Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis

Rio-CF Study Group, Nico Derichs, Jennifer L Taylor-Cousar, Jane C Davies, Isabelle Fajac, Elizabeth Tullis, Dilip Nazareth, Damian G Downey, Daniel Rosenbluth, Anne Malfroot, Clare Saunders, Renee Jensen, George M Solomon, Francois Vermeulen, Andreas Kaiser, Stefan Willmann, Soundos Saleh, Karoline Droebner, Peter Sandner, Christine E BearAnja Hoffmann, Felix Ratjen, Steven M Rowe

Onderzoeksoutput: Articlepeer review

Samenvatting

BACKGROUND: Riociguat is a first-in-class soluble guanylate cyclase stimulator for which preclinical data suggested improvements in cystic fibrosis transmembrane conductance regulator (CFTR) function.

METHODS: This international, multicenter, two-part, Phase II study of riociguat enrolled adults with cystic fibrosis (CF) homozygous for Phe508del CFTR. Part 1 was a 28-day, randomized, double-blind, placebo-controlled study in participants not receiving CFTR modulator therapy. Twenty-one participants were randomized 1:2 to placebo or oral riociguat (0.5 mg three times daily [tid] for 14 days, increased to 1.0 mg tid for the subsequent 14 days). The primary and secondary efficacy endpoints were change in sweat chloride concentration and percent predicted forced expiratory volume in 1 second (ppFEV1), respectively, from baseline to Day 14 and Day 28 with riociguat compared with placebo.

RESULTS: Riociguat did not alter CFTR activity (change in sweat chloride) or lung function (change in ppFEV1) at doses up to 1.0 mg tid after 28 days. The most common drug-related adverse event (AE) was headache occurring in three participants (21%); serious AEs occurred in one participant receiving riociguat (7%) and one participant receiving placebo (14%). This safety profile was consistent with the underlying disease and the known safety of riociguat for its approved indications.

CONCLUSIONS: The Rio-CF study was terminated due to lack of efficacy and the changing landscape of CF therapeutic development. The current study⁠, within its limits of a small sample size, did not provide evidence that riociguat could be a valid treatment option for CF.

CLINICAL TRIAL REGISTRATION NUMBER: NCT02170025.

Originele taal-2English
Pagina's (van-tot)1018-1025
Aantal pagina's8
TijdschriftJournal of Cystic Fibrosis
Volume20
Nummer van het tijdschrift6
DOI's
StatusPublished - nov 2021

Bibliografische nota

Copyright © 2021. Published by Elsevier B.V.

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