In the constantly evolving Covid-19 landscape, a lot can change in a short time. Two years after beginning a Phase IIa trial of OP-101 in severe Covid-19 infections, Ashvattha Therapeutics is now pivoting to long Covid with the same drug. The California-based biotech is in discussions with the FDA to run a 300–400 patient trial of OP-101 in long Covid patients beginning in mid-2023, CEO Jeff Cleland tells Clinical Trials Arena.
Although the Phase IIa trial (NCT04458298) of OP-101 reported positive results in July, Cleland says acute Covid-19 no longer makes sense as a target indication. With vaccines and antivirals now widely available in the US, it has become increasingly difficult to recruit patients with severe Covid-19 and demonstrate a significant survival benefit in trials, he explains.
The possible trial of OP-101 would target the subset of long Covid patients with chronic inflammation, Cleland says, adding that further study details will depend on regulatory discussions. Ideally, Ashvattha will only need to run one trial for an approval in long Covid, with a possible commitment to confirm results in a second trial after approval, he notes. Long Covid describes the myriad symptoms some people experience at least one month after an acute Covid-19 infection, including breathing complications, fatigue, and brain fog.
The study will select patients with elevated C-reactive protein (CRP) levels, a widely used bloodstream biomarker of inflammation, Cleland says. In the previous Phase IIa trial, OP-101 reduced CRP levels and overall inflammation in patients with severe Covid-19.
OP-101 is an intravenously (IV) therapeutic that reduces inflammation by targeting reactive macrophages and microglia. By shutting down chronic inflammation in long Covid patients, OP-101 could improve lung function, fatigue, and cognitive loss, Cleland explains. OP-101 was originally developed for neurodegenerative diseases.
Long Covid endpoints
Overall, Ashvattha’s strategy will be to prioritise functional outcomes over surrogate markers, Cleland explains. The long Covid field still lacks any standardised clinical trial endpoints, making late-stage trial design a largely uncharted territory.
As a primary outcome, Ashvattha is considering lung function, which the FDA has accepted as an endpoint for trials in idiopathic pulmonary fibrosis, Cleland says. For a possible co-primary or secondary endpoint, Ashvattha will likely use a fatigue test score, he adds.
Ashvattha will also likely include a cognitive test as a secondary outcome, Cleland says. However, this endpoint will probably not achieve statistical significance, as that would likely require close to 1,000 patients, he notes.
Overall, clinical trials targeting long Covid have had somewhat limited success as experts struggle to understand the condition’s underlying causes. As Covid-19 enters an endemic state, the need for new treatments looms large.