Authorities in the Democratic Republic of the Congo and the World Health Organization (WHO) are in discussions to speed up the launch of a Phase 3 clinical trial for vaccines aimed at controlling the Bundibugyo virus outbreak in the country’s northeast. The director-general of WHO cautioned that this outbreak is on the path to becoming the most extensive Ebola outbreak to date.
“It’s already the second-biggest Ebola epidemic on record, and it’s moving faster than any previous Ebola outbreak. At its current pace, it’s on track to eclipse the West African Ebola outbreak of 2014-2016,” stated Tedros Adhanom Ghebreyesus during a news conference in Geneva.
The initial vaccine slated for field trials is Merck’s Ervebo, which targets the Ebola Zaire species. Although initially hesitant, the advisory panel to WHO has been influenced by numerous studies on animals and humans, suggesting the vaccine might provide cross-protection against the Bundibugyo virus. This vaccine should be tested for its potential effectiveness.
Tedros noted, “WHO has recommended inclusion of the vaccine in a Phase 3 trial, which we hope to start as soon as possible. We do not know whether this vaccine is efficacious against Bundibugyo disease in humans. The Phase 3 trial is the best way to ensure a safe and effective vaccine is available as soon as possible for this and future outbreaks.”
As of Monday, the outbreak has confirmed over 4,500 Ebola cases in the DRC’s Ituri province, near Uganda and South Sudan, resulting in more than 2,060 deaths.
Vasee Moorthy, head of WHO’s R&D blueprint program, mentioned that the agency is close to submitting a trial protocol to regulatory and ethics committees in the DRC for approval. If approved, the study would involve randomizing known contacts of cases to receive either Ervebo or a placebo. As vaccines targeting the Bundibugyo species become available, they will be added to the trial.
The trial does not employ the ring vaccination strategy used in the Ebola Ça Suffit trial in Guinea, which demonstrated Ervebo’s effectiveness during the West African outbreak. In that trial, contact rings of cases were randomized to receive the vaccine either immediately or after a delay. Field studies later estimated Ervebo’s effectiveness against Ebola Zaire at about 84%.
Moorthy explained that results from various Ebola trials over the years led officials to decide that individual randomization of contacts, rather than using contact rings, is more efficient. “It is more efficient to individually randomize,” he stated.
WHO officials did not comment on a report suggesting that the DRC wants to deploy Ervebo for general use outside a clinical trial, a plan supported by the Africa Centres for Disease Control and Prevention.
Access to the necessary number of vaccine doses for such a rollout in the DRC remains uncertain. The existing stockpile of approximately 500,000 doses of Ervebo is managed by the International Coordinating Group on Vaccine Provision, comprising the International Federation of Red Cross and Red Crescent Societies, Doctors Without Borders (MSF), UNICEF, and WHO. Despite inquiries, a response from the WHO was pending at the time of publication.
Moorthy mentioned the potential inclusion of several Bundibugyo-specific vaccines in the trial by early autumn. The Oxford Vaccine Group at the University of Oxford is conducting a Phase 1 trial of its experimental vaccine, with the Serum Institute of India working to produce large quantities. Moderna has also initiated a Phase 1 trial of an mRNA vaccine in Canada.
Both organizations anticipate having initial safety and dosing data from these trials by September, which could lead to their inclusion in the Phase 3 trial, provided the data supports their use.
While both groups aim for single-dose vaccines, it remains uncertain if they will be effective without a booster. Ervebo is currently a one-dose vaccine.
A third Bundibugyo-specific vaccine, developed by the nonprofit IAVI and using the same platform as Ervebo, is still several months away from having enough doses for a Phase 3 trial.
