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 Infectio

Phase 1

Conditions: Severe COVID-19 Infection
MedDRA version: 20.0Level: LLTClassification code 10051905Term: Coronavirus infectionSystem Organ Class: 100000004862
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2020-001411-25-FR

Lead Sponsor: Karyopharm Therapeutics Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 230

Inclusion Criteria

Patients are eligible to be included in the study only if they meet all of the following criteria:
1. Age =18 years
2. Clinically suspected and subsequently confirmed; or laboratory diagnosis confirming patient is positive for SARS-CoV2 nucleic acid by RT-PCR (by local labs)
3. Currently hospitalized and consented within the first 48 hours of hospitalization
4. Informed consent provided as above
5. Has symptoms of severe COVID-19 as demonstrated by:
a. Respiratory rate =24 breaths/minute OR
b. Pulse Oxygen Saturation (SpO2) =94% without oxygen inhalation, OR
c. PaO2/FiO2 (fraction of inspired oxygen) =300 mm Hg
6. Concurrent anti-virals and/or anti-inflammatory agents are permitted at baseline for patients entering the study
7. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment. Highly effective methods of contraception are listed in Protocol Section 8.3.1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180

Exclusion Criteria

Patients are excluded from the study if any of the following criteria apply:
1. Evidence of critical COVID-19 based on:
a. Mechanical ventilation (invasive or non-invasive) or ECMO or hemofiltration required
b. Shock
2. In the opinion of the investigator, unlikely to survive for at least 48 hours from screening or anticipate mechanical ventilation within 48 hours
3. Inadequate renal and liver function as indicated by the following labs:
a. Creatinine clearance (CCL) <20 mL/min
b. Aspartate transaminase (AST) or alanine transaminase (ALT) >5 x upper limit of normal (ULN)
4. Unable to take oral medication

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Time to Clinical Improvement (TTCI);Secondary Objective: - Mortality<br>- Additional Clinical Endpoints<br>- To determine the anti-inflammatory and immune effect of selinexor<br>- To assess safety and tolerability of selinexor [time frame: up to 28 days];Primary end point(s): Absence of fever, oral temperature <38°C x 24 hours without antipyretics (acetaminophen) AND one of the following:<br>- Respiratory rate =24/minute OR<br>- Oxygen saturation >94% on room air OR<br>- Hospital discharge;Timepoint(s) of evaluation of this end point: Throughout the study

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • All-cause mortality by D 28 after randomization<br>• Rate of mechanical ventilation<br>• Length of hospitalization<br>• Length of ICU stay<br>• Duration of oxygen supplementation<br>• Duration of mechanical ventilation<br>• Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission<br>• Vivi Disease Score<br>• TTCI in patients =70 years old<br>• TTCI in patients >70 years old<br>• TTCI in patients that are immune compromised, have hypertension, or have pulmonary disease (smoking history or moderate to severe COPD)<br>• Reduction of C-reactive protein (CRP)<br>• Reduction in ferritin levels<br>• LDH<br>• Listing and documentation of frequency and severity of adverse effects;Timepoint(s) of evaluation of this end point: Mortality at day 28<br>Rest of endpoints during the course of the study

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