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).
- infectious diseases
- general medicine (see internal medicine)
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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.
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