Proof of Concept Study to Assess Safety and Efficacy of Phage Therapy in Hip or Knee Prosthetic Joint Infections Due to Staphylococcus Aureus Treated by DAIR. (GLORIA)
- Conditions
- Hip or Knee prosthetic joint infection due to Staphylococcus aureus
- Registration Number
- 2024-516555-40-00
- Lead Sponsor
- Phaxiam Therapeutics
- Brief Summary
To assess the safety and efficacy of phage therapy + DAIR compared with placebo + DAIR up to 3 months
- Detailed Description
Total joint replacement serves as valuable interventions in the management of chronic refractory pain when the other conservative treatments have not worked. They play a vital role in alleviating discomfort and improving the quality of life of subjects battling with joint diseases. However, the joint replacements present the challenge of Prosthetic Joint Infection (PJI). PJI have serious complications and can lead to significant mortality, morbidity, and healthcare expenditure.
The leading cause of PJI is gram-positive cocci, specifically Staphylococcus aureus. Bacterial biofilms, mainly formed with Staphylococcus, represent a significant challenge in the treatment of PJIs due to their resistance to antibiotic therapy. Standard of Care (SOC) for these complex infections is characterized primarily by an initial surgery (Debridment Antibiotics and Implant Retention (DAIR) and various regiments and combinations of antibiotics. While the patterns of utilization vary between institutions and geography, DAIR is considered low-invasive procedure, characterized by the possibility of not explanting the prosthetic implant and resecting the bone. The growing demand for joint arthroplasty and current PJI rates, combined with antibacterial resistance, clearly indicate an unmet medical need in treating biofilm-based PJIs.
Bacteriophage therapy could potentially improve the treatment paradigm for PJIs. Bacteriophages naturally occur with highly specific bacterial viruses that infiltrate bacterial cells, disrupting their metabolism, and causing bacterial lysis. Initial in vivo studies of phage therapy for bone-related infections have shown promise.
Phaxiam Therapeutics, a biotechnology company specializing in the research and development of anti-infective therapies using bacteriophages., has collections of phages against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. These phages have shown promise in preliminary tests and studies.
The objective of GLORIA study Is to assess the safety and efficacy of phage therapy versus placebo in treating Staphylococcus aureus infections in hip or knee PJI patients undergoing DAIR.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 51
Male or female ≥ 18 years
Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months)
Negative pregnancy test for women of childbearing potential
Signing a written informed consent before any study related procedures including [redacted]
Affiliated to a national social security system and / or private health insurance in compliance with the recommendations of National Law in force relating to biomedical research.
Knee or Hip PJI according to EBJIS or ICM guidelines (Appendix 6 of protocol)
Monobacterial Infection due to S. aureus
Without preoperative diagnosis of superinfection due to another pathogen if treatment is administered [redacted] the DAIR (presence of a contaminant is not considered clinically relevant)
Without diagnosis of superinfection due to another pathogen identified within 72h after bacteriological sample performed [redacted] DAIR if treatment is administered [redacted] the DAIR
Indication for Open DAIR decided by the Multidisciplinary Team and/or Principal Investigator
S. aureus in [redacted] during the pre-inclusion period or in case of relapse of infection under antibiotics therapy in the last 6 months before inclusion
Patient with a life expectancy of 1 year and more as determined by the principal investigator.
Females of childbearing potential/sexually active males with partner of childbearing potential: commitment to consistently and correctly use an acceptable effective method of birth control until 1 month after the last study drug administration. These include, but not limited to: a.Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal), b.Progestogen-only hormonal contraception (oral, injectable, or implantable), c.Intrauterine device, Intrauterine hormone-releasing system, d.Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. e.For non-vasectomized men having a female partner of childbearing potential, men must agree to use condom until 30 days after the last administration of the study drug.
Relapse between DAIR and study drug administration [redacted].
Any known phage allergy and/or to its excipients
Elevated ALT or AST above 4 times ULN
Medical history which in the opinion of the investigator would mean that the patient is unsuitable for participation in the study.
Patient who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development.
Currently in exclusion period from a previous study
Participate or plan to receive any other investigational drug or therapy or vaccine during the study period.
Patients who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the treatment period or 1 month after the last administration of study drug.
Women/Men refusing to use an acceptable effective contraception until 1 month after the last administration of study drug.
Minors, persons deprived of liberty by judicial or administrative decision, persons receiving psychiatric care and persons admitted to a health or social institution, to adult patient under legal protection or unable to express consent.
Patients who have two planned DAIR in sequence (double DAIR)
Patients with ASA score ≥ 4
Severe sepsis or Septic shock or hemodynamic instability
Patients with an indication for prosthesis exchange, or for joint fusion or for amputation
Indication for suppressive antibiotherapy
Immunosuppressed patients: Patients having a weakened immune system due to diseases conditions (i.e genetic disorders, malnutrition) or treatment (i.e anticancer drugs or organ transplant)
Positive HIV test or active hepatitis B and C
Previous treatment by bacteriophages
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of serious adverse events up to 3 months Incidence of serious adverse events up to 3 months
Percentage of Patients with clinical cure up to 3 months Percentage of Patients with clinical cure up to 3 months
- Secondary Outcome Measures
Name Time Method Percentage of patients with clinical cure from S.aureus infection up to 3 months and 12 months. Percentage of patients with relapse exclusively due to another germ than Staphylococcus aureus up to 3 month and 12 months Percentage of patients with clinical cure from S.aureus infection up to 3 months and 12 months. Percentage of patients with relapse exclusively due to another germ than Staphylococcus aureus up to 3 month and 12 months
Incidence of all adverse events and assessment of all safety parameters (Vital signs, ECG/ Echocardiography, hematology, hemostasis and biochemistry) up to 3 months and up to 12 months Incidence of all adverse events and assessment of all safety parameters (Vital signs, ECG/ Echocardiography, hematology, hemostasis and biochemistry) up to 3 months and up to 12 months
Percentage of Patient with clinical cure of PJI and up to 12 months. Percentage of Patient with clinical cure of PJI and up to 12 months.
Titration of anti-S. aureus phage antibodies: -In [redacted] at [redacted] in case of relapse and at Early End Visit if it’s occurred before [redacted] for all patients. -In [redacted] at [redacted] in case of relapse if it’s occurred before [redacted] (all patient) and only for knee PJI patients at [redacted]. Titration of anti-S. aureus phage antibodies: -In [redacted] at [redacted] in case of relapse and at Early End Visit if it’s occurred before [redacted] for all patients. -In [redacted] at [redacted] in case of relapse if it’s occurred before [redacted] (all patient) and only for knee PJI patients at [redacted].
Quantitative or Semi-Quantitative Analysis of bacterial load at [redacted] (all patient) and only for knee PJI patient at [redacted]. Quantitative or Semi-Quantitative Analysis of bacterial load at [redacted] (all patient) and only for knee PJI patient at [redacted].
Quantification and identification of polynuclear of [redacted] at [redacted] (all patients) and [redacted] (only knee PJI). Quantification and identification of polynuclear of [redacted] at [redacted] (all patients) and [redacted] (only knee PJI).
Number and Duration of hospitalization up to 3 months and up to 12 months Number and Duration of hospitalization up to 3 months and up to 12 months
Quality-of-life questionnaires [redacted] at [redacted]. Quality-of-life questionnaires [redacted] at [redacted].
[redacted] Questionnaires at [redacted]. [redacted] Questionnaires at [redacted].
X Ray during [redacted] period and at [redacted] to check potential appearance of abnormal loosening (border with shifting of the prosthesis), periprosthetic border. X Ray during [redacted] period and at [redacted] to check potential appearance of abnormal loosening (border with shifting of the prosthesis), periprosthetic border.
Trial Locations
- Locations (10)
Centre Hospitalier Regional Et Universitaire De Brest
🇫🇷Brest, France
Centre Hospitalier De Tourcoing
🇫🇷Tourcoing Cedex, France
Hospices Civils De Lyon
🇫🇷Lyon Cedex 04, France
Centre Hospitalier Universitaire De Poitiers
🇫🇷Poitiers, France
Centre Hospitalier Universitaire De Nimes
🇫🇷Nimes Cedex 9, France
Centre Hospitalier Universitaire De Toulouse
🇫🇷Toulouse, France
Centre Hospitalier Regional Universitaire De Tours
🇫🇷Tours, France
Hospital De La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario 12 De Octubre
🇪🇸Madrid, Spain
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Centre Hospitalier Regional Et Universitaire De Brest🇫🇷Brest, FranceLuc QUAESAETSite contact+33298145053luc.quaesaet@chu-brest.fr