Clinical research related to the coronavirus disease 2019 (COVID-19) has exploded in recent months as public and private researchers look for ways to test, treat and prevent the illness. When it comes to vaccines, there are five selected by the U.S. federal government for funding and accelerated development under Operation Warp Speed: Moderna’s mRNA-1273, The University of Oxford and AstraZeneca’s AZD1222, Pfizer and BioNTech’s BNT162, and two more efforts by Johnson & Johnson and Merck.
The first vaccine up for a phase III clinical trial is Moderna’s version. A network of institutions and hospitals are part of this trial, including UNC School of Medicine. UNC Health infectious disease expert Cynthia Gay, MD is leading the trial at UNC.
How did we get to this phase?
All new medical drugs and treatments have to be thoroughly tested in clinical trials before they are licensed and available for patients. Some crucial things have to happen before you reach phase III of a clinical trial, which is usually the last hurdle before a drug is submitted to the U.S. Food and Drug Administration (FDA) for evaluation. Research on a vaccine begins in a lab setting on cells. After successful testing there, it moves forward to phase I and II clinical trials, only moving forward if certain criteria are met. Before moving to a large phase III trial, a product has to be shown as safe to use in people, and has to show beneficial effect in smaller groups of participants.
Under normal circumstances, each phase of a trial could take years, including months in between trials when results from each phase are published in peer-reviewed medical journals, Dr. Gay says. Because of the urgent need for a COVID-19 vaccine, research partnerships, such as the COVID-19 Prevention Network (COVPN), have been created to speed up this timeline, while still adhering to strict and important protocols that ensure safety.
Another challenge with this trial is its size. An average phase III trial has the largest number of participants out of all trial phases – usually several thousand volunteers. The Moderna mRNA-1273 vaccine trial is recruiting 30,000 participants across the United States, with UNC aiming to recruit 500-1,000 participants. In this phase, researchers will further evaluate the safety and effectiveness of the vaccine.
How does the vaccine work?
There are several types of vaccines used to produce antibodies in an effort to prevent you from getting sick when you encounter a certain disease, or being less sick if you do get infected. In some cases a live virus is used in a vaccine to create an immune response and its desired antibodies. An inactive vaccine uses a virus that has been killed by heat or chemicals but is still recognizable by the body’s immune system. To get the same effect as a live vaccine, an inactive vaccine usually requires additional shots, or boosters, after the initial dose. The Moderna version is a messenger RNA (mRNA) vaccine. That means it uses just a piece of the SARS-CoV-2 virus, which causes COVID-19.
“A spike protein in the SARS-CoV-2 virus that is responsible for getting into and infecting cells is used in this vaccine,” Dr. Gay says. “When you only use a piece of the virus in a vaccine, not the whole virus, the vaccine cannot cause infection or illness related to the virus.
The SARS-CoV-2 spike protein is attached to something called messenger RNA that acts as a delivery system to carry the SARS protein into a person’s cells, where it triggers an immune response and creates antibodies. Then, if an immunized person is infected with COVID-19, he or she should have have pre-existing immunity thanks to the antibodies created from the vaccine.
Such mRNA vaccines have been in development to treat different types of cancer and other viruses, but none have been approved for use outside of clinical trials.
How does the trial work?
This phase III trial will test the vaccine on people 18 years and older who have not had COVID-19, but are most at risk for getting it. This includes healthcare workers and other frontline workers, or those who live in a virus hotspot zone. Researchers are aiming for healthcare workers to make up 30-40 percent of the total number of study participants. The study also will seek out volunteers at risk for COVID-19 who are also more at risk for severe illness if they get the virus; people above age 65 and people with chronic lung disease, cardiac disease, severe obesity, diabetes or liver disease.
“We also feel very committed to enrolling participants who are being the hardest hit in our communities. In North Carolina, that also means Black and Latinx populations,” Dr. Gay says.
Recruitment for the trial is expected to last several weeks.
This is a randomized placebo-controlled trial. The vaccine’s effectiveness will be compared to a placebo (substance that has no therapeutic effect) of saline solution. Half of the participants will be randomly designated to receive the vaccine, and half will receive the placebo. Participants and research staff will not know which they receive.
What’s it like to be a participant?
Being a participant in this trial is a two-year commitment. Volunteers will have seven in-person visits at their designated trial site over 24 months. Two of those visits will include receiving an injection of either the vaccine or placebo, both of which will happen in the first two months of the trial. There will be five more in-person visits to check how volunteers are reacting to the injections.
Participants also will be asked to track how they feel on a weekly basis by keeping an electronic diary. In addition, research staff will call participants to track how participants are feeling and monitor for any symptoms of COVID-19. Volunteers will not be exposed to the virus that causes COVID-19 as part of the trial. If a participant tests positive for COVID-19 during the trial, coordinators will work to ensure they get the care they need.
When the trial is complete, all participants will be able to view the results. In this case, results may be shared with the public before the trial is complete in an effort to produce a viable vaccine as quickly as possible.
How can you help?
Volunteers truly help researchers gain knowledge about how the virus behaves, how it impacts the well-being of our communities, and how new vaccines and treatments work for people of all backgrounds, ages and walks of life. The number of clinical trials in progress for COVID-19 tests, treatments and vaccines means we need your help to get this research done.
Register on the national COVPN website and answer a few simple questions, to see if you are eligible to participate in a COVID-19 clinical trial, including the Moderna phase III vaccine trial. If you are interested in participating in a trial at UNC in Chapel Hill, NC, please enter the UNC site code “CHNC” when prompted.