Clinical trial NCT04349098: Evaluation of Activity and Safety of Oral Selinexor in Participants With Severe COVID-19 Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronavirus Infection
Keywords: COVID-19
SARS-CoV-2
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2020-04-16
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With At-least a 2-Point Improvement in Ordinal Scale
timeFrame: Baseline up to Day 14
Secondary outcomes:
measure: Percentage of Participants With at Least a 2-Point Improvement in the Ordinal Scale up to Day 7
timeFrame: Baseline up to Day 7
measure: Percentage of Participants With at Least a 1-Point Improvement in the Ordinal Scale
timeFrame: Baseline up to Day 7 and 14
measure: Time to Clinical Improvement of 2-points Using Ordinal Scale (TTCI-2)
timeFrame: Baseline up to Day 28
measure: Overall Death Rate
timeFrame: Baseline up to Day 28
measure: Rate of Mechanical Ventilation (RMV)
timeFrame: Baseline up to Day 28
measure: Rate of Intensive Care Unit (ICU) Admission
timeFrame: Baseline up to Day 28
measure: Length of Hospitalization
timeFrame: Baseline up to Day 67
measure: Change From Baseline in C-reactive Protein (CRP) Levels
timeFrame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
measure: Change From Baseline in Ferritin Levels
timeFrame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
measure: Change From Baseline in Lactate Dehydrogenase (LDH) Levels
timeFrame: Baseline, Day 3, 5, 8, 12, 15, 19, 22 and 26
measure: Changes From Baseline in Blood Plasma Cytokines Levels-Interleukin-6 (IL-6)
timeFrame: Baseline, Day 3, 5, 8, 12, 15, 22 and 26
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From start of study drug administration up to Day 58
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland
state: California
city: Sacramento
country: United States
facility: UC Davis Health
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Sacramento
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Norton Healthcare
state: Kentucky
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos
state: Michigan
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: Royal Oak
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute-Atrium Health University City
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Scott & White Dallas
state: Texas
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation (Puget Sound)
state: Washington
city: Vienna
country: Austria
facility: Hospital Hietzing, 2. Medical department - Center for Diagnosis and Therapy of Rheumatic Diseases
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Lyon
country: France
facility: CHU Lyon
city: Nantes
country: France
facility: CHU Nantes
city: Jerusalem
country: Israel
facility: Hadassah MC
city: Petah Tiqva
country: Israel
facility: Hasharon Medical Center
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Salamanca
country: Spain
facility: Servicio de Medicina Interna, Hospital Universitario de Salamanca, Universidad de Salamanca
city: Kent
country: United Kingdom
facility: Princess Royal University Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
Study officials:
References: