseline at the indicated time points was calculated as the value at the indicated time points minus the value at Baseline.	Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
Secondary	Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6)	The anti-inflammatory and immune effects of selinexor were assessed by blood plasma cytokines like IL-6. Baseline was defined as the most recent non-missing measurement prior to the first administration of study treatment. Change from Baseline at the indicated time points was calculated as the value at the indicated time points minus the value at Baseline.	Baseline, Day 3, 5, 8, 12, 15, 22 and 26
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	Adverse events are defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. Serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs are defined as those AEs that develop or worsen after the first dose of study drug. TEAEs included both Serious and non-serious TEAEs.	From start of study drug administration up to Day 58