tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2023 Jul 14;10(8)
fad354.
doi: 10.1093/ofid/ofad354. eCollection 2023 Aug. Intramuscular vs Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Noninferiority Clinical Trial
Adrienne E Shapiro[SUP] 1 2 [/SUP], Elias Sarkis[SUP] 3 [/SUP], Jude Acloque[SUP] 4 [/SUP], Almena Free[SUP] 5 [/SUP], Yaneicy Gonzalez-Rojas[SUP] 6 [/SUP], Rubaba Hussain[SUP] 7 [/SUP], Erick Juarez[SUP] 8 [/SUP], Jaynier Moya[SUP] 9 [/SUP], Naval Parikh[SUP] 10 [/SUP], David Inman[SUP] 11 [/SUP], Deborah Cebrik[SUP] 12 [/SUP], Ahmed Nader[SUP] 13 [/SUP], Nadia Noormohamed[SUP] 13 [/SUP], Qianwen Wang[SUP] 11 [/SUP], Andrew Skingsley[SUP] 14 [/SUP], Daren Austin[SUP] 14 [/SUP], Amanda Peppercorn[SUP] 15 [/SUP], Maria L Agostini[SUP] 12 [/SUP], Sergio Parra[SUP] 12 [/SUP], Sophia Chow[SUP] 12 [/SUP], Erik Mogalian[SUP] 12 [/SUP], Phillip S Pang[SUP] 12 [/SUP], David K Hong[SUP] 12 [/SUP], Jennifer E Sager[SUP] 12 [/SUP], Wendy W Yeh[SUP] 12 [/SUP], Elizabeth L Alexander[SUP] 12 [/SUP], Leah A Gaffney[SUP] 12 [/SUP], Anita Kohli[SUP] 16 17 [/SUP]
Affiliations
Background: Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19.
Method: This multicenter phase 3 study based on a randomized open-label design tested the noninferiority of IM to IV administration according to an absolute noninferiority margin of 3.5%. From June to August 2021, patients aged ≥12 years with COVID-19, who were neither hospitalized nor receiving supplemental oxygen but were at high risk for progression, were randomized 1:1:1 to receive sotrovimab as a single 500-mg IV infusion or a 500- or 250-mg IM injection. The primary composite endpoint was progression to (1) all-cause hospitalization for >24 hours for acute management of illness or (2) all-cause death through day 29.
Results: Sotrovimab 500 mg IM was noninferior to 500 mg IV: 10 (2.7%) of 376 participants vs 5 (1.3%) of 378 met the primary endpoint, respectively (absolute adjusted risk difference, 1.06%; 95% CI, -1.15% to 3.26%). The 95% CI upper limit was lower than the prespecified noninferiority margin of 3.5%. The 250-mg IM group was discontinued early because of the greater proportion of hospitalizations vs the 500-mg groups. Serious adverse events occurred in <1% to 2% of participants across groups. Four participants experienced serious disease-related events and died (500 mg IM, 2/393, <1%; 250 mg IM, 2/195, 1%).
Conclusions: Sotrovimab 500-mg IM injection was well tolerated and noninferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.
Clinical trials registration: ClinicalTrials.gov: NCT04913675.
Keywords: COMET-TAIL; COVID-19 treatment; intramuscular administration; neutralizing monoclonal antibody; sotrovimab.
. 2023 Jul 14;10(8)
fad354.doi: 10.1093/ofid/ofad354. eCollection 2023 Aug. Intramuscular vs Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Noninferiority Clinical Trial
Adrienne E Shapiro[SUP] 1 2 [/SUP], Elias Sarkis[SUP] 3 [/SUP], Jude Acloque[SUP] 4 [/SUP], Almena Free[SUP] 5 [/SUP], Yaneicy Gonzalez-Rojas[SUP] 6 [/SUP], Rubaba Hussain[SUP] 7 [/SUP], Erick Juarez[SUP] 8 [/SUP], Jaynier Moya[SUP] 9 [/SUP], Naval Parikh[SUP] 10 [/SUP], David Inman[SUP] 11 [/SUP], Deborah Cebrik[SUP] 12 [/SUP], Ahmed Nader[SUP] 13 [/SUP], Nadia Noormohamed[SUP] 13 [/SUP], Qianwen Wang[SUP] 11 [/SUP], Andrew Skingsley[SUP] 14 [/SUP], Daren Austin[SUP] 14 [/SUP], Amanda Peppercorn[SUP] 15 [/SUP], Maria L Agostini[SUP] 12 [/SUP], Sergio Parra[SUP] 12 [/SUP], Sophia Chow[SUP] 12 [/SUP], Erik Mogalian[SUP] 12 [/SUP], Phillip S Pang[SUP] 12 [/SUP], David K Hong[SUP] 12 [/SUP], Jennifer E Sager[SUP] 12 [/SUP], Wendy W Yeh[SUP] 12 [/SUP], Elizabeth L Alexander[SUP] 12 [/SUP], Leah A Gaffney[SUP] 12 [/SUP], Anita Kohli[SUP] 16 17 [/SUP]
Affiliations
- PMID: 37577112
- PMCID: PMC10414803
- DOI: 10.1093/ofid/ofad354
Background: Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19.
Method: This multicenter phase 3 study based on a randomized open-label design tested the noninferiority of IM to IV administration according to an absolute noninferiority margin of 3.5%. From June to August 2021, patients aged ≥12 years with COVID-19, who were neither hospitalized nor receiving supplemental oxygen but were at high risk for progression, were randomized 1:1:1 to receive sotrovimab as a single 500-mg IV infusion or a 500- or 250-mg IM injection. The primary composite endpoint was progression to (1) all-cause hospitalization for >24 hours for acute management of illness or (2) all-cause death through day 29.
Results: Sotrovimab 500 mg IM was noninferior to 500 mg IV: 10 (2.7%) of 376 participants vs 5 (1.3%) of 378 met the primary endpoint, respectively (absolute adjusted risk difference, 1.06%; 95% CI, -1.15% to 3.26%). The 95% CI upper limit was lower than the prespecified noninferiority margin of 3.5%. The 250-mg IM group was discontinued early because of the greater proportion of hospitalizations vs the 500-mg groups. Serious adverse events occurred in <1% to 2% of participants across groups. Four participants experienced serious disease-related events and died (500 mg IM, 2/393, <1%; 250 mg IM, 2/195, 1%).
Conclusions: Sotrovimab 500-mg IM injection was well tolerated and noninferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.
Clinical trials registration: ClinicalTrials.gov: NCT04913675.
Keywords: COMET-TAIL; COVID-19 treatment; intramuscular administration; neutralizing monoclonal antibody; sotrovimab.