Safety, Immunogenicity, and Efficacy of the NVX-CoV2373 COVID-19 Vaccine in Adolescents: A Randomized Clinical Trial

Abstract

Importance: Greater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents.

Objective: To evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents.

Design, setting, and participants: The NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized.

Interventions: Participants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart.

Main outcomes and measures: Serologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18-25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety.

Results: Among 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3-1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57-69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31-6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42-23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%-92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%-95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation.

Conclusions and relevance: The findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents.

Trial registration: ClinicalTrials.gov Identifier: NCT04611802.

Figure 1.. Trial Disposition

The full analysis set (FAS) included all participants who were randomly assigned to treatment and received at least 1 dose, regardless of protocol violations or missing data, and are analyzed according to the trial vaccine group as randomized. ITT indicates intention to treat; NP, nucleoprotein; and RT-PCR, reverse transcriptase–polymerase chain reaction. ^aParticipants could have more than 1 reason for exclusion.

Figure 2.. Solicited Local and Systemic Adverse Events

The percentage of participants in each treatment group with solicited local (A) and systemic (B) adverse events during the 7 days after each vaccination is plotted by US Food and Drug Administration toxicity grade, as any (mild, moderate, severe, or potentially life-threatening) or as grade 3 or higher (severe or potentially life-threatening).

Figure 3.. Cumulative Incidence Plot of Overall Efficacy of NVX-CoV2373 Against Symptomatic COVID-19

Prospective surveillance of COVID-19 illness in the full analysis population started from the first dose of NVX-CoV2373 or placebo. The per-protocol symptomatic COVID-19 cases were defined as beginning at least 7 days after the second dose (ie, day 28) through approximately 3 to 4 months of follow-up (the implementation of blinded crossover), unblinding or receipt of emergency use authorization vaccine. MDI indicates mean disease incidence; PY, person-years; and VE, vaccine efficacy.