Resumen

Se necesitan tratamientos para mejorar los resultados de los pacientes hospitalizados por COVID-19, incluyendo agentes antivirales de acción directa (AAD) que mitiguen la patología generada por la replicación viral continua. Este ensayo clínico evaluará S-217622 (ensitrelvir), un inhibidor de la proteasa 3C-símil anti-SARS-CoV-2 (IP) desarrollado por Shionogi & Co. Ltd. El diseño del estudio es un ensayo clínico aleatorizado, controlado con placebo, multicéntrico e internacional que evaluará la eficacia clínica de ensitrelvir administrado como complemento al tratamiento estándar (TE) en pacientes internados por COVID-19. El TE será determinado por las guías locales vigentes y podrá incluir AAD adicionales (por ejemplo, remdesivir) y estrategias de tratamiento inmunomodulador. Ciertos tratamientos del TE serán preespecificados antes de la aleatorización.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Age ≥18 years.
Informed consent for trial participation.
Hospital admission (or boarding in an emergency department or other area awaiting hospital admission) with signs and/or symptoms of a respiratory infection.
Confirmation of SARS-CoV2 infection by nucleic acid test (NAT) or equivalent non- NAT test \[list of approved tests is in the PIM\] collected within the prior 14 days.
Onset of symptoms attributable to SARS-CoV2 infection occurred within 14 days before randomization.
Hospitalized for the management of COVID-19, with signs and/or symptoms suggestive of lower respiratory tract infection.

Criterios de exclusión

The patient is expected to be discharged from the hospital within the next 24 hours.
Medical condition other than the acute respiratory infection (and its manifestations) that is likely to result in death within 7 days of randomization.
Use of a strong CYP3A inducer within 14 days prior to enrollment
Moribund condition, defined as prior cardiac arrest during this hospitalization and life expectancy less than 48 hours of randomization.
Patient undergoing comfort care measures only such that treatment focuses on end-of- life symptom management over prolongation of life.
Expected inability or unwillingness to participate in study procedures.
In the opinion of the investigator, participation in a trial is not in the best interest of the patient.
Allergy to investigational agent or vehicle
Use of a concomitant medication that is contraindicated due to a drug-drug interaction with S-217622
Moderate to severe hepatic impairment (i.e., Child-Pugh class B or C) or acute liver failure.
Known estimated glomerular filtration rate (eGRF) \<30 mL/min/1.73m 2
Continuous renal replacement therapy or chronic dialysis
Current pregnancy
Current breastfeeding and unwillingness to defer breastfeeding for 30 days after the last dose of investigational agent.
Women of child-bearing potential who are unwilling to abstain from sexual intercourse with men or practice appropriate contraception through 30 days from the last dose of the investigational agent.
Men who are unwilling to abstain from sexual intercourse with women of child- bearing potential or to use barrier contraception through 30 days from the last dose of the investigational agent.
Inability to take investigational agent in tablet form by mouth.

Intervenciones

drug

Shionogi Protease Inhibitor (S-217622)

S-217622 (ensitrelvir) is an oral anti-SARS-CoV2 PI that does not require ritonavir co-administration The dose is 375/125 (375 mg on Day 0, followed by 125 mg daily on Days 1-4).

drug

placebo

Placebo is an oral tablet administered once (3 tabs) on Day 0 and once (1 tab) daily on days 1-4, 5-day course.

Ubicaciones

Instituto Medico Platense (Site 611-025)

La Plata, Buenos Aires, Argentina

Sanatorio Allende (Site 611-030)

Córdoba, Córdoba Province, Argentina

Clínica Central S.A. (611-028)

Villa Regina, Río Negro Province, Argentina

Sanatorio Británico S.A. (611-027)

Rosario, Santa Fe Province, Argentina

CEMIC (Site 611-021)

Buenos Aires, Argentina

Hospital Rawson (Site 611-012)

Córdoba, Argentina

Sanatorio Medico de Diagnostico y Tratamiento (611-029)

Santa Fe, Argentina

Estrategias y Tratamientos para Infecciones Respiratorias y Emergencias Virales (STRIVE): Inhibidor de Proteasa de Shionogi