Phase 2 Study of Oral Acebilustat in Treating Lung Inflammation Fully Enrolled in US, Europe

Celtaxsys announced it has completed enrollment of its Phase 2b clinical trial evaluating the company’s lead anti-inflammatory candidate, oral acebilustat, in adult patients with cystic fibrosis (CF).

Acebilustat (formerly known as CTX-4430) is a once-daily, oral anti-inflammatory being evaluated for its safety and efficacy in treating diseases like CF. It is a new small molecule inhibitor of leukotriene A4 hydrolase (LTA4H), the key enzyme in the production of  leukotriene B4 (LTB4), a molecule that causes inflammation and is known to be elevated in CF patients.

The EMPIRE-CF trial (NCT02443688) will investigate the potential of acebilustat to reduce lung inflammation and preserve lung function over the course of 48 weeks in patients, regardless of CFTR genotype, who are at high risk of rapid decline in lung function. Topline data are expected by mid-2018.

In total, 200 CF patients across North America and Europe have been enrolled, and are being randomly assigned to receive either 50 mg or 100 mg doses of oral acebilustat or placebo, in addition to CF standard of care, including CFTR modulator therapies (Orkambi or Kalydeco).

Efficacy will be determined by assessing acebilustat’s effects on lung function (FEV1 percent predicted) as a primary trial endpoint, with secondary goals including measures of change from baseline, or the study’s start, on pulmonary exacerbations, and in patient-reported outcomes.

Investigators will also assess inflammation biomarkers associated with the treatment’s immunomodulatory mechanism of action, including sputum neutrophil elastase and serum C-reactive protein. A reduction of certain inflammatory markers was observed in a previous Phase 1 study (NCT01944735) of oral acebilustat in CF patients.

“This acebilustat phase 2b trial has the potential to take the next crucial step in transforming the way we treat underlying pulmonary inflammation in CF patients, which is not currently adequately addressed, even by the best available care today,” Steven Rowe, MD, the trial’s U.S. principal investigator, said in a press release.

“If acebilustat exhibits adequate safety and beneficial effects  in preserving lung function, the outcome of this trial could herald the coming of a new era for anti-inflammatory treatment of CF patients, one which could change CF patient treatment standards moving forward,” said Greg Duncan, chief executive officer of Celtaxsys. “The efforts of all the investigators, site staff, and, in particular, the patients enrolled in the study are highly appreciated.”

The trial is being supported by the Cystic Fibrosis Foundation Therapeutics (CFFT), the foundation’s drug discovery and development arm.