Adaptive COVID-19 Treatment Trial 3 (ACTT-3)
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Interferon beta-1a; Placebo; Remdesivir
Intervention description: Rebif (R) is a purified 166 amino acid human interferon beta glycoprotein with an amino acid sequence identical to natural fibroblast derived human interferon beta. Each 0.5 mL prefilled syringe contains 44 mcg of interferon beta-1a, 4 mg human albumin, USP; 27.3 mg mannitol, USP; 0.4 mg sodium acetate; and water for injection, USP.; The interferon beta-1a placebo contains either 0.5 mL 0.9% normal saline or 0.5 mL sterile water for injection.; Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a; Remdesivir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 969.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Adaptive; COVID-19; Efficacy; Multicenter; novel coronavirus; Safety

Summary:

      ACTT-3 will evaluate the combination of interferon beta-1a and remdesivir compared to
      remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are
      discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For
      discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain
      safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for
      secondary research as well as clinical outcome data. However, infection control or other
      restrictions may limit the ability of the subject to return to the clinic. In this case,
      these visits may be conducted by phone, and only clinical data will be obtained. The Day 22
      visit does not have laboratory tests or collection of samples and is conducted by phone. The
      primary outcome is time to recovery by Day 29.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Admitted to a hospital with symptoms suggestive of COVID-19.

          2. Subject (or legally authorized representative) provides 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 polymerase chain
             reaction (PCR) or other commercial or public health assay in any respiratory specimen
             or saliva, as documented by either of the following:

               -  PCR or other assay positive in sample collected < 72 hours prior to
                  randomization; OR

               -  PCR or other assay positive in sample collected >/= 72 hours but < 7 days prior
                  to randomization AND progressive disease suggestive of ongoing SARS-CoV-2
                  infection.

             Note: if written documentation of the positive test result is not available at
             enrollment (e.g., report from other institution), the subject may be enrolled but the
             PCR should be repeated at the time of enrollment.

          6. Illness of any duration, and at least one of the following:

               -  Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR

               -  SpO2 < / = 94% on room air, OR

               -  Requiring supplemental oxygen.

          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 (both pharmacologic and other
             types of interventions) for the treatment of COVID-19 through Day 29.

        Exclusion Criteria:

          1. Anticipated discharge from the hospital or transfer to another hospital which is not a
             study site within 72 hours.

          2. Subject meets criteria for ordinal scale category 6 or 7 at the time of screening.

          3. Subject has a positive test for influenza virus during this current hospital
             admission.

          4. Subjects with an estimated glomerular filtration rate (eGFR) < 30 mL/min are excluded
             unless in the opinion of the PI, the potential benefit of receiving remdesivir
             outweighs the potential risk of study participation.

          5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper
             limits of normal.

          6. Total white cell blood cell count (WBC) <1500 cells/microliter.

          7. Platelet count <50,000/microliter.

          8. History of chronic liver disease (e.g., jaundice, ascites, hepatic encephalopathy,
             history of bleeding esophageal or gastric varices). No laboratory testing is needed.

          9. Pregnancy or breast feeding (lactating women who agree to discard breast milk from Day
             1 until three weeks after the last study product is given are not excluded).

         10. Allergy to any study medication including history of hypersensitivity to natural or
             recombinant interferon beta or human albumin.

         11. Patient has a chronic or acute medical condition or is taking a medication that cannot
             be discontinued at enrollment, that in the judgement of the PI, places them at
             unacceptable risk for a poor clinical outcome if they were to participate in the
             study.

         12. Received three or more doses of remdesivir, including the loading dose, outside of the
             study for COVID-19.

         13. Received convalescent plasma or intravenous immunoglobulin [IVIg] for the treatment of
             COVID-19.

         14. Received any interferon product within two weeks of screening, either for the
             treatment of COVID-19 or for a chronic medical condition (e.g., multiple sclerosis,
             HCV infection).

         15. Received any of the following in the two weeks prior to screening as treatment of
             COVID-19:

               -  Small molecule tyrosine kinase inhibitors (e.g. baricitinib, imatinib, gefitinib,
                  acalabrutinib, etc.);

               -  Monoclonal antibodies targeting cytokines (e.g., TNF inhibitors,
                  anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], etc.);

               -  Monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19.

         16. Prior enrollment in ACTT-3.