A Phase 1/2 Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Efficacy of TNP-2092 Administered Via Intra-articular Injection in Participants With Prosthetic Joint Infection

Phase 1

Recruiting

• Conditions: Periprosthetic Joint Infection (PJI)
• Interventions: Drug: TNP-2092 for injection; Drug: Vancomycin Hydrochloride for Injection (IA); Drug: Vancomycin Hydrochloride for Injection (IV); Drug: Oral antibiotics

• Registration Number: NCT06889701
• Lead Sponsor: TenNor Therapeutics Inc.

Brief Summary

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 IA 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.

Detailed Description

The study population is participants with confirmed or suspected Gram-positive bacteria causing early (ie, within 1 month of TKA) or acute hematogenous (within 3 weeks of infection symptoms) PJI requiring or not requiring DAIR therapy following TKA. Participants will undergo screening assessments within 7 days prior to study start.

Study Timeline

• Study First Submitted: 2025-03-14
• Study First Submitted QC: 2025-03-19
• Study First Posted: 2025-03-21
• Status Verified: 2025-04
• Study Start: 2025-04-03
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-08
• Primary Completion: 2026-08
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• 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.
• 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).
• The implanted prosthetic joint was well fixed.
• No sinus tract that communicates with the prosthesis.
• Body mass index (BMI) ≥ 18 kg/m 2 and ≤ 34 kg/m 2.
• Agree to voluntarily use effective contraception from signing the ICF through 8 weeks after the last dose of investigational product (in case of premature withdrawal from the study) or through completion of the end-of-study visit. Male participants must refrain from donating sperm during this period.

Exclusion Criteria

• 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 2 years.

• Female participant is pregnant, lactating, or has a positive screening/baseline pregnancy test.

• Surgical or medical conditions that, in the opinion of the investigator, could affect the participant's ability to participate in the study, or affect the administration of investigational product, or affect the interpretation of study results, including but not limited to active malignancy, metabolic disease, alcohol or drug abuse, or clinically significant laboratory abnormalities.

• Presence of serious liver, blood, or immune system disorders as evidenced by the following:

  1. Acute hepatitis of any cause within the past year.
  2. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels > 2 times the upper limit of normal (ULN).
  3. Presence of end-stage liver disease-related manifestations such as ascites or hepatic encephalopathy.
  4. Current or anticipated neutropenia (ie, neutrophil count < 0.5 x 10 9/L).
  5. Chemotherapy for cancer, radiation therapy, or potent noncorticosteroid immunosuppressants (eg, cyclosporine, azathioprine, tacrolimus, immunomodulatory monoclonal antibody therapy, etc) within the past 3 months or corticosteroids (≥ 40 mg prednisone/day) for more than 14 days within 30 days prior to randomization.

• Positive AIDS antibody screening.

• History or evidence of severe renal disease or creatinine clearance < 30 mL/min based on the Cockcroft-Gault formula.

• Systemic antibiotics for more than 3 days within 2 weeks prior to enrollment, except for infections other than PJI that are treated with non-systemic or narrow-spectrum anti-gram-negative antibiotics.

• Rifampicin within 4 weeks prior to enrollment.

• Treatment with an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.

• Participants who, in the opinion of the investigator, were unable to comply with the protocol and study drug administration procedures or complete the clinical study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sentinel group	TNP-2092 for injection	In the sentinel group, participants will receive TNP-2092 50 mg IA+vancomycin IV+oral antibiotics.
Sentinel group	Vancomycin Hydrochloride for Injection (IV)	In the sentinel group, participants will receive TNP-2092 50 mg IA+vancomycin IV+oral antibiotics.
Sentinel group	Oral antibiotics	In the sentinel group, participants will receive TNP-2092 50 mg IA+vancomycin IV+oral antibiotics.
Experimental group	TNP-2092 for injection	In the experimental group, participants will receive TNP-2092 50 mg IA+vancomycin IV+oral antibiotics.
Experimental group	Vancomycin Hydrochloride for Injection (IV)	In the experimental group, participants will receive TNP-2092 50 mg IA+vancomycin IV+oral antibiotics.
Experimental group	Oral antibiotics	In the experimental group, participants will receive TNP-2092 50 mg IA+vancomycin IV+oral antibiotics.
Control group	Vancomycin Hydrochloride for Injection (IA)	In the control group, participants will receive vancomycin IA + vancomycin IV + oral antibiotics.
Control group	Vancomycin Hydrochloride for Injection (IV)	In the control group, participants will receive vancomycin IA + vancomycin IV + oral antibiotics.
Control group	Oral antibiotics	In the control group, participants will receive vancomycin IA + vancomycin IV + oral antibiotics.

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of TNP-2092 by Assessment of the Number of Adverse Events (AEs)	Day 1 to Day 187	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.

Secondary Outcome Measures

Name	Time	Method
TNP-2092 concentrations in synovial fluid	At 12, 24 hours after the first dose of TNP-2092, before dosing on study Day 7, before the last dose, and at 12, 24, 48, 72 hours after the last dose.
Time to Reach the Maximum Observed Plasma Concentration (Tmax) after the first dose	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours 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.
Maximum Observed Plasma Concentration (Cmax) of TNP-2092 after the first dose	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours 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	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours 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 infinity (AUC 0-∞) after the first dose	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours 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.
Elimination half-life (t 1/2) after the first dose	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours 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.
Maximum observed concentration at steady state (Cmax, ss) after the last dose	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last 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 maximum concentration at steady state (Tmax, ss) after the last dose	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last 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 at steady state (AUC 0-t, ss) after the last dose	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last 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 infinity at steady state (AUC 0-∞, ss) after the last dose	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last 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 over the dosing interval at steady state (AUC 0-tau, ss)	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours after the last 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.
Elimination half-life at steady state (t 1/2, ss)	Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last 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.
Accumulation ratio (Rac)	Before administration (within 1 hour) of the first dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the first dose; Before administration (within 1 hour) of the last dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last 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.
Early Assessment (EA) response rate	Day 14	Participants who met all the following criteria will be judged as responders: * At least 2 body temperature measurements within the last 24 hours separated by more than 6 hours were ≤ 37.6ºC.; * Peripheral white blood cell (WBC) count returned to normal range (as determined by local laboratory reference range).; * Synovial fluid WBC \< 3000 cell/μL and polymorphonuclear leukocytes percentage (PMN%) \< 80%.; * Inflammatory manifestations (pain, erythema, edema, wound exudate) at the primary infection site resolved, with pain requiring resolution or tolerance.; * Inflammatory markers (ie, C-reactive protein \[CRP\]) improved to 50% of normal or baseline values.
End of treatment (EOT) response rate	Day 71 to Day 77	Participants who met all the following criteria were judged as responders: * Joint pain was tolerable.; * Joint function improvement.; * Inflammatory markers (ie, CRP) returned to ≤ 10 mg/L.
Treatment failure rate	Within 6 months after the start of study treatment	Those who meet any of the following criteria are treatment failures: * No response at EA assessment.; * No response at EOT assessment.; * Receiving systemic antibiotics for infected joints after the end of study treatment.; * Additional surgical treatment of infected joints is required during the study.; * Death due to primary joint infection.

Trial Locations

Locations (1)

The First Affiliated Hospital of Xinjiang Medical University; 🇨🇳 Urumqi, Xinjiang, China