A Phase 1/2 Study to Evaluate the Safety, PK and Efficacy of TNP-2092 Administered Via IA Injection in PJI Participants

NCT06889701 | Recruiting Phase 1 FDA Drug

• 1 other identifier: TNP-2092-IA-01
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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 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).

Conditions

Periprosthetic Joint Infection (PJI)

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 1 to Day 187

Secondary Outcomes (16)

• TNP-2092 concentrations in synovial fluid

  At 12, 24 hours after the first dose of TNP-2092, before dosing on Day 7, before the last dose, and at 12, 24, 48 hours after the last dose.

• Maximum Observed Plasma Concentration (Cmax) of TNP-2092 after the first dose

  Before administration (within 1 hour), 1, 4, 12, 24 hours after the first dose

• Time to Reach the Maximum Observed Plasma Concentration (Tmax) after the first dose

  Before administration (within 1 hour), 1, 4, 12, 24 hours after the first dose

• 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), 1, 4, 12, 24 hours after the first dose

• Area under the curve from the time of dosing to infinity (AUC 0-∞) after the first dose

  Before administration (within 1 hour), 1, 4, 12, 24 hours after the first dose

Study Arms (4)

Sentinel group

EXPERIMENTAL

In the sentinel group, participants will receive TNP-2092 50 mg IA+vancomycin IV+oral antibiotics.

Drug: TNP-2092 for injection; Drug: Vancomycin Hydrochloride for Injection (IV); Drug: Oral antibiotics

Experimental group

EXPERIMENTAL

In the experimental group, participants will receive TNP-2092 50 mg IA + vancomycin IV + oral antibiotics.

Drug: TNP-2092 for injection; Drug: Vancomycin Hydrochloride for Injection (IV); Drug: Oral antibiotics

Control group

ACTIVE COMPARATOR

In the control group, participants will receive vancomycin IA + vancomycin IV + oral antibiotics.

Drug: Vancomycin Hydrochloride for Injection (IA); Drug: Vancomycin Hydrochloride for Injection (IV); Drug: Oral antibiotics

Expansion group

EXPERIMENTAL

In the expansion group, participants will receive TNP-2092 50 mg IA based on the background treatment.

Drug: TNP-2092 for injection; Drug: Background Treatment

Interventions

Vancomycin Hydrochloride for Injection (IV) DRUG

Vancomycin Hydrochloride for Injection, 0.5 g/vial, Intravenous infusion, 250 mL (1 g) q12h ± 1h per day, for 14 days.

Control group; Experimental group; Sentinel group

Oral antibiotics DRUG

Rifampicin 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).

Control group; Experimental group; Sentinel group

Background Treatment DRUG

Background treatment will be determined by the investigator.

Expansion group

TNP-2092 for injection DRUG

TNP-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.

Also known as: rifaquizinone for injection

Expansion group; Experimental group; Sentinel group

Vancomycin Hydrochloride for Injection (IA) DRUG

Vancomycin Hydrochloride for Injection, 0.5 g/vial, Intra-articular administration, 10 mL (0.5 g) once daily for 14 days.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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:
• Acute hepatitis of any cause within the past year.
• Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels \> 2 times the upper limit of normal (ULN).
• Presence of end-stage liver disease-related manifestations such as ascites or hepatic encephalopathy.
• Current or anticipated neutropenia (ie, neutrophil count \< 0.5 x 10\^9/L).
• 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.

Sponsors & Collaborators

• TenNor Therapeutics Inc.: lead
• First Affiliated Hospital of Xinjiang Medical University: collaborator

Study Sites (1)

The First Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, China

RECRUITING

MeSH Terms

Interventions

TNP-2092; Injections; Vancomycin; Anti-Bacterial Agents

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Li Cao

CONTACT

+86 991-4366553; xjbone@sina.com

Jing Chen

CONTACT

+86 512 86861979; jing.chen@tennorx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Three eligible participants will be enrolled as sentinel group. 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 group and the control group. Ten subjects requiring long-term suppressive antibiotic therapy for PJI (including PJI occurring after various joint replacement surgeries) will be enrolled in the expansion group and could be enrolled in parallel with the sentinel group.

Study Record Dates

• First Submitted: March 14, 2025
• First Posted: March 21, 2025
• Study Start: April 3, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 5, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)