knee or hip prosthetic joint infection (PJI) due to Staphylococcus aureus, with the indication of DAIR and Suppressive Antibiotics Therapy (SAT
Conditions
Interventions
Product Name: Anti-Staphylococcus aureus Bacteriophages- PP1493
Pharmaceutical Form: Suspension for injection
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the
Sponsors
PHERECYDES PHARMA
Eligibility
Sex/Gender
All
Inclusion criteria
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 in joint fluid during the pre-inclusion period or in case of relapse of under antibiotics therapy in the first 6 months after a DAIR 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, diaphragm or condoms) 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 for women with childbearing potential 10.Signing a written informed consent before any study related procedyres including phagogramprior to the phagogram 11.Affiliated to a national social security system and / or private health insuranceCovered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
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. No active anti Staphylococcus aureus bacteriophages in phagogram 4. Patients with ASA score = 4 5. Severe sepsis or Septic shock or hemodynamic instability 6. Immunosuppressed patients 7. Any known phage allergy 8. Medical history which in the opinion of the investigator would mean that the patient is unsuitable for participation in the study 9. 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 10. Currently in exclusion period from a previous study 11. Concomitant participation to another interventional clinical trial. 12. 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 13. Women/Men refusing to use an effective contraception during 1 month after the last administration of study drug 14. No possibility of contact in case of emergency 15. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of two different therapeutic regimens: DAIR + curative antibiotics therapy combined with bacteriophages or solution of NaCl 0,9%; by clinical control of the infection due to Staphylococcus aureus at Week 12, in patients presenting a Prosthesis Joint Infection (PJI) later than 3 months after the arthroplasty, with the indication of DAIR + Suppressive Antibiotics Therapy (SAT).;Secondary Objective: 1. evaluate the safety of two different therapeutic regimens (DAIR + curative antibiotics therapy combined with bacteriophages or Solution of NaCl 0,9%) during the whole study; 2. describe initial activity of phages on patients’ Staphylococcus aureus strain and the clinical outcome (infection control or relapse) of patients at Week 12; 3. describe superinfected patients (other species found in per operative sample) in terms of clinical control of the infection at Week 12; 4. describe the profile of the Staphylococcus aureus strain in case of failure before Week 12; 5. describe the Staphylococcus Aureus quantification in blood and in serum at D0, D0-T2H, D2, D4, D14, D28 and Week 12; and in case of rescue treatment 6. describe the immunological response in serum at D0, D14, D28 and Week 12, and in joint fluid at D0 and D14 only for patients with a Total Knee Arthroplasty (TKA); and in case of rescue treatment ;Primary end point(s): Clinical control of infection at Week 12±2 will be defined by: -no clinical signs of active infection (no fever, no recurrent or worsening local post-surgical painful or swelling joint, no abnormal discharge or fistula, no abnormal aspect of scar as erythema or local inflammatory or necrosis or unknitting) at Week 12±2 -and no new surgical procedure requested and no Staphylococcus aureus detected in joint fluid in case of aspiration before Week 12±2 ;Timepoint(s) of evaluation of this end point: Week 12 +/-2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety parameters: adverse events, physical examination, biological tests as hematology and biochemistry during the whole study; 2. Initial activity of phages: active bacteriophages (PP1493 and/or PP1815) according to phagogram results in regard of the clinical outcome (infection control or relapse) of patients at Week 12±2 3. Clinical control of the infection (as described in primary endpoint) at Week 12±2 for superinfected patients (other species isolated during the surgical procedure) 4. In case of failure before Week 12±2, aspiration of joint fluid at time of failure for microbiological test and identification of Staphylococcus aureus strain: antibiogram and phagogram 5. Microbiology: - Blood: Staphylococcus aureus quantification (CFU) at D0, D0-T2H, D2, D4, D14±1, D28±2 and Week 12±2; - Serum: Staphylococcus aureus quantification (qPCR) at D0, D0-T2H, D2, D4, D14±1, D28±2 and Week 12±2 6. Immunology: - Serum: anti S.aureus phage antibodies, cytokine IL6 at D0, D14±1, D28±2 and Week 12±2 - Joint fluid: anti S.aureus phage antibodies at D0 and at D14±1 only for patients with TKA 7. Pharmacokinetics: - Serum: quantification of the phages by qPCR at D0, D0T2H, D2, D4, D14±1, D28±2 and Week 12±2 - Blood: quantification of the phages by plaque assay at D0, D0T2H, D2, D4, D14±1, D28±2 and Week 12±2 for patients in sites (France) in Paris, Nantes and Lyon - Joint Fluid: quantification of the phage by qPCR and plaque assay at D0 and at D14±1 only for patients with TKA; the plaque assay will be performed only for patients in sites (France) in Paris, Nantes and Lyon; 8. Bacteriological Infection Control at D14±1 in joint fluid (only patients with TKA): microbiological culture, quantification of S. aureus by qPCR, WBC count, C-Reactive Protein, IL6; 9. Duration of hospitalization 10. Questionnaire EQ-5D-5L for quality of life at each visit (except D14±1 and D28±2); 11. Evaluation of joint function at D-1 or D0, Week 12±2, Month 6 ±2 | — |
Countries
France, Spain
Contacts
Public ContactSophie Moulin
Eurofins Optimed
Outcome results
None listed