Clinical trial NCT06889701: 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
Official title: A Phase 1/2, Randomized, Controlled, Open-label, Proof-of-concept Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Efficacy of TNP-2092 Administered Via Intra-articular Injection (IA) in Adult Participants With Early or Acute Hematogenous Prosthetic Joint Infection (PJI) Requiring or Not Requiring Debridement, Antibiotics, and Implants Retention (DAIR) After Total Knee Arthroplasty (TKA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Periprosthetic Joint Infection (PJI)
Lead sponsor: TenNor Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: First Affiliated Hospital of Xinjiang Medical University
First posted: 2025-03-21
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three eligible participants will be enrolled as sentinel arms. After all sentinel participants are tolerable safety at EA assessment and complete the PK study, an additional 20 participants will be enrolled and randomize in 1:1 ratio to the experimental arm and the control arm.
Primary purpose: TREATMENT

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.

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.
* 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.

Primary outcomes:
measure: Safety and Tolerability of TNP-2092 by Assessment of the Number of Adverse Events (AEs)
timeFrame: Day 1 to Day 187
Secondary outcomes:
measure: TNP-2092 concentrations in synovial fluid
timeFrame: 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.
measure: Maximum Observed Plasma Concentration (Cmax) of TNP-2092 after the first dose
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours after the first dose
measure: Time to Reach the Maximum Observed Plasma Concentration (Tmax) after the first dose
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours after the first dose
measure: Area under the curve from the time of dosing to the last measurable concentration (AUC 0-t) after the first dose
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours after the first dose
measure: Area under the curve from the time of dosing to infinity (AUC 0-∞) after the first dose
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours after the first dose
measure: Elimination half-life (t 1/2) after the first dose
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours after the first dose
measure: Maximum observed concentration at steady state (Cmax, ss) after the last dose
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last dose
measure: Time to maximum concentration at steady state (Tmax, ss) after the last dose
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last dose
measure: 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
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last dose
measure: Area under the curve from the time of dosing to infinity at steady state (AUC 0-∞, ss) after the last dose
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last dose
measure: Area under the curve over the dosing interval at steady state (AUC 0-tau, ss)
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24 hours after the last dose
measure: Elimination half-life at steady state (t 1/2, ss)
timeFrame: Before administration (within 1 hour), 0.5, 1, 2, 4, 8, 12, 24, 48, 72 hours after the last dose
measure: Accumulation ratio (Rac)
timeFrame: 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
measure: Early Assessment (EA) response rate
timeFrame: Day 14
measure: End of treatment (EOT) response rate
timeFrame: Day 71 to Day 77
measure: Treatment failure rate
timeFrame: Within 6 months after the start of study treatment
Other outcomes:
Locations:
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
Study officials:
References: