Evaluation of Activity and Safety of Two Regimens of Low Dose Oral Selinexor in Participants With Moderate or Severe COVID-19

A Phase 2 Randomized, Open-Label, Multicenter Study to Evaluate the Activity and Safety of Two Regimens of Low Dose Oral Selinexor in Patients With Moderate or Severe COVID-19

The main purpose of this study is to evaluate the activity, safety and reduction in mortality of two regimens of low dose selinexor (KPT-330) in patients with moderate or severe COVID-19.

Study Overview

• Status: Withdrawn
• Conditions: Coronavirus Infection
• Intervention / Treatment: Drug: Selinexor

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed laboratory diagnosis of SARS-CoV2 by standard approved reverse transcription polymerase chain reaction (RT-PCR) assay or equivalent approved testing (by local labs).
• Currently hospitalized and consented within the first 48 hours of hospitalization.
• Informed consent provided as above (patients must be dosed with study drug within 12 hours of consent).
• Has symptoms of moderate or severe COVID-19 as demonstrated by:

Moderate COVID-19:

1. Currently hospitalized and requiring medical care for COVID-19, and
2. Peripheral capillary oxygen saturation (SpO2, pulse oximetry) > 94% on room air at screening, and
3. Radiographic evidence of pulmonary infiltrates

Severe COVID-19:

1. 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 AND

2. 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, Oxygen saturation (SpO2) <93% on room air or requires > 2L/minute oxygen by NC in order to maintain SaO2 ≥93%, PaO2/FiO2 <300 millimeter per mercury (mm/hg)

   • Female patients of childbearing potential must have a negative serum pregnancy test at Screening and must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
   • Males who are sexually active must commit to use a highly effective method of contraception while receiving selinexor and for 3 months after the last selinexor dose, or consent to total sexual abstinence (abstinence must occur from enrollment and continue for 3 months after the last selinexor dose).

Exclusion Criteria:

• Evidence of critical COVID-19 based on:

  1. Respiratory failure (defined by endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, or clinical diagnosis of respiratory failure in setting of resource limitations)
  2. Septic shock (defined by SBP < 90 mm Hg, or Diastolic BP < 60 mm Hg)
  3. 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
• Concurrent anti-viral and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) are not permitted.

• Inadequate hematologic parameters as indicated by the following labs:

  1. Patients with severe neutropenia (ANC <1,000 x 10^9/liter [L]) or
  2. Thrombocytopenia (e.g., platelets <100,000 per microliter of blood)
• Inadequate renal function as indicated by creatinine clearance (CrCl) <20 milliliter per minute (mL/min) using the formula of Cockcroft and Gault.
• Inadequate hepatic function defined as AST or ALT > 5x the upper limit of normal OR serum direct bilirubin > 2.5x the upper limit of normal.
• Hyponatremia defined as sodium < 135 milliequivalents per liter (mEq/L).
• In the opinion of the Investigator, patients who are below their ideal body weight and would be unduly impacted by changes in their weight.
• Unable to take oral medication when informed consent is obtained.
• Patients with a legal guardian or who are incarcerated.
• Pregnant and breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selinexor 40mg; Participants will receive 40 milligram (mg) of selinexor as oral tablets on Days 1 and 3 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; 20 mg selinexor oral tablet.; Other Names: KPT-330; XPOVIO
Experimental: Selinexor 20mg; 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; 20 mg selinexor oral tablet.; Other Names: KPT-330; XPOVIO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with at Least a 2 Point Improvement in the Ordinal Scale	Baseline to Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Clinical Improvement (TTCI)	Up to Day 28
Overall Death Rate	Day 14, Day 28
Rate of Mechanical Ventilation	Up to Day 28
Time to Mechanical Ventilation	Up to Day 28
Overall Survival	Up to Day 28
Time to Improvement (2 points) in Clinical Measures Using the Ordinal Scale	Up to Day 28
Time to Intensive Care Unit (ICU) Admission	Up to Day 28
Rate of Intensive Care Unit (ICU) Admission	Up to Day 28
Length of Stay in Hospital	Up to Day 28
Percentage of Participants Discharged From Hospital	Up to Day 28
Length of Stay in Intensive Care Unit (ICU)	Up to Day 28
Duration of Oxygen Supplementation	Up to Day 28
Duration of Mechanical Ventilation	Up to Day 28
Time to Clinical Improvement in Participants ≤ 70 Years Old	Up to Day 28
Time to Clinical Improvement in Participants > 70 Years Old	Up to Day 28
Time to Clinical Improvement in Participants with Pre-existing Diseases	Up to Day 28
Change in Oxygenation Index	Up to Day 28
Time to Improvement of One Point Using WHO Ordinal Scale Improvement	Up to Day 28
Percentage of Participants Experiencing WHO Ordinal Scale Improvement of >1 point	Up to Day 28
Change from Baseline in C-reactive protein (CRP) Levels	Up to Day 28
Change from Baseline in Ferritin Levels	Up to Day 28
Change from Baseline in Lactate Dehydrogenase (LDH) Levels	Up to Day 28
Number of Participants with Adverse Events (AE)	From start of study drug administration up to follow-up (Day 30)

Collaborators and Investigators

• Sponsor: Karyopharm Therapeutics Inc
• Investigators: Study Director: Dayana Michel, Karyopharm Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2020
• Primary Completion (Actual): August 30, 2020
• Study Completion (Actual): August 30, 2020

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: XPORT-CoV-1002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No