Santhera Starting Phase 1b/2a Trial Testing Potential CF therapy POL6014

A Phase 1b/2a, dose-escalating clinical trial evaluating the effects of POL6014 in patients with cystic fibrosis (CF) was recently launched, according to Santhera Pharmaceuticals, developer of the investigational therapy.

The Phase 1b/2a (EudraCT 2016-005110-22) will evaluate the safety, tolerability, pharmacokinetics (drug absorption, distribution, and elimination by the body), and pharmacodynamics (the drug’s effects) of orally inhaled POL6014 in patients with CF.

Researchers will also assess the highest tolerated dose of POL6014 and associated dose regimen. Other primary objectives are the effect of the treatment on patients’ lung function, assessed by spirometry tests, and blood oxygen levels.

The study plans to enroll up to 40 patients, who will be treated for 15 days with either a placebo or one of three ascending doses of POL6014, given once or twice daily. The study is taking place at centers in Germany and Poland, and is expected to conclude in the second half of 2019.

POL6014 is a highly potent and selective inhibitor of human neutrophil elastase (hNE), an enzyme released by neutrophils and macrophages (a type of white blood cell) that normally works to kill bacteria during infections. But neutrophil elastase was also found to be associated with many inflammatory lung conditions, including CF, where high levels of the enzyme correlate with stronger disease severity and poorer lung function.

Because POL6014 works by blocking hNE function, it is expected to halt or slow down airway inflammation and damage, relieving CF respiratory symptoms.

In prior Phase 1 studies conducted in healthy volunteers and CF patients, the therapy seemed to be well-tolerated and to inhibit hNE activity.

“POL6014 brings new promise to patients with CF, who, despite the introductions of various new treatment options, continue to experience lung tissue inflammation which contributes to pulmonary exacerbations. I am very excited to be part of this Phase 1b/2a trial, which will further profile POL6014 as an innovative treatment option,” Marcus Mall, MD, professor and head of the pediatrics department in the Division of Pneumonology, Immunology and Intensive Medicine at the Charité – Universitätsmedizin Berlin, said in a press release.

Throughout the development of POL6014, Santhera will be working with leading experts in CF, as well as the Therapeutics Development Network, supported by the U.S. Cystic Fibrosis Foundation, and the Clinical Trial Network from the European Cystic Fibrosis Society, according to Kristina Sjöblom Nygren, MD, chief medical officer and head of development at Santhera.

In February, Santhera purchased the rights to POL6014 from Polyphor. Recently, the therapy has been recommended for orphan drug designation in the European Union.