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TNP-2092 to Treat Acute Bacterial Skin and Skin Structure Infection

Phase 2
Completed
Conditions
Skin and Subcutaneous Tissue Bacterial Infections
Gram-Positive Bacterial Infections
Interventions
Registration Number
NCT03964493
Lead Sponsor
TenNor Therapeutics Limited
Brief Summary

The purpose of this study is to evaluate safety, tolerability, pharmacokinetic characteristics and efficacy of TNP-2092 in adults with ABSSSI suspected or confirmed to be caused by gram-positive pathogens.

Detailed Description

This Phase 2, double-blind, randomized, multicenter, parallel, controlled study is conducted to evaluate safety, tolerability, pharmacokinetics and efficacy of TNP-2092, and vancomycin in adults with ABSSSI suspected or confirmed to be caused by gram-positive pathogens. The duration of the treatment period is a minimum of 7 days and a maximum of 14 days.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
Inclusion Criteria
  • Subjects may be included in the study if they meet all of the following inclusion criteria:

    • Males or females, 18 years of age or older;
    • ABSSSI suspected or confirmed to be caused by gram-positive pathogens, including:
    • Cellulitis/erysipelas;
    • Wound infection;
    • Major cutaneous abscess;
    • Lesion with a minimum surface area of 75 cm2;
    • Capable of giving signed informed consent.
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Exclusion Criteria
  • Subjects will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

    • History or hypersensitivity or intolerability to any fluoroquinolone, rifamycin or glycopeptide classes;
    • ABSSSI suspected or confirmed to be caused by pathogens that are resistant to the glycopeptide class;
    • Prior administration of systemic antibacterial therapy within 96 hours before randomization;
    • ABSSSI with suspected or confirmed infection caused by gram-negative or anaerobic organisms;
    • ABSSSI with suspected or confirmed infection caused by fungal, mycobacterial, parasitic, or viral pathogens;
    • Evidence of significant hepatic, hematologic, or immunologic disease;
    • History or evidence of severe renal disease.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VancomycinVancomycinvancomycin 1 g intravenous every 12 hours
TNP-2092TNP-2092TNP-2092 300 mg intravenous every 12 hours
Primary Outcome Measures
NameTimeMethod
Early Clinical Response at the Early Assessment Visit in the Modified Intent-to-Treat (mITT) Population48 to 72 hours after the first dose of study treatment

Early clinical response is defined as responder meeting two criteria: (1) patient had at least a 20% reduction of acute bacterial skin and skin structure infection (ABSSSI) primary lesion size compared to baseline measurements; (2) patient did not die of any cause within 72 hours of the first dose of study treatment. An indeterminate classification is used for a response that could not be adequately inferred because study data are unavailable for evaluation of efficacy for any reason (eg, missing data, lost to follow-up, did not attend the EA clinic appointment), or if the early assessment visit is out of the 48 to 72 hours window after the intravenous study treatment starts.

Early Clinical Response at the Early Assessment Visit in the Micro-Intent-to-Treat (Micro-ITT) Population48 to 72 hours after the first dose of study treatment

Early clinical response is defined as responder meeting two criteria: (1) patient had at least a 20% reduction of acute bacterial skin and skin structure infection (ABSSSI) primary lesion size compared to baseline measurements; (2) patient did not die of any cause within 72 hours of the first dose of study treatment. An indeterminate classification is used for a response that could not be adequately inferred because study data are unavailable for evaluation of efficacy for any reason (eg, missing data, lost to follow-up, did not attend the EA clinic appointment), or if the early assessment visit is out of the 48 to 72 hours window after the intravenous study treatment starts.

Early Clinical Response at the Early Assessment (EA) Visit in the Intent-to-Treat (ITT) Population48 to 72 hours after the first dose of study treatment

Early clinical response is defined as responder meeting two criteria: (1) patient had at least a 20% reduction of acute bacterial skin and skin structure infection (ABSSSI) primary lesion size compared to baseline measurements; (2) patient did not die of any cause within 72 hours of the first dose of study treatment. An indeterminate classification is used for a response that could not be adequately inferred because study data are unavailable for evaluation of efficacy for any reason (eg, missing data, lost to follow-up, did not attend the EA clinic appointment), or if the early assessment visit is out of the 48 to 72 hours window after the intravenous study treatment starts.

Secondary Outcome Measures
NameTimeMethod
Cmax After Last Infusion57 to 60 minutes, 1.5 to 3 hours, 4 to 6 hours, 12 hours, after the last infusion

Maximum observed concentration

Cmax After First Infusion57 to 60 minutes, 1.5 to 3 hours, 4 to 6 hours, 12 hours, after the first infusion

Maximum observed concentration

Investigator's Assessment of Clinical Response at the End of Treatment (EOT) Visit in the mITT PopulationAfter a minimum of 7 days up to 14 days of study treatment

At the EOT Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; the ABSSSI sufficiently resolved such that further antibacterial therapy is not needed. Clinical Failure: any of the following: (1)Investigator discontinued study treatment and indicated that the ABSSSI had responded inadequately such that alternative (rescue) non-study antibacterial therapy was needed; (2)participant received antibacterial therapy for a different infection that may be effective for the ABSSSI under study; (3) participant developed an adverse event (AE) that required discontinuation of study treatment before completion of the planned treatment regimen; (4) unplanned major surgical treatment for the ABSSSI under study; (5) participant died of any cause up to the specified visit. Indeterminate: study data are unavailable for evaluation of efficacy for any reason (eg, missing data, lost to follow-up).

Investigator Assessment of Clinical Response at Post Treatment Evaluation (PTE) Visit in the mITT Population7 to 14 days after the end of study treatment

At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; the ABSSSI sufficiently resolved such that further antibacterial therapy is not needed. Clinical Failure: any of the following: (1)Investigator discontinued study treatment and indicated that the ABSSSI had responded inadequately such that alternative (rescue) non-study antibacterial therapy was needed; (2)participant received antibacterial therapy for a different infection that may be effective for the ABSSSI under study; (3) participant developed an adverse event (AE) that required discontinuation of study treatment before completion of the planned treatment regimen; (4) unplanned major surgical treatment for the ABSSSI under study; (5) participant died of any cause up to the specified visit. Indeterminate: study data are unavailable for evaluation of efficacy for any reason (eg, missing data, lost to follow-up).

Investigator Assessment of Clinical Response at Post Treatment Evaluation (PTE) Visit in the Micro-ITT Population7 to 14 days after the end of study treatment

At the PTE Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; the ABSSSI sufficiently resolved such that further antibacterial therapy is not needed. Clinical Failure: any of the following: (1)Investigator discontinued study treatment and indicated that the ABSSSI had responded inadequately such that alternative (rescue) non-study antibacterial therapy was needed; (2)participant received antibacterial therapy for a different infection that may be effective for the ABSSSI under study; (3) participant developed an adverse event (AE) that required discontinuation of study treatment before completion of the planned treatment regimen; (4) unplanned major surgical treatment for the ABSSSI under study; (5) participant died of any cause up to the specified visit. Indeterminate: study data are unavailable for evaluation of efficacy for any reason (eg, missing data, lost to follow-up).

AUC0-12h After First Infusion0 to 12 hours post-dose

Partial area under the concentration versus time curve from time zero to time 12 hours.

AUC0-12h After Last Infusion0 to 12 hours post-dose

Partial area under the concentration versus time curve from time zero to time 12 hours

Investigator's Assessment of Clinical Response at the End of Treatment (EOT) Visit in the Micro-ITT PopulationAfter a minimum of 7 days up to 14 days of study treatment

At the EOT Visit the investigator indicated one of the following outcomes relating to the primary infection under study: Clinical Success: participant was alive; the ABSSSI sufficiently resolved such that further antibacterial therapy is not needed. Clinical Failure: any of the following: (1)Investigator discontinued study treatment and indicated that the ABSSSI had responded inadequately such that alternative (rescue) non-study antibacterial therapy was needed; (2)participant received antibacterial therapy for a different infection that may be effective for the ABSSSI under study; (3) participant developed an adverse event (AE) that required discontinuation of study treatment before completion of the planned treatment regimen; (4) unplanned major surgical treatment for the ABSSSI under study; (5) participant died of any cause up to the specified visit. Indeterminate: study data are unavailable for evaluation of efficacy for any reason (eg, missing data, lost to follow-up).

Trial Locations

Locations (1)

eStudy Site

🇺🇸

San Diego, California, United States

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