First patients enrolled in record-breaking Ebola treatment trial in DR Congo

Hind Al Soulia - Riyadh - LONDON — First patients have been enrolled in a Ebola treatment trial in the Democratic Republic of Congo as two drugs are being trialed in the Ituri region in a program set up just six weeks after the outbreak was declared, according to the Guardian newspaper.

Meanwhile, another vaccine to tackle the Bundibugyo species of Ebola will now be tested on people after the UK regulator gave permission for trials to take place, according to the BBC.

There are other vaccines being developed.

These include one from biotechnology company Moderna using their mRNA vaccine technology. The International Aids Vaccine Initiative and Public Health Vaccines, based out of the US, are using the same technique that has been proven to work for another species of Ebola, but is slower to manufacture.

It is a record pace to set up and start this kind of research, scientists said, with patients enrolled in a treatment trial just six weeks after the outbreak being declared a public health emergency of international concern by WHO.

Scientists at the University of Oxford started developing the vaccine eight weeks ago when a public health emergency was declared on May 17.

Volunteers are being recruited, with the first doses expected to be given to healthy adults in the UK "within weeks".

The Ebola epidemic, centered on DR Congo, has killed at least 625 people so far.

It is caused by the Bundibugyo species of Ebola, which has started two outbreaks before.

The six different species of Ebola are known as "sisters rather than twins" because while they are similar, they need separate treatments and vaccines. It means there are no approved drugs or vaccines this time.

The outbreak is still not under control and is taking place in a conflict zone with very mobile populations – heightening the need for a vaccine to help stop the spread of disease.

Dr Katrina Pollock, the chief investigator of the trial based at the University of Oxford, told the BBC: "We're doing phase one (early stage) trials of new vaccines all of the time, precisely to be ready for exactly this kind of outbreak."

The trial will be on 50 healthy adults aged 18-55. Researchers are also working with partners in Uganda to prepare for trials in Africa.

Volunteers will be monitored for a year, but scientists should know quickly whether the vaccine is producing the right kind of immune response or any unexpected side effects.

The Oxford team have been able to develop their vaccine in a matter of weeks because they are using the same technology that shot to fame during the Covid pandemic and was used in the Oxford/AstraZeneca Covid vaccine.

It uses a common cold virus that infects chimpanzees that has been genetically modified to make it safe.

This acts like an envelope and all the researchers need to do is change the letter inside before posting it into the body.

In Covid, the letter being delivered was a snippet of genetic code from the Covid virus.

This time it's a snippet from the Bundibugyo species of Ebola.

The vaccine does not cause an infection, but the piece of the genetic code starts producing one viral protein from Ebola inside the body.

This is enough to trigger the immune system to recognise a threat and mount an immune response.

That means the body should already have a head start if it encounters Ebola virus for real.

The vaccine has been developed, tested on mice and macaque monkeys, and is being manufactured to a clinical standard by the Serum Institute of India. It has manufactured and stockpiled around 620,000 doses.

Based on that data, the UK's Medicines and Healthcare Products Regulatory Agency has given the go-ahead for human trials.

Vaccine researcher Alex Sampson told the BBC: "As soon as we heard there was an outbreak, we were able to scale up really, really quickly."

Vaccines can normally take up to a decade to research, develop and prove effective. But Sampson says no corners are being cut.

"We're doing all the same tests that we would normally do, just we're able to do them in parallel, so it means a lot of teams working in lots of different places around the clock, but we're still doing everything that we would normally," he added.

The Oxford Covid vaccine was estimated to have saved six million lives in the first year it was used around the world and hundreds of millions of doses have been taken.

However, the vaccine was also restricted for use in some countries because of rare blood clots which affected up to one in 100,000 people.

It is possible this vaccine carries the same risk, although this is much lower than the threat from the Bundibugyo species of Ebola which kills around a third of those infected.

Pollock said severe side effects are "very rare" and they thought "very deeply" about the implications for trials on healthy people, and that any risk would be communicated to volunteers.

"I want to stress that the Covid AstraZeneca vaccine was given to millions of people safely," she added.

As of 9 July, there had been 1,792 confirmed cases and 625 deaths caused by the Bundibugyo strain of the virus, for which there is no vaccine and no approved treatment.

Hopes of turning the tide now rest with scientists searching for effective medicines.

The PARTNERS (Platform Adaptive Randomised Trial for New and Repurposed Filovirus Treatments) trial has opened in DR Congo with two drugs on its books – remdesivir, and MBP134. Patients will be randomly allocated to receive either drug, a combination of the two, or simply standard, supportive care.

Remdesivir is an antiviral made by pharma company Gilead Sciences, while MBP134 is a monoclonal antibody developed by Mapp Biopharmaceutical, containing two specially engineered immune proteins that recognize and neutralize the virus.

Both are given intravenously – MBP134 as a one-off infusion, and remdesivir as 10 days of intravenous therapy.

“These two drugs actually have been proven to work against the Bundibugyo virus in animal models,” said Prof Laurens Liesenborghs of the Institute of Tropical Medicine, Antwerp, who is working on the trial in Ituri.

“They showed great efficacy, but now we need to test it in humans. Basically, what we want to see is if they indeed can lower mortality.”

Bundibugyo typically has a lower death rate than the Zaire strain of Ebola, which has caused most previous outbreaks, but it still kills about one in three of those infected.

Researchers are watching carefully for any difference in death rates between the groups given experimental drugs and the group receiving standard care. “Any improvement is good,” said Liesenborghs. “But it needs to be statistically detected, so we need to see a substantial drop.”

In trials looking at the impact of monoclonal antibodies on Ebola cases caused by the Zaire strain, it lowered death rates from 50% to 35%, he said. “Hopefully we will see something in the order of that magnitude.”

The trial’s design allows other potential treatments to be added should they become available. A result is likely to need between 700 and 1,000 patients to be enrolled, Liesenborghs said.

“We opened one site, hopefully we’ll open additional sites very quickly, but still then it will take a couple of months, depending on how the outbreak is going, obviously.”

WHO officials said enough remdesivir and MBP134 had been donated, by Gilead and the US government respectively, for 1,200 patients to be enrolled. The WHO is in discussions to ensure sufficient supplies will be available after the trial, should they prove safe and effective, it said.

Patients of any age, including pregnant and breastfeeding women, who are often excluded from medical research, can enrol in the trial.

“We always think of risk-benefit,” says Liesenborghs. “Here the benefit is potentially very high because you offer a potentially life-saving treatment to someone who has a very high chance of dying.”

“It’s just fantastic we’ve managed to get started so quickly,” says Prof Amanda Rojek, international principal investigator for PARTNERS, of the University of Oxford.

She said strong scientific leadership in the DRC, which has hosted major trials during earlier outbreaks of Ebola and other diseases such as mpox, had been vital.

“If we look back at west Africa (an Ebola outbreak in 2014-16 that saw more than 28,000 cases and 11,000 deaths), where it took us over a year to start clinical trials, we’re very proud of the team led by INRB (the DRC’s National Biomedical Research Institute) that we’ve managed to achieve that in kind of six weeks since the outbreak was first announced.”

The focus, Rojek said – as in the Recovery trial during Covid, delivered by the same Oxford group – was on keeping the trial as simple as possible.

PARTNERS is sponsored by the WHO, with funding from the Wellcome Trust, FCDO and UKRI.

Prof Yap Boum, head of emergency response with continental health watchdog Africa CDC, warned that the danger was not over, but added: “What limits an outbreak is our capacity to provide care, our surveillance capacity and our ability to isolate people. These trials will enable us to access treatment, and when we treat people, it also sends a message to the community.”

Another trial is due to begin this week, looking at whether giving people who have been in contact with Bundibugyo cases a drug called obeldesivir can stop them developing the disease.

Africa CDC said that trial needed around $18 million to proceed, with $6 million committed to date.