Safety, Tolerability and early signs of efficacy with riociguat for the treatment of adult PHE508DEL homozygous cystic fibrosis patients: safety data from the RIO-CF study

J. L. Taylor-Cousar, N Derichs, D. E. Tullis, J.C. Davies, D. Nazareth, D. Downey, D Rosenbluth, I Fajac, Anne Malfroot, M. Bakker, G. Wirsching, A. Hoffmann, S M Rowe, Felix Ratjen

Research output: Contribution to journalMeeting abstract (Journal)


Objectives: The only approved CFTR-modulating therapy for CF patients homozygous for the Phe508del mutation is ivacaftor+lumacaftor. Preclinical data indicate that the soluble guanylate cyclase stimulator rio- ciguat may improve CFTR channel function. The primary objectives of the Rio-CF study are to assess safety, tolerability and early signs of efficacy of riociguat in patients not receiving CFTR modulator therapy. Methods: Rio-CF is a sequential-group, multicenter, international, Phase II trial. Eligibility criteria include adults with CF who are homozy- gous for Phe508del with mild-to-moderate pulmonary disease (forced expi- ratory volume in 1 second (FEV 1 ) 40—100% of predicted and stable lung disease). In Part 1 of the study, patients were randomized (1:2) to placebo or riociguat 0.5 mg three times daily (tid) for 14 days, then 1 mg tid for 14 days. Safety and tolerability were continuously assessed by monitoring vital signs and adverse events (AEs). Results: Part 1 of the study closed with 21 patients randomized (mean age 27.8 [range 19–40] years; 16 men [76%]; mean BMI 22.41 [range 19.1–32.0] kg/m 2 ; mean FEV 1 66.12 [range 48–91]%). Nineteen patients completed study drug treatment, including the uptitration to 1 mg. Study drug-related AEs occurred in 12 patients (42 events in total), and were of mild or moderate intensity in four and seven patients (25 and 16 events), respectively. One patient experienced an AE [headache (HA)] of severe intensity, leading to discontinuation. The most common AEs considered study-drug related were HA and changes in sputum. Treatment-emergent AEs occurring in > 10% of patients were HA (23.8%), cough (19.0%), abdominal pain (14.3%), fatigue (14.3%), infective pulmonary exacerba - tion (PEx) of CF (14.3%), nasopharyngitis (14.3%) and sputum discolor- ation (14.3%). Three serious AEs were reported in the study: two PEx (one during screening, resulting in screening failure) and one distal intestinal obstruction syndrome leading to discontinuation. The AEs of special safe- ty interest were predefined as symptomatic hypotension (no events) and hemoptysis (one mild event). Assessment of unblinded data by an indepen - dent Data and Safety Monitoring Board revealed no safety concerns and study continuation was recommended. Conclusions: Safety data obtained from Part 1 of the Rio-CF study are consistent with the underlying disease being studied and known safety pro- file of riociguat in the indications for which it is approved (pulmonary arte - rial hypertension and chronic thromboembolic pulmonary hypertension).
Original languageEnglish
Pages (from-to)S307
Number of pages1
JournalPediatric Pulmonology
Issue numberS47
Publication statusPublished - Sep 2017
EventThe 31st Annual North American Cystic Fibrosis Conference, Indiana Convention Center, Indianapolis, Indiana - Indiana Convention Center, United States
Duration: 2 Nov 20174 Nov 2017


  • Riociguat
  • Phe508del homozygous
  • CF patients
  • Rio-CF Study

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