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

Study Overview
=================
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.

Official Title
-----------------
Phase 2, Double-Blind, Randomized, Multicenter, Parallel, Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TNP-2092 to Treat Acute Bacterial Skin and Skin Structure Infection in Adults

Conditions
-----------------
Skin and Subcutaneous Tissue Bacterial Infections, Gram-Positive Bacterial Infections

Intervention / Treatment
-----------------
* Drug: TNP-2092
* Drug: Vancomycin


Participation Criteria
=================
Eligibility Criteria
-----------------
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. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: TNP-2092 300 mg intravenous every 12 hours vancomycin 1 g intravenous every 12 hours
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNP-2092<br>TNP-2092 300 mg intravenous every 12 hours | Drug: TNP-2092<br>* TNP-2092 100mg/vial<br>|
| Active Comparator: Vancomycin<br>vancomycin 1 g intravenous every 12 hours | Drug: Vancomycin<br>* Vancomycin 1g/vial<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early Clinical Response at the Early Assessment (EA) Visit in the Intent-to-Treat (ITT) Population | 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. | 48 to 72 hours after the first dose of study treatment | 
| Early Clinical Response at the Early Assessment Visit in the Modified Intent-to-Treat (mITT) Population | 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. | 48 to 72 hours after the first dose of study treatment | 
| Early Clinical Response at the Early Assessment Visit in the Micro-Intent-to-Treat (Micro-ITT) Population | 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. | 48 to 72 hours after the first dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator Assessment of Clinical Response at Post Treatment Evaluation (PTE) Visit in the mITT Population | 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). | 7 to 14 days after the end of study treatment | 
| Investigator Assessment of Clinical Response at Post Treatment Evaluation (PTE) Visit in the Micro-ITT Population | 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). | 7 to 14 days after the end of study treatment | 
| Investigator's Assessment of Clinical Response at the End of Treatment (EOT) Visit in the mITT Population | 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). | After a minimum of 7 days up to 14 days of study treatment | 
| Investigator's Assessment of Clinical Response at the End of Treatment (EOT) Visit in the Micro-ITT Population | 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). | After a minimum of 7 days up to 14 days of study treatment | 
| AUC0-12h After First Infusion | Partial area under the concentration versus time curve from time zero to time 12 hours. | 0 to 12 hours post-dose | 
| AUC0-12h After Last Infusion | Partial area under the concentration versus time curve from time zero to time 12 hours | 0 to 12 hours post-dose | 
| Cmax After Last Infusion | Maximum observed concentration | 57 to 60 minutes, 1.5 to 3 hours, 4 to 6 hours, 12 hours, after the last infusion | 
| Cmax After First Infusion | Maximum observed concentration | 57 to 60 minutes, 1.5 to 3 hours, 4 to 6 hours, 12 hours, after the first infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TNP-2092, ABSSSI, Safety, Efficacy