Single Dose vs. Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections

Study Overview
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Brief Summary
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To compare the efficacy of treatment with a single dose of dalbavancin 1500 mg to treatment with a two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in participants with known or suspected Gram-positive acute bacterial skin and skin structure infections (ABSSSI) at 48 -72 hours after initiation of treatment.

Official Title
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A Phase 3b, Double-Blind, Multicenter, Randomized Study to Compare the Efficacy and Safety of Single Dose Dalbavancin to a Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections

Conditions
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Abscess, Wound Infection, Surgical Site Infection, Cellulitis

Intervention / Treatment
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* Drug: Dalbavancin
* Drug: Dalbavancin-matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants 18 - 85 years of age. Signed and dated informed consent document. Major abscess, surgical site infection, traumatic wound infection or cellulitis suspected or confirmed to be caused by Gram-positive bacteria. At least two (2) local signs and symptoms of acute bacterial skin and skin structure infection (ABSSSI and at least one systemic sign of infection. Participant willing and able to comply with study procedures. Exclusion Criteria: A contra-indication to dalbavancin. Pregnant or nursing females. Sustained shock. Participation in another study of an investigational drug or device within 30 days. Receipt of a systemically or topically administered antibiotic with a Gram-positive spectrum that achieves therapeutic concentrations in the serum or at the site of the ABSSSI within 14 days prior to randomization. An exception is allowed for participants receiving a single dose of a short-acting (half-life ≤ 12 hours) antibacterial drug prior to randomization; up to 25% of participants may have received such therapy. Infection due to an organism known prior to study entry to be resistant to dalbavancin or vancomycin (vancomycin MIC (minimum inhibitory concentration) >8 μg/mL). Evidence of meningitis, necrotizing fasciitis, gas gangrene, gangrene, septic arthritis, osteomyelitis; endovascular infection, such as clinical and/or echocardiographic evidence of endocarditis or septic thrombophlebitis. Infections caused exclusively by Gram-negative bacteria (without Gram-positive bacteria present) and infections caused by fungi, whether alone or in combination with a bacterial pathogen. Venous catheter entry site infection. Infections involving a diabetic foot ulceration, perirectal abscess or a decubitus ulcer. Participant with an infected device, even if the device is removed. Examples include infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint prosthesis, hemodialysis catheter, implantable pacemaker or defibrillator, intra-aortic balloon pump, left ventricular assist device, a peritoneal dialysis catheter, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter. Gram-negative bacteremia, even in the presence of Gram-positive infection or Gram-positive bacteremia. Note: If a Gram-negative bacteremia develops during the study, or is subsequently found to have been present at Baseline, the participant should be removed from study treatment and receive appropriate antibiotic(s) to treat the Gram-negative bacteremia. Such participants must have an end of treatment (EOT) visit performed within 3 calendar days after discontinuing study medication but are required to have AEs (adverse events) reported through the Final Visit. Participants whose ABSSSI is the result of having sustained full or partial thickness burns. Participants with an infection involving a limb with evidence of critical ischemia of an affected limb defined as any of the following criteria: absent or abnormal Doppler wave forms, toe blood pressure of <45 mm Hg, ankle brachial index <0.5, and/ or critical ischemia as assessed by a vascular surgeon. Participants with ABSSSI such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure. Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study. Anticipated need of antibiotic therapy for longer than 14 days. Participants who are placed in a hyperbaric chamber as adjunctive therapy for the ABSSSI. More than 2 surgical interventions (defined as procedures conducted under sterile technique and typically unable to be performed at the bedside) for the ABSSSI, or participants who are expected to require more than 2 such interventions. Medical conditions in which chronic inflammation may preclude assessment of clinical response to therapy even after successful treatment (e.g., chronic stasis dermatitis of the lower extremity). Absolute neutrophil count <500 cells/mm^3. Known or suspected human immunodeficiency virus (HIV) infected participants with a CD4 (cluster of differentiation 4) cell count <200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count. Participants with a recent bone marrow transplant (in post-transplant hospital stay). Participants receiving oral steroids >20 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation. Participants with a rapidly fatal illness, who are not expected to survive for 3 months. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participants inappropriate for entry into this study. Prior participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-Dose Dalbavancin<br>Single-dose of dalbavancin 1500 mg intravenous (IV) infusion over 30 minutes on Day 1 followed by dalbavancin-matching placebo IV infusion over 30 minutes on Day 8 for participants with creatinine clearance (CrCl) ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin dose was 1000 mg. | Drug: Dalbavancin<br>* Dalbavancin IV infusion over 30 minutes.<br>* Other names: DALVANCE®;Drug: Dalbavancin-matching Placebo<br>* Dalbavancin-matching placebo IV infusion over 30 minutes.<br>|
| Experimental: Two-Dose Dalbavancin<br>Two-dose regimen of dalbavancin 1000 mg IV infusion over 30 minutes on Day 1 followed by 500 mg IV infusion over 30 minutes on Day 8 for participants with CrCl ≥30 mL/min or with CrCl <30 mL/min who were receiving regular hemodialysis or peritoneal dialysis. For participants with CrCl <30 mL/min who were not receiving regular hemodialysis or peritoneal dialysis, the dalbavancin doses were 750 mg on Day 1 and 375 mg on Day 8. | Drug: Dalbavancin<br>* Dalbavancin IV infusion over 30 minutes.<br>* Other names: DALVANCE®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Were Clinical Responders 48-72 Hours After the Initiation of Study Drug | Clinical responder was defined as a participant who was alive and had received no rescue therapy for acute bacterial skin and skin structure infection (ABSSSI) prior to the 48-72 hour infection site assessment (if an antibiotic has been given for another reason, the participant will not be considered a non-responder for this reason); and examination of the participant's ABSSSI lesion demonstrates a decrease of ≥ 20% in lesion area (calculated as the longest length multiplied by the longest perpendicular width) relative to the baseline measurement. | Up to 48-72 hours after the initiation of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants by Clinical Status at End of Treatment (EOT) and Final Visit (FV) | Clinical Success is defined as follows: For evaluation at EOT visit, lesion area must be decreased by ≥80% from baseline and at FV lesion area must be decreased by ≥90% from baseline; Temperature is ≤37.6°C; Local signs of tenderness to palpation and swelling/induration are no worse than mild; For evaluation at EOT visit, local signs of fluctuance and localized heat/warmth must be improved from baseline and no worse than mild, and at FV local signs of fluctuance and localized heat/warmth must be absent; for participants with a wound infection the severity of purulent drainage is improved and no worse than mild relative to baseline. Clinical Failure is defined as the opposite to success or if the participant died during the study period up to visit or received study therapy for ABSSSI beyond the protocol treatment period. Clinical status is Indeterminate if any of the data needed to determine clinical success or clinical failure were missing. | End of Treatment (Day 14-15 after the initiation of study drug) and Final Visit (28 ±2 days after the initiation of study drug) |