One of South Africa’s three COVID-19 vaccine trials was recently put on hold after a participant in the United Kingdom developed an unexplained illness. After an independent review, AstraZeneca’s candidate, which was considered to be a frontrunner in the field, is expected to resume locally this week. But results are still a long shot for this year, says the trial’s lead investigator.
Results of the South African arm of the pharmaceutical company, AstraZeneca’s COVID-19 vaccine trial, are likely to be delayed until early next year, the study’s chief South African investigator, Shabir Madhi says. The research in all four countries where the study is being conducted, including South Africa, was halted last week because of an adverse reaction in one of the United Kingdom study participants.
The research, which is being carried out in the United Kingdom, the United States, Brazil and South Africa, resumed in the UK on Sunday and Madhi confirmed that the South African trial restarted on Tuesday. This followed approval from the ethics committee of the country’s regulatory body, the South African Health Products Regulator (Sahpra), which reviewed the findings of an independent safety committee appointed by AstraZeneca.
“We expected to have an answer as to whether the vaccine works or not by the end of November, but now it’s extremely unlikely,” Madhi, who is a professor of vaccinology at Wits University and the director of the South African Medical Research Council’s (SAMRC) meningeal pathogens research unit, says. “Even though the interruption of the trial was brief, I would say that we now probably would only get an answer in the first quarter of next year.”
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The vaccine candidate, known as AZD1222, was developed in partnership with the Jenner Institute at Oxford University and is considered by many to be a frontrunner among potential candidates, with Europe already set to receive 400 million doses by the end of the year. It is the first COVID-19 vaccine trial to have reached Africa — South Africa enrolled its first participant on June 24.
Although AstraZeneca did not publicly release information on the condition of the patient who brought the trial to a halt, it has been widely reported that the patient concerned was a woman from the United Kingdom with neurological symptoms consistent with a rare but serious spinal inflammatory disorder, transverse myelitis. According to the research organisation Mayo Clinic, transverse myelitis interrupts the messages that the spinal cord nerves send throughout the body. This can cause pain, muscle weakness, paralysis, sensory problems or bladder and bowel dysfunction.
But an independent data safety and monitoring board has now found that “it’s unlikely that the adverse event was due to the vaccinations”, Madhi said during a Daily Maverick webinar on Sunday.
Around 90% — 1 800 of 2 000 — of participants in South Africa have enrolled in the trial, of which about half have received a placebo and the other half the candidate vaccine.
Madhi says because South Africa’s rate of SARS-CoV-2 infections — the virus that causes COVID-19 — is now much slower than when the local leg of the trial started in June, this too, will contribute towards the study taking longer to produce the necessary results.
In order to be able to analyse if the AZD1222 vaccine is effective, Madhi and his team need at least 42 of the 2 000 trial participants to have developed COVID-19. Vaccine researchers set “end points” in their trials — or “outcomes”, which by virtue of carefully considered assumptions and using statistical formulas helps them calculate how many people need to be enrolled. They can then work out how many infection cases they need to determine if the vaccine they’re testing can be deemed effective beyond simply chance. In the case of this study the trial needs to produce at least 42 “outcomes” or infections among the participants across the board.
Trials traditionally go through several stages, beginning with laboratory tests and animal studies, to ensure that they work and are safe. If positive results are obtained during this stage, by means of an immune response against the virus, the research can then progress to human trials, which occur in three phases. Each stage gets progressively bigger in size and finetunes details such as the correct dosage required, with phase three being the final stage before seeking regulatory approval if the vaccine works.
Madhi says it’s not unusual for trials to be paused for safety reasons. “The reason why it’s made the news now is because of COVID-19.”
But, Mitchell Warren, executive director of the US-based advocacy organisation AVAC, says while the rapid advancements being made with COVID-19 vaccines — vaccines that normally take 10 years to develop are now being fast-tracked to two years — are promising, there is also a need to be cautious.
“We all are living in this moment, everywhere, of urgency, fear and anxiety about COVID and we all want a vaccine. So we want to go as fast as we can, but that speed must never come at the expense of the scientific process,” he says.
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Madhi says if the AZD1222 vaccine turns out to be effective, it is likely to provide “the same sort of immunity as would natural infection”. “We don’t yet know for how long that immunity will last … Although reinfection is likely to occur, the second episode of infection is likely to be less severe than the first episode.”
Although having South African arms of vaccine trials don’t necessarily guarantee the country easier access to such products, it does provide us with data on whether the vaccines are safe and effective to use in our setting, says Linda-Gail Bekker, deputy director of the Desmond Tutu HIV Centre. Bekker will be heading up the local arm of the drug company Johnson & Johnson’s vaccine trial alongside SAMRC president Glenda Gray.
The phase 3 study is expected to start later this month.
South Africa is currently also recruiting participants for a phase 2 vaccine trial of the pharmaceutical company, Novavax.
Madhi says that within the context of an epidemic, COVID-19 vaccines that have shown positive results in trials, could potentially be introduced in some countries for emergency use before they have been licensed and approved by regulatory authorities.
“But that wouldn’t be unique to COVID-19, it was also done in the Democratic Republic of the Congo and West Africa with the Ebola vaccine.”
[Updated 14:45 16 September 2020: This article was updated to reflect that the South African trial of the AstraZeneca/Oxford vaccine had resumed on Tuesday.]
[Updated 14:39 15 September 2020: This article was updated to reflect that South Africa’s leg of the AstraZeneca trial is in a merged phase 1 and 2 trial and not a phase 3 trial as previously stated.]