The Phase 3 trial of another investigational COVID-19 vaccine has begun enrolling adult volunteers. The randomized, placebo-controlled trial will enroll approximately 30,000 people at roughly 115 sites in the United States and Mexico.
The trial will evaluate the safety and efficacy of NVX-CoV2373, a vaccine candidate developed by Novavax of Gaithersburg, Maryland, which is leading the trial as the regulatory sponsor.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, are funding the trial.
The trial is being conducted in collaboration with Operation Warp Speed, a multi-agency collaboration overseen by HHS and the Department of Defense that aims to accelerate development, manufacture and distribution of medical countermeasures for the coronavirus. Some of the U.S. trial sites participating are part of the NIAID-supported COVID-19 Prevention Network (CoVPN). The CoVPN includes existing NIAID-supported clinical research networks with infectious disease expertise, and was designed for rapid and thorough evaluation of vaccine candidates and monoclonal antibodies for preventing COVID-19.
WHAT’S THE IMPACT
Volunteers will be asked to give informed consent prior to their participation in the trial. They will be grouped into two cohorts: individuals 18 through 64 years old and those aged 65 and older, with a goal of enrolling at least 25% of all volunteers who are 65 years old or older.
Trial organizers also are emphasizing recruitment of people who are at higher risk of severe COVID-19 disease, including those who are Black (including African Americans), Native American or of Latino or Hispanic ethnicity, and people who have underlying health conditions such as obesity, chronic kidney disease or diabetes.
After providing a baseline nasopharyngeal and blood sample, participants will be assigned at random to receive an intramuscular injection of either the investigational vaccine or a saline placebo. Randomization will be in a 2:1 ratio with two volunteers receiving the investigational vaccine for each one who receives placebo. Because the trial is blinded, neither investigators nor participants will know who is receiving the candidate vaccine. A second injection will be administered 21 days after the first.
Participants will be followed closely for potential vaccine side effects and will be asked to provide blood samples at specified times after each injection and during the following two years. Scientists will analyze the blood samples to detect and quantify immune responses to SARS-CoV-2, the virus that causes COVID-19. Notably, specialized assays will be used to distinguish between immunity as a result of natural infection and vaccine-induced immunity. The trial’s primary endpoint is to determine whether NVX-CoV2373 can prevent symptomatic COVID-19 disease seven or more days after the second injection relative to placebo.
The investigational vaccine is made from a stabilized form of the coronavirus spike protein using Novax’s recombinant protein nanoparticle technology. The purified protein antigens in the vaccine cannot replicate nor cause COVID-19. The vaccine also contains a proprietary adjuvant, MatrixM. Adjuvants are additives that enhance desired immune system responses to vaccines. NVX-CoV2373 is administered in liquid form and can be stored, handled and distributed at above-freezing temperatures (35° to 46°F.). A single vaccine dose contains 5 micrograms of protein and 50 mcg of adjuvant.
In animal tests, vaccination produced antibodies that blocked the coronavirus spike protein from binding to the cell surface receptors targeted by the virus, preventing viral infection. In results of a Phase 1 clinical trial published in the New England Journal of Medicine, NVX-CoV2373 was generally well-tolerated and elicited higher levels of antibodies than those seen in blood samples drawn from people who had recovered from clinically significant COVID-19.
NVX-CoV2373 also is being evaluated in a Phase 2b trial in South Africa, now fully enrolled with 4,422 volunteers, and data from a Phase 1/2 continuation trial in the U.S. and Australia is expected as early as first quarter 2021. Novavax also recently completed enrollment of more than 15,000 volunteers in a Phase 3 trial of the candidate vaccine in the United Kingdom, which is also testing two injections of 5 mcg of protein and 50 mcg of Matrix-M adjuvant administered 21 days apart.
An independent Data and Safety Monitoring Board (DSMB) will provide oversight to ensure the safe and ethical conduct of the study. All Phase 3 clinical trials of candidate vaccines supported through OWS are overseen by a common DSMB developed in consultation with the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines initiative.
THE LARGER TREND
The development and rollout of coronavirus vaccines has been closely monitored by the public and the healthcare industry. Just days before Christmas, the Department of Health and Human Services and Department of Defense announced they will purchase another 100 million doses of Pfizer’s COVID-19 vaccine. Officials are confident that this deal will ensure that there are enough vaccines available for every American who wants one by June 2021.
Under the agreement, Pfizer will manufacture and distribute the 100 million doses to government-designated locations. At least 70 million doses will be delivered by the end of June 2021, with the remaining doses to be delivered by the end of July.
This week, CareFirst BlueCross BlueShield announced that costs associated with all FDA-authorized COVID-19 vaccines will be fully covered for all members, including members in self-insured plans.
Initial vaccine supplies are expected to be limited. Most states will distribute the vaccines in phases, using Centers for Disease Control and Prevention recommendations to determine which populations will be vaccinated during each phase. As vaccines become more widely and readily available, each state will communicate when and where vaccinations will occur.
Throughout the public health emergency, it’s important to continue practicing social distancing behaviors such as wearing a mask, staying at least six feet apart, and washing one’s hands, according to CareFirst.