Primary ciliary dyskinesia: Idrevloride shows promising results in phase 2 trial

Significantly increased pulmonary function was observed after 4 weeks of idrevloride plus hypertonic saline in patients with primary ciliary dyskinesia (PCD). Safety evaluations found adverse events that were consistent with PCD manifestations.

“Primary ciliary dyskinesia is a rare genetic disorder that is characterised by impaired motile ciliary function, and it leads to diverse clinical manifestations including chronic upper and lower respiratory tract disease, laterality defects, and subfertility,” Prof. Thomas Ferkol Jr (University of North Carolina, NC, USA) described. The phase 2 CLEAN-PCD trial (NCT02871778) investigated the sodium channel blocker idrevloride for its safety and efficacy as therapy for PCD [1]. When combined with hypertonic saline, 2 actions were predicted: the saline draws water into the airway lumen and idrevloride stimulates the secretion of chloride while inhibiting sodium and water absorption, thus rehydrating the mucus in the airway lumen.

The multinational trial randomised 123 patients, of at least 12 years of age, to 4 different regimens over 28 days in part A of the study: hypertonic saline or idrevloride alone, combination of hypertonic saline with idrevloride, or placebo. Then, treatments were crossed over for another 28 days, after a washout period of 4 weeks. “Individuals were also invited to continue their current therapy for another 28 days in part B, where we added ivacaftor, a CFTR-modifying drug, to see if that improved mucus hydration even further,” Prof. Ferkol. All participants were on stable therapy, baseline mean age was 28 years, mean percentage predicted forced expiratory volume in 1 second (ppFEV₁) was 66, and mean percentage predicted forced vital capacity (ppFVC) was 84.

“We were able to demonstrate that participants who were receiving combination therapy had a greater effect than those who were just receiving hypertonic saline, which was our primary comparator in this study,” Prof. Ferkol disclosed. The absolute change from baseline in ppFEV₁ was statistically significantly greater on hypertonic saline plus idrevloride versus hypertonic saline alone (+1.0 vs -0.5; P=0.04; see Figure). Similarly, ppFVC ameliorated most on the combination treatment in contrast with hypertonic saline alone (+1.3 vs -0.1; P=0.03) and in comparison with placebo (+1.3 vs -2.1; P=0.01), respectively. Adding ivacaftor to the medication regimen in part B of the trial, however, did not affect pulmonary function. “But what we did find, is that in individuals who were treated for 2 months as opposed to 1 month with idrevloride, there appeared to be a greater absolute change in ppFEV₁,” Prof. Ferkol added. Moreover, parameters of quality-of-life were improved. Based on these results, idrevloride for PCD is currently advanced to phase 3 investigations.

Figure: Absolute change in ppFEV₁ at day 28 in comparison with baseline [1]

1. Ferkol T. Safety and efficacy of idrevloride in people with primary ciliary dyskinesia: a double-blind, randomised, placebo-controlled crossover trial (CLEANPCD). Abstract 801, ERS International Congress 2023, 9–13 September, Milan, Italy.

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Posted on 29 October 202329 October 2023