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
Year: 2021
Type: preprint
Study designs: Randomized Controlled Trial, Clinical Trial
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.
Source: medRxiv
Authors: Jenny G. Low, Ruklanthi de Alwis, Shiwei Chen, Shirin Kalimuddin, Yan Shan Leong, Tania Ken Lin Mah, Natalene Yuen, Hwee Cheng Tan, Summer L Zhang, Jean X.Y. Sim, Yvonne F.Z. Chan, Ayesa Syenina, Jia Xin Yee, Eugenia Z. Ong, Rose Sekulovich, Brian B. Sullivan, Kelly Lindert, Sean B. Sullivan, Pad Chivukula, Steven G. Hughes, Eng Eong. Ooi
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3176098528