Phase 2 Trial Starts Testing Multiple Doses of Ensifentrine in Inhaler Formulation

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by Forest Ray PhD |

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Verona Pharma has started the second part of a Phase 2 trial evaluating its investigational therapy ensifentrine (RPL544) in patients in the U.K. with moderate to severe chronic obstructive pulmonary disease (COPD), following delays related to COVID-19, the company announced in a press release.

Part B of the study (NCT04091360) will evaluate multiple doses of the pressurized metered-dose inhaler (pMDI) formulation of ensifentrine. Results are expected in the first half of 2021.

Part A of the trial evaluated 40 participants taking single doses of the investigational therapy. Results showed a statistically significant and clinically meaningful improvement in lung function as measured by forced expiratory volume in one second (FEV1), compared to a placebo. FEV1 is a standard measure of lung function that refers to how much air can be exhaled in one second after a deep breath.

The second part of the study had been delayed out of concern for the safety of patients and study staff, because of the ongoing pandemic. The decision to now continue the trial followed an assessment of local infection rates and control measures that were enacted, in addition to procedures already in place at the U.K. clinical sites.

“We are pleased to start the multiple dose part of this pMDI study,” David Zaccardelli, Verona’s president and CEO, said. “Data from the single dose part of this pMDI study are very encouraging and consistent with data from Phase 2 clinical trials with our nebulized and dry powder inhaler (“DPI”) formulations of ensifentrine.”

Ensifentrine inhibits the phosphodiesterase (PDE) proteins PDE3, involved in smooth muscle contraction, and PDE4, involved in immune cell-derived inflammation. This dual inhibition is designed to act as both a bronchodilator, relaxing the muscles of the airways, and as an anti-inflammatory.

Of note, Verona is developing several formulations of ensifentrine, including pMDI and DPI.

The second part of the trial testing ensifentrine pMDI will include approximately 30 patients who participated in Part A, at two sites in the U.K.

Patients will be randomized to receive twice-daily doses of 300 micrograms (mcg), 1,000 mcg, or 3,000 mcg of pDMI ensifentrine or placebo over the course of one week.

After a given seven-day treatment course, patients will cross over to the other doses until all patients have received all three dose levels and the placebo over four seven-day treatment periods.

The trial’s primary endpoint — the main goal to be assessed — is the improvement in lung function, as measured by peak FEV1, from baseline (the beginning of the trial) after a single dose.

Other measures of lung function, such as trough FEV1 — the change from baseline to day seven — and average FEV1 will serve as secondary endpoints. Other secondary endpoints include ensifentrine’s safety and tolerability and its pharmacokinetic profile — how the body absorbs, distributes, metabolizes, and excretes the therapy.

“The development of pMDI and DPI formulations of ensifentrine provides expanded opportunities,” Zaccardelli said. “We look forward to providing further updates on this pMDI study.”