Verona Pharma has started a Phase 2 clinical trial to evaluate the potential of its nebulized RPL554 as an add-on treatment to the approved Stiolto Respimat (tiotropium bromide/olodaterol) for the treatment of moderate to severe chronic obstructive pulmonary disease (COPD).
A total of 75 patients are expected to be recruited for the trial, taking place in the U.S. and U.K. The randomized, double-blind trial has already enrolled and dosed the first COPD patients.
RPL554 is a first-in-class, inhaled, dual inhibitor of the proteins phosphodiesterase (PDE) 3 and 4. The investigational medicine acts as both a bronchodilator and an anti-inflammatory agent. RPL554, delivered via a nebulizer, is in development for the treatment of cystic fibrosis and COPD, and potentially also for asthma. Verona has already reported positive data for the treatment of COPD.
Stiolto Respimat, marketed by Boehringer Ingelheim, is a dual, long-acting anti-muscarinic (LAMA; tiotropium bromide) and long-acting beta2-agonist (LABA; olodaterol). It is approved for controlling COPD symptoms in adults.
In the trial, participants already receiving inhaled corticosteroid (ICS) anti-inflammatory therapy will continue to receive a stable ICS dose. This will allow researchers to test a triple therapy — a combination of RPL554, Stiolto Respimat, and ICS treatments.
After completing seven to 14 days of a washout period, participants will receive either 1.5 mg or 6 mg of RPL554, or a placebo, twice daily for three days.
The primary objective of the study is improvements in lung function, measured by forced expired volume in one second (FEV1), in patients taking RPL554, compared with those on a placebo.
“We have already demonstrated that RPL554 is an effective add-on treatment to short- and long-acting bronchodilators in COPD patients. This Phase 2 trial will now examine the effect of RPL554 as an add-on to LAMA/LABA therapy, and in some patients to triple therapy, as many of these COPD patients continue to experience breathing difficulties and daily symptoms that impair their quality of life despite concomitant treatment with two bronchodilators,” Jan-Anders Karlsson, Verona’s CEO, said in a press release.
“We believe the bronchodilator and anti-inflammatory properties of RPL554 may be particularly useful in this large group of patients with high, unmet medical need. This Phase 2 trial is intended to provide important data to inform the design of pivotal Phase 3 studies with RPL554, expected to commence later next year,” Karlsson said.
Top-line data of the Phase 2 trial are expected in the first quarter of 2019.
Previous studies have shown that RPL554 is a safe therapy with bronchodilator action when used alone or in combination with other COPD bronchodilators. The treatment can lead to clinically meaningful and statistically significant improvements in lung function in COPD patients.
In May, Verona presented data at the 2018 American Thoracic Society International Conference in San Diego, showing a strong bronchodilation effect when RPL554 was used together with Spiriva (tiotropium).