This is a Phase 2b, randomized, controlled, open-label clinical study evaluating the efficacy, safety, and local PK profiles of TNP-2092 administered via IA injection on a background of antibiotic treatment in participants with early postoperative (within 3 months after index arthroplasty) or acute hematogenous (within 4 weeks of infection) PJI after knee arthroplasty, without debridement, and in participants with chronic PJI (including PJI occurring after various joint arthroplasties and revision arthroplasties) requiring long-term antibiotic suppressive treatment.
Participants with PJI that is early postoperatively (within 3 months of index arthroplasty) or acute hematogenous (within 4 weeks of infectious symptoms) after knee arthroplasty; or participants with chronic PJI requiring long-term antibiotic suppressive therapy (including PJI occurring after any type of joint arthroplasty or revision arthroplasty).
PJI that, in the investigator's judgment, is suspected or confirmed to be caused by Gram-positive bacteria.
Agrees to receive local IA injection of TNP-2092.
Age ≥18 years and ≤80 years at the time of signing the informed consent form (ICF), regardless of sex.
Known history of hypersensitivity or intolerance to any of the following medications: vancomycin or TNP-2092.
Confirmed PJI caused by Gram-positive bacteria mixed with other pathogens, or PJI caused solely by fungi, mycobacteria, or Gram-negative bacteria infection.
Documented sepsis or septicemia.
Life expectancy of less than 1 year.
Parallel
TNP-2092 for injection
DrugStarting on D1, administer by intra-articular injection either once daily or once weekly. Participants in Arm A will receive once-daily dosing for 14 days, and participants in Arm B and Arm C will receive once-weekly dosing for 4 weeks. Doses should be administered at approximately the same time whenever possible (no more than 1 hour earlier or later than the time of the first dose).
Vancomycin Hydrochloride for Injection
DrugParticipants receive empiric treatment with vancomycin 1 g administered via IV infusion every 12 hours (q12h). For participants aged 65 years or older, the vancomycin dose may be adjusted to 0.5 g q12h; during the study, it may also be adjusted according to renal function.
Oral antibiotics
DrugAfter 14 days of IV infusion, participants who meet the criteria for IV to oral switch may switch to oral antibiotic treatment (minocycline or levofloxacin, as determined by the investigator). After 7 days of IV infusion, if IV administration cannot be continued due to tolerability or other reasons, participants may also switch to oral antibiotic treatment if they meet the criteria for IV to oral switch. Oral treatment lasts 56-63 days and combined IV plus oral treatment lasts a total of 10 weeks (70 days). * Levofloxacin tablets: 0.5 g (1 tablet) orally once daily, taken within 1 hour before breakfast, for 56-63 days. * Minocycline hydrochloride capsules: administered orally twice daily; the first dose is 200 mg (2 capsules), and all subsequent doses are 100 mg (1 capsule), for 56-63 days.
Appropriate intravenous and/or oral antibiotics
DrugThe investigator will select appropriate intravenous and/or oral antibiotics based on the participant's condition and with reference to domestic and international guidelines, to be continued for 10 weeks (70 days).
Treatment failure rate
Participants will be considered as treatment failures if any of the following criteria are met: * Failure to meet the intravenous (IV) to oral switch criteria at the end of background intravenous treatment (only for early postoperative or acute hematogenous PJI participants) * The end of IA treatment (EOIA) assessment is non-response. * The end of treatment(EOT) assessment is non- response. * Requiring surgical treatment or systemic antibiotic treatment beyond the study regimen for the primary infected joint during the study. * Death due to the primary joint infection.
Treatment failure rate
End of IA treatment (EOIA) response rate
Participants will be considered as responders if the following criterion is met: a Evaluation of the primary infection site shows improvement compared to baseline, defined as improvement in pain, erythema, edema, or wound drainage in the infected joint. Specifically, improvement in pain is defined as a pain score lower than baseline or ≤3 points.
End of treatment (EOT) response rate
Participants will be considered as responders if all of the following criteria are met: a Serum C-reactive protein (CRP) ≤ 10 mg/L, or lower than baseline level and ≤ 20 mg/L. b Joint pain resolved (numeric rating scale score lower than baseline) or tolerable (numeric rating scale score 0-3 points). c The score of injected joint function scale is higher than baseline.
Adverse Events (AEs)
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug.
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