A phase 1/2 randomized, double-blinded, placebo controlled ascending dose trial to assess the safety, tolerability and immunogenicity of ARCT-021 in healthy adults

Abstract

Background The pandemic of coronavirus disease-19 (Covid-19) continues to afflict the lives and livelihoods of many as global demand for vaccine supply remains unmet. Methods Phase 1 of this trial (N=42) assessed the safety, tolerability and immunogenicity of ascending levels of one-dose ARCT-021, a self-amplifying mRNA vaccine against Covid-19. Phase 2 (N=64) tested two-doses of ARCT-021 given 28 days apart. Both young and older adults were enrolled. The primary safety outcomes were local and systemic solicited adverse events (AEs) reported immediately and up to 7 days post-inoculation and unsolicited events reported up to 56 days after inoculation. Secondary and exploratory outcomes were antibody and T cell responses to vaccination, respectively. Results ARCT-021 was well tolerated up to one 7.5 μg dose and two 5.0 μg doses. Local solicited AEs, namely injection-site pain and tenderness, as well as systemic solicited AEs, such as fatigue, headache and myalgia, were more common in ARCT-021 than placebo recipients, and in younger than older adults. Seroconversion rate for anti-S IgG was 100% in all cohorts except for the 1 μg one-dose in younger adults and the 7.5 μg one-dose in older adults, which were each 80%. Neutralizing antibody titers increased with increasing dose although the responses following 5.0 μg and 7.5 μg ARCT-021 were similar. Anti-S IgG titers overlapped with those in Covid-19 convalescent plasma. ARCT-021 also elicited T-cell responses against the S glycoprotein. Conclusion Taken collectively, the favorable safety and immunogenicity profiles support further clinical development of ARCT-021.

The Importance of RNA-Based Vaccines in the Fight against COVID-19: An Overview

“…Neutralizing antibody titers increased with increasing dose, in addition to triggering the T-cell response against the S protein of SARS-CoV-2. ARCT-021 at a dose of 7.5 µg also showed satisfactory tolerability, with no vaccine-related serious AEs reported [169]. These results supported the further clinical development of ARCT-021, with a phase 2 clinical trial being conducted in the United States and Singapore with 600 participants (NCT04480957) to provide guidance for a subsequent phase 3 clinical trial.…”

Efficacy and safety of COVID‐19 vaccines: A network meta‐analysis

“…The citations of the full list of the excluded studies are provided in the Supplementary Material 2. Finally, 51 articles were included in data extraction, 28–68 3 of them 36,38,51 were excluded because in both of them 36,51 the number of the events exceeded the number of participants in the treatment and placebo groups and such studies do not provide any information about the relative risk of the event. The other one 38 included HIV patients solely and no other trials included/provided data about HIV patients thus it was excluded.…”

“…As a result, 49 trials from 48 articles [28][29][30][31][32][33][34][35]37,[39][40][41][42][43][44][45][46][47][48][49][50] that included 421,173 participants and assessed 28 vaccines of 9 different types were included in the final analysis. The detailed selection process is described in Figure S1.…”

“…The other one 38 included HIV patients solely and no other trials included/provided data about HIV patients thus it was excluded. As a result, 49 trials from 48 articles 28–35,37,39–50,52–78 that included 421,173 participants and assessed 28 vaccines of 9 different types were included in the final analysis. The detailed selection process is described in Figure S1.…”

A self-amplifying RNA vaccine against COVID-19 with long-term room-temperature stability

“…11,22,23 Indeed, saRNAs have been successfully used to create COVID-19 vaccines [24][25][26][27][28][29][30] that have reached clinical trials. 31,32 However, thermostability of these vaccine formulations is either unknown 24,25,[27][28][29][30] or 1 week at refrigerated or room-temperature conditions. 26 The stability of saRNA vaccines encapsulated in LNPs is unlikely to differ significantly from LNP-encapsulated mRNA vaccines.…”