Abstract
Background OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF.
Methods A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050 mg per day (10 capsules three times daily) or matching placebo for 28 days, with 28-day washout periods following each treatment period. The primary end-point was absolute change in percentage predicted forced expiratory volume in 1 s (FEV1) at the end of 28-day treatment. The intention-to-treat (ITT) population (n=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation.
Results In this study, 90 adult subjects were screened and 65 were randomised. Statistically significant improvement in FEV1 was not observed in the ITT population. Adverse events included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with adverse events and serious adverse events were similar between OligoG and placebo group.
Conclusions Inhalation of OligoG-dry powder over 28 days was safe in adult CF subjects. Statistically significant improvement of FEV1 was not reached. The planned analyses did not indicate a significant treatment benefit with OligoG compared to placebo. Post hoc exploratory analyses showed subgroup results that indicate that further studies of OligoG in this patient population are justified.
Abstract
Inhalation of OligoG-DPI over 28 days was shown to be safe in adult CF subjects. Statistically significant improvement of FEV1 was not reached. Post hoc subgroup analyses support mechanism of action for OligoG and warrant further prospective studies. https://bit.ly/2PHq6Z0
Footnotes
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This study is registered at www.clinicaltrials.gov with identifier number NCT02157922. Individual participant data that underlie the results reported in this article after deidentification (text, tables, figures and appendices) will be made available to researchers who provide a methodologically sound proposal for subsequent meta-analysis of trial data up to 36 months following publication. Requests can be made to the corresponding author.
The following investigators and their teams (in alphabetical order) conducted this study. Mary Carroll, General Hospital, Southampton, UK; Jane Davies, Royal Brompton and Harefield NHS Foundation Trust, London, UK (the study was supported by the NIHR Biomedical Research Unit and Clinical Research Facility); Carsten Schwarz and Nico Derichs, Christiane Herzog Zentrum, Charité Berlin, Germany; Damian Downey, Centre for Experimental Medicine, Queen's University, Belfast, UK; Olaf Eickmeier, University Hospital, Frankfurt a.M., Germany; Pal Leyell Finstad, University Hospital, Oslo, Norway; Rainald Fischer, Pneumologische Praxis Pasing, Munich, Germany; Marie Øbro Fossbøl, Rigshospitalet, Copenhagen, Denmark; Marita Gilljam, Sahlgrenska Universitetssjukhuset, Göteborg, Sweden; Charles Haworth, Papworth Hospital, Cambridge, UK; Lena Hjelte, Karolinska Universitetssjukhuset, Stockholm, Sweden; Alan Knox, City Hospital, Nottingham, UK; Silke van Koningsbruggen-Rietschel, University Hospital, Cologne, Germany; Gordon MacGregor, Queen Elizabeth University Hospital, Glasgow, UK; Jann Mortensen, Rigshospitalet, Copenhagen, Denmark; Susanne Nährig, LMU, Munich, Germany; Tacjana Pressler, Rigshospitalet, Copenhagen, Denmark; Joachim Riethmüller, University Hospital, Tübingen, Germany; Felix C. Ringshausen, MHH, Hannover, Germany; Martin Walshaw, Heart and Chest Hospital, Liverpool, UK; qualified person responsible for pharmacovigilance: Hugo Flaten, AlgiPharma AS, Sandvika, Norway; statistician: Nils Meland, Smerud Medical Research International AS, Oslo, Norway. The MCC substudy was performed at three sites: Laura Gow, Bio-Images Research Ltd, Glasgow, UK; Joy Conway, University of Southampton, Southampton, UK; Jann Mortensen, Marie Øbro Fosbøl, Rigshospitalet, Copenhagen, Denmark. Data was evaluated and reviewed by Scott H. Donaldson and William Bennett, UNC Chapel Hill, NC, USA. Culture-independent molecular analyses were performed by Eshwar Mahenthiralingam and Rebecca Weiser, Dept of Biosciences, Cardiff University, Cardiff, UK.
Conflict of interest: S. van Koningsbruggen-Rietschel reports grants from Horizon 2020 and personal fees from DZIF, outside the submitted work.
Conflict of interest: J.C. Davies reports work on an advisory board and as a clinical trial lead for Algipharma AS, work as UK Lead Investigator and on an advisory board for Bayer AG, work on an advisory board for Boehringer Ingelheim Pharma GmbH & Co. KG, work on an advisory board and clinical trial leadership for Galapagos NV, advisory and clinical trial design assistance for ImevaX GmbH, work on an advisory board for Nivalis Therapeutics, Inc., work on an advisory board and clinical trial design advice for ProQR Therapeutics III B.V., advisory work and clinical trial leadership for Proteostasis Therapeutics, Inc., advisory work for Raptor Pharmaceuticals, Inc., work on an advisory board and National Co-ord/Global Co-I for Vertex Pharmaceuticals (Europe) Limited, work on advisory boards for Enterprise, Novartis, Pulmocide and Flatley, grants from the CF Trust, and educational activities for Teva, outside the submitted work.
Conflict of interest: T. Pressler has nothing to disclose.
Conflict of interest: R. Fischer has nothing to disclose.
Conflict of interest: G. MacGregor has nothing to disclose.
Conflict of interest: S.H. Donaldson reports grants from AlgiPharma during the conduct of the study; and grants from Vertex Pharmaceuticals, AstraZeneca and Proteostasis Therapeutics outside the submitted work.
Conflict of interest: K. Smerud reports that his employer, Smerud Medical Research International AS, is a contract research organisation that delivered clinical trial management services (clinical trial management, clinical trial applications, data management, statistical planning and analysis, monitoring, and medical writing) to Algipharma and was remunerated for that work.
Conflict of interest: N. Meland reports grants from AlgiPharma AS during the conduct of the study.
Conflict of interest: J. Mortensen has nothing to disclose.
Conflict of interest: M.Ø. Fosbøl has nothing to disclose.
Conflict of interest: D.G. Downey reports grants and personal fees from Vertex, Proteostasis, Chiesi and Gilead, outside the submitted work.
Conflict of interest: A.H. Myrset reports grants from Cystic Fibrosis Foundation during the conduct of the study, and holds stock in AlgiPharma AB outside the submitted work.
Conflict of interest: H. Flaten reports grants from Cystic Fibrosis Foundation during the conduct of the study; and is a qualified person for Pharmacovigilance for AlgiPharma and holds stock in AlgiPharma AB, outside the submitted work.
Conflict of interest: P.D. Rye reports grants from Cystic Fibrosis Foundation during the conduct of the study, and is Chief Scientific Officer at AlgiPharma and holds stock in AlgiPharma AB, outside the submitted work; in addition, he has patents WO 2015/128495 and WO 2016/151051 pending.
Support statement: Funding for this study was received from the Cystic Fibrosis Foundation, Bethesda, MD, USA, with additional funding provided by the study sponsor AlgiPharma AS, Sandvika, Norway. The study sponsor and the contract research organisation (CRO) (Smerud Medical Research) participated in the study design, data collection, data analysis, data interpretation and writing of the study report. Following completion of the trial, the data were held and analysed by the sponsor and employees of the CRO. The authors had full access to all data and had final responsibility for publication. The final decision on content was exclusively retained by the contributing authors. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received March 18, 2020.
- Accepted July 25, 2020.
- Copyright ©ERS 2020
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