TNP-2092 injection for knee prosthetic joint infection

Inclusion Criteria:

1. 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).
2. PJI that, in the investigator's judgment, is suspected or confirmed to be caused by Gram-positive bacteria.
3. Agrees to receive local IA injection of TNP-2092.
4. Age ≥18 years and ≤80 years at the time of signing the informed consent form (ICF), regardless of sex.
5. The implanted joint prosthesis is well fixed.
6. No sinus tract in the affected joint.
7. Body mass index (BMI) ≥18 kg/m² and ≤40 kg/m².
8. Female participants who are of childbearing potential and those who are \<2 years postmenopausal and have not been permanently sterilized must have a negative pregnancy test at baseline and agree to voluntarily use effective contraception from the time of signing the ICF until 8 weeks after the last study treatment. Female participants who are not of childbearing potential (i.e., have undergone tubal ligation, hysterectomy, or bilateral oophorectomy, or are ≥2 years postmenopausal) or whose partner has undergone a vasectomy do not need to use contraception. If a male participant's female partner is of childbearing potential, the male participant must agree to voluntarily use effective contraception and must avoid donating sperm from the time of signing the ICF until 8 weeks after the last study treatment.

Exclusion Criteria:

1. Known history of hypersensitivity or intolerance to any of the following medications: vancomycin or TNP-2092.
2. Confirmed PJI caused by Gram-positive bacteria mixed with other pathogens, or PJI caused solely by fungi, mycobacteria, or Gram-negative bacteria infection.
3. Documented sepsis or septicemia.
4. Life expectancy of less than 1 year.
5. Female participants who are pregnant or breastfeeding.
6. Any surgical or medical condition that, in the investigator's opinion, may affect the participant's ability to participate in the study, affect administration of the investigational product, or affect interpretation of the study results, including but not limited to active malignancy, metabolic disease, alcohol or drug abuse, or clinically significant laboratory abnormalities.
7. Presence of severe hepatic, hematologic, or immune system disease, as evidenced by any of the following:

   a Acute hepatitis of any cause within the past year.

   b Serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 2 × upper limit of normal (ULN), or total bilirubin \> 1.5 × ULN.

   c Manifestations associated with end-stage liver disease, such as ascites or hepatic encephalopathy.

   d Current or anticipated neutropenia (i.e., neutrophil count \< 0.5 × 10⁹/L).

   e Receipt of cancer chemotherapy, radiotherapy, or potent non-corticosteroid immunosuppressants (e.g., cyclosporine, azathioprine, tacrolimus, immunomodulatory monoclonal antibody therapy, etc.) within the past 3 months, or receipt of corticosteroid therapy for more than 14 days (≥40 mg prednisone/day) within 30 days before enrollment; or participants expected to require immunosuppressive therapy during the study.
8. Positive HIV antibody results during screening.
9. History of severe renal disease or evidence of such disease, or creatinine clearance \< 30 mL/min calculated using the Cockcroft-Gault formula.
10. Receipt of another investigational drug within 30 days or 5 half-lives (whichever is longer) before the first dose of the investigational product in this study, or participation in a medical device clinical study.
11. In the investigator's opinion, the participant is unable to comply with the protocol and investigational product administration procedures or to complete the clinical study.