The Phase 2a single-dose trial is being conducted in the United Kingdom. The primary objective of this double-blind, placebo-controlled study will evaluate the pharmacokinetic and pharmacodynamics profile and tolerability of RPL554 in up to 10 CF patients, as well as examine the effect on lung function.
Verona Pharma received its second Venture and Innovation Award from the UK Cystic Fibrosis Trust in October 2016 to fund this clinical trial. Verona Pharma received its first Venture and Innovation Award to fund exploratory pre-clinical studies of RPL554 for the treatment of CF in 2014.
The trial is being performed at the Cambridge Centre for Medical Research at Papworth Hospital, Cambridge, UK, one of the largest specialist cardiothoracic hospitals in Europe, by lead investigator Professor Andres Floto.
RPL554 is a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 (PDE3/PDE4) with anti-inflammatory as well as bronchodilatory properties, currently in development for the treatment of chronic obstructive pulmonary disease (COPD) and CF.
In pre-clinical studies, RPL554 has been observed to stimulate the CF transmembrane conductance regulator, a protein whose mutation results in dysfunctional ion channels in epithelial cells, leading to CF.
Based on available data, RPL554 has the potential to enhance mucociliary clearance (reduce phlegm in the airways), reduce airway obstruction and inhibit inflammation.
In previous clinical trials in patients with COPD, RPL554 has been observed to result in statistically significant improvements in lung function as compared to placebo and has shown clinically meaningful and statistically significant improvements in lung function when added to two commonly used bronchodilators as compared to either bronchodilator administered as a single agent.
RPL554 has also shown anti-inflammatory effects in a standard challenge study with COPD-like inflammation in human subjects. In these previous studies, RPL554 has been well tolerated.
Jan-Anders Karlsson, PhD, CEO of Verona Pharma said: "Cystic fibrosis is the most common fatal inherited disease in the United States and Europe. More than 30,000 people in the U.S. and more than 70,000 people worldwide are living with cystic fibrosis.
"Two recently approved therapies are indicated only for a subset of CF patients, and there is a need for novel, effective anti-inflammatory medications to treat the underlying inflammation in cystic fibrosis.
“RPL554 has a differentiated mechanism of action and pre-clinical data in cystic fibrosis combined with our positive clinical data in COPD leads us to believe it has the potential to be an important new treatment for this debilitating condition. We look forward to progressing the drug through this study and expect to announce top-line data in the first half of 2018."
Paula Sommer, Head of Research of the UK Cystic Fibrosis Trust, said: "The Venture Innovation Awards are designed to ensure that the Trust's funds go as far as possible to supporting ground-breaking treatments and innovative research by bringing in vital external funding.
"The RPL554 trial has the potential to make a difference to the lives of people with CF, and we are thrilled that the drug is moving into this important trial stage."