The hold will likely delay trial results, and scientists say the pause is proof that safety protocols in clinical trials are working as they should.
Aseries of late-stage clinical trials establishing the effectiveness and safety of a joint AstraZeneca and University of Oxford COVID-19 vaccine are on hold after one UK participant in a Phase 3 trial developed a severe and unexplained illness.
The incident was first reported on Tuesday (September 8) by STAT. The pause will delay results from one of the world’s largest COVID-19 vaccine development efforts. A company spokesperson says the measure has been taken out of an abundance of caution.
“This is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated,” AstraZeneca shared in a prepared statement. “We are working to expedite the review of the single event to minimize any potential impact on the trial timeline. We are committed to the safety of our participants and the highest standards of conduct in our trials.”
Details of the adverse event that initiated the pause, including how serious it is and when it happened, have not been shared publicly. A person familiar with the situation, speaking on condition of anonymity with The New York Times, says that the participant had been diagnosed with transverse myelitis, an inflammatory condition in the spinal cord that is often sparked by viral infections.
Gabriella Garcia, a neurologist at Yale New Haven Hospital, tells the Times transverse myelitis is often treatable with steroids. When asked to confirm the diagnosis, AstraZeneca declined to comment. “The event is being investigated by an independent committee, and it is too early to conclude the specific diagnosis,” the company says.
Currently, there are nine vaccine candidates in Phase 3 trials, and AstraZeneca is the first to announce a pause. It is unknown how long the hold will continue. Marie-Paule Kieny, a vaccine researcher at INSERM, the national health research institute in Paris, tells Nature that if AstraZeneca can quickly rule out the vaccine as a source of the illness, the trial could be running again “in a matter of weeks.”
One Phase 3 trial has been underway in the US since late August with plans to enroll up to 30,000 participants at 80 sites across the country. Other trials of the same vaccine are also progressing in other countries, including Brazil and South Africa, with additional trials planned for Japan and Russia. Money to fund the US trial came from Operation Warp Speed, a US federal initiative to quickly disperse funds to the most promising vaccine candidates. AstraZeneca received $1.2 billion dollars to produce 300 million doses, Buzzfeed reports.
The company’s vaccine relies on an experimental method, based on an adenovirus vector from chimpanzees, that has yet to lead to any approved immunizations, although it was used previously in studies to treat influenza and Ebola, according to STAT. Scientists engineered the virus to smuggle the gene for the SARS-CoV-2 spike protein into human cells. Once inside, the protein prompts a natural immune response, priming immune cells to recognize SARS-CoV-2.
The Phase 1 and 2 trials of the vaccine involved 1,077 patients, Buzzfeed reports, and the results showed that 90 percent of participants subsequently tested positive for neutralizing antibodies. While roughly 60 percent of patients reported mild or moderate side effects such as fever, headaches, and muscle aches, these symptoms resolved before the end of the trial.
Phase 3 trials, which assess efficacy, can also look for less common side effects only be detected when vaccines are tested on large numbers of people. Because of their large size, these studies are considered the most important for establishing safety, according to the Associated Press.
Some scientists are saying the pause is not unexpected, and in fact shows that the clinical trial protocol is operating as it should. On the same day that AstraZeneca announced the suspension, the company’s CEO joined eight other pharmaceutical companies in announcing a commitment to integrity and safety moving forward with vaccine trials.
“This is the whole point of doing these Phase 2, Phase 3 trials,” Phyllis Tien, an infectious disease physician at the University of California, San Francisco, tells the Times. “We need to assess safety, and we won’t know the efficacy part until much later. I think halting the trial until the safety board can figure out whether or not this was directly related to the vaccine is a good idea.”
Pauses in trials can happen for any number of reasons. Any unexplained illness that requires hospitalization, for example, could trigger a safety assessment to determine if it is linked to an injection with an experimental vaccine. “It does happen. It’s not common, but it does happen,” Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia, tells BuzzFeed. “The vaccine is to stop SARS-CoV-2. It’s not designed to stop everything else that happens in life. You want to make sure it was related to the vaccine, especially if it happened a short period of time after the vaccine begins.”
Joe Walters, one of the participants in the University of Oxford trial in the UK, spoke this week to The Guardian about his experiences, sharing that he developed a persistent fever after receiving his initial injection (although it’s unknown whether he received the vaccine candidate or a control). He was briefly hospitalized and tested for COVID-19, and after his test came back negative, he learned that other participants had experienced similar side effects.
Walters heard about the pause the day he came to receive his second dose. For now, his participation is on hold, but Walters says he plans to continue “in the name of science,” adding that the trial is “something positive to do in the face of something that rendered everyone rather helpless.”
AstraZeneca is one of three companies testing vaccines in late-stage clinical trials in the US. The other two companies, Moderna and BioNTech, are developing vaccines using different methods than those used by AstraZeneca. A spokesperson for Moderna tells the Times the firm’s work has not been affected by the latest pause.