UC San Diego Health will be part of a second, massive clinical trial to assess the safety, efficacy and immunogenicity of a vaccine designed to protect against SARS-CoV-2, the novel coronavirus that causes COVID-19.
Like the Moderna clinical trial, which launched in late-July, the Phase III national AstraZeneca study will recruit up to 30,000 participants at multiple sites across the country. The trial arm at UC San Diego will involve an estimated 1,600 participants, with particular outreach intended for underserved communities. The UC San Diego trial is slated to begin September 8, 2020.
UC San Diego researchers are collaborating with El Centro Regional Medical Center (ECRMC) in the Imperial Valley, which has been hard-hit by the pandemic, to create a subsite of the trial.
The virus has dealt a devastating blow to both the medical and financial well-being of the region. A successful vaccine trial - our target is more than 1,000 participants -; will give hope as we stop the spread of this disease in such a vulnerable community."
Chris Tomaszewski, MD, Chief Medical Officer at ECRMC
The UC San Diego trial will also deploy a specially equipped bus to bring vaccine testing to communities in San Diego County disproportionately affected by COVID-19 and historically under-represented in medical research. Two other vehicles will serve as mobile clinics for participants who develop COVID-19 during the study.
"The SARS-CoV-2 pandemic has disproportionately impacted communities of color across the United States," said Susan Little, MD, professor of medicine at UC San Diego School of Medicine and principal investigator of the UC San Diego trial. "These vehicles will help our research team bring vaccine trial opportunities to high-burden communities that might otherwise be underserved."
The trial is sponsored by the National Institutes of Health's (NIH) COVID-19 Prevention Network (CoVPN) and is part of Operation Warp Speed, a program sponsored by the U.S. Department of Health and Human Services, with a goal to deliver 300 million doses of a safe, effective vaccine for COVID-19 by end of year or early 2021. Currently, Operation Warp Speed has now committed a reported $8 billion to development and/or purchase of different vaccines under investigation by AstraZeneca, Moderna, Janssen/Johnson & Johnson, Pfizer/BioNTech SE, NovaVax, Merck and Sanofi/GSK, the last a European-based partnership.
The latest vaccine, known as AZD1222, is a collaboration between the pharmaceutical giant AstraZeneca and Oxford University, both based in the United Kingdom. It is made from a weakened version of an adenovirus (which causes the common cold) derived from chimpanzees and modified so it cannot replicate in humans. Little said the approach is similar to the strategy used safely in previous human vaccine trials for prevention of Middle East Respiratory Syndrome, a coronavirus closely related to COVID-19.
The virus contains the full-length structural surface glycoprotein of SARS-CoV-2 that gives the novel coronavirus its characteristic spikes. These spikes are used by the virus to fuse with host cell membranes. When the adenovirus binds to host cells, the SARS-CoV-2 genetic material it contains prompts an immune response and ideally, the development of neutralizing antibodies.
Neutralizing antibodies are part of the body's adaptive immune system. By interfering with how pathogens, such as viruses, bacteria and microbial toxins, interact with host cells, the antibodies can render pathogens non-infectious.
In data published in The Lancet, researchers found that the vaccine was generally well tolerated in Phase I/II trials, with the most common adverse effects being temporary pain, fever, muscle ache, headache, chills, fatigue or malaise. These effects were less frequent after the second dose and less frequent in trial participants who were pre-treated with Tylenol.
Preliminary findings found that study participants receiving two vaccines 28 days apart developed fewer vaccine side effects (than those receiving one vaccine) and all developed SARS-CoV-2-specific neutralizing antibody responses. Additionally, AZD1222 vaccines have generated production of immune cells called T cells, which are important for long-lived immunity.
The Phase III AZD1222 trial will be randomized, double-blind and placebo-controlled -; the gold standard for clinical trials. Up to 30,000 participants will be recruited, spread across 81 sites. Two-thirds of the participants will receive the test vaccine, given as two injections with the second shot 28 days after the first. The other third will receive two injections of a saline placebo on the same timetable.
Qualifying participants must be 18 or older and be in reasonably good health. They must be at increased risk of SARS-CoV-2 infection due to where they live (higher community spread of the virus) or personal circumstances, such as working in essential jobs like first responders, health care, maintenance, construction, grocery stores or assisted living facilities.
The study is scheduled to last for two years, with seven scheduled study visits to monitor participants' health and well-being. Participants will be asked to monitor for symptoms of COVID-19, such as fever, shortness of breath, cough, headache and loss of sense of taste. Participants are asked to contact study coordinators immediately if they develop symptom(s) suggestive of COVID-19 that persist for a day or more -; at which time they will be tested for SARS-CoV-2. Participants who develop COVID-19 while on study will wear an armband device that measures temperature, blood oxygen saturation, respiratory rate and heart rate to assess their well-being for up to 28 days. They will provide blood and nasal samples during the scheduled study visits.
Folegatti, P.M., et al. (2020) Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet. doi.org/10.1016/S0140-6736(20)31604-4.