Phase 3 study: The efficacy of monovalent SARS-CoV-2 vaccine with AS03 adjuvant in adults

In a recent study published in eClinicalMedicine, researchers assessed the effectiveness of a novel monovalent recombinant protein vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study: Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study. Image Credit: Ground Picture/Shutterstock.comStudy: Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, multi-country study. Image Credit: Ground Picture/Shutterstock.com

Background

Most existing coronavirus disease 2019 (COVID-19) vaccines were developed based on the spike sequence of the ancestral SARS-CoV-2; however, they are less effective against emergent variants, such as SARS-CoV-2 Delta and Omicron. New vaccines will help facilitate protection across populations in different regions.

Sanofi developed a monovalent recombinant protein vaccine (CoV2 preS dTM-AS03) against SARS-CoV-2 with the AS03 adjuvant.

Interim findings from the phase 2 study reveal acceptable reactogenicity, safety, and robust immunogenicity of the two-dose vaccine in adults with or without prior SARS-CoV-2 exposure.

About the study

In the present study, researchers presented data on the efficacy, immunogenicity, and safety of the two-dose monovalent CoV2 preS dTM-AS03 vaccine as the primary series.

This phase 3 trial comprised two stages; the first stage assessed the monovalent vaccine, and the second evaluated a bivalent vaccine. Data from the first stage were reported in this study.

Adults without prior SARS-CoV-2 vaccination were recruited and randomized to receive the vaccine or placebo. Participants received two 0.5 ml vaccine injections or 0.9% saline 21 days apart. Each vaccine shot contained 10 μg of the antigen.

Nasopharyngeal swabs and blood samples were obtained before each vaccination. Participants were contacted weekly to investigate if they tested positive for COVID-19 during the study or had symptoms of a COVID-19-like illness.

The primary efficacy endpoint was symptomatic COVID-19 ≥ 14 days post-dose 2 (PD2) in SARS-CoV-2-naïve subjects. Secondary efficacy endpoints were symptomatic COVID-19, irrespective of serostatus and hospitalization ≥ 14 days PD2.

Neutralizing antibody (nAb) profiles were assessed against the D614G variant at days 1, 22, and 43 in a subset of participants.

Subjects reported adverse events (AEs) to investigators during study visits or follow-up contact. The primary efficacy analysis was performed in the modified full analysis set (mFAS), which included participants receiving both doses without vaccine contraindications or discontinuation within 14 days PD2. Subjects with COVID-19 onset between the first dose and 14 days PD2 were excluded from the mFAS.

Findings

The team randomized 10,131 individuals to receive a vaccine or placebo from May 26 to November 7, 2021. The mFAS subset included 4,702 vaccinated participants and 4,675 placebo recipients. Of these, 2,051 subjects were SARS-CoV-2-naïve at days 1 and 22. Overall, 10,114 subjects received at least one injection and were included in the safety analysis.

Participants were aged, on average, 37.9; 56.6% were males, 73.8% were non-naïve at enrolment, and 31.6% had high-risk medical conditions.

The longest follow-up was 248 days PD1 and 227 days PD2 until January 28, 2022 (cut-off date). Symptomatic COVID-19 was confirmed for 308 subjects ≥ 14 days PD2. Most cases were reported during the Omicron wave, with fewer cases early in the study.

Eighty-one and 88 SARS-CoV-2-naïve individuals in the vaccine and placebo groups had symptomatic COVID-19 ≥ 14 days PD2, and the vaccine effectiveness (VE) was 15.3%.

Regardless of the serostatus, 126 vaccinated subjects and 182 placebo recipients developed symptomatic disease ≥ least 14 days PD2. Thirteen severe COVID-19 cases were reported in the naïve population and four among non-naïve subjects. Five patients, all SARS-CoV-2-naïve and placebo recipients, were hospitalized.

Among subjects with adjudicated cases of COVID-19 in the SARS-CoV-2-naïve population, the causative variants were Delta and Omicron in 25 and 72 cases, respectively.

SARS-CoV-2 Omicron (BA.1 and BA.2) was detected in 44 vaccinated subjects and 28 placebo recipients. Among non-naïve subjects, the Delta variant was only identified in seven placebo recipients; Omicron was detected in 16 vaccinated individuals and 34 placebo subjects.

The clinical presentation of Omicron cases was similar between naïve subjects in vaccine and placebo groups. Non-naïve subjects had increased nAb titers against the D614G variant at day 43 relative to naïve participants.

Immediate unsolicited AEs occurred in 0.1% of subjects in both groups. Nine deaths occurred in the placebo group; none among the vaccinated. Deaths were unrelated to study interventions.

Conclusions

The findings suggest acceptable safety and tolerability of the monovalent CoV2 preS dTM-AS03 vaccine. Efficacy could not be demonstrated against variants circulating at the time among naïve subjects.

However, efficacy was observed in non-naïve participants. VE in naïve subjects was 15.3%, and 52.7% in non-naïve participants.

Although the primary efficacy endpoint was not met, the vaccine was effective against symptomatic COVID-19 in the non-naïve population, and there were no safety concerns, even among subjects with high-risk conditions.

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.

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