Trial design and oversight
SARS-Cov-2 infection, Toxicity
VIRUS, BLIND, RECRUITMENT, GROUP B
The trial was prospectively registered in PRIISA.BA (Registration Code 6564) and in ANMAT. Registration was performed in February 2022, before the study beginning and before enrollment of the first participant. Also the same protocol with no changes was retrospectively registered on December 23, 2022 in ClinicalTrials.gov (NCT05656508). The trial was conducted at Clinical Pharma (Clínica CIAREC, Intense Life S.A, Buenos Aires, Argentina). In this open-label, first-in-human, dose-escalation, phase 1 clinical trial, eligible volunteers were healthy men and nonpregnant women, aged 18 to 55, with a body-mass index of 18 to 30 and with a complete COVID-19 vaccine primary schedule. Health status, assessed during the screening period, was based on medical history and extensive clinical laboratory tests, vital signs, and physical examination. Participants with a history of SARS-Cov-2 infection or COVID-19 within 60 days prior to recruitment into the study, or who tested positive in real-time polymerase-chain-reaction (RT-PCR) assay at screening or worked in an occupation with high risk of exposure to SARS-CoV-2, as well as those with an incomplete COVID-19 vaccine primary schedule or who had received the last COVID19 primary vaccine shot within 4 months prior to recruitment into the study or have received a booster dose of any COVID-19 vaccine, were excluded. Participants sex (male, female) was assigned based on sex assigned at birth, as self-reported by the participant.The study protocol was initiated on April 10, 2022. Twenty seven out of 107 volunteers (13 males, 14 females) were excluded for not complying with eligibility criteria. Participants were recruited between April 28 and June 23, 2022, and sequentially assigned to one of two vaccine groups, one receiving a 25 µg dose of ARVAC CG (Group A) and the other a 50 µg dose (Group B). A sequential assignment plan was prespecified in the study protocol. In the first stage of enrollment, the first five enrolled participants received the low dose vaccine (25 µg/dose). Only one participant per day was vaccinated. Afterwards in the second stage of enrollment, participants 6th to 10th received the high dose vaccine formulation (50 µg/dose). Only one participant per day was vaccinated. The next fifty-five enrolled participants received the 25 µg/dose (stage 3), and then the last fifteen participants received the 50 µg/dose (stage 4). Of the 80 volunteers who received at least one intramuscular dose of ARVAC CG in the deltoid, three were excluded 28 days after the first dose of the vaccine due to impossibility to complete the protocol for personal reasons. Of the 77 remaining, 59 were inoculated with two 25 μg vaccine doses, and 18 with two 50 μg vaccine doses. One study participant was tested as SARS-CoV-2 positive in the fifth visit of the protocol (day 28 after first dose). The participant was completely asymptomatic and following protocol instructions the application of the second dose was delayed. While the safety data of this volunteer at 28 days and after the second booster are included, the immunogenicity data at day 28 and at later time points were excluded because the immunogenicity against the virus may shape the antibody response and lead to misinterpretation of the results. Investigators, and laboratory personnel involved in assays were blind to assignment until the end of the follow-up period.Missing data or deviations from original protocol were infrequent and inconsequential.Safety was assessed according to the scheme established in the Guidance for Industry, Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical TrialsCausality assessment of AE was based on the standard definition and application of terms for vaccine pharmacovigilance as stated by the Report of the CIOMS/WHO Working Group on Vaccine PharmacovigilanceThe immunogenicity of ARVAC CG was compared to 18 samples obtained during the COVID-19 serology surveillance strategy implemented by the Ministry of Health of the Province of Buenos Aires, between February 4 and March 31, 2022. These were individuals with similar demographic characteristics who received a heterologous booster with the Ancestral-based BNT162b2 mRNA vaccine administered at least 3 months after a two-dose primary schedule (Table 