Study to Evaluate the Safety and Tolerability of Single-Dose Intravenous (IV) Oritavancin

This protocol describes a randomized, open-label study to evaluate the safety and tolerability of single-dose intravenous (IV) oritavancin diphosphate (oritavancin) versus standard of care (SoC) antibiotics for the treatment of pediatric subjects with acute bacterial skin and skin structure infections (ABSSSIs).This study involves two oritavancin products, ORBACTIV® and KIMYRSATM. Oritavancin is the active drug substance in both ORBACTIV and KIMYRSA. This study protocol distinguishes the differences between ORBACTIV and KIMYRSA by providing product-specific data, and information and guidance for Investigators. "Oritavancin" is used to describe drug product data, and information and guidance that is not specific to ORBACTIV or KIMYRSA (i.e., applies to both).The study involves pharmacokinetic (PK) sampling and will evaluate clinical outcome assessments. The study was designed to capture adequate data while minimizing the impact to subjects and their caregivers.

Inclusion Criteria:Male or female, 3 months to <18 years of age at randomizationDiagnosis of at least one of the following ABSSSI infections (known or suspected to be caused by a gram-positive pathogen):Wound infection: that is either traumatic or surgical in origin, defined as an infection characterized by purulent drainage from a wound with surrounding erythema, edema, and/or indurationCellulitis/erysipelas: a diffuse skin infection characterized by spreading areas of erythema, edema, and/or indurationMajor cutaneous abscess: an infection characterized by a collection of pus within the dermis or subcutaneous tissue that is accompanied by surrounding erythema, edema, and/or indurationABSSSI must present with at least two of the following signs and symptoms:Purulent drainage or dischargeErythema (>1 cm beyond edge of wound or abscess)FluctuanceHeat or localized warmthEdema/indurationPain or tenderness to palpation AND at least one of the following signs of systemic inflammation:Proximal lymph node swelling and tendernessIncreased temperature (>38.0°C [>100.4°F])Decreased temperature (<36.0°C [<96.8°F])Decreased white blood count (WBC) (<4000/mm3) or increased WBC (>12,000mm3)Bandemia >10%C-reactive protein (CRP) >upper limit of normal (ULN)Written informed consent obtained from parent(s) or legal guardian(s), with written or documented verbal assent of the child obtained, when appropriate, before initiation of any assessments conducted solely for study purposes.Exclusion Criteria:Subjects who have received more than 72 hours of effective antibacterial drug therapy for treatment of the current episode of ABSSSISubjects who have received a glycopeptide antibiotic (e.g., vancomycin, telavancin, teicoplanin) within 24 hours of randomizationSubjects who have received dalbavancin within 45 days prior to randomizationSubjects who have been treated with oritavancin within the last 50 daysSubjects with infection suspected to be associated with a device or implantSubjects with septic shock or hemodynamic instabilitySubjects with ABSSSI due to, or associated with any of the following:Infection suspected or documented to be caused solely by gram-negative pathogens (e.g., human or animal bite, injury contaminated with fresh or saltwater, external malignant otitis), fungi, or virusesWound infection (surgical or traumatic) or abscess with only gram-negative pathogensConcomitant infection at another site, not including a secondary ABSSSI lesion (e.g., septic arthritis, endocarditis, osteomyelitis).Infected burnPrimary infection superimposed on a pre-existing skin disease with associated inflammatory changes, e.g., atopic dermatitis, eczemaAny evolving necrotizing process (e.g., necrotizing fasciitis), gangrene, or infection suspected or proven to be caused by clostridioides species (e.g., crepitance on examination of the ABSSSI site and/or surrounding tissue(s), radiographic evidence of subcutaneous gas in proximity to the infection)Clinically significant viral infection (e.g., influenza, COVID-19) which, in the Investigator's judgement, will impact the study clinical outcome assessments (e.g., subject is febrile due to the viral infection)Subjects currently receiving chronic systemic immunosuppressive therapySubjects with neutropenia, defined as absolute neutrophil count (ANC) <500 cells/mm3Creatinine clearance (CrCl) < 30 mL/min/1.73 m2 as calculated using the updated Schwartz bedside formula:eGFR = k x (height in cm) ÷ serum Creatinine k = 0.33 in pre-term infants. k = 0.45 in term infants to 1 year of age. k = 0.55 in children and adolescent girls. k = 0.70 in adolescent boysMenstruating females with a positive result for the urine or serum human chorionic gonadotropin (HCG) test administered at screeningFemales of childbearing potential (and males with female partners of childbearing potential) unwilling to practice abstinence or use at least two methods of contraception (e.g., oral contraceptives, barrier methods, approved contraceptive implants) during the entire study periodSubjects with a history of infusion-related immunoglobulin E (IgE)-mediated allergic reaction or hypersensitivity reaction to glycopeptides (e.g., vancomycin, telavancin, dalbavancin, oritavancin, teicoplanin) or any of their excipientsSubjects who are taking heparin (other than heparin flush for line patency) or warfarin, and/or require anticoagulant monitoring [activated partial thromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR)]Subjects receiving treatment with an investigational medicinal product or investigational device within 3 months before enrollment or during the studySubjects whom the investigator considers unlikely to adhere to the protocol, comply with Study Drug administration, or complete the clinical study (e.g., unlikely to survive 28 days from initiation of Study Drug)Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x ULN or total bilirubin ≥2x ULN.