Chinese state-backed vaccine developer China National Biotec Group (CNBG), of Beijing, published an interim analysis of randomized phase I/II trials of its inactivated SARS-CoV-2 vaccine candidate in the Journal of the American Medical Association (JAMA) last week. With the added detail, the data encouraged the company in its plans to produce 220 million doses per year.
Developed by CNBG’s subsidiary, Wuhan Institute of Biological Products, the vaccine demonstrated immunogenicity and had a low rate of adverse reactions in the 96-subject phase I trial and 224-subject phase II trial, according to the interim report.
“This is the first report of phase I and II clinical trials of a whole-virus inactivated COVID-19 vaccine among healthy adults. The inactivated vaccine was well-tolerated in all dose groups under different injection procedures with no vaccine-related serious adverse events,” researchers said in JAMA on Aug. 13.
In the phase I trial, the low-dose, medium-dose and high-dose groups received three injections at 2.5 μg/dose, 5 μg/dose and 10 μg/dose, respectively, on days 0, 28 and 56. The geometric mean titers of neutralizing antibodies in these groups at day 14 after the third injection were 316, 206 and 297, respectively, with a 100% seroconversion rate in both low- and high-dose groups.
In the phase II trial, subjects were given two injections at 5 μg/dose, with the second dose given either 14 or 21 days later. The geometric mean titers of neutralizing antibodies were 121 in a 14-day group and 247 in the 21-day group. The seroconversion rate in both groups was 97.6%. The full results from the interim study are here.
“Most participants started to generate antibody responses after the second injection and remained at high levels 14 days after the third injection,” the researchers noted.
They said the results in both phase I and II trials showed that a longer interval (21 days and 28 days) between the first and second injections produced higher antibody responses vs. a shorter interval schedule (14-day group). The antibody titers began to increase after the second dose and further increased after the third, suggesting a booster injection is needed.
They also noted that the antibody titers that CNBG’s vaccine produced were comparable with the levels observed in Moderna Inc.’s mRNA-1273 vaccine, Biontech SE’s BNT-162b1 RNA vaccine, and Astrazeneca plc and Oxford University’s ChAdOx1 nCoV-19 vaccine, and higher than Cansino Biologics Inc.’s Ad5-vectored vaccine, Ad5-nCoV.
Regarding safety, no subjects reported other than mild adverse reactions within seven days after taking the full course of treatment. In the phase I trial, 20.8%, 16.7% and 25% of the subjects in the low-dose, medium-dose and high-dose groups, respectively, reported adverse reactions. In the phase II trial, the seven-day adverse reactions occurred in 6% and 19% of subjects who received the medium dose at either days 0 and 14, or days 0 and 21.
The most common adverse reaction was injection site pain, followed by fever. All adverse reactions were mild and self-limiting that did not require any treatment. There were also no major differences across three injections in the phase I trial or two injections in the phase II trial.
“The interim report showed that the vaccine candidate had positive outcomes. The body was able to induce antibody production against the coronavirus and there were no serious adverse reactions,” Kwan-long Mung, a cancer researcher from The University of Turku, told BioWorld.
“But it remains to be seen how long the antibodies will last. This is also just an interim report, in which the number of memory B cells and plasma cells were not discussed. We will need to see a formal report to determine if this candidate vaccine will work or not,” he added.
CNBG’s researchers also noted that it is unclear whether vaccine-induced antibody levels will persist and whether the long-lasting memory T cells will affect susceptibility and pathogenesis of SARS-CoV-2 infection. Subjects in the phase I/II studies will be followed for up to a year.
The interim analysis was conducted on June 16 and updated on July 27. In June, the company made a brief statement that the seroconversion rate was 97.6% for the middle-dose group, who received injections on a 14-day and 21-day schedule, and 100% for those who received doses 28 days apart.
The vaccine candidate is now in phase III trials that will enroll 15,000 subjects in Abu Dhabi, United Arab Emirates. It is a randomized, double-blind, parallel placebo-controlled study to evaluate the vaccine’s protective effect in preventing severe cases of SARS-CoV-2 pneumonia and deaths accompanied by COVID-19 in the period from 14 days after two injections. The study is expected to be completed by July 15, 2021.
However, the state-backed vaccine maker is eager to make the vaccine accessible as soon as possible. CNBG Chairman Liu Jingzhen told Chinese state media last month that its vaccine could go to market this year. The company is preparing to ensure an annual production capacity of 220 million doses from its manufacturing units in Beijing and Wuhan.
CNBG also has a second inactivated COVID-19 vaccine candidate, known as BBIBP-CorV, developed by its subsidiary the Beijing Institute of Biological Products. It is reported that phase I/II data of this vaccine will be unveiled soon