- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02052388
Efficacy and Safety Study of Brilacidin to Treat Serious Skin Infections
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Chula Vista, California, United States, 91911
- eStudy Site
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La Mesa, California, United States, 91942
- eStudy Site
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Oceanside, California, United States, 92056
- eStudy Site
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Nevada
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Las Vegas, Nevada, United States, 89109
- eStudy Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Low Single Dose Brilacidin
0.6mg/kg Brilacidin IV (single dose)
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Experimental Drug
Other Names:
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Experimental: High Single Dose Brilacidin
0.8mg/kg Brilacidin IV (single dose)
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Experimental Drug
Other Names:
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Experimental: 3-Day Regimen Brilacidin
0.6mg/kg Brilacidin IV on Day 1, followed by 0.3mg/kg Brilacidin IV on Days 2 & 3
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Experimental Drug
Other Names:
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Active Comparator: Standard dosing regimen Daptomycin
4mg/kg Daptomycin IV daily for 7 Days
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Active Comparator
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Early clinical response
Time Frame: 48-72 hours after first dose of study drug
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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.
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48-72 hours after first dose of study drug
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Response
Time Frame: Day 7-8; Day 10-14; Day 21-28
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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. |
Day 7-8; Day 10-14; Day 21-28
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Microbiological response
Time Frame: 48-72 hours; Day 7-8; Day 10-14
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Microbiological responses for those subjects who had a relevant skin pathogen isolated at baseline (MITT and ME populations)
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48-72 hours; Day 7-8; Day 10-14
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma drug levels
Time Frame: Days 1 (peak), 2 (trough) and 3 (trough and peak)
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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.
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Days 1 (peak), 2 (trough) and 3 (trough and peak)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: William O'Riordan, MD, eStudy Site
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTIX-BRI-204
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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