COVID Vaccine, March 9: Lancet publishes the Interim efficacy results and Phase 2 results of covaxin to combat the COVID-19. The novel coronavirus SARS-CoV-2 has spread worldwide. To date, 194 vaccine candidates are being developed to prevent the virus.
Vaccines from multiple manufacturers will be needed to address the global need for SARS-CoV-2 vaccines covaxin. Several such vaccines have received emergency use authorization for immunization of health-care workers and at-risk individuals.
There is currently an insufficient supply of vaccines, and the mRNA-based vaccines have cold chain hurdles that countries need to overcome.
BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine covaxin formulated with a toll-like receptor (TLR) 7/8 agonist molecule adsorbed to alum (Algel-IMDG). BBV152 is stored between 2°C and 8°C, which will ease immunization cold chain requirements.
Preclinical studies in mice, rats, and rabbits showed appropriate safety profiles and humoral and cell-mediated responses.
But the live viral challenge protective efficacy studies in hamsters and non-human primates showed rapid viral clearance in the lower and upper respiratory tracts and the absence of lung pathology after viral challenge.
In the phase 1 trial, it is reported interim findings from a double-blind, randomized on the safety and immunogenicity of three different formulations of BBV152 and one Algel only control (without antigen).
This phase 1 trial was done to select two formulations. Based on acceptable safety outcomes, and humoral and cell-mediated responses, the 3 μg with Algel-IMDG and 6 μg with Algel-IMDG formulations were selected for progression to a phase 2 trial.
The decision to change the dosing schedule from a 14-day interval between the first and second doses (phase 1 trial) to a 28-day interval between the two doses (phase 2 trial) was based on ensuring commonality with other licensed COVID-19 vaccines covaxin.
In the phase 1 trial, no difference in the safety and immunogenicity between the 3 μg with Algel-IMDG and 6 μg with Algel-IMDG groups was observed.
In this phase 2 trial, the inclusion of a placebo group was not planned. Our objective was to increase the sample size to establish whether there are differences in immunogenicity between the 3 μg with Agel-IMDG and 6 μg with Algel-IMDG groups.
Therefore, no control or Algel alone group was included in this study.
In phase 2 clinical trial to evaluate the immunogenicity and safety of the whole-virion inactivated SARS-CoV-2 vaccine BBV152 in healthy male and female volunteers at nine hospitals across nine states in India.
Participants were aged 12–65 years at the time of enrolment. At the screening visit, participants were tested using both SARS-CoV-2 nucleic acid and serology tests, which were done at a central laboratory (Dr Dangs Laboratory, New Delhi, India) using commercially available assays.
If individuals were positive for either test, they were excluded from the trial. The median time between the screening visit and vaccination visit was 3 days (range 2–4). Individuals aged older than 65 years, pregnant or lactating women, and individuals with comorbidities were excluded.
All study-related activities and the opportunity to decline or withdraw from the study were explained to participants.
All participants were screened for eligibility based on their health status, including their medical history, vital signs, and physical examination results, and were enrolled after providing signed and dated informed consent forms.
The trial was approved by the National Regulatory Authority (India) and the respective ethics committees of each participating hospital and was conducted in compliance with all International Council for Harmonization Good Clinical Practice guidelines.
Vaccines were provided as a sterile liquid that was injected through an intramuscular route (deltoid muscle) at a volume of 0·5 mL per dose in a two-dose regimen on day 0 and day 28.
Each glass vial contained a single dose of one of the vaccine formulations and required no additional dilution steps, therefore, no on-site dose preparation was required. No prophylactic medication (ibuprofen or acetaminophen) was prescribed either before or after vaccination covaxin.
The follow-up visits were scheduled on days 42, 56, 118, and 208 after vaccination for blood collection.
The primary outcome was SARS-CoV-2 wild-type neutralizing antibody titers and seroconversion rates at 4 weeks after the second dose (day 56).
A key secondary outcome was the number and proportion of participants with solicited local and systemic reactogenicity. Participants were observed for 2 h post-vaccination to assess reactogenicity.
They were instructed to record local and systemic reactions within 7 days (days 0–7 and days 28–35) post-vaccination using a paper-based memory aid.
The memory aid contained fields for symptom onset, severity, time to resolution, and concomitant medications, and participants were instructed to complete the form daily.
The form was collected during the next visit to the site. Routine telephone calls were scheduled following the first 7 days after each vaccination.
Solicited local adverse events were pain and swelling at the injection site, and systemic adverse events were fever, fatigue or malaise, myalgia, body aches, headache, nausea or vomiting, anorexia, chills, generalized rash, and diarrhoea.
All unsolicited adverse events were reported by participants throughout the study. The grading scale for most adverse events was based on the US Food and Drug Administration (FDA) document for the toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine covaxin clinical trials.
Adverse events for which grading was not described in the FDA guidance document were graded by use of the Common Terminology Criteria for Adverse Events.
Adverse events were graded according to severity score (mild, moderate, or severe) and whether they were related or unrelated to the investigational vaccine, as detailed in the protocol.
Between September 5 and 12, 2020, 921 potential participants were screened, 380 of whom were enrolled and randomly assigned to either the 3 μg with Algel-IMDG group (n=190) or the 6 μg with Algel-IMDG group (n=190; figure 1).
Among the 541 individuals who were initially screened but excluded, 48 had positive nucleic acid tests and 123 had positive serology tests for SARS-CoV-2.
Due to competitive recruitment, 190 individuals who were screened and found to be eligible were not enrolled. Other notable exclusions were due to inconclusive RT-PCR results (n=168).
The retention rates at day 56 were 97% (184 of 190 participants) in the 3 μg with Algel-IMDG group and 93% (177 of 190 participants) in the 6 μg with Algel-IMDG group. The demographic characteristics of participants are shown in.