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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 240
- Locations
- 19
- Primary Endpoint
- Reduction in Treatment Failure Post DAIR
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female participants age between 18 and <86 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 confirmed PJI of the affected knee, including prior DAIR or revision surgery for PJI
- •Two or more prior revisions in the affected joint for reasons other than infection
- •Epithelialized sinus tract with evidence of communication to the joint or visualization of prosthesis
- •Diabetes mellitus and with an A1c ≥9% within 3 months, according to medical history
- •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)
Arms & Interventions
Placebo
Placebo (normal saline) will be administered as an irrigation solution during DAIR procedure
Intervention: Placebo (Drug)
PLG0206
PLG0206 will be administered as an irrigation solution during DAIR procedure
Intervention: PLG0206 (Drug)
Outcomes
Primary Outcomes
Reduction in Treatment Failure Post DAIR
Time Frame: From treatment through 12 months
Proportion of participants with PJI treatment failure following DAIR
Secondary Outcomes
- Safety of PLG0206(From treatment through 12 months)
- Area Under the Concentration-time Curve Through Infinity(From time O (pre-dose) to infinity [AUCinf]; last protocol specified time-point is Day 3)
- Reduction Rate of PJI-related Surgical Intervention(From treatment through 12 months)
- Survival(From treatment through 12 months)
- Efficacy of PLG0206 on Clinical Outcome(At Days 14, 30, 90, 180, 270, and 365)
- Time to Treatment Failure(From treatment through 12 months)
- PJI-related Healthcare Resource Utilization(From treatment through 12 months)
- Microbiological Efficacy Outcome(From treatment through 12 months)
- Functional Change Post-DAIR(From Baseline through 9 months)
- Effect of PLG0206 on the inflammatory biomarker C-reactive Protein(Measured at Baseline and Days 14, 90, and 365)
- Maximum Plasma Concentration (Cmax) of PLG0206(From Baseline through Day 3)
- Maximum Plasma Concentration (Cmax) of PLG0206(From Baseline through Day 2)
- Time to Maximum Plasma Concentration (Tmax) of PLG0206(Baseline through Day 2)
- Half-life of PLG0206 in Plasma(Baseline through Day 2)
- Area Under the Concentration-time Curve Through Last Quantifiable Concentration(From time O (pre-dose) through last quantifiable result; last protocol specified time-point is Day 2)
- Area Under the Concentration-time Curve Through Infinity(From time O (pre-dose) to infinity [AUCinf]; last protocol specified time-point is Day 2)
- Microbiological Efficacy Outcome(From treatment through 12 months)
- Reduction Rate of PJI-related Surgical Intervention(From treatment through 12 months)
- Safety of PLG0206(From treatment through 12 months)
- Survival(From treatment through 12 months)
- Efficacy of PLG0206 on Clinical Outcome(At Days 14, 30, 90, 180, 270, and 365)
- Time to Treatment Failure(From treatment through 12 months)
- Frequency of PJI-related Surgical Procedures Following DAIR(From treatment through 12 months)
- PJI-related Healthcare Resource Utilization(From treatment through 12 months)
- Functional Change Post-DAIR(From Baseline through 9 months)
- Effect of PLG0206 on the inflammatory biomarker C-reactive Protein(Measured at Baseline and Days 14, 90, and 365)
- Maximum Plasma Concentration (Cmax) of PLG0206(From Baseline through Day 3)
- Area Under the Concentration-time Curve Through Infinity(From time O (pre-dose) to infinity [AUCinf]; last protocol specified time-point is Day 3)
- Concentration of PLG0206 in Irrigation Solution(Measured at Study Day 1 at end of study drug exposure)
- Immunogenicity of PLG0206(from Baseline through 12 months)
- Time to Maximum Plasma Concentration (Tmax) of PLG0206(Baseline through Day 3)
- Half-life of PLG0206 in Plasma(Baseline through Day 3)
- Area Under the Concentration-time Curve Through Last Quantifiable Concentration(From time O (pre-dose) through last quantifiable result; last protocol specified time-point is Day 3)