COVID-19 ACTT-EU/UK

1. The overall objective of the study is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19.
2. Subject clinical status (8-point ordinal scale) at Day 15 is the default primary endpoint.

• Evaluate the clinical efficacy of different investigational therapeutics as compared to the control arm as assessed by:
• Clinical Severity
  • Ordinal scale:
    • Time to an improvement of one category and two categories from Day 1 (baseline) using an ordinal scale.
    • Subject clinical status using ordinal scale at Days 3, 5, 8, 11, 22, and29.
    • Mean change in the ordinal scale from Day 1 to Days 3, 5, 8, 11, 15, 22, and 29.
• [...]

1. Admitted to a hospital with symptoms suggestive of COVID-19 infection.
2. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
4. Male or non-pregnant female adult ≥18 years of age at time of enrollment.
5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen collected < 72 hours prior to randomization.
6. Illness of any duration, and at least one of the following:
   • Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
   • Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air, OR
   • Requiring supplemental oxygen, OR
   • Requiring mechanical ventilation.
7. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29.
8. Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2. through Day 29.

1. ALT/AST > 5 times the upper limit of normal.
2. Estimated glomerular filtration rate (eGFR) < 50 or requiring dialysis.
3. Pregnancy or breast feeding.
4. Anticipated transfer to another hospital which is not a study site within 72 hours.
5. Allergy to any study medication.

Initially, the trial will have two arms and subjects will be randomized to receive either active product or placebo as follows:

• Remdesivir will be administered as a 200 mg intravenous (IV) loading dose on Day 1, followed by a 100 mg once-daily IV maintenance dose for the duration of the hospitalization up to a 10-day total course.
• A placebo of normal saline will be given at an equal volume at the same schedule. IV bags of study treatment will be covered to mask the slight color difference between the remdesivir solution and placebo to maintain the study blind.