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

NCT ID: NCT04349098

Last Updated: 2023-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 190 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-17
• Study Completion Date: 2020-10-05

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. 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.

Conditions

Coronavirus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Participants will receive 20 mg of selinexor.

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Participants will receive 20 mg of placebo matched to selinexor.

Interventions

Selinexor

Participants will receive 20 mg of selinexor.

Intervention Type: DRUG

Placebo

Participants will receive 20 mg of placebo matched to selinexor.

Intervention Type: OTHER

Other Intervention Names

KPT-330; XPOVIO

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UCLA

Los Angeles, California, United States

Kaiser Permanente Oakland

Oakland, California, United States

UC Davis Health

Sacramento, California, United States

Kaiser Permanente Sacramento

Sacramento, California, United States

Kaiser Permanente San Francisco

San Francisco, California, United States

Miami Cancer Institute at Baptist Health

Miami, Florida, United States

Emory University

Atlanta, Georgia, United States

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Norton Healthcare

Louisville, Kentucky, United States

Boston Medical Center

Boston, Massachusetts, United States

Karmanos

Detroit, Michigan, United States

Michigan Center of Medical Research

Farmington Hills, Michigan, United States

Michigan Center of Medical Research

Royal Oak, Michigan, United States

Columbia University

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Levine Cancer Institute-Atrium Health University City

Charlotte, North Carolina, United States

Lehigh Valley Hospital

Allentown, Pennsylvania, United States

Baylor Scott & White Dallas

Dallas, Texas, United States

MultiCare Institute for Research & Innovation (Puget Sound)

Tacoma, Washington, United States

Hospital Hietzing, 2. Medical department - Center for Diagnosis and Therapy of Rheumatic Diseases

Vienna, , Austria

CHU Bordeaux

Bordeaux, , France

CHU Lyon

Lyon, , France

CHU Nantes

Nantes, , France

Hadassah MC

Jerusalem, , Israel

Hasharon Medical Center

Petah Tikva, , Israel

Sheba Medical Center

Tel Litwinsky, , Israel

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca

Salamanca, , Spain

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 Kingdom

Countries

United States; Austria; France; Israel; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-001411-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

XPORT-CoV-1001

Identifier Type: -

Identifier Source: org_study_id