Eine multizentrische, adaptive, randomisierte, Placebo-kontrollierte Doppelblindstudie zur Wirksamkeit, Sicherheit und Verträglichkeit von experimentellen Therapeutika zur Behandlung von COVID-19 bei hospitalisierten Patienten

Biological: LY3819253;Drug: Placebo;Biological: Remdesivir;Biological: VIR-7831;Biological: BRII-196/BRII-198;Biological: AZD7442;Drug: MP0420;Drug: PF-07304814

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

- Signed informed consent.

- Positive test for COVID-19 and progressive disease suggestive of ongoing COVID-19
infection.

- Symptoms of COVID-19 for = 12 days.

- Require admission to hospital for acute medical care (not for purely public health or
quarantine purposes).

Exclusion Criteria:

- Patients who have received plasma from a person who recovered from COVID-19 or who
have received neutralizing monoclonal antibodies at any time prior to hospitalization.

- Patients not willing to abstain from participation in other COVID-19 treatment trials
until after Day 5 of the study. Co-enrollment in certain trials that compare
recommended Standard of Care treatments may be allowed, based on the opinion of the
study leadership team.

- Any condition which, in the opinion of the responsible investigator, participation
would not be in the best interest of the participant or that could prevent, limit, or
confound the protocol-specified assessments.

- Patients considered unable to participate in study procedures.

- Women of child-bearing potential who are not already pregnant at study entry and who
are unwilling to acknowledge strong advice to abstain from sexual intercourse with men
or practice appropriate contraception through 18 months of the study.

- Women of child-bearing potential who are unwilling to acknowledge the strong advice to
abstain from sexual intercourse with men or practice appropriate contraception through
5 weeks of the study (PF-07304814 investigational agent).

- Pregnant women (PF-07304814 investigational agents).

- Nursing mothers (PF-07304814 investigational agents).

- Men who are unwilling to acknowledge the strong advice to abstain from sexual
intercourse with women of child-bearing potential or to use barrier contraception
through 18 months of the study.

- Men who are unwilling to acknowledge the strong advice to abstain from sexual
intercourse with women of child-bearing potential or to use barrier contraception
through 5 weeks of the study (PF-07304814 investigational agent).

- Presence at study enrollment of any of the following:

1. stroke

2. meningitis

3. encephalitis

4. myelitis

5. myocardial ischemia

6. myocarditis

7. pericarditis

8. symptomatic congestive heart failure

9. arterial or deep venous thrombosis or pulmonary embolism

- Current or imminent requirement for any of the following:

1. invasive mechanical ventilation

2. ECMO (extracorporeal membrane oxygenation)

3. Mechanical circulatory support

4. vasopressor therapy

5. commencement of renal replacement therapy at this admission (i.e. not patients on
chronic renal replacement therapy).

- Participants with moderate to severe hepatic impairment (i.e. Child-Pugh class B or C)
or acute liver failure (PF-07304814 investigational agent).

- Participants receiving any medications or substances that are strong inhibitors or
inducers of cytochrome P450 (CYP) 3A4 (PF-07304814 investigational agent).

- Patients will be excluded if taking drugs which have a narrow therapeutic window that
are substrates of CYP3A4, including but not limited to: astemizole, cisapride,
cyclosporine, dihydroergotamine, ergotamine, pimozide, quinidine, sirolimus,
tacrolimus, and terfenadine (PF-07304814 investigational agent).

- Patients with a history of deep vein thrombosis or pulmonary thrombotic embolism
(Prior to initial futility assessment of PF-07304814 investigational agent).