Long-term amikacin liposome inhalation suspension in cystic fibrosis patients with chronic P. aeruginosa infection
Diana Bilton, Isabelle Fajac, Tacjana Pressler, John Paul Clancy, Dorota Sands, Predrag Minic, Marco Cipolli, Ivanka Galeva, Amparo Solé, Alexandra L Quittner, Zhanna Jumadilova, Monika Ciesielska, Michael W Konstan, CLEAR-110 Study Group, Diana Bilton, Isabelle Fajac, Tacjana Pressler, John Paul Clancy, Dorota Sands, Predrag Minic, Marco Cipolli, Ivanka Galeva, Amparo Solé, Alexandra L Quittner, Zhanna Jumadilova, Monika Ciesielska, Michael W Konstan, CLEAR-110 Study Group
Abstract
Background: . In CLEAR-108-a phase 3, randomised, open-label study-once-daily amikacin liposome inhalation suspension (ALIS) was noninferior to twice-daily tobramycin inhalation solution (TIS) in improving lung function in patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection after 3 treatment cycles (28 days on/28 days off). The CLEAR-110 extension study (ClinicalTrials.gov: NCT01316276; EudraCT: 2011-000443-24) assessed long-term safety, tolerability, and efficacy of ALIS in eligible patients who completed CLEAR-108.
Methods: . Patients received once-daily ALIS 590 mg for 12 treatment cycles (96 weeks). Patients were grouped by prior treatment: the "prior-ALIS" cohort received ALIS in CLEAR-108, and the "ALIS-naive" cohort received TIS in CLEAR-108.
Results: . Overall, 206 patients (prior-ALIS, n=92; ALIS-naive, n=114) entered CLEAR-110 and received ≥1 dose of ALIS. Most patients (88.8%) experienced ≥1 treatment-emergent adverse event (TEAE) through day 672 (end of year 2). Most TEAEs (72.3%) were mild or moderate in severity. Severe TEAEs were reported in 31 patients (15.0%). Two life-threatening TEAEs (haemoptysis; intestinal obstruction) and 1 death (cardiac failure) were reported. Twenty-one patients (10.2%) discontinued treatment due to a TEAE (mostly infective pulmonary exacerbation of CF). Mean change from baseline in forced expiratory volume in 1 second percent predicted at day 672 was -3.1% (prior-ALIS, -4.0%; ALIS-naive, -2.3%). Mean change from baseline in sputum density of P. aeruginosa at day 672 was 0.02 (prior-ALIS, -0.16; ALIS-naive, 0.19) log CFU/g.
Conclusions: . Long-term treatment with ALIS was well tolerated with a favourable adverse event profile and demonstrated continued antibacterial activity in CF patients with chronic P. aeruginosa infection.
Keywords: ALIS; Amikacin; Cystic fibrosis; Liposomal; Pseudomonas aeruginosa.
Conflict of interest statement
Declaration of Competing Interest D. Bilton: National Institute for Health Research funding support through the Imperial College, Royal Brompton Hospital, Specialist Respiratory Bio-Medical Research Unit; has received research contract support from Insmed Incorporated. I. Fajac: Received research contract support from Insmed Incorporated, has received a research grant from Actelion, and has served on advisory boards for Gilead Sciences and Vertex. T. Pressler: Received research contract support from Insmed Incorporated. J. P. Clancy: Serves on the Scientific Advisory Board and has received clinical trial support for phase II studies of ALIS in CF for Insmed Incorporated. D. Sands: Received research contract support from Insmed Incorporated. P. Minic: Received research contract support from Insmed Incorporated. M. Cipolli: Received research contract support from Insmed Incorporated, a grant from Vertex Pharmaceuticals, and served on advisory boards for Chiesi and Vertex. I. Galeva: Received research contract support from Insmed Incorporated. A. Solé: Has served on the advisory board for Gilead Sciences and Vertex. A. L. Quittner: Consulting for AbbVie, Aradigm, Insmed Incorporated, and Vertex; investigator-initiated studies for the Cystic Fibrosis Foundation. Z. Jumadilova: Employee of Insmed Incorporated. M. Ciesielska: Employee of Insmed Incorporated. M. Konstan: Has served on the Arikayce Clinical Program Steering Committee; has received grants and personal fees from Insmed Incorporated, Laurent Pharmaceuticals, Anthera, the Cystic Fibrosis Foundation, and AzurRX; has received personal fees from Chiesi, Celtazsys, Ionis Pharmaceuticals, Merck, Paranta Biosciences, Santhera, Ph Pharma, and Kala Pharmaceuticals; and has received nonfinancial support from Insmed Incorportated.
Copyright © 2021. Published by Elsevier B.V.
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Source: PubMed