drugset / Trial / NCT04501978
ACTIV-3: Therapeutics for Inpatients With COVID-19
Phase 3
Completed
2753 enrolled
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections · collabAstraZeneca · collabBrii Biosciences Limited · collabCardiothoracic Surgical Trials Network · collabEli Lilly and Company · collabGlaxoSmithKline · collabInternational Network for Strategic Initiatives in Global HIV Trials (INSIGHT) · collabKirby Institute · collabMedical Research Council · collabMolecular Partners AG · collabNational Heart, Lung, and Blood Institute (NHLBI) · collabPfizer · collabPrevention and Early Treatment of Acute Lung Injury · collabUS Department of Veterans Affairs · collabUniversity of Copenhagen · collabUniversity of Minnesota · collabVir Biotechnology, Inc. · collabWashington D.C. Veterans Affairs Medical Center · collab
RandomizedParallel-groupTriple-blindTreatment
Summary
This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.
Timeline
- Start
- 2020-08-04
- Primary completion
- 2022-04-06
- Completion
- 2023-07-14
Outcome
Missed primary endpoint
release “today announced that its antibodies BRII-196 and BRII-198 failed to meet pre-specified efficacy criteria permitting expansion into the Phase 3 component of ACTIV-3.” reads as missed primary endpoint briibio.com ↗
release “planned futility analysis of ensovibep in the NIH-sponsored ACTIV-3 clinical study did not meet the thresholds required to continue enrollment” reads as unknown molecularpartners.com ↗
Publications
- Slotkin R, Kyriakides TC, Yu V, Chen X, Kundu A, Gupta S. CoVimmune COVID-19 Immunity Calculator: Web Application Development and Validation Study. JMIR Form Res. 2025 Apr 22;9:e59467. doi: 10.2196/59467.
- Mourad A, Grandits GA, Siegel LK, Engen N, Barkauskas C, Eriobu N, Jain MK, Jensen TO, Ginde A, Higgs E, Knox DB, Kitonsa J, Kim K, Malin JJ, Rapti V, Price DA, Mena Lora AJ, Mathews G, Mylonakis E, Murray TA, Sandkovsky U, Paredes R, Ramachandruni S, Reilly C, Vock D, Williamson JC, Young BE, Self WH, Lundgren J, Holland TL; INSIGHT ACTIV-3/TICO Study Group and the STRIVE Network. Long-term outcomes of passive immunotherapy for COVID-19: a pooled analysis of a large multinational platform randomized clinical trial. Clin Microbiol Infect. 2025 Jun;31(6):1053-1060. doi: 10.1016/j.cmi.2025.02.002. Epub 2025 Feb 6.
- Jensen TO, Grandits GA, Jain MK, Murray TA, Grund B, Shaw-Saliba K, Matthay MA, Abassi M, Ardelt M, Baker JV, Chen P, Dewar RL, Goodman AL, Hatlen TJ, Highbarger HC, Holodniy M, Lallemand P, Laverdure S, Leshnower BG, Looney D, Moschopoulos CD, Mugerwa H, Murray DD, Mylonakis E, Nagy-Agren S, Rehman MT, Rupert A, Stevens RA, Turville S, Weintrob A, Wick K, Lundgren J, Ko ER; ACTIV-3/TICO Study Group. Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19. J Infect Dis. 2024 Mar 14;229(3):671-679. doi: 10.1093/infdis/jiad446.
- ACTIV-3/TICO Study Group; Barkauskas C, Mylonakis E, Poulakou G, Young BE, Vock DM, Siegel L, Engen N, Grandits G, Mosaly NR, Vekstein AM, Rogers R, Shehadeh F, Kaczynski M, Mylona EK, Syrigos KN, Rapti V, Lye DC, Hui DS, Leither L, Knowlton KU, Jain MK, Marines-Price R, Osuji A, Overcash JS, Kalomenidis I, Barmparessou Z, Waters M, Zepeda K, Chen P, Torbati S, Kiweewa F, Sebudde N, Almasri E, Hughes A, Bhagani SR, Rodger A, Sandkovsky U, Gottlieb RL, Nnakelu E, Trautner B, Menon V, Lutaakome J, Matthay M, Robinson P, Protopapas K, Koulouris N, Kimuli I, Baduashvili A, Braun DL, Gunthard HF, Ramachandruni S, Kidega R, Kim K, Hatlen TJ, Phillips AN, Murray DD, Jensen TO, Padilla ML, Accardi EX, Shaw-Saliba K, Dewar RL, Teitelbaum M, Natarajan V, Laverdure S, Highbarger HC, Rehman MT, Vogel S, Vallee D, Crew P, Atri N, Schechner AJ, Pett S, Hudson F, Badrock J, Touloumi G, Brown SM, Self WH, North CM, Ginde AA, Chang CC, Kelleher A, Nagy-Agren S, Vasudeva S, Looney D, Nguyen HH, Sanchez A, Weintrob AC, Grund B, Sharma S, Reilly CS, Paredes R, Bednarska A, Gerry NP, Babiker AG, Davey VJ, Gelijns AC, Higgs ES, Kan V, Matthews G, Thompson BT, Legenne P, Chandra R, Lane HC, Neaton JD, Lundgren JD. Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial. Ann Intern Med. 2022 Sep;175(9):1266-1274. doi: 10.7326/M22-1503. Epub 2022 Aug 9.
- ACTIV-3-Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2022 Oct;10(10):972-984. doi: 10.1016/S2213-2600(22)00215-6. Epub 2022 Jul 8.
- Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.
- Wick KD, Siegel L, Neaton JD, Oldmixon C, Lundgren J, Dewar RL, Lane HC, Thompson BT, Matthay MA; ACTIV-3/TICO study group. RAGE has potential pathogenetic and prognostic value in nonintubated hospitalized patients with COVID-19. JCI Insight. 2022 May 9;7(9):e157499. doi: 10.1172/jci.insight.157499.
- ACTIV-3/Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. Lancet Infect Dis. 2022 May;22(5):622-635. doi: 10.1016/S1473-3099(21)00751-9. Epub 2021 Dec 23.
- ACTIV-3/TICO Bamlanivimab Study Group; Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, Brown SM, Knowlton KU, Self WH, Files DC, Jain MK, Benfield T, Bowdish ME, Leshnower BG, Baker JV, Jensen JU, Gardner EM, Ginde AA, Harris ES, Johansen IS, Markowitz N, Matthay MA, Ostergaard L, Chang CC, Goodman AL, Chang W, Dewar RL, Gerry NP, Higgs ES, Highbarger H, Murray DD, Murray TA, Natarajan V, Paredes R, Parmar MKB, Phillips AN, Reilly C, Rupert AW, Sharma S, Shaw-Saliba K, Sherman BT, Teitelbaum M, Wentworth D, Cao H, Klekotka P, Babiker AG, Davey VJ, Gelijns AC, Kan VL, Polizzotto MN, Thompson BT, Lane HC, Neaton JD. Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial. Ann Intern Med. 2022 Feb;175(2):234-243. doi: 10.7326/M21-3507. Epub 2021 Dec 21.
- Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
- ACTIV-3/TICO LY-CoV555 Study Group; Lundgren JD, Grund B, Barkauskas CE, Holland TL, Gottlieb RL, Sandkovsky U, Brown SM, Knowlton KU, Self WH, Files DC, Jain MK, Benfield T, Bowdish ME, Leshnower BG, Baker JV, Jensen JU, Gardner EM, Ginde AA, Harris ES, Johansen IS, Markowitz N, Matthay MA, Ostergaard L, Chang CC, Davey VJ, Goodman A, Higgs ES, Murray DD, Murray TA, Paredes R, Parmar MKB, Phillips AN, Reilly C, Sharma S, Dewar RL, Teitelbaum M, Wentworth D, Cao H, Klekotka P, Babiker AG, Gelijns AC, Kan VL, Polizzotto MN, Thompson BT, Lane HC, Neaton JD. A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19. N Engl J Med. 2021 Mar 11;384(10):905-914. doi: 10.1056/NEJMoa2033130. Epub 2020 Dec 22.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | AMUBARVIMAB | Monoclonal antibody | 1000 mg | Intravenous |
| Subject | Bamlanivimab | Monoclonal antibody | — | — |
| Subject | ROMLUSEVIMAB | Monoclonal antibody | 1000 mg | Intravenous |
| Subject | Sotrovimab | Monoclonal antibody | — | — |
| Subject | cilgavimab | Monoclonal antibody | — | — |
| Subject | ensovibep | Protein / enzyme biologic | 600 mg | Intravenous |
| Subject | lufotrelvir | Small molecule | 250 mg | Intravenous |
| Subject | tixagevimab | Monoclonal antibody | — | — |
| Background | Remdesivir | Small molecule | — | — |