Phase 3
Completed N=969
Adaptive COVID-19 Treatment Trial 3 (ACTT-3)
Source: ClinicalTrials.gov NCT04492475 ↗Enrolled (actual)
969
Serious AEs
16.2%
Results posted
Nov 2021
Primary outcomePrimary: Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 — 5.0; 5.0 Days — p=0.880
◆ Published Evidence
Highly cited
306citations · ~61 / year
COVID-19 and Solid Organ Transplantation: A Review Article.
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.
Linked Publications (4)
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COVID-19 and Solid Organ Transplantation: A Review Article.
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Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.
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SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
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Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 |
5.0; 5.0 | 0.880 |
| PRIMARY Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Race |
8.0; 8.0; 4.0; 4.0; 4.0; 5.0 | — |
| PRIMARY Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Ethnicity |
5.0; 5.0; 6.0; 5.0 | — |
| PRIMARY Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Sex |
5.0; 5.0; 4.5; 5.0 | — |
| SECONDARY Change From Baseline in Alanine Aminotransferase (ALT) |
17.6; 2.6; 5.0; 10.9; 41.4; 1.5 | — |
| SECONDARY Change From Baseline in Aspartate Aminotransferase (AST) |
8.0; -5.1; -4.6; -10.0; 13.2; -11.3 | — |
| SECONDARY Change From Baseline in C-reactive Protein (CRP) |
-44.3; -46.6; -40.0; -37.6; -59.0; -55.6 | — |
| SECONDARY Change From Baseline in Creatinine |
-0.076; 0.054; -0.069; -0.074; -0.122; 0.121 | — |
| SECONDARY Change From Baseline in D-dimer Concentration |
-0.2; 2.2; 0.1; 0.5; -0.2; -4.0 | — |
| SECONDARY Change From Baseline in Hemoglobin |
-0.19; -0.14; -0.20; -0.10; -0.04; -0.47 | — |
| SECONDARY Change From Baseline in Prothrombin International Normalized Ratio (INR) |
-0.03; 0.05; 0.07; -0.08; -0.03; 0.02 | — |
| SECONDARY Change From Baseline in Platelets |
46.5; 38.4; 57.6; 58.8; 82.1; 63.9 | — |
| SECONDARY Change From Baseline in Total Bilirubin |
-0.08; 0.07; -0.07; 0.03; -0.07; 0.03 | — |
| SECONDARY Change From Baseline in White Blood Cell Count (WBC) |
-0.166; 0.255; 0.720; 0.856; 0.486; 0.434 | — |
| SECONDARY Change From Baseline in Neutrophils |
-0.622; -0.324; 0.329; 0.479; -0.307; -0.123 | — |
| SECONDARY Change From Baseline in Lymphoctyes |
0.301; 0.237; 0.227; 0.137; 0.492; 0.289 | — |
| SECONDARY Change From Baseline in Monocytes |
0.157; 0.112; 0.127; 0.179; 0.229; 0.136 | — |
| SECONDARY Change From Baseline in Basophils |
0.000; 0.003; 0.001; 0.002; 0.002; 0.011 | — |
| SECONDARY Change From Baseline in Eosinophils |
0.011; 0.014; 0.013; 0.006; 0.016; 0.037 | — |
| SECONDARY Change in National Early Warning Score (NEWS) From Baseline |
-0.7; 1.0; -0.6; -0.7; -1.1; 1.6 | — |
| SECONDARY Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) |
38.9; 60.0; 31.7; 36.4 | — |
| SECONDARY Percentage of Participants Reporting Serious Adverse Events (SAEs) |
14.7; 60.0; 13.3; 24.2 | — |
| SECONDARY Duration of Hospitalization |
6; 28; 6; 10; 6; 16.5 | — |
| SECONDARY Duration of Invasive Mechanical Ventilation |
28; 23; 26.5; 28; 14; 19 | — |
| SECONDARY Duration of New Non-invasive Ventilation or High Flow Oxygen Use |
5; 6; 4; 5 | — |
| SECONDARY Duration of New Oxygen Use |
3; 3; 3; 3 | — |
| SECONDARY Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
28; 23; 26.5; 28; 14; 19 | — |
| SECONDARY Duration of Non Invasive Ventilation or High Flow Oxygen Use |
5; 6; 6; 5.5; 4; 4 | — |
| SECONDARY Duration of Oxygen Use |
6; 28; 7.5; 21.5; 6; 27.5 | — |
| SECONDARY Number of Participants With Discontinuation or Temporary Suspension of Study Product Administration |
400; 25; 382; 22; 337; 13 | — |
| SECONDARY Proportion of Participants With New Non-invasive Ventilation or High Flow Oxygen Use |
0.15; 0.15 | — |
| SECONDARY Proportion of Participants With New Oxygen Use |
0.51; 0.57 | — |
| SECONDARY Proportion of Participants With New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
0.04; 0.54; 0.05; 0.15 | — |
| SECONDARY Mean Change From Baseline in the Ordinal Scale |
0.1; 0.1; 0.1; 0.0; -0.1; 0.3 | — |
| SECONDARY Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 for Participants With Baseline Ordinal Score 4 and 5 |
1.3; 2.0; 2.2; 3.1; 1.1; 1.8 | — |
| SECONDARY Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 1 |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 3 |
0.0; 0.0; 0.2; 0.0; 0.9; 17.1 | — |
| SECONDARY Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 5 |
0.2; 2.9; 0.7; 0.0; 1.8; 37.1 | — |
| SECONDARY Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 8 |
0.2; 5.7; 0.9; 5.9; 2.7; 45.7 | — |
| SECONDARY Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 11 |
0.9; 8.6; 1.6; 5.9; 3.1; 42.9 | — |
| SECONDARY Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 15 |
1.3; 14.3; 2.0; 8.8; 2.2; 31.4 | — |
| SECONDARY Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 22 |
2.2; 17.1; 2.5; 11.8; 1.8; 22.9 | — |
| SECONDARY Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 29 |
3.1; 20.0; 2.9; 11.8; 1.8; 17.1 | — |
| SECONDARY 14-day Participant Mortality |
0.02; 0.02 | — |
| SECONDARY 28-day Participant Mortality |
0.05; 0.03 | — |
| SECONDARY Time to an Improvement of One Category Using an Ordinal Scale |
12.0; 15.0; 12.0; 5.0 | — |
| SECONDARY Time to an Improvement of Two Categories Using an Ordinal Scale |
13.0; NA; 13.0; 14.0 | — |
| SECONDARY Time to Discharge or to a National Early Warning Score (NEWS) of </= 2 and Maintained for 24 Hours, Whichever Occurs First |
4.0; NA; 4.0; 9.0 | — |
| SECONDARY Time to Recovery for Patients With a Baseline Ordinal Score of 4 and 5 |
5.0; 5.0 | — |
Eligibility Criteria
Inclusion Criteria
- Admitted to a hospital with symptoms suggestive of COVID-19.
- Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
- Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
- Male or non-pregnant female adult > / = 18 years of age at time of enrollment.
- 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 but 5 times the upper limits of normal.
- Total white cell blood cell count (WBC) <1500 cells/microliter.
- Platelet count <50,000/microliter.
- History of chronic liver disease (e.g., jaundice, ascites, hepatic encephalopathy, history of bleeding esophageal or gastric varices). No laboratory testing is needed.
- 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).
- Allergy to any study medication including history of hypersensitivity to natural or recombinant interferon beta or human albumin.
- 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.
- Received three or more doses of remdesivir, including the loading dose, outside of the study for COVID-19.
- Received convalescent plasma or intravenous immunoglobulin [IVIg] for the treatment of COVID-19.
- 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).
- 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.
- Prior enrollment in ACTT-3.
Data sourced from ClinicalTrials.gov (NCT04492475) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.