This is a Phase 1/2, randomized, controlled, open-label, proof-of-concept study to evaluate the safety and tolerability, local and systemic PK profiles of TNP-2092 administered via IA injection on the basis of vancomycin IV and oral antibiotics therapy in participants with early (within 1 month of TKA) or acute hematogenous (within 3 weeks of infectious symptoms) PJI requiring or not requiring DAIR therapy after TKA, or requiring long-term antibiotic suppression therapy for PJI (including PJI occurring after various joint replacements and revision surgeries).
Early (within 1 month of TKA) or acute hematogenous (within 3 weeks of infectious symptoms) PJI requires or does not require DAIR therapy after TKA, or results of treatment for PJI (including PJI occurring after various joint replacements and revision surgeries) did not meet the clinical cure criteria and requiring long-term antibiotic suppression therapy as judged by investigators before enrollment.
Suspected or confirmed PJI was caused by a Gram-positive bacterial infection, including methicillin-resistant and ciprofloxacin-resistant Staphylococcus aureus and Staphylococcus epidermidis, as judged by the investigator.
Agree to be hospitalized for 2 weeks with local intra-articular injection.
18 years of age or older (of either sex) at the time of signing the informed consent form (ICF).
History of hypersensitivity or intolerance to any of the following agents: vancomycin or TNP-2092.
Definite PJI of Gram-negative infection, fungal infection, or Enterococcus infection, or Mycobacterium infection, or Gram-positive mixed Gram-negative and/or fungal infection.
Definite systemic infection (sepsis).
Expected survival less than 1 years.
Parallel
TNP-2092 for injection
DrugTNP-2092 for injection, 100 mg/vial, Intra-articular administration (IA), 10ml (50 mg) once daily for 14 days. TNP-2092 dose volume, dose, frequency, and duration can be adjusted according to the sentinel group synovial fluid TNP-2092 concentration, PK characteristics, and safety results at the EA visit.
Vancomycin Hydrochloride for Injection (IA)
DrugVancomycin Hydrochloride for Injection, 0.5 g/vial, Intra-articular administration, 10 mL (0.5 g) once daily for 14 days.
Vancomycin Hydrochloride for Injection (IV)
DrugVancomycin Hydrochloride for Injection, 0.5 g/vial, Intravenous infusion, 250 mL (1 g) q12h ± 1h per day, for 14 days.
Oral antibiotics
DrugRifampicin capsules: 0.15 g/capsule. 0.45 g (3 capsules) orally once daily within 1 h before breakfast for 8 weeks (56 days). Levofloxacin Tablets: 0.5 g/tablet. 0.5 g (1 tablet) orally once daily within 1 hour before breakfast for 8 weeks (56 days). If susceptibility testing results show resistance to rifampicin and/or levofloxacin, or intolerance by the patient 's participant, treatment with oral minocycline hydrochloride capsules will be substituted as follows:Minocycline hydrochloride capsules: 100 mg/capsule. Administered orally q12h ± 1h daily, doubling the first dose, 200 mg (2 capsules) orally, then 100 mg (1 capsule) each time for 8 weeks (56 days). The total duration of oral treatment during the oral administration period was 8 weeks (56 days) regardless of whether oral medication will be changed (eg, intolerance).
Background Treatment
DrugBackground treatment will be determined by the investigator.
Safety and Tolerability of TNP-2092 by Assessment of the Number of Adverse Events (AEs)
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
TNP-2092 concentrations in synovial fluid
Synovial fluid concentrations of TNP-2092 were measured by a specific and validated assay.
Maximum Observed Plasma Concentration (Cmax) of TNP-2092 after the first dose
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Time to Reach the Maximum Observed Plasma Concentration (Tmax) after the first dose
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Area under the curve from the time of dosing to the last measurable concentration (AUC 0-t) after the first dose
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
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TenNor Therapeutics Inc.
Lead sponsor
First Affiliated Hospital of Xinjiang Medical University
Collaborator
