E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe COVID-19 Infection |
Infección grave por COVID-19 |
|
E.1.1.1 | Medical condition in easily understood language |
Severe infection caused by a novel coronavirus COVID-19 |
Infección grave causada por el nuevo 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) |
Tiempo hasta mejora clnica (THMC) |
|
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] |
- Mortalidad - Variables clnicas adicionales - Determinar los efectos antiinflamatorios e immunolgicos de selinexor - Evaluar la seguridad y la tolerabilidad de selinexor |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age > or =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 > or = 24 breaths/minute OR b. Pulse Oxygen Saturation (SpO 2 ) < or = 94% without oxygen supplementation, OR c. PaO 2 /FiO 2 (fraction of inspired oxygen) < OR = 300 mm Hg 6. Concurrent anti-virals and/or anti-inflammatory agents (e.g., biologics, hydroxychloroquine) 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. |
1. Edad> o = 18 aos 2. Sospecha clnica y posterior confirmacin; o diagnstico de laboratorio que confirma que el paciente es positivo para el SARS-CoV2 por RT-PCR (por laboratorios locales) 3. Actualmente hospitalizado y con consentimiento otrogado dentro de las primeras 48 horas de hospitalizacin 4. Consentimiento informado provisto segn se indica arriba 5. Tiene sntomas de COVID-19 grave segn a. Frecuencia respiratoria > o = 24 respiraciones / minuto O b. Saturacin de oxgeno (SpO 2) < o = 94% sin suplementacin de oxgeno, O C. PaO 2 / FiO 2 (fraccin de oxgeno inspirado) < o = 300 mm Hg 6. Los antivirales y / o antiinflamatorios concurrentes (por ejemplo, productos biolgicos, hidroxicloroquina) estn permitidos al inicio del estudio para los pacientes que participan en el estudio 7. Las pacientes en edad frtil deben tener una prueba de embarazo en suero negativa en la visita de seleccin. Las mujeres con potencial de procrear y pacientes masculinos frtiles que son sexualmente activos con una mujer en edad frtil debe utilizar mtodos anticonceptivos altamente efectivos durante todo el estudio y durante 1 semana despus de la ltima dosis de tratamiento del estudio. |
|
E.4 | Principal exclusion criteria |
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 |
1. Evidencia de COVID-19 crtica basada en: a. Se requiere ventilacin mecnica (invasiva o no invasiva) o ECMO o hemofiltracin b. Shock 2. En opinión del investigador, es poco probable que sobreviva al menos 48 horas despus de la deteccin o estime ventilacin mecnica dentro de las 48 horas. 3. Inadecuada funcin renal y heptica segn lo indicado por los siguientes valores de laboratorio: a. aclaramiento de creatinina <20 ml / min si. Aspartato transaminasa (AST) o alanina transaminasa (ALT)> 5 x lmite superior de la normalidad (LSN) 4. Incapaz de tomar medicacin oral |
|
E.5 End points |
E.5.1 | Primary end point(s) |
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 |
Ausencia de fiebre: temperatura oral < 38 C durante 24 horas sin antipirticos (paracetamol) Y uno de los siguientes: - Frecuencia Respiratoria < o = 24/minuto O - Saturacin de oxgeno > o = 94% en aire ambiente O - Alta del hospital |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the study |
A lo largo del estudio |
|
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 |
• Mortalidad por todas las causas a los 28 das despus de la aleatorizacin • Tasa y duracin de la ventilacin mecnica. • Duracin de la suplementacin con oxgeno. • Duracin de la hospitalizacin. • Duracin de la estancia en la UCI • Tiempo hasta el fracaso clnico, definido como el tiempo hasta la muerte, ventilacin mecnica o ingreso en la UCI • Puntuacin de la enfermedad de Vivi • THMCen pacientes < o =70 aos • THMC en pacientes > 70 aos • THMC en pacientes con inmunodeficiencia, hipertensin o enfermedad pulmonar (antecedentes de tabaquismo o EPOC de moderada a grave) • Efectos sobre los niveles de protena C reactiva (PCR) • Efectos sobre los niveles de ferritina. • Efectos sobre la lactato deshidrogenasa (LDH) • Listado y documentacin de frecuencia y gravedad de los efectos adversos. |
|
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 |
Mortalidad a los 28 das Restos de variables durante el curso del estudio |
|
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 |
inclusión estratificada por: región y uso de terapias concomitantes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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. |
Se considerará que un paciente ha completado el estudio si completa hasta 14 días de tratamiento (o 28 días a discreción del médico) |
|
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 |