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Efficacy and Safety Study of Brilacidin to Treat Serious Skin Infections

Primary Purpose

Skin Infection, Bacterial Infection

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Daptomycin
Brilacidin
Sponsored by
Cellceutix Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Skin Infection focused on measuring Skin Infection, Staph aureus, MRSA, MSSA, Cellulitis/Erysipelas, Wound Infection, Abscess

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provision of written informed consent
  • Be ≥ 18 and ≤ 85 years of age
  • Have one of the following types of ABSSSI:

    1. A post-traumatic or post-surgical wound infection, occurring within 30 days of the trauma or surgery, characterized by purulent or seropurulent drainage from the wound and surrounding erythema, edema and/or induration of a minimum surface area of 75 cm2.
    2. A major cutaneous abscess, characterized by a collection of pus within the dermis or deeper tissues, accompanied by erythema, edema, and/or induration of a minimum surface area of 75 cm2. Note: patients with major cutaneous abscess will be limited to 30% of total enrollment
    3. Cellulitis/erysipelas, characterized by spreading areas of erythema, edema, and/or induration of a minimum surface area of 75 cm2.
  • Have two or more of the following signs:

    1. Purulent or seropurulent drainage or discharge
    2. Erythema
    3. Fluctuance
    4. Heat or localized warmth
    5. Pain or tenderness to palpation
  • Have one or more of the following systemic signs:

    1. Temperature (oral or tympanic) ≥ 38⁰ C/100.4 F, as measured by the subject/caregiver or investigator up to 24 hours prior to baseline
    2. WBC count > 10,000/mm3
    3. Greater than 10% bands or other immature neutrophils (total), irrespective of WBC count
    4. Elevated C-reactive protein (CRP) (> 40 mg/L), if tested
    5. Presence of lymphadenitis or lymphadenopathy proximal to the infected area
  • Must not have received more than a single dose of a short-acting systemic antibiotic for the current ABSSSI within 72 hours prior to randomization, unless either of the following situations apply:

    1. Clinical evidence of treatment failure following at least 48 hours of prior systemic antimicrobial therapy; or
    2. The subject recently completed a course of antibiotic treatment for an infection other than ABSSSI and that drug is not active against the bacterial pathogens that typically cause ABSSSI.

Exclusion Criteria:

  • Female subjects who are pregnant, lactating (breast milk feeding), or planning a pregnancy during the course of the study.
  • Skin or skin structure infection with any of the following characteristics:

    1. Presence of an uncomplicated skin or skin structure infection, such as folliculitis, furunculosis, or minor abscess likely to respond to incision and drainage alone
    2. Suspected or confirmed osteomyelitis
    3. Suspected or confirmed septic arthritis
    4. Suspected or confirmed infection caused exclusively by Gram-negative pathogens or by any anaerobes
  • Known hypersensitivity to daptomycin
  • Known creatinine clearance <50 mL/min (based on the Cockcroft-Gault formula using ideal body weight)
  • Immunosuppression, defined as chronic corticosteroid use (20 mg prednisone/day or equivalent), solid organ or bone marrow transplantation, current cytotoxic chemotherapy, neutropenia (absolute neutrophil count < 500/mm3), or known HIV infection with CD4+ count < 200/mm3
  • Platelet count <50 x 103/L
  • Exhibits signs of sepsis:

    1. Shock or profound hypotension, defined as systolic blood pressure <90 mm Hg or a decrease of >40 mm Hg from baseline that is not responsive to fluid challenge;
    2. Hypothermia (core temperature <35.6°C or <96.1°F);
    3. Disseminated intravascular coagulation as evidenced by prothrombin time (PT) or activated partial thromboplastin time (aPTT) 2 times the upper limit of normal;
  • Inability or unwillingness to adhere to the study-specified procedures and restrictions

Sites / Locations

  • eStudy Site
  • eStudy Site
  • eStudy Site
  • eStudy Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Low Single Dose Brilacidin

High Single Dose Brilacidin

3-Day Regimen Brilacidin

Standard dosing regimen Daptomycin

Arm Description

0.6mg/kg Brilacidin IV (single dose)

0.8mg/kg Brilacidin IV (single dose)

0.6mg/kg Brilacidin IV on Day 1, followed by 0.3mg/kg Brilacidin IV on Days 2 & 3

4mg/kg Daptomycin IV daily for 7 Days

Outcomes

Primary Outcome Measures

Early clinical response
The primary efficacy outcome, early clinical response 48-72 hours after the first dose of study drug, will be determined in the ITT population. A subject will be considered a Clinical Success if 1) the lesion area has decreased by ≥20% compared to baseline and 2) no additional systemic antibacterials that are potentially effective against gram positive organisms have been administered.

Secondary Outcome Measures

Clinical Response
For Days 7/8 and 10-14, a response of Clinical Success will be assigned if all signs and symptoms of infection present at baseline have improved and/or resolved and no additional antibiotics are considered necessary. Subjects who have a response of Clinical Success at Day 10-14 will be assessed for sustained efficacy at Day 21-28. A response of Sustained Clinical Success will be assigned if all signs and symptoms remain resolved and no additional antibiotics are considered necessary. If signs and symptoms of infection recurred at the original site of infection and require additional antibiotic therapy, a response of Relapse will be assigned.
Microbiological response
Microbiological responses for those subjects who had a relevant skin pathogen isolated at baseline (MITT and ME populations)

Full Information

First Posted
January 30, 2014
Last Updated
September 24, 2018
Sponsor
Cellceutix Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT02052388
Brief Title
Efficacy and Safety Study of Brilacidin to Treat Serious Skin Infections
Official Title
A Randomized, Double-Blind Study Comparing Three Dosing Regimens of Brilacidin to Daptomycin in the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cellceutix Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine the safety and efficacy of three different dosing regimens of brilacidin compared to daptomycin for the treatment of serious skin infections. This study will aid in selecting the appropriate dose of brilacidin for later stage studies.
Detailed Description
This is a randomized, multi-center, double-blind study to evaluate the efficacy and safety of three regimens of brilacidin compared to an active control, daptomycin, in subjects with ABSSSI. Subjects must have infections that warrant intravenous therapy but may be treated as either inpatients or outpatients. Eligible subjects will be randomized to one of 4 treatment groups in a 1:1:1:1 ratio. Subjects randomized to brilacidin will receive either a single intravenous infusion (0.6 mg/kg or 0.8 mg/kg) followed by six days of once daily placebo, or a three day regimen (0.6 mg/kg on Day 1 followed by 0.3 mg/kg on Days 2 and 3) followed by 4 days of once daily placebo. Subjects randomized to daptomycin will receive 7 days of treatment. Subjects will be assessed for both clinical and microbiologic efficacy 48-72 hours after the first dose of study drug. After an assessment at Day 7-8, subjects will be again be evaluated for efficacy at Day 10-14 and via a phone contact at Day 21-28. Approximately 200 subjects randomized in a 1:1:1:1 ratio to receive one of the three brilacidin regimens or daptomycin will be evaluable. The primary efficacy outcome, early clinical response 48-72 hours after the first dose of study drug, will be determined in the Intent-to treat (ITT) population. Additional efficacy and safety analyses will be performed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Skin Infection, Bacterial Infection
Keywords
Skin Infection, Staph aureus, MRSA, MSSA, Cellulitis/Erysipelas, Wound Infection, Abscess

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
215 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low Single Dose Brilacidin
Arm Type
Experimental
Arm Description
0.6mg/kg Brilacidin IV (single dose)
Arm Title
High Single Dose Brilacidin
Arm Type
Experimental
Arm Description
0.8mg/kg Brilacidin IV (single dose)
Arm Title
3-Day Regimen Brilacidin
Arm Type
Experimental
Arm Description
0.6mg/kg Brilacidin IV on Day 1, followed by 0.3mg/kg Brilacidin IV on Days 2 & 3
Arm Title
Standard dosing regimen Daptomycin
Arm Type
Active Comparator
Arm Description
4mg/kg Daptomycin IV daily for 7 Days
Intervention Type
Drug
Intervention Name(s)
Daptomycin
Other Intervention Name(s)
Cubicin
Intervention Description
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Brilacidin
Other Intervention Name(s)
PMX63
Intervention Description
Experimental Drug
Primary Outcome Measure Information:
Title
Early clinical response
Description
The primary efficacy outcome, early clinical response 48-72 hours after the first dose of study drug, will be determined in the ITT population. A subject will be considered a Clinical Success if 1) the lesion area has decreased by ≥20% compared to baseline and 2) no additional systemic antibacterials that are potentially effective against gram positive organisms have been administered.
Time Frame
48-72 hours after first dose of study drug
Secondary Outcome Measure Information:
Title
Clinical Response
Description
For Days 7/8 and 10-14, a response of Clinical Success will be assigned if all signs and symptoms of infection present at baseline have improved and/or resolved and no additional antibiotics are considered necessary. Subjects who have a response of Clinical Success at Day 10-14 will be assessed for sustained efficacy at Day 21-28. A response of Sustained Clinical Success will be assigned if all signs and symptoms remain resolved and no additional antibiotics are considered necessary. If signs and symptoms of infection recurred at the original site of infection and require additional antibiotic therapy, a response of Relapse will be assigned.
Time Frame
Day 7-8; Day 10-14; Day 21-28
Title
Microbiological response
Description
Microbiological responses for those subjects who had a relevant skin pathogen isolated at baseline (MITT and ME populations)
Time Frame
48-72 hours; Day 7-8; Day 10-14
Other Pre-specified Outcome Measures:
Title
Plasma drug levels
Description
Brilacidin levels will be determined at specified times to aid in pharmacokinetic-pharmacodynamic analyses. These data will aid in dose selection for later stage trials.
Time Frame
Days 1 (peak), 2 (trough) and 3 (trough and peak)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of written informed consent Be ≥ 18 and ≤ 85 years of age Have one of the following types of ABSSSI: A post-traumatic or post-surgical wound infection, occurring within 30 days of the trauma or surgery, characterized by purulent or seropurulent drainage from the wound and surrounding erythema, edema and/or induration of a minimum surface area of 75 cm2. A major cutaneous abscess, characterized by a collection of pus within the dermis or deeper tissues, accompanied by erythema, edema, and/or induration of a minimum surface area of 75 cm2. Note: patients with major cutaneous abscess will be limited to 30% of total enrollment Cellulitis/erysipelas, characterized by spreading areas of erythema, edema, and/or induration of a minimum surface area of 75 cm2. Have two or more of the following signs: Purulent or seropurulent drainage or discharge Erythema Fluctuance Heat or localized warmth Pain or tenderness to palpation Have one or more of the following systemic signs: Temperature (oral or tympanic) ≥ 38⁰ C/100.4 F, as measured by the subject/caregiver or investigator up to 24 hours prior to baseline WBC count > 10,000/mm3 Greater than 10% bands or other immature neutrophils (total), irrespective of WBC count Elevated C-reactive protein (CRP) (> 40 mg/L), if tested Presence of lymphadenitis or lymphadenopathy proximal to the infected area Must not have received more than a single dose of a short-acting systemic antibiotic for the current ABSSSI within 72 hours prior to randomization, unless either of the following situations apply: Clinical evidence of treatment failure following at least 48 hours of prior systemic antimicrobial therapy; or The subject recently completed a course of antibiotic treatment for an infection other than ABSSSI and that drug is not active against the bacterial pathogens that typically cause ABSSSI. Exclusion Criteria: Female subjects who are pregnant, lactating (breast milk feeding), or planning a pregnancy during the course of the study. Skin or skin structure infection with any of the following characteristics: Presence of an uncomplicated skin or skin structure infection, such as folliculitis, furunculosis, or minor abscess likely to respond to incision and drainage alone Suspected or confirmed osteomyelitis Suspected or confirmed septic arthritis Suspected or confirmed infection caused exclusively by Gram-negative pathogens or by any anaerobes Known hypersensitivity to daptomycin Known creatinine clearance <50 mL/min (based on the Cockcroft-Gault formula using ideal body weight) Immunosuppression, defined as chronic corticosteroid use (20 mg prednisone/day or equivalent), solid organ or bone marrow transplantation, current cytotoxic chemotherapy, neutropenia (absolute neutrophil count < 500/mm3), or known HIV infection with CD4+ count < 200/mm3 Platelet count <50 x 103/L Exhibits signs of sepsis: Shock or profound hypotension, defined as systolic blood pressure <90 mm Hg or a decrease of >40 mm Hg from baseline that is not responsive to fluid challenge; Hypothermia (core temperature <35.6°C or <96.1°F); Disseminated intravascular coagulation as evidenced by prothrombin time (PT) or activated partial thromboplastin time (aPTT) 2 times the upper limit of normal; Inability or unwillingness to adhere to the study-specified procedures and restrictions
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William O'Riordan, MD
Organizational Affiliation
eStudy SIte
Official's Role
Principal Investigator
Facility Information:
Facility Name
eStudy Site
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
eStudy Site
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
eStudy Site
City
Oceanside
State/Province
California
ZIP/Postal Code
92056
Country
United States
Facility Name
eStudy Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Efficacy and Safety Study of Brilacidin to Treat Serious Skin Infections

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