E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe COVID-19 Infection |
|
E.1.1.1 | Medical condition in easily understood language |
Severe infection caused by a novel coronavirus COVID-19 |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 100000004862 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Time to Clinical Improvement (TTCI) |
|
E.2.2 | Secondary objectives of the trial |
- Mortality
- Additional Clinical Endpoints
- To determine the anti-inflammatory and immune effect of selinexor
- To assess safety and tolerability of selinexor [time frame: up to 28 days] |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Absence of fever, oral temperature <38°C x 24 hours without antipyretics (acetaminophen) AND one of the following:
− Respiratory rate ≤24/minute OR
− Oxygen saturation >94% on room air OR
− Hospital discharge |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• All-cause mortality by D 28 after randomization
• Rate of mechanical ventilation
• Length of hospitalization
• Length of ICU stay
• Duration of oxygen supplementation
• Duration of mechanical ventilation
• Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission
• Vivi Disease Score
• TTCI in patients ≤70 years old
• TTCI in patients >70 years old
• TTCI in patients that are immune compromised, have hypertension, or have pulmonary disease (smoking history or moderate to severe COPD)
• Reduction of C-reactive protein (CRP)
• Reduction in ferritin levels
• LDH
• Listing and documentation of frequency and severity of adverse effects |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Mortality at day 28
Rest of endpoints during the course of the study |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
enrollment stratified by: Region and Use of concomitant therapies |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Canada |
France |
Germany |
India |
Israel |
Italy |
Malaysia |
Spain |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
A patient will be considered having completed the study if he/she has completed up to 14 days of therapy (or 28 days per treating physician’s discretion) or died. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |