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

NCT04349098 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: XPORT-CoV-10012020-001411-25
• Study Type: interventional
• Target: 190
• Locations: 6 countries
• Sites: 33

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

Keywords

COVID-19; SARS-CoV-2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7

  Baseline up to Day 7

• Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale

  Baseline up to Day 7 and 14

• Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2)

  Baseline up to Day 28

• Overall Death Rate

  Baseline up to Day 28

• Rate of Mechanical Ventilation (RMV)

  Baseline up to Day 28

Study Arms (2)

Selinexor 20 mg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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).

Other: Placebo

Interventions

Selinexor DRUG

Participants will receive 20 mg of selinexor.

Also known as: KPT-330, XPOVIO

Selinexor 20 mg

Placebo OTHER

Participants will receive 20 mg of placebo matched to selinexor.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (33)

UCLA

Los Angeles, California, 90095, United States

Location

Kaiser Permanente Oakland

Oakland, California, 94612, United States

Location

UC Davis Health

Sacramento, California, 95817, United States

Location

Kaiser Permanente Sacramento

Sacramento, California, 95825, United States

Location

Kaiser Permanente San Francisco

San Francisco, California, 94115, United States

Location

Miami Cancer Institute at Baptist Health

Miami, Florida, 33176, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 64113, United States

Location

Norton Healthcare

Louisville, Kentucky, 40202, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Karmanos

Detroit, Michigan, 48201, United States

Location

Michigan Center of Medical Research

Farmington Hills, Michigan, 48336, United States

Location

Michigan Center of Medical Research

Royal Oak, Michigan, 48073, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Levine Cancer Institute-Atrium Health University City

Charlotte, North Carolina, 28204, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18103, United States

Location

Baylor Scott & White Dallas

Dallas, Texas, 75201, United States

Location

MultiCare Institute for Research & Innovation (Puget Sound)

Tacoma, Washington, 98405, United States

Location

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

Vienna, Austria

Location

CHU Bordeaux

Bordeaux, 33076, France

Location

CHU Lyon

Lyon, 69004, France

Location

CHU Nantes

Nantes, 44093, France

Location

Hadassah MC

Jerusalem, Israel

Location

Hasharon Medical Center

Petah Tikva, Israel

Location

Sheba Medical Center

Tel Litwinsky, Israel

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

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

Salamanca, 37007, Spain

Location

Princess Royal University Hospital

Kent, BR6 8ND, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

University Hospitals Plymouth NHS Trust

Plymouth, PL6 5FP, United Kingdom

Location

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

selinexor

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Jatin Shah, MD
• Organization: Karyopharm Therapeutics Inc

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2020
• First Posted: April 16, 2020
• Study Start: April 17, 2020
• Primary Completion: October 5, 2020
• Study Completion: October 5, 2020
• Last Updated: January 20, 2023
• Results First Posted: November 1, 2021

Record last verified: 2023-01

Locations

US (20); FR (3); AU (1); IL (3); ES (2); GB (4)