Evaluation of PLG0206 in Prevention of Recurrent Infection in Patients Undergoing Debridement, Antibiotics, and Implant Retention (DAIR) for Treatment of a Periprosthetic Joint Infection (PJI) Following Knee Arthroplasty

Official title

RETAIN: A Phase 2/3 Randomized, Placebo-Controlled Study to Evaluate the Efficacy of PLG0206 in Prevention of Recurrent Infection in Patients Undergoing Debridement, Antibiotics, and Implant Retention (DAIR) for Treatment of a Periprosthetic Joint Infection (PJI) Following Total Knee Arthroplasty (TKA)

Overview

The goal of this clinical trial is to evaluate whether the investigational drug PLG0206 can help reduce recurrence of infection in adults who have undergone total knee replacement and are receiving a DAIR (Debridement, Antibiotics, and Implant Retention) surgical procedure to treat a Prosthetic Joint Infection (PJI). The study will also assess the safety of PLG0206 when used as an irrigation solution during the DAIR procedure. Participants will receive either PLG0206 or a placebo (an inactive substance that looks like the investigational drug), in addition to standard of care treatments. All participants will be monitored for approximately one year following their DAIR procedure.

Detailed description

This study is designed to assess the efficacy and safety of PLG0206 administered intraoperatively by local irrigation to participants undergoing a DAIR procedure for treatment of Prosthetic Joint Infection (PJI) occurring after total knee arthroplasty (TKA), also known as knee joint replacement.

Eligible participants will undergo a DAIR procedure according to the treating hospital's standard of care (SOC). Participant eligibility will be based on clinical and diagnostic assessments, including laboratory results.

Once debridement during DAIR is complete, the Investigator will follow a standardized irrigation protocol, with the final irrigation step being administration of a single dose of blinded study drug (PLG0206 or matching placebo). The study drug will be administered as a single intra-articular irrigation.

Following study drug administration, all participants will receive standard post-operative care per institutional guidelines and will be discharged from the hospital in accordance with local standards. Participants may receive IV/oral antimicrobial therapy, as part of post-operative SOC.

Participants will be monitored for safety and signs of PJI recurrence or persistent infection for 365 days post study drug administration. After hospital discharge, study visits will occur in-clinic on Days 14, 90, and 365, and on Days 30, 180, and 270 via a telephone or virtual visit.

Interventions

• Drug PLG0206
  PLG0206 Solution
• Drug Placebo
  Placebo

Primary outcome measures

• Reduction in Treatment Failure Post DAIR [Time frame: From treatment through 12 months]

Secondary outcome measures (12)

• Reduction Rate of PJI-related Surgical Intervention [Time frame: From treatment through 12 months]
• Safety of PLG0206 [Time frame: From treatment through 12 months]
• Survival [Time frame: From treatment through 12 months]
• Efficacy of PLG0206 on Clinical Outcome [Time frame: At Days 14, 30, 90, 180, 270, and 365]
• Time to Treatment Failure [Time frame: From treatment through 12 months]
• PJI-related Healthcare Resource Utilization [Time frame: From treatment through 12 months]
• Frequency of PJI-related Surgical Procedures Following DAIR [Time frame: From treatment through 12 months]
• Microbiological Efficacy Outcome [Time frame: From treatment through 12 months]
• Functional Change Post-DAIR [Time frame: From Baseline through 9 months]
• Immunogenicity of PLG0206 [Time frame: from Baseline through 12 months]
• Effect of PLG0206 on the inflammatory biomarker C-reactive Protein [Time frame: Measured at Baseline and Days 14, 90, and 365]
• Maximum Plasma Concentration (Cmax) of PLG0206 [Time frame: From Baseline through Day 3]

Eligibility criteria

Inclusion criteria

• Male or female participants age between 18 and <80 years
• Able to provide informed consent, geographically stable, and able to comply with the required follow-up visits
• Suspected or confirmed PJI of the knee
• Well-fixed and positioned prosthesis and good condition of surrounding soft tissue (no sinus tract)
• A single DAIR procedure is indicated as treatment of PJI
• Agree to use contraceptives if of childbearing potential

Exclusion criteria

• Loose prosthesis or surgical treatment planned for removal of well-fixed, nonmodular implants
• Anticipated to require antibiotic therapy for >6 months after DAIR procedure
• Infection spread beyond the affected knee joint (e.g., osteomyelitis)
• History of a prior PJI of the affected knee
• Two or more prior revisions in the affected joint
• Epithelialized sinus tract with evidence of communication to the joint or visualization of prosthesis
• Diabetes mellitus and with an A1c ≥9%
• History of malignant disease and having received immunosuppressive therapy, radiation therapy, or chemotherapy within the past year
• Known immunodeficiency (e.g., splenectomy; sickle cell anemia; human immunodeficiency virus \[HIV\] with recent CD4 count <200 cells/mm3; or primary humoral, bone marrow, or other transplantation)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 14 centers

• Clinical Trial Site — Sarasota
• Clinical Trial Site — Tamarac
• Clinical Trial Site — Shreveport
• Clinical Trial Site — Baltimore
• Clinical Trial Site — Boston
• Clinical Trial Site — New York
• Clinical Trial Site — Leland
• Clinical Trial Site — Cincinnati
• … and 6 more centers

United Kingdom · 1 center

• Clinical Trial Site — Leeds

Identifiers

NCT: NCT07214311 · PLG0206-PJI-300

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗