In the early months of the pandemic, human challenge clinical trials drew amplified public interest on its potential to accelerate the hunt for Covid-19 vaccines. Fast forward two years later, while mainstream media buzz around this trial design has somewhat tempered, this does not seem to be the case in the clinical trials sector, at least according to one service provider.
“There’s been unprecedented demand for human challenge trials recently,” says Open Orphan chief scientific officer Andrew Catchpole. “We are fully booked for the next 12 months. We added 19 extra beds to our pre-existing 24 last year and are considering adding an extra seven in the coming year.”
Catchpole says there’s an uptick in interest in influenza challenge trials – either to study new approaches or candidates developed years ago but are now drawing renewed interest. As an example, Poolbeg Pharma announced July 20 it is about to commence a placebo-controlled Phase Ib human challenge trial investigating its potential influenza candidate POLB 001.
Human challenge trial attractive
“Sponsors seeking our [Open Orphan] help often ask us about the benefit of challenge trials,” Catchpole says. And the attraction can vary depending on the company size.
With small biotechs, these human challenge trials offer clear proof-of-concept data, much better than data from animal studies, which can be plagued with translation issues on how it would perform in humans, he says. “It is a good first step in getting early human data,” adds Poolbeg CEO Jeremy Skillington.
As for big pharma, human challenge trial data can be used to argue their case for internal funding over other assets in the pipeline, Catchpole says. “It is a way to de-risk the asset,” Skillington adds.
In Covid-19, there is still a place for human challenge design, to investigate vaccine boosters and how they should be paced, Catchpole says. Such a trial design can help establish early human data for potential new candidates with a new technology, administration method, or tweaks for a certain variant, he adds. On June 30, Vaxart announced it has engaged Open Orphan to make plans for a Phase II human challenge trial investigating the company’s oral Covid-19 vaccine against the SARS-CoV-2 Omicron variant.
Execution challenges exist
But there are also execution challenges. One challenge is the need to recruit healthy volunteers, which necessitate financial compensation to secure participants. On June 24, the UK’s NHS University Hospital Southampton revealed plans for a whooping cough human challenge study to test a new vaccine. In this trial, participants are compensated £3,775.
Human challenge trials also require specialised facilities. For its Phase Ib, Poolbeg is working with the Foundation Center for Human Drug Research (CHDR) in the Netherlands which has its own hospital, laboratories, and facilities, Skillington says.
With Open Orphan’s human challenge trials, participants are put in isolation for two weeks and their activities are tightly regulated, Skillington says. This is important because the regulated environment means that the data is very clean – you know what the volunteer is like when they are healthy, sick, and recovered, he adds.
Poolbeg is a demerged company from Open Orphan. In 2019, Open Orphan purchased hVIVO, which had a biotech arm and a CRO arm. The CRO arm stayed with Open Orphan and the biotech spun out along with some key data assets and POLB 001 to become Poolbeg.
Some infections better fit than others
Challenge models can only be done if subjects are expected to clear the infection without treatment, as is the case for respiratory syncytial virus, influenza, human rhinoviruses, and coronaviruses. It can also be done in conditions for which a proven treatment is available.
There are infectious diseases where human challenge trials are harder to execute. “In malaria [human challenge trials], we treat [participants] as early as possible before they get a full-blown disease, before symptoms show up. We need to clear the infection as it can be dangerous,” Catchpole says. But such malaria trials can be safely conducted as there are treatments available, he adds.
And then there’s Ebola, where it is “absolutely impossible” to run a human challenge trial, Catchpole says. Ebola has a mortality rate of 40% and there is no way to predict who will have severe disease, he explains.
As for advice for sponsors looking to get into human challenge trials: Catchpole says they should consult with service providers as early as possible due to the nuances involved in running such a trial. “[Open Orphan] is heavily involved in study design. This is in contrast with traditional CROs where sponsors can come in with their own trial design. There are subtleties in designing human challenge trials – down to the wording of endpoints.”
Influenza trial to recruit 36 participants
Poolbeg’s Phase lb POLB 001 trial is looking to enrol 36 healthy volunteers, whose immune system will be triggered by bacterial lipopolysaccharide (LPS), and then test POLB 001 for efficacy in terms of blocking an immune response, Skillington tells Clinical Trials Arena. The Phase Ib will investigate three different doses of POLB 001, he adds.
“In our human challenge trial, we plan to induce the immune system to react to a foreign body, in contrast to an approach where the healthy participant is exposed to a virus. Our volunteers do not get sick, per se. We are using a bacterial fragment versus [having the participant] be infected,” Skillington notes.
POLB 001 is envisioned to be a therapeutic asset for severe influenza that also blocks the excessive immune response that can cause tissue damage, he says. In severe influenza, a severe immune response can lead to lung and tissue damage. POLB001 is a p38 MAP kinase inhibitor, where the p38 pathway is triggered during an immune response. With initial data expected in Q4 2022, Skillington adds: “Once we get Phase Ib data we would like to partner the asset so having that human data is attractive.”