The trials — called ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) — are each expected to enroll up to 800 patients with moderate-to-severe COPD at clinical sites across the U.S. and Europe. Recruitment has started for ENHANCE-2 — more information is available here — but is not yet underway for ENHANCE-1.
“We are excited to start our pivotal ENHANCE Phase 3 studies. If successful, the data will support the submission of a New Drug Application in the U.S. for nebulized ensifentrine for the maintenance treatment of COPD,” David Zaccardelli, president and CEO of Verona Pharma, said in a press release.
“This is an important milestone for Verona Pharma and we look forward to addressing the urgent need for a novel therapy for the treatment of COPD,” Zaccardelli added.
Both studies will assess the safety and efficacy of a nebulized suspension of ensifentrine in patients when given alone or alongside another bronchodilator — either a long acting muscarinic antagonist (LAMA) or a long acting beta-agonist (LABA). Bronchodilators work to relax the muscles surrounding the lungs’ airways, opening them and making it easier for patients to breathe.
Trial participants will be randomly assigned to either a nebulized suspension containing 3 mg of ensifentrine, or a placebo, both twice-a-day for 24 weeks in the case of ENHANCE-2, and for either 24 or 48 weeks in the case of ENHANCE-1 (a patient subgroup will be treated long term to further evaluate safety).
The main goal of each study is to assess if ensifentrine can improve patients’ lung function, based on changes in forced expiratory volume in one second (FEV1) over 12 hours of exposure to the medication after 12 weeks of treatment.
Secondary goals include assessing changes in symptom severity and patients’ health-related quality of life, evaluated over the trials’ course. Safety assessments will also be conducted over the 24 weeks of treatment, as well as during the 48 weeks of ENHANCE-1.
Ensifentrine, formerly known as RPL554, is a first-in-class dual inhibitor of phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4), two enzymes involved in lung airway muscle contraction and inflammation. By blocking their activity, ensifentrine is expected not only to open the airways and make it easier for patients to breathe, but also to have an anti-inflammatory effect.
Earlier clinical trials of ensifentrine have shown the medication to be well-tolerated, with promising efficacy at improving lung function, reducing symptom severity, and ameliorating quality of life when used alone or with other bronchodilators.