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
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
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.
Article activity feed
-
SciScore for 10.1101/2021.07.01.21259831: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The trial was conducted at the Singapore Health Services (SingHealth) Investigational Medicine Unit, following approvals by the SingHealth Centralized Institutional Review Board (CIRB F/2020/2553) and the Singapore Health Sciences Authority.
Consent: Written informed consent was provided by all the participants before enrollment.Sex as a biological variable not detected. Randomization Trial design, participants and oversight: ARCT-021-01 is a randomized, double-blinded, placebo (0.9% saline) controlled study to assess the safety, tolerability and immunogenicity of different dose levels of ARCT-021. Blinding not detected. Power Analysis Statistical Analysis: No formal sample size calculation … SciScore for 10.1101/2021.07.01.21259831: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The trial was conducted at the Singapore Health Services (SingHealth) Investigational Medicine Unit, following approvals by the SingHealth Centralized Institutional Review Board (CIRB F/2020/2553) and the Singapore Health Sciences Authority.
Consent: Written informed consent was provided by all the participants before enrollment.Sex as a biological variable not detected. Randomization Trial design, participants and oversight: ARCT-021-01 is a randomized, double-blinded, placebo (0.9% saline) controlled study to assess the safety, tolerability and immunogenicity of different dose levels of ARCT-021. Blinding not detected. Power Analysis Statistical Analysis: No formal sample size calculation was performed. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04480957 Recruiting Ascending Dose Study of Investigational SARS-CoV-2 Vaccine A… NCT04668339 Active, not recruiting A Trial Evaluating the Safety and Effects of an RNA Vaccine … Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
