Intramuscular Versus Intravenous SARS-CoV-2 Neutralising Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomised Non-Inferiority Clinical Trial

Shapiro, Adrienne E.; Sarkis, Elias; Acloque, Jude; Free, Almena; Gonazalez-Rojas, Yaneicy; Hussain, Rubaba; Juárez, Erick Stanley Petersen; Moya, Jaynier; Parikh, Naval; Inman, David R.; Cebrik, Deborah; Nadeer, Ahmed; Noormohamed, Nadia; Wang, Qianwen; Skingsley, Andrew; Austin, Daren; Peppercorn, Amanda; Parra, Sergio; Chow, Sophia; Mogalian, Erik; Pang, Phillip S.; Hong, David K.; Sager, Jennifer E.; Yeh, Wendy W.; Alexander, Elizabeth; Gaffney, Leah A; Kohli, Anita

doi:10.2139/ssrn.4111060

Cited by 4 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10 In the COMET-TAIL clinical trial, efficacy of intramuscular (IM) sotrovimab 500 mg demonstrated non-inferiority a compared with IV sotrovimab given at the same dose, with a low incidence of COVID-19 progression observed for both routes of administration. 16 Sotrovimab was well tolerated in these studies, specifically with a low frequency of infusion-related reactions and only mild and transient injection-site reactions.…”

Section: Introductionmentioning

confidence: 84%

“…Details of the clinical study designs are published or available elsewhere. 9,10,16,17,18,19 All participants who received sotrovimab and had at least one measurable concentration of drug were included in the popPK analysis dataset. Study participants in the analysis dataset received sotrovimab as single IV (500 mg) or IM (250 mg or 500 mg) doses.…”

Section: Clinical Studiesmentioning

confidence: 99%

“…13,14,15 The efficacy of early treatment with sotrovimab in preventing the progression of COVID-19 in those who are at risk for hospitalization or death has been demonstrated in two pivotal clinical trials of non-hospitalized patients with mild to moderate COVID-19 at high risk for disease progression. 9,10,16 In the COMET-ICE study, a 500-mg dose of sotrovimab, administered intravenously (IV), demonstrated a relative risk reduction of 79% in hospitalization greater than 24 hours for acute management of any illness, or death due to any cause through Day 29 compared with placebo. 10 In the COMET-TAIL clinical trial, efficacy of intramuscular (IM) sotrovimab 500 mg demonstrated non-inferiority a compared with IV sotrovimab given at the same dose, with a low incidence of COVID-19 progression observed for both routes of administration.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Population pharmacokinetics and exposure-response analysis of sotrovimab in the early treatment of COVID-19

Sager

El-Zailik

Passarell

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Sotrovimab is a recombinant human monoclonal antibody that has been shown to prevent progression to hospitalization or death from severe disease in non-hospitalized high-risk patients with mild-to-moderate COVID-19 following either intravenous (IV) or intramuscular (IM) administration. Population pharmacokinetic (popPK) and exposure-response (ER) analyses were performed to characterize sotrovimab PK and the relationship between exposure and response (probability of progression), as well as covariates that may contribute to between-participant variability in sotrovimab PK and efficacy following IV or IM administration. Sotrovimab PK was described by a two-compartment model with linear elimination; IM absorption was characterized by a sigmoid absorption model. PopPK covariate analysis led to the addition of the effect of body weight on systemic clearance and peripheral volume of distribution, sex on IM bioavailability and first-order absorption rate (KA), and body mass index on KA. However, the magnitude of covariate effect was not pronounced and was therefore not expected to be clinically relevant based on available data to date. For ER analysis, sotrovimab exposure measures were predicted using the final popPK model. An ER model was developed using the exposure measure of sotrovimab concentration at 168 hours that described the relationship between exposure and probability of progression within the ER dataset for COMET-TAIL. The number of risk factors (≤1 vs >1) was incorporated as an additive shift on the model-estimated placebo response but had no impact on overall drug response. Limitations in the ER model may prevent generalization of these results to describe the sotrovimab exposure-progression relationship across SARS-COV-2 variants.

show abstract

Section: Introductionmentioning

confidence: 84%

Section: Clinical Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Population pharmacokinetics and exposure-response analysis of sotrovimab in the early treatment of COVID-19

Sager

El-Zailik

Passarell

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Details of the primary COMET-TAIL study have been reported previously [14]. The primary objective of this open-label, nonrandomized, single-arm substudy of COMET-TAIL was to describe the safety and tolerability of high-dose (2000 mg) IV sotrovimab, with an optional arm up to 3000 mg IV.…”

Section: Methodsmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted February 7, 2023. ; https://doi.org/10.1101/2023.02.02.23285352 doi: medRxiv preprint participants with mild to moderate COVID-19, treatment with IV sotrovimab at a dose of 500 mg was associated with a 79% reduction in the risk of hospitalization >24 hours for acute management of any illness or death due to any cause through Day 29 when compared with placebo. A second study, COMET-TAIL, conducted from June to August 2021, compared 500 mg IV sotrovimab with intramuscular (IM) administration of 250 mg or 500 mg sotrovimab in adults and adolescents with mild to moderate COVID-19 at high risk for progression to severe COVID-19 [14]. That enrollment period coincided with a surge of the Delta variant of SARS-CoV-2, and this was the predominant variant detected in COMET-TAIL participants [15].…”

Section: Introductionmentioning

confidence: 99%

Safety, Virology, Pharmacokinetics, and Clinical Experience of High-dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-label Clinical Trial

Moya

Temech

Parra

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Background: 500 mg intravenous (IV) sotrovimab has been shown to be well tolerated and efficacious against pre-Omicron strains in treating patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk for disease progression. Methods: This was an open-label, single-arm substudy of phase 3 COMET-TAIL (NCT04913675) assessing the safety and tolerability of a 2000 mg IV dose of sotrovimab. Symptomatic patients (aged ≥18 years) with COVID-19 at high risk for progression were enrolled from June 30 through July 11, 2022, when Omicron BA.5, BA.2.12.1, and BA.4 were the predominant circulating variants in the United States. The primary endpoint was occurrence of adverse events (AEs), serious AEs (SAEs), AEs of special interest, and COVID-19 disease-related events (DREs) through Day 8. Safety, pharmacokinetics, viral load, and hospitalization >24 hours for acute management of illness or death through Day 29 were assessed. Results: All participants (n=81) were Hispanic, 58% were female, and 51% were aged ≥55 years. Through Day 8, no AEs, including infusion-related reactions or hypersensitivity, were reported; 2 participants reported DREs (mild cough, n=2). One SAE (acute myocardial infarction), which was considered unrelated to sotrovimab or COVID-19 by the investigator, occurred on Day 27 and was the only hospitalization reported. Maximum serum concentration (geometric mean) was 745.9 μg/mL. Viral load decreased from baseline through Day 29; only 2 participants (3%) had persistently high viral load (≥4.1 log10 copies/mL) at Day 8. Conclusions: 2000 mg IV sotrovimab was well tolerated, with no new unanticipated safety signals observed.

show abstract

Safety and Efficacy of Combined Tixagevimab and Cilgavimab Administered Intramuscularly or Intravenously in Nonhospitalized Patients With COVID-19

et al. 2023

View full text Add to dashboard Cite

ImportanceDevelopment of effective, scalable therapeutics for SARS-CoV-2 is a priority.ObjectiveTo test the efficacy of combined tixagevimab and cilgavimab monoclonal antibodies for early COVID-19 treatment.Design, Setting, and ParticipantsTwo phase 2 randomized blinded placebo-controlled clinical trials within the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)–2/A5401 platform were performed at US ambulatory sites. Nonhospitalized adults 18 years or older within 10 days of positive SARS-CoV-2 test and symptom onset were eligible and were enrolled from February 1 to May 31, 2021.InterventionsTixagevimab-cilgavimab, 300 mg (150 mg of each component) given intravenously (IV) or 600 mg (300 mg of each component) given intramuscularly (IM) in the lateral thigh, or pooled placebo.Main Outcomes and MeasuresCoprimary outcomes were time to symptom improvement through 28 days; nasopharyngeal SARS-CoV-2 RNA below the lower limit of quantification (LLOQ) on days 3, 7, or 14; and treatment-emergent grade 3 or higher adverse events through 28 days.ResultsA total of 229 participants were randomized for the IM study and 119 were randomized for the IV study. The primary modified intention-to-treat population included 223 participants who initiated IM tixagevimab-cilgavimab (n = 106) or placebo treatment (n = 117) (median age, 39 [IQR, 30-48] years; 113 [50.7%] were men) and 114 who initiated IV tixagevimab-cilgavimab (n = 58) or placebo treatment (n = 56) (median age, 44 [IQR, 35-54] years; 67 [58.8%] were women). Enrollment in the IV study was stopped early based on a decision to focus on IM product development. Participants were enrolled at a median of 6 (IQR, 4-7) days from COVID-19 symptom onset. Significant differences in time to symptom improvement were not observed for IM tixagevimab-cilgavimab vs placebo or IV tixagevimab-cilgavimab vs placebo. A greater proportion in the IM tixagevimab-cilgavimab arm (69 of 86 [80.2%]) than placebo (62 of 96 [64.6%]) had nasopharyngeal SARS-CoV-2 RNA below LLOQ at day 7 (adjusted risk ratio, 1.33 [95% CI, 1.12-1.57]) but not days 3 and 14; the joint test across time points favored treatment (P = .003). Differences in the proportion below LLOQ were not observed for IV tixagevimab-cilgavimab vs placebo at any of the specified time points. There were no safety signals with either administration route.ConclusionsIn these 2 phase 2 randomized clinical trials, IM or IV tixagevimab-cilgavimab was safe but did not change time to symptom improvement. Antiviral activity was more evident in the larger IM trial.Trial RegistrationClinicalTrials.gov Identifier: NCT04518410

show abstract

Intramuscular Versus Intravenous SARS-CoV-2 Neutralising Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomised Non-Inferiority Clinical Trial

Cited by 4 publications

References 0 publications

Population pharmacokinetics and exposure-response analysis of sotrovimab in the early treatment of COVID-19

Population pharmacokinetics and exposure-response analysis of sotrovimab in the early treatment of COVID-19

Safety, Virology, Pharmacokinetics, and Clinical Experience of High-dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-label Clinical Trial

Safety and Efficacy of Combined Tixagevimab and Cilgavimab Administered Intramuscularly or Intravenously in Nonhospitalized Patients With COVID-19

Contact Info

Product

Resources

About