In a recent study published in Open Forum Infectious Diseases, researchers evaluated the prophylactic immune protection conferred by a single intramuscular (I.M.) injection of adintrevimab (ADG20) against symptomatic coronavirus disease 2019 (COVID-19).
Study: Prevention of COVID-19 Following a Single Intramuscular Administration of Adintrevimab: Results From a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial (EVADE). Image Credit: Treecha/Shutterstock.com
Background
COVID-19 has caused unprecedented mortality and morbidity across the globe, and the continual emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) has threatened the efficacy of therapeutics such as vaccines and monoclonal antibodies (mAbs), warranting the development of novel agents. In addition, the affected individuals may experience persistent symptoms in the post-acute phase of COVID-19, worsening their quality of life.
Therefore, COVID-19 prevention among high-risk individuals has become a population health priority worldwide. The EVADE study was a multicenter, phase II/III, double-blinded, randomized, and placebo-controlled clinical trial of ADG20, a human immunoglobulin G1 (IgG1) mAb, as a post-exposure (PEP) and pre-exposure prophylactic (PrEP) agent to prevent symptomatic SARS-CoV-2 infections.
About the study
In the present study, researchers reported the EVADE randomized controlled trial's safety and prophylactic efficacy outcomes.
The trial included vaccine-naive individuals aged 12 years or older randomized in a 1:1 ratio for receiving one I.M. injection of 300.0 mg of either ADG20 or placebo. The participants were recruited across 88 sites in eight nations and were those who tested negative for previous SARS-CoV-2 infection by serological assessments, including rapid antigen tests, as well as for current SARS-CoV-2 infection via reverse-transcription polymerase chain reaction (RT-PCR) at baseline.
Individuals who had been administered COVID-19 vaccines, convalescent sera, or mAbs and those included in other clinical trials were excluded from the analysis. The primary study endpoints included RT-PCR-verified symptomatic SARS-CoV-2 infection within week 4.0 among PEP participants and within month 3.0 among PrEP group individuals who were randomized before the SARS-CoV-2 Omicron variant of concern (VOC) emerged, i.e., before November 30, 2021. Secondary efficacy endpoints included the period between randomization and the first symptomatic SARS-CoV-2 infection verified by RT-PCR and maximal COVID-19 severity within four weeks of diagnosis.
Cox proportional hazard regression modeling was performed to calculate the hazard ratios (HRs) and the percentages of relative risk reductions (RRR) for the PEP and PrEP participants. Safety outcomes were assessed over six months and included monitoring of vital signs, treatment-emergent adverse events (TEAEs), solicited injection-site reactions (ISRs), serious AEs, and laboratory evaluations. The participants were followed up for six months through July 25, 2022. Whole-genome sequencing (WGS) analysis was performed to identify the causative VOC from the participants’ saliva samples or nasopharyngeal swabs.
Results
From April 27, 2021, to January 11, 2022, 5,951 individuals were screened, among whom 2,582 were randomized, including 487 and 2,095 participants from the PEP and PrEP groups, respectively. The median participant age was 47.0 years; 10 were children, 31 were ≥55.0 years of age, and most of them were female (52%) and Whites (79%).
Concerning the primary endpoints, RT-PCR-verified symptomatic SARS-CoV-2 infections occurred among three of 175 (2.0%) adintrevimab recipients versus 12 of 176 (7.0%%) placebo recipients of the PEP group (RRR of 75%), and among 12 of 752 (2.0%%) versus 40 of 728 (6.0%) adintrevimab-treated and placebo-receiving PrEP individuals (RRR of 71%). WGS findings indicated that all infections among the PEP group individuals were caused by the Delta VOC.
The secondary endpoints of time to the initial RT-PCR-verified symptomatic SARS-CoV-2 infection indicated that adintrevimab significantly lowered symptomatic SARS-CoV-2 infection risk compared to placebo administration (HR 0.2). Adintrevimab also lowered the maximal COVID-19 severity. None of the SARS-CoV-2 infection cases within week 4.0 were severe or critical, whereas three severe SARS-CoV-2 infections were reported in the placebo group.
In the PrEP cohort, similar findings were obtained: the period for the initial RT-PCR-verified symptomatic SARS-CoV-2 infection indicated significantly lowered symptomatic SARS-CoV-2 infection risk following adintrevimab versus placebo administration (HR 0.3). One and seven severe cases of COVID-19 occurred within week 4.0 in adintrevimab- and placebo-treated individuals, respectively.
In the exploratory analysis, including 60 adintrevimab- and 56 placebo-treated individuals, adintrevimab showed an RRR of 85% for RT-PCR-verified symptomatic SARS-CoV-2 infection within six months. Among PEP individuals randomized after Omicron emergence, RT-PCR-verified COVID-19 with symptoms within week 4.0 occurred among 9.0% and 4.0% of adintreviamb- and placebo-treated individuals, respectively. WGS findings indicated that 83% of cases were Omicron infections.
Among PReP individuals randomized after Omicron emerged, RT-PCR-verified symptomatic SARS-CoV-2 infections within three months were observed among 27 of 215 (13%) and 45 of 213 (21%) of individuals treated by ADG20 and placebo, respectively (RRR 41%). WGS findings indicated that 86% of cases were Omicron infections, except for two Delta infections.
TEAE, serious TEAEs, and solicited ISR rates were comparable between the two groups. The serious TEAEs were unrelated to adintrevimab, and the drug was considered safe based on vital signs and laboratory assessments. TEAEs included pain at the site of injection, upper respiratory tract (URT) infections, and influenza-like diseases. Solicited ISRs included erythema, tenderness, and swelling.
Based on the study findings, 300.0 mg of intramuscularly injected adintrevimab demonstrated prophylactic efficacy against SARS-CoV-2 VOCs with no serious safety concerns.
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