Clinical trial NCT06605651: 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.
Official title: A Phase II Proof of Concept Multicenter, Randomized, Double-Blind Study to Assess the Safety and Efficacy of Phage Therapy in Patients with Hip or Knee Prosthetic Joint Infection Due to Staphylococcus Aureus Treated by DAIR
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hip Prosthesis Infection
Knee Prosthesis Infection
Keywords: Prosthetic Joint Infection
PJI
Bacteriophages
Phages
DAIR
Phage Therapy
Antimicrobials
Lead sponsor: Phaxiam Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-09-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an international, multicentric, phase II (proof of concept), randomized, double-blind, parallel group, placebo-controlled study.
Primary purpose: TREATMENT

Brief summary: Total joint replacements are effective for chronic pain but can lead to Prosthetic Joint Infections (PJI), primarily caused by Staphylococcus aureus and resistant to antibiotics. Standard treatment involves DAIR surgery and antibiotics, but there's a need for better solutions due to rising infections and antibiotic resistance. Bacteriophage therapy, which targets specific bacteria, shows promise. Phaxiam Therapeutics is studying the safety and efficacy of phage therapy in treating Staphylococcus aureus infections in hip or knee PJI patients undergoing DAIR.

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years
2. Knee or Hip PJI according to EBJIS (European Bone and Joint Infection) or ICM (International Consensus Meeting) guidelines
3. Monobacterial Infection due to S. aureus
4. Without preoperative diagnosis of superinfection due to another pathogen if treatment is administered at the end of the DAIR (presence of a contaminant is not considered clinically relevant)
5. Without diagnosis of superinfection due to another pathogen identified within 72h after bacteriological sample performed during the DAIR if treatment is administered up to 14 days after the DAIR
6. Indication for Open DAIR decided by the Multidisciplinary Team and/or Principal Investigator
7. S. aureus in joint fluid during the pre-inclusion period or in case of relapse of infection under antibiotics therapy in the last 6 months before inclusion
8. Patient with a life expectancy of 1 year or more as determined by the principal investigator.
9. 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.
10. Females of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal (amenorrhea duration at least 12 months)

Exclusion Criteria:

1. Relapse between DAIR and study drug administration planned up to 14 days after the DAIR.
2. Patients who have two planned DAIR in sequence (double DAIR)
3. Patients with ASA score ≥ 4
4. Severe sepsis or Septic shock or hemodynamic instability
5. Patients with an indication for fixed prosthesis exchange, or for joint fusion or for amputation
6. Indication for suppressive antibiotherapy
7. 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)
8. Positive Human Immunodeficiency Viruses (HIV) test or active hepatitis B and C
9. Previous treatment by bacteriophages
10. Any known phage allergy and/or to its excipients
11. Elevated ALT or AST above 4 times ULN

Primary outcomes:
measure: To assess the safety of phage therapy + DAIR compared with placebo + DAIR
timeFrame: From enrollment up to 3 months
measure: To assess the efficacy of phage therapy + DAIR compared with placebo + DAIR
timeFrame: From enrollment up to 3 months
Secondary outcomes:
measure: To assess the safety of phage therapy + DAIR compared with placebo + DAIR
timeFrame: From enrollment up to 12 months
measure: To assess the efficacy of phage therapy + DAIR compared with placebo + DAIR
timeFrame: From enrollment up to 12 months
measure: To describe the immunological response in serum and in joint fluid
timeFrame: From enrollment up to 3 months
measure: To describe the S. aureus bacterial load (bacteriology) in the joint fluid up to 1 month
timeFrame: From enrollment up to 1 month
measure: To describe Cytology in the joint fluid
timeFrame: From enrollment up to 1 month
measure: To describe the hospitalization duration
timeFrame: From enrollment up to 3 months and up to 12 months
measure: To describe the hospitalization duration
timeFrame: From enrollment up to 3 months and up to 12 months
measure: To describe the quality of life for patients
timeFrame: From enrollment up to 3 months and up to 12 months
measure: To describe joint function rehabilitation
timeFrame: From enrollment up to 3 months and up to 12 months
measure: To describe the evolution of the prosthetic joint infection by X Ray image
timeFrame: From screening up to 3 months and up to 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Phaxiam Therapeutics
name: Pascal Chief Medical Officer
role: STUDY_DIRECTOR
affiliation: Phaxiam Therapeutics
name: Audrey Study Team Leader
role: STUDY_DIRECTOR
References: