Phase II randomized non-inferiority trial comparing the humoral immunogenicity of NDV-HXP-S and BNT162b2 vaccines in Brazil
TL;DR
This was a multicenter, randomized, double-blind, active-controlled and non-inferiority Phase II clinical trial, to evaluate the immunogenicity and safety of a fifth-dose booster of NDV-HXP-S, an egg-derived, inactivated COVID-19 vectored-vaccine virus using the Newcastle disease virus.
Abstract
Coronavirus disease 2019 (COVID-19) prompted an unprecedented global vaccine development response and accelerated regulatory pathways for clinical vaccine development. Despite the end of the public health emergency, sustained preparedness, including the availability of scalable and affordable vaccine platforms, remains essential. This was a multicenter, randomized, double-blind, active-controlled and non-inferiority Phase II clinical trial, to evaluate the immunogenicity and safety of a fifth-dose booster of NDV-HXP-S 10 µg, an egg-derived, inactivated COVID-19 vectored-vaccine virus using the Newcastle disease virus (NDV) expressing stabilized prefusion S protein from the Wuhan-Hu-1 strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), versus BNT162b2 30 µg. Healthy participants aged 18–59 years ( n = 200) or ≥ 60 years ( n = 200) were randomized at a 1:1 ratio to receive a single intramuscular dose on Day 1. Primary immunogenicity endpoints (per-protocol) were the Day 29 geometric mean titer (GMT) ratio of the 50% neutralizing titer (NDV-HXP-S/BNT162b2) against SARS-CoV-2 Wuhan-Hu-1 and the difference in seroconversion proportions (≥ 4-fold rise if seropositive at baseline, or NT 50 > lower limit of quantification if seronegative). Non-inferiority margins were a point estimate ≥ 0.80 for GMT ratio, the lower bound of the one-tailed 97.5% confidence interval (CI) > 0.67 for GMT ratio, and a 97.5% CI lower bound > − 10% for seroconversion. Primary safety endpoints were vaccine-related solicited adverse events (AEs) through Day 7 and vaccine-related unsolicited AEs and serious adverse events (SAEs) through Day 28. Follow-up occurred for 12 and 6 months for safety and immunogenicity evaluation, respectively. Between February 28 and August 30, 2023, 389 eligible participants were included in the safety population. Of 389 participants, 263 (67.6%) were female, median age of 60.1 years (IQR, 40.8–65.4) and most were White, 218 (56.0%). Among the 311 (77.8%), the GMT ratio (NDV-HXP-S/BNT162b2) of neutralizing antibodies against SARS-CoV-2 (Wuhan-Hu-1) was 0.50 (95% CI: 0.40‒0.60), measured on Day 29. The difference in seroconversion was − 36.7% (-45.3% to -28.0%). Vaccine-related solicited AEs occurred in 132 (67.3%) in NDV-HXP-S and 149 (77.2%) in BNT162b2 ( P = 0.032) within 7 days post-vaccination, while vaccine-related unsolicited AE occurred in 46 (23.5%) in NDV-HXP-S vs. 51 (26.4%) in BNT162b2 ( P = 0.558) within 28 days. There were no vaccine-related SAEs within 28 days post-vaccination. Inactivated NDV-HXP-S at 10 µg did not meet the criteria for non-inferiority in comparison to BNT162b2 at 30 µg in SARS-CoV-2 Wuhan-Hu-1 seroconversion and neutralization as a fifth-dose booster. Both vaccines were generally well tolerated during the observed follow-up. ClinicalTrials.gov Identifier : NCT05354024 (Registration date: 2022-04-27).
