Either you have JavaScript disabled or your browser does not support Javascript . To work properly, this page requires JavaScript to be enabled.
How to enable JavaScript in your browser?

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

Trial Profile

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

Status: Discontinued
Phase of Trial: Phase II

Latest Information Update: 04 Aug 2020

At a glance

  • Drugs Selinexor (Primary)
  • Indications COVID 2019 infections
  • Focus Therapeutic Use
  • Sponsors Karyopharm Therapeutics
  • Most Recent Events

    • 04 Aug 2020 Results published in the Karyopharm Therapeutics financial media release.
    • 04 Aug 2020 According to a Karyopharm Therapeutics media release, the protocol was amended to allow enrollment of patients with more severe disease in May 2020.
    • 04 Aug 2020 According to a Karyopharm Therapeutics media release, will continue to analyze the data to further characterize the specific subpopulation that will likely benefit from selinexor and will work with the FDA to identify a path forward for future clinical development and seek potential partners and external funding to advance future clinical studies.

Trial Overview

Purpose

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.

Comments

According to a Karyopharm Therapeutics media release, the Data Safety Monitoring Board (DSMB) has recommended to discontinue this trial following a planned interim analysis (115 patients included in the efficacy analysis and 113 patients included in the safety analysis) as the trial is unlikely to demonstrate a statistically significant efficacy benefit across the entire heterogenous patient population studied.

Primary Endpoints

Percentage of Participants with at Least a 2 Point Improvement in the Ordinal Scale

time_frame: Baseline to Day 14

Absence of fever: oral temperature <38C x 24 hours without antipyretics (acetaminophen) AND one of the following

− Respiratory rate < or =24/minute OR
− Oxygen saturation > or = 94% on room air OR
− Hospital discharge
Timepoint(s) of evaluation of this end point: Throughout the study

Other Endpoints

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 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 300

  • Sex male & female
  • Age Group ≥18 years; adult; elderly

Patient 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.

Patient 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.

Trial Details

Identifiers

Identifier Owner
NCT04349098 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001411-25 European Clinical Trials Database
XPORT-CoV1001 -

Organisations

  • Sponsors Karyopharm Therapeutics
  • Affiliations Karyopharm Therapeutics

Trial Dates

  • Initiation Dates

    Planned : 30 Apr 2020

    Actual : 17 Apr 2020

  • Primary Completion Dates

    Planned : 31 Aug 2020

  • End Dates

    Planned : 31 Aug 2020

Other Details

  • Design multicentre; parallel; prospective; randomised; single-blind
  • Phase of Trial Phase II
  • Location Australia; Austria; Belgium; Canada; England; France; Germany; India; Israel; Italy; Malaysia; Spain; United Kingdom; USA
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
SelinexorPrimary Drug Oral Tablet

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).
Drug: Selinexor (Participants will receive 20 mg of selinexor.) Other Name: KPT-330, XPOVIO

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

Results

Publications

  1. Karyopharm Therapeutics. Karyopharm Reports Second Quarter 2020 Financial Results and Highlights Recent Company Progress. Media-Rel 2020;.

    Media Release

Authors

Author Total Publications First Author Last Author
Karyopharm Therapeutics 1 1 1

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Arnaud Desclaux CHU Bordeaux France
Benito Almirante Hospital Universitari Vall d'Hebron Spain
Catherine Small Weill Cornell Medical College USA
Charles Hare Kaiser Permanente San Francisco USA
Don Stevens Norton Healthcare USA
Dror Diker Hasharon Medical Center Israel
Enrico Lallana Kaiser Permanente Sacramento USA
Florent Valor CHU Lyon France
Francois Raffi CHU Nantes France
Gennatas Spyridon The Royal Marsden Hospital United-Kingdom
George Lyon Emory University USA
George Thompson UC Davis Health USA
Guenther Koehne Miami Cancer Institute at Baptist Health USA
Itzchak Levy Sheba Medical Center Israel
Jacek Skarbinksi Kaiser Permanente Oakland USA
Jatin Shah, Chief Medical Officer
(617) 658-0600
jshah@karyopharm.com
show details
, Karyopharm Therapeutics
-
Jeff Zonder Karmanos USA
Khalid Rao Michigan Center of Medical Research USA
Kurt Redlich Hospital Hietzing, 2. Medical department - Center for Diagnosis and Therapy of Rheumatic Diseases Austria
Mansour Ceesay Princess Royal University Hospital United-Kingdom
Marcelo Gareca Lehigh Valley Hospital USA
Matthew Cramp University Hospitals Plymouth NHS Trust United-Kingdom
Matthew Ingham Columbia University USA
Mezgebe Berhe Baylor Scott & White Dallas
-
Miguel Marcos Martin Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca Spain
Nathan Bahr University of Kansas Medical Center USA
Otto Yang UCLA USA
Piers Patten Kings College Hospital United-Kingdom
Ran Nir-Paz Hadassah MC Israel
Ronda Oram Advocate Christ Medical Center USA
Sharon Shacham, President and CSO
(617) 658-0600
sshacham@karyopharm.com
show details
, Karyopharm Therapeutics
-
Steven Katzman Michigan Center of Medical Research USA
Vaishali Sanchorawala Boston Medical Center USA
Vinay Malhotra MultiCare Institute for Research & Innovation (Puget Sound)
-
Zainab Shahid Levine Cancer Institute-Atrium Health University City USA

Centres

Centre Name Location Trial Centre Country
-
-
-
Advocate Christ Medical Center Oak Lawn, Illinois USA
Baylor Scott & White Dallas Dallas, Texas USA
Boston Medical Center Boston, Massachusetts USA
CHU Bordeaux Bordeaux France
CHU Lyon Lyon France
CHU Nantes Nantes France
Columbia University New York, New York USA
Emory University Atlanta, Georgia USA
Hadassah MC Jerusalem Israel
Hasharon Medical Center Petah Tiqva Israel
Hospital Hietzing, 2. Medical department - Center for Diagnosis and Therapy of Rheumatic Diseases Vienna Austria
Hospital Universitari Vall d'Hebron Barcelona Spain
Kaiser Permanente Oakland Oakland, California USA
Kaiser Permanente Sacramento Sacramento, California USA
Kaiser Permanente San Francisco San Francisco, California USA
Karmanos Detroit, Michigan USA
Karyopharm Therapeutics
-
-
Karyopharm Therapeutics Inc.
Clinical Trial Information Desk
Street Address 85 Wells Ave
Town/ city Newton
Post code MA 02459
Country United States
Telephone number +34923 291 100
clinicaltrials@karyopharm.com
show details
Newton, Massachusetts USA
Kings College Hospital London United-Kingdom
Lehigh Valley Hospital Allentown, Pennsylvania USA
Levine Cancer Institute-Atrium Health University City Charlotte, North Carolina USA
Miami Cancer Institute at Baptist Health Miami, Florida USA
Michigan Center of Medical Research Farmington Hills, Michigan USA
Michigan Center of Medical Research Royal Oak, Michigan USA
MultiCare Institute for Research & Innovation (Puget Sound) Tacoma, Washington USA
Norton Healthcare Louisville, Kentucky USA
Princess Royal University Hospital Kent United-Kingdom
Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca Salamanca Spain
Sheba Medical Center Tel HaShomer Israel
The Royal Marsden Hospital London United-Kingdom
UC Davis Health Sacramento, California USA
UCLA Los Angeles, California USA
University Hospitals Plymouth NHS Trust Plymouth United-Kingdom
University of Kansas Medical Center Kansas City, Kansas USA
Weill Cornell Medical College New York, New York USA

Trial History

Event Date Event Type Comment
04 Aug 2020 Interim results Results published in the Karyopharm Therapeutics financial media release. Updated 06 Aug 2020
04 Aug 2020 Other trial event According to a Karyopharm Therapeutics media release, the protocol was amended to allow enrollment of patients with more severe disease in May 2020. Updated 06 Aug 2020
04 Aug 2020 Other trial event According to a Karyopharm Therapeutics media release, will continue to analyze the data to further characterize the specific subpopulation that will likely benefit from selinexor and will work with the FDA to identify a path forward for future clinical development and seek potential partners and external funding to advance future clinical studies. Updated 06 Aug 2020
04 Aug 2020 Other trial event According to a Karyopharm Therapeutics media release, the Data Safety Monitoring Board (DSMB) has recommended to discontinue this trial following a planned interim analysis (115 patients included in the efficacy analysis and 113 patients included in the safety analysis) as the trial is unlikely to demonstrate a statistically significant efficacy benefit across the entire heterogenous patient population studied. Updated 06 Aug 2020
04 Aug 2020 Status change - discontinued Status changed from recruiting to discontinued, according to a Karyopharm Therapeutics media release. Updated 06 Aug 2020
16 Jul 2020 Other trial event This trial has been discontinued in Austria, as per European Clinical Trials Database record. Updated 16 Jul 2020
16 Jul 2020 Other trial event Last checked against European Clinical Trials Database record. Updated 16 Jul 2020
10 Jul 2020 Other trial event This trial has been suspended in Spain, as per European Clinical Trials Database record. Updated 10 Jul 2020
10 Jul 2020 Other trial event This trial has been discontinued in Germany, as per European Clinical Trials Database record. Updated 10 Jul 2020
24 May 2020 Other trial event Planned number of patients changed from 230 to 300. Updated 26 May 2020
11 May 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 11 May 2020
30 Apr 2020 Other trial event According to a PROMETRIKA and Karyopharm Therapeutics media release, this study will be conducted in collaboration of the PROMETRIKA. Updated 05 May 2020
22 Apr 2020 Other trial event According to a Precision for Medicine media release, Precision will be responsible for ensuring site engagement, obtaining regulatory and clinical governing authority approvals, documentation preparation, as well as collecting and monitoring data. Updated 22 Apr 2020
22 Apr 2020 Other trial event According to a Precision for Medicine media release, Precision for Medicine is collaborating with Karyopharm Therapeutics to help conduct this first global randomized clinical trial for low dose selinexor in hospitalized patients with severe COVID-19.Precision for Medicine will oversee implementation of the clinical trial in Europe. The countries planning to participate in the study and where sites will be located include the United Kingdom, Italy, France, Spain, Germany, and Austria. Updated 22 Apr 2020
21 Apr 2020 Other trial event New source identified and integrated (European Clinical Trials Database EudraCT2020-001411-25). Updated 21 Apr 2020
20 Apr 2020 Other trial event According to a Karyopharm Therapeutics media release, first patient has been dosed. Updated 22 Apr 2020
20 Apr 2020 Other trial event New source identified and integrated(ClinicalTrials.gov: US National Institutes of Health;NCT04349098). Updated 20 Apr 2020
19 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 22 Apr 2020
14 Apr 2020 Other trial event Status changed from planning to not yet recruiting. Updated 21 Apr 2020
08 Apr 2020 Other trial event According to a Karyopharm Therapeutics media release, Komodo Health announced a collaboration with Karyopharm Therapeutics to accelerate clinical trial recruitment and site identification in an effort to speed patient access to a potential new treatment for COVID-19. Within hours of determining the project scope and appropriate patient cohort, Komodos Healthcare Map provided a snapshot of virology and infectious disease patterns to inform trial site identification. Updated 13 Apr 2020
08 Apr 2020 New trial record New trial record Updated 08 Apr 2020
07 Apr 2020 Other trial event According to a Karyopharm media release, the company plans to initiate a global randomized clinical trial for low dose oral selinexor in hospitalized patients with severe COVID-19. Selinexor, marketed as XPOVIO, is currently approved at higher doses by the Food and Drug Administration (FDA) as a treatment for patients with relapsed or refractory multiple myeloma Updated 08 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Karyopharm Therapeutics, Komodo Health. Komodo Health Teams Up with Karyopharm Therapeutics to Accelerate New Global Clinical Trial to Treat Patients with COVID-19. Media-Rel 2020;.

    Media Release
  3. Karyopharm Therapeutics. Karyopharm to Evaluate Low Dose Selinexor as a Potential Treatment for Hospitalized Patients with COVID-19. Media-Rel 2020;.

    Media Release
  4. PROMETRIKA, Karyopharm. PROMETRIKA and Karyopharm: Partners in Global COVID-19 Trial. Media-Rel 2020;.

    Media Release
  5. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  6. Karyopharm Therapeutics. Karyopharm Announces Dosing of First Patient in Randomized Study Evaluating Low Dose Selinexor in Patients with Severe COVID-19 . Media-Rel 2020;.

    Media Release
  7. Karyopharm Therapeutics. Karyopharm Reports Second Quarter 2020 Financial Results and Highlights Recent Company Progress. Media-Rel 2020;.

    Media Release
  8. Precision for Medicine. Precision For Medicine Partners With Karyopharm Therapeutics To Initiate New Global Clinical Trial To Treat Patients With COVID-19. Media-Rel 2020;.

    Media Release
Back to top