| Title: |
P-1960. Safety and Pharmacokinetics of Long-acting SARS-CoV-2 Antibodies Tixagevimab/Cilgavimab (AZD7442) are Consistent after Repeat Dosing: Results from the PROVENT Substudy |
| Authors: |
Ustianowski, Andrew; Levin, Myron J; De Wit, Stéphane; Launay, Odile; Bollen, Hilde; Rampling, Tommy; Sullivan, James G; Vishnepolsky, Mark; Wijewardane, Priyantha; Sharbaugh, Audrey; Beavon, Rohini; Thissen, Jesse; Hirao, Lauren; Dzutseva, Vitalina; Seegobin, Seth; Streicher, Katie; Kiazand, Alexandre; Esser, Mark T; Cohen, Taylor; Chang, Lee-Jah; Perez, John L |
| Source: |
Open Forum Infectious Diseases ; volume 12, issue Supplement_1 ; ISSN 2328-8957 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Description: |
Background The SARS-CoV-2 antibody combination tixagevimab/cilgavimab (AZD7442) was efficacious in preventing COVID-19 over 6 months following a single 300 mg intramuscular (IM) dose in the PROVENT study. Participants included those that: (a) were immunocompromised and/or at increased risk for inadequate response to COVID-19 vaccination, or (b) were at increased severe COVID-19 risk. Following PROVENT, emergence of Omicron variants with reduced AZD7442 susceptibility prompted increase in the authorized dose and dosing frequency. Here, we report safety and pharmacokinetics (PK) of repeated doses of AZD7442 300–600 mg in participants who opted to continue in the PROVENT substudy. Methods Participants who entered the PROVENT open-label sub-study (NCT04625725) were assigned initially to 2 groups: Group 1 (n=234) received 1x AZD7442 300 mg in the parent study, then 1x 300 mg ∼10–14 months later (substudy Day 1). Group 2 (n=119) received placebo in the parent study, then 2x AZD7442 300 mg doses in the substudy. Group 3a (n=76) was a subset of Group 1 who received 2x 300 mg then 2x 600 mg doses. Group 3b (n=74) was a subset of Group 2 who received 1x 300 mg then 2x 600 mg doses (Table 1). The primary endpoint was safety; PK and antibodies to AZD7442 were also assessed. Results Baseline characteristics were overall similar across the groups. Adverse events (AEs) were reported in 75.7–81.5% and serious AEs in 13.2–16.8% of participants across the groups (Table 2). There were 14 deaths: 8 (3.4%) in Group 1, 5 (4.2%) in Group 2, and 1 (1.4%) in Group 3b. There was no clinically meaningful increase of AEs due to repeat doses of AZD7442 and no deaths were considered related to AZD7442. AZD7442 PK was consistent following redosing and between groups (Figure 1). The percentage of participants positive for treatment-emergent antibodies to AZD7442 was 10.5% (Group 1), 5.2% (Group 2), 10.7% (Group 3a), and 4.1% (Group 3b). Conclusion Safety and PK of AZD7442 were consistent after repeat dosing, regardless of whether ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/ofid/ofae631.2119 |
| Availability: |
https://doi.org/10.1093/ofid/ofae631.2119; https://academic.oup.com/ofid/article-pdf/12/Supplement_1/ofae631.2119/61673683/ofae631.2119.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.B04E8026 |
| Database: |
BASE |