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)

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.

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.

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