Phage Therapy in Prosthetic Joint Infection Due to Staphylococcus Aureus Treated With DAIR. (PhagoDAIRI)

A Pilot, Multicenter, Randomized, Non-Comparative, Double-Blind Study of Phage Therapy in Patients With Hip or Knee Prosthetic Joint Infection Due to Staphylococcus Aureus Treated With DAIR and Antibiotic Therapy.

Pilot non comparative study assessing the clinical control of infection of DAIR + SAT +NaCl and DAIR + SAT + Phages anti-Staphylococcus aureus in patients with Staphylococcus aureus Prosthetic Joint Infection with an indication of DAIR + SAT.

Study Overview

• Status: Recruiting
• Conditions: Infection of Total Hip Joint Prosthesis; Infection of Total Knee Joint Prosthesis
• Intervention / Treatment: Biological: Anti-Staphylococcus aureus Bacteriophages

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alexandra TIZON; Phone Number: +33184861613; Email: alexandra.tizon@pherecydes-pharma.com

Study Locations

• France
  • Lyon, France, 69004
    • Recruiting
    • Pr Tristan Ferry
    • Contact: Tristan FERRY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female ≥ 18 years
2. Staphylococcus aureus monomicrobial knee or hip PJI ˃3 months after prosthesis implantation with clinical signs of infection and with indication of DAIR with direct closure and Suppressive Antibiotics Therapy (SAT)
3. Staphylococcus aureus only in joint fluid within 6 months before randomization or in case of relapse of infection under antibiotics therapy after a DAIR performed within 6 months before pre-inclusion visit
4. Without preoperative diagnosis of superinfection due to another pathogen
5. Phagogram displaying the susceptibility of the strain to at least one of the phages.
6. Patient with a life expectancy of 2 years and more as determined by the principal investigator
7. Females of childbearing potential/Sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable method of birth control (oral, transdermal, systemic or implant contraception birth control, intrauterine devices) for 1 month after the last study drug administration
8. Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months)
9. Negative pregnancy test

Exclusion Criteria:

1. Early Staphylococcus aureus Prosthesis Joint infection (˂3months after the prosthesis implantation)
2. Other germ found in culture of joint fluid sample
3. Phagogram displaying no susceptibility of the strain to anti-Staphylococcus aureus bacteriophages
4. Patients with ASA score ≥ 4
5. Severe sepsis or Septic shock or hemodynamic instability
6. Patients with an indication to prosthesis replacement or amputation
7. Immunosuppressed patients
8. ALT or AST > 5 x ULN, creatinine > 1.53 mg/dl in men and > 1.24 mg/dl in women
9. Known allergic reactions to components of phages products
10. Medical history which in the opinion of the investigator would mean that the patient is unsuitable for participation in the study
11. Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period and 1 month after the last administration of study drug
12. Women/Men refusing to use an effective contraception during 1 month after the last administration of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bacteriophages arm; 1 mL (PP1493 or PP1815) or 2 mL (PP1493 and PP1815) of suspension of bacteriophages diluted in solution of NaCl 0,9% at the end of DAIR procedure.	Biological: Anti-Staphylococcus aureus Bacteriophages; Single intra-articular injection
Placebo Comparator: Control Arm; One local administration of NaCl 0,9% solution is administered at the end of the DAIR procedure.	Biological: Anti-Staphylococcus aureus Bacteriophages; Single intra-articular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical control of infection at week 12 visit	No Fever, no recurrence, no worsening of pain, no periarticular inflammatory and clinical infectious signs, no new surgical request, no Staphylococcus aureus detected in joint fluid.	week 12 visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events and Serious Adverse Events	Incidence, severity and type of adverse events and serious adverse events	From the time of signing the informed consent form up to study end visit (Months 24)
Clinical laboratory tests	Number of participants with abnormal clinical laboratory tests	From the time of signing the informed consent form up to study end visit (Months 24)
Physical examination	Number of participants with clinically abnormal physical examination findings	From the time of signing the informed consent form up to study end visit (Months 24)
Clinical control of infection after Week 12 visit	No Fever, no recurrence, no worsening of pain, no periarticular inflammatory and clinical infectious signs, no new surgical request, no Staphylococcus aureus detected in joint fluid	Month 6, Month 12, Month 18 and Month 24.

Collaborators and Investigators

• Sponsor: Pherecydes Pharma

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Anticipated): December 16, 2023
• Study Completion (Anticipated): June 16, 2025

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): June 22, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Staphylococcus aureus; Joint Infection; Phagotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: 2021-004469-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No