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Infectious diseases
Protocol
Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial
  1. Ameneh Khatami1,2,
  2. David A Foley3,4,
  3. Morgyn S Warner5,6,
  4. Elizabeth H Barnes7,
  5. Anton Y Peleg8,9,
  6. Jian Li8,
  7. Stephen Stick10,11,
  8. Nettie Burke12,
  9. Ruby C Y Lin13,14,
  10. Julia Warning15,
  11. Thomas L Snelling1,16,
  12. Steven Y C Tong17,18,
  13. Jonathan Iredell14,19
  14. for the Phage Australia Clinical Network
  1. 1The Children's Hospital at Westmead Department of Infectious Diseases and Microbiology, The Sydney Children's Hospitals Network, Westmead, New South Wales, Australia
  2. 2Children's Hospital Westmead Clinical School, The University of Sydney, Sydney, New South Wales, Australia
  3. 3Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia, Australia
  4. 4Department of Microbiology, PathWest Laboratory Medical WA, Nedlands, Western Australia, Australia
  5. 5Infectious Diseases Unit, Central Adelaide Local Health Network, Adelaide, South Australia, Australia
  6. 6Discipline of Medicine, The University of Adelaide Faculty of Health and Medical Sciences, Adelaide, South Australia, Australia
  7. 7NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
  8. 8Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia
  9. 9Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Clayton, Victoria, Australia
  10. 10Wal-yan Respiratory Research Centre, Telethon Kids Institute, Nedlands, Western Australia, Australia
  11. 11Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, Western Australia, Australia
  12. 12Former CEO, Cystic Fibrosis Australia, North Ryde, New South Wales, Australia
  13. 13Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
  14. 14Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, Westmead, New South Wales, Australia
  15. 15Office for Health and Medical Research, New South Wales Ministry of Health, St Leonards, New South Wales, Australia
  16. 16School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
  17. 17Department of Infectious Diseases, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  18. 18Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  19. 19Department of Infectious Diseases, Westmead Hospital, Westmead, New South Wales, Australia
  1. Correspondence to Dr Ameneh Khatami; ameneh.khatami{at}health.nsw.gov.au

Abstract

Introduction There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy.

Methods and analysis We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia’s Therapeutic Goods Administration Special Access Scheme. A phage product with high in vitro activity against the targeted pathogen(s) must be available in line with relevant regulatory requirements. We aim to recruit 50–100 patients over 5 years, from any public or private hospitals in Australia. The standardised protocol will specify clinical assessments and biological sampling at scheduled time points. The primary outcome is safety at day 29, assessed by the frequency of adverse events, and overseen by an independent Data Safety Monitoring Board. Secondary outcomes include long-term safety (frequency of adverse events until at least 6 months following phage therapy), and feasibility, measured as the proportion of participants with>80% of minimum data available for analysis. Additional endpoints assessed include clinical response, patient/guardian reported quality of life measures, phage pharmacokinetics, human host immune responses and microbiome analysis. All trial outcomes will be summarised and presented using standard descriptive statistics.

Ethics and dissemination Participant inclusion will be dependent on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Sydney Children’s Hospitals Network Human Research Ethics Committee in December 2021 (Reference 2021/ETH11861). In addition to publication in a peer-reviewed scientific journal, a lay summary of study outcomes will be made available for participants and the public on the Phage Australia website (https://www.phageaustralia.org/).

Trial registration number Registered on ANZCTR, 10 November 2021 (ACTRN12621001526864; WHO Universal Trial Number: U1111-1269-6000).

  • paediatrics
  • infectious diseases
  • microbiology
  • general medicine (see internal medicine)
  • therapeutics
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2022-065401

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    Footnotes

    • Twitter @PhageAustralia

    • Contributors AK and JI conceived the study. AK, JI, SYCT and MSW initiated the study design and protocol development. AP, TLS, JL, SS and RCYL contributed to refinement of the study protocol. NB provided input into the protocol development in her role as an advocate for the cystic fibrosis community; and JW provided input in her role as the Principal Policy Officer for Advanced Therapeutics at the Office for Health and Medical Research, New South Wales Ministry of Health. JI and AK are grant holders. TLS and EHB provided statistical expertise. DAF and AK drafted the initial manuscript for publication. All authors reviewed and approved the final manuscript for submission.

    • Funding Initial set-up costs for the trial, including database design and development and project management, are funded by a Medical Research Futures Fund (MRFF) Frontiers Stage 1 grant (RFRHPI000017; PHAGE AUSTRALIA: Integrating Australian Phage Biobanking and Therapeutic Networks and Delivering Solutions for Antimicrobial Resistance, CIA Iredell); and National Health and Medical Research Council Investigator Grants 2008024 (Phage Therapy: A novel solution for difficult-to-treat infections in children, CIA Khatami) and 1197534 (Positive solutions for critical infection, CIA Iredell). Local phage production and development of companion diagnostics are supported by the MRFF Frontiers Stage 1 grant, and a National Health and Medical Research Council Investigator Grant (1197534: Positive Solutions for Critical Infection, CIA Iredell).

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.