Talks are underway between authorities in the Democratic Republic of the Congo and the World Health Organization to expedite the start of a multi-armed Phase 3 clinical trial of vaccines geared toward helping to contain the spread of the Bundibugyo virus in the northeast of the country, which the director-general of the global health agency warned Wednesday is on track to become the largest Ebola outbreak on record.
“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,” Tedros Adhanom Ghebreyesus said during a news conference in Geneva.
The first vaccine to be pushed into the field for study will be Merck’s Ervebo, a vaccine that targets a different species of the virus, Ebola Zaire. An expert panel that advises the WHO was initially reluctant to recommend its use, but an increasing number of studies in animals and in people have persuaded it that the vaccine could offer some cross-protection against Bundibugyo, and should be tested to see if it could help.
“WHO has recommended inclusion of the vaccine in a Phase 3 trial, which we hope to start as soon as possible,” Tedros said. “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, more than 4,500 cases of Ebola have been confirmed in this outbreak, centered in the DRC’s Ituri province, near the borders of Uganda and South Sudan. More than 2,060 of those cases have died.
Vasee Moorthy, head of the WHO’s R&D blueprint program, said the agency is on the verge of submitting a trial protocol to regulatory and ethics committee officials in the DRC to seek their approval. If greenlit, the study would see known contacts of cases randomized to receive Ervebo or a placebo. As other vaccines — specifically ones that directly target the Bundibugyo species of Ebola — become available, they too would be added to the trial.
The trial is not using the ring vaccination approach employed in the Ebola Ça Suffit trial — French for “Ebola, that’s enough” — that proved Ervebo’s effectiveness and was conducted in Guinea during the West African outbreak. In that trial, rings of contacts of cases, as well as contacts of the contacts, were randomized to either get the vaccine immediately or on a delayed basis. Field studies have later estimated Ervebo’s effectiveness against Ebola Zaire at about 84%.
Moorthy said the results of multiple Ebola trials conducted in the intervening years led officials to conclude that randomizing contacts individually, rather than as part of a ring of contacts of an infected person, would be a better approach. “It is more efficient to individually randomize,” he said.
The WHO officials did not address — nor were they asked to address — a report this week in which DRC authorities announced they want to roll out Ervebo for general use outside of a clinical trial. The approach has received the support of the Africa Centres for Disease Control and Prevention.
It is unclear whether the DRC could access the number of vaccine doses that would be needed to put such a plan into action. There is a roughly 500,000-dose stockpile of Ervebo, but it is controlled by the International Coordinating Group on Vaccine Provision, which is run by the International Federation of Red Cross and Red Crescent Societies, Doctors Without Borders (MSF), the United Nations Children’s Fund (UNICEF), and the WHO. STAT asked the WHO about the idea after the press conference but had not yet received a response when this report was published.
Several Bundibugyo-specific vaccines could join the trial in the early autumn, Moorthy suggested. The Oxford Vaccine Group at the University of Oxford is currently conducting a Phase 1 trial of its experimental vaccine, with production partner the Serum Institute of India racing to produce large quantities of doses. And Moderna has begun a Phase 1 trial of a messenger RNA vaccine in Canada.
Both groups expect to have results of these trials — which provide initial safety and dosing data — in September, Moorthy said, and could be added to the Phase 3 trial if the Phase 1 data support their use.
Though both groups are hoping these vaccines can be used in a single dose, it remains to be seen if they can be effective without a booster. Ervebo is a one-dose vaccine.
A third Bundibugyo-specific vaccine is being developed by the nonprofit group IAVI; it uses the same platform as Ervebo. But it will be several months before enough doses of the vaccine are available for use in a Phase 3 trial.