Evaluating TNP-2092 for treating joint infections after knee surgery

A Phase 1/2 Study to Evaluate the Safety, PK and Efficacy of TNP-2092 Administered Via IA Injection in Participants With Early or Acute Hematogenous PJI Requiring or Not Requiring DAIR After TKA, or Requiring Long-term Antibiotic Therapy

This study is testing a new treatment called TNP-2092 to see if it can help people with joint infections after knee surgery feel better compared to the standard antibiotic treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: TenNor Therapeutics Inc. (Industry-sponsored)
• Drugs / interventions: Chemotherapy, radiation, prednisone
• Locations: 1 site (Ürümqi, Xinjiang)
• Trial ID: NCT06889701 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics, and efficacy of TNP-2092 administered via intra-articular injection in patients with periprosthetic joint infections (PJI) following total knee arthroplasty (TKA). Participants will be randomized and receive either TNP-2092 or standard vancomycin treatment, with evaluations conducted to monitor both local and systemic responses. The study focuses on individuals with early or acute hematogenous PJI caused by Gram-positive bacteria, requiring or not requiring debridement and implant retention (DAIR) therapy. Screening assessments will occur within a week prior to the study commencement.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed or suspected Gram-positive bacterial infections following total knee arthroplasty.

Not a fit: Patients with chronic infections, significant comorbidities, or those whose prosthetic joints are not well fixed may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a targeted and effective option for patients suffering from joint infections, potentially reducing the need for more invasive procedures.

How similar studies have performed: While there have been studies on similar treatments for joint infections, this specific approach using TNP-2092 is novel and has not been extensively tested.

Eligibility criteria

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, 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).
* 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 1 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.
* 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.

Where this trial is running

Ürümqi, Xinjiang

• The First Affiliated Hospital of Xinjiang Medical University — Ürümqi, Xinjiang, China (Recruiting)

Study contacts

• Study coordinator: Li Cao

Conditions Periprosthetic Joint Infection