Olatec Therapeutics has initiated patient enrolment in a Phase II trial to analyse the safety and efficacy of oral NLRP3 inhibitor, dapansutrile, for treating patients with moderate Covid-19 symptoms and early cytokine release syndrome (CRS).
The SARS-CoV-2 virus that causes Covid-19 activates the innate immune signalling sensor NLRP3 and produces IL-1β, a pro-inflammatory cytokine. The activation of NLRP3 results in CRS, an intense inflammatory response found in Covid-19 patients.
Dapansutrile can potentially reduce or prevent hyper inflammation associated with CRS by hindering the production of Interleukin-1 beta (IL‑1β) early to stop progression to a severe cytokine storm.
Olatec Therapeutics co-founder and CEO Damaris Skouras said: “In a previous clinical trial, dapansutrile was observed to suppress IL-1β and downstream cytokines and chemokines of the inflammatory cascade in patients with the acute gout flares.
“In our Covid-19 programme, the aim for dapansutrile is similar, to inhibit IL-1β, preventing Cytokine Release Syndrome from becoming a Cytokine Storm, which clinically could keep patients from progressing into severe disease stages of inflammation requiring hospitalisation.”
In the randomised, double-blind, placebo-controlled trial, about 80 ambulatory adult patients will receive two doses of 250mg dapansutrile capsules or placebo for 14 days.
As a primary outcome, the trial will analyse the number of patients with complete resolution of fever symptoms and shortness of breath.
Secondary outcomes are the incidence of severe adverse events (SAE), time to clinical improvement, clinical improvement in Covid-19 symptoms, and time to sustained absence of fever among many others.
Dapansutrile is currently in Phase II clinical development and was well-tolerated and demonstrated improvement in clinical outcomes in patients with acute gout flare and heart failure.
It has also shown anti-inflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models.