A Phase 2 clinical trial is enrolling participants to evaluate the safety and efficacy of Verona Pharma’s dry powder inhaler RPL554 as a potential maintenance treatment for people with moderate to severe chronic obstructive pulmonary disease (COPD).
RPL554 is a dual inhibitor of the proteins phosphodiesterase (PDE) 3 and 4, both linked to COPD. The therapy has bronchodilator and anti-inflammatory properties, and is in development for the maintenance treatment of COPD, cystic fibrosis, and asthma.
The new Phase 2 trial, taking place at a clinical site in the U.S., is divided into two parts and expects to recruit 36 patients.
In the first part, patients receive a single dose of RPL554 administered as a dry powder inhaler. This phase’s main objective is to evaluate the therapy’s pharmacokinetics, i.e. the movement of the therapy into, through, and out of the body.
Secondary objectives include the assessment of RPL554’s safety, tolerability, and the therapy’s efficacy as a bronchodilator after a single dose.
In the study’s second part, RPL554 is administered in multiple doses, and researchers will evaluate its bronchodilator effects by measuring participants’ peak forced expiratory volume in one second (FEV1), a measure of how much air can be exhaled in one second after a deep inhaled breath.
Secondary aims include the assessment of the doses’ safety and tolerability, as well as the pharmacokinetics, time to take action, and whether and how much rescue medication patients require during the trial.
Data from the single-dose portion of the study are expected during the first half of 2019.
Previous results showed that RPL554 alone can effectively improve lung function in COPD patients. In addition, when administered as an add-on treatment to standard short- and long-acting bronchodilators, RPL554 enhanced the bronchodilator’s action, while also reducing hyperinflation (overinflated lungs, considered a cause of breathlessness in COPD).
The studies also showed that the therapy was well-tolerated.
By now, RPL554 delivered as a nebulizer has been tested in 12 clinical trials involving more than 730 subjects.
“Positive results using inhaler formulations could dramatically expand the clinical utility and commercial opportunity for RPL554 in the maintenance treatment of COPD and potentially broaden its use for other respiratory indications, such as asthma,” Jan-Anders Karlsson, PhD, CEO of Verona Pharma, said in a press release.
“With an estimated 5.4 million people using inhalers for the maintenance treatment of COPD in the U.S. alone, and another one million patients using nebulized formulations, we believe it is important to understand how RPL554 works via these different delivery platforms in order to fully realize and leverage its clinical potential for patients with respiratory diseases,” Karlsson said. “We look forward to building upon the positive results that have been garnered to date utilizing the nebulized formulation of RPL554.”
Another Phase 2 trial (NCT03673670), currently recruiting participants, is evaluating nebulized RPL554 as an add-on therapy to Stiolto Respimat (a combination therapy of tiotropium bromide and olodaterol, marketed by Boehringer Ingelheim).
Verona also plans to further test RPL554 as an add-on therapy to long-acting bronchodilator combinations (LAMA/LABA) plus low-dose inhaled corticosteroids, and to assess the therapy’s efficacy as a metered-dose inhaler.