Let’s get it started.
That Black Eyed Peas song was probably not about clinical trials, since most popular songs are about topics like love, breakups, personal struggles, partying, or letting the dogs out. Nevertheless, the Phase 3 clinical trial in the U.S. for AstraZeneca’s Covid-19 coronavirus vaccine candidate is now officially runnin’ runnin. About a quarter of the 80 total clinical sites have now kicked off enrolling patients.
The vaccine candidate bears the not-so-easy-to-remember name of AZD1222, which incidentally rhymes with B2B1222 or goatee1222. This is what’s been called the Oxford vaccine as researchers at Oxford University were developing the vaccine before entering into a partnership with AstraZeneca back in April. The goal is to ultimately get around 30,000 study participants enrolled into this Phase 3 trial. That’s about the attendance for a large Harry Styles concert. So it’s a big trial.
When it comes to human studies on a vaccine’s road to the market, Phase 3 is the big one. It’s often called the pivotal trial because it’s supposed to confirm the safety and efficacy of a vaccine. Phase 1 and 2 clinical trials can give you a sense of the dosing required and the safety of the vaccine. These early trials may offer some idea of the vaccine’s efficacy, in other words how much protection it may be able to offer. So, for AZD1222, as a publication in The Lancet described, a Phase 1/2 clinical trial showed that a month after getting vaccinated with AZD1222, 95% of the study participants still had a four-fold increase in the amount of antibodies against the SARS-CoV-2 spike protein in their blood. (The SARS-CoV2 sort of looks like one of those spiky massage balls with spikes made out of protein. Except, you shouldn’t massage yourself with this ball.) The trial also found that all participants had signs of a T-cell mediated immune response even two months after getting vaccinated.
However, finding an immune response doesn’t exactly tell you how well the vaccine can protect you against the virus. That’s why you need a Phase 3, randomized double-blinded placebo-controlled clinical trial. A Phase 3 random-double-dutch-blinded-with-science-Tai-Bo-controlling-clinic-jury-trial-what-the-who?
To understand what this means, let’s break down each of the words. It’s “Phase 3” so that it’s likely the last hurdle to the U.S. Food and Drug Administration (FDA) approval of the vaccine, albeit a big hurdle. It’s “randomized,” meaning that each study participant will be randomly assigned to one of two groups. It’s “double-blinded, which means that neither the study participant nor the researchers will know who is assigned to which group. It’s “placebo-controlled,” meaning that one group, the experimental group, will actually receive the AZD1222 vaccine, while the other, the control group, will get a fake vaccine, otherwise known as a placebo. This will allow the researchers to compare what happens to the two groups to tell how much of a difference the vaccine makes.
Each study participant will get one injection on the first day of the trial and then a second injection 28 days later. While the first dose may elicit an immune response, the second can help boost it. Or serve as a reminder to the immune system, as in “hey, you know this virus here? Not good.” The researchers aim to follow each study participant for about two years, checking antibody levels periodically and checking if they get sick from the Covid-19 coronavirus.
“Through the two-year period, we will follow-up with each participant from five to nine times,” explained William Hartman, MD, an Assistant Professor of Anesthesiology at the University of Wisconsin School of Medicine and Public Heath and the Principal Investigator for the University of Wisconsin Health clinical trial site. “The study will include both those who have had Covid-19 already and those who haven’t.”
Hartman indicated that the University of Wisconsin (UW) is one of the Tier 1 sites, which were deemed more ready to rumble than the Tier 2 sites, based on having things in place and the amount of Covid-19 coronavirus that was circulating in the surrounding community. “ The Tier 1 sites were deemed ready to go on a call this past Friday,” said Hartman. “We are hoping to enroll between 200 and 250 study participants each week for a total of eight weeks.” If you do the math, this comes out to 1600 or more participants.
If you are wondering about how difficult it will be to get people to participate in the trial, Hartman relayed that “We started recruiting at 9 am today and by 9:15 am, about 150 people had already responded.” He said, “We are recruiting throughout UW Madison. This includes emails to faculty and staff, internal advertisements to all health care workers and staff members, and larger community outreach.”
Of course, they don’t want to be like the Atlanta Falcons in the 2017 Super Bowl, starting fast and then petering off before reaching their goal. “A challenge will be maintaining momentum and enthusiasm to reach our enrollment target,” said Hartman.
Another challenge will be getting enough diversity among trial participants, including enough persons of color.
“The pandemic has disproportionately affected Blacks, indigenous people, and other persons of color,” said Shiva Bidar-Sielaff, MA, Vice President and Chief Diversity Officer at UW Health. “At the same time, many communities of color have had a long history of lack of trust in clinical trials and this type of research.” Justifiably so. History has plenty of examples of researchers taking advantage of racial minorities when studying diseases. One example is the Tuskegee Syphilis Study that went from 1932 until 1972. The goal of the study was to see what happened to untreated syphilis in Black American men without telling them that’s the goal. If that sounds awful, it was and still is.
Therefore, UW Health is making extra efforts to build trust when seeking to enroll persons of color. “We’ve established very close partnerships with community-based organizations led by persons of color,” explained Bidar-Sielaff. “Being transparent will be important. This has included explaining the trials, their importance, and what participation means to community members via Zoom calls and social media. We also have a hotline available in Spanish and Hmong,” since Madison has significant Spanish-speaking and Hmong communities.
She also said that they “have approved funds for the transportation needs for those enrolled in the trials. When participants come for the visits, there will be qualified medical interpreters. We have been going through Spanish-speaking radio stations.”
This trial certainly won’t be your typical “run-of-the-mill” clinical trial. Lots of eyes will be on the trial. As you have probably seen and heard, some political leaders have been applying pressure, trying to push vaccine development faster and faster. But proper vaccine development takes time. It’s already moving faster than it’s ever moved. You can’t take shortcuts and risk developing a vaccine that’s not safe or effective enough. That could be like just sticking whole unpeeled bananas into a loaf of bread and calling it banana bread. “We need to assure everyone that no corners will be cut,” explained Hartman. “One third of the population has already said that they don’t want a vaccine that’s come up this quickly.”
As the Black Eyed Peas sang, “ Don’t move too fast, people, just take it slow.”