Evaluation of Safety and Tolerability of Single-Dose Intravenous Oritavancin Versus Standard Care in Pediatric Acute Bacterial Skin and Skin Structure Infections

The primary objective of this study is to evaluate the **safety** and **tolerability** of single-dose intravenous **oritavancin** (ORBACTIV and KIMYRSA) compared to standard of care (SoC) treatments in pediatric subjects with Acute Bacterial Skin and Skin Structure Infections (ABSSSI). This is clinically relevant as it aims to determine the potential of oritavancin as a safer and more tolerable treatment option for this patient population, which could lead to improved therapeutic outcomes and reduced adverse effects.

Secondary objectives include:

• Evaluating the clinical response of single-dose IV oritavancin compared with SoC in pediatric subjects with ABSSSI.
• Assessing the pharmacokinetic (PK) profile of single-dose IV oritavancin in pediatric subjects with ABSSSI.

The clinical trial involves a total of **39 participants** diagnosed with **Acute Bacterial Skin and Skin Structure Infections** (ABSSSI). The study population comprises both male and female subjects aged from 3 months to less than 18 years. Participants were selected based on specific inclusion criteria, including the presence of ABSSSI infections such as wound infections, cellulitis/erysipelas, or major cutaneous abscesses, all suspected to be caused by gram-positive pathogens. The trial does not focus on a vulnerable population, and participants are required to exhibit at least two signs and symptoms of ABSSSI, along with at least one sign of systemic inflammation. The general health status of the participants is not specified beyond the presence of the infection, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection process.

The clinical trial is designed to evaluate the **safety** and tolerability of single-dose intravenous **oritavancin** compared to standard care treatments in pediatric subjects with **acute bacterial skin and skin structure infections** (ABSSSI). This is a multicenter, open-label, evaluator-blinded, randomized study. The trial is expected to commence on June 1, 2023, and conclude by June 30, 2025. Participants will be randomly assigned to receive either a single dose of oritavancin or standard care, with the primary endpoint being the safety assessment of oritavancin in the pediatric population. Secondary endpoints include all-cause mortality assessed at the Time of Cure (ToC) visit.

The trial will include several study visits, beginning with a screening visit to determine eligibility based on specific inclusion criteria, such as age and diagnosis of ABSSSI. Participants must be between 3 months and less than 18 years of age and present with at least one type of ABSSSI infection, such as wound infection, cellulitis/erysipelas, or major cutaneous abscess. The screening visit will also involve obtaining informed consent from parents or legal guardians and assent from the child when appropriate. Following randomization, participants will receive the assigned treatment and undergo follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will mark the completion of the trial for each participant, where final assessments will be conducted.

The expected duration of participant involvement in the trial is up to 14 days, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or any situation where continued participation is deemed not in the best interest of the participant by the investigator. The trial is conducted in accordance with ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Oritavancin**, a chemical-origin active substance, in the form of a **solution for infusion**. The pharmaceutical product is available under the names **KIMYRSA** and **ORBACTIV**, both manufactured by Melinta Therapeutics Inc. The medication is administered intravenously, with a maximum daily dose of 15 mg/kg and a total maximum dose of 1200 mg. The treatment period does not exceed 14 days. The trial aims to evaluate the safety and tolerability of a single-dose intravenous administration of Oritavancin in pediatric subjects with acute bacterial skin and skin structure infections (ABSSSI).

In addition to the experimental treatment, the study includes a comparator group receiving the **Standard of Care (SoC)** treatments for ABSSSI. The SoC treatments serve as a benchmark to assess the relative safety and tolerability of Oritavancin. The trial is designed as a multicenter, open-label, evaluator-blinded, and randomized study, ensuring a robust comparison between the experimental and standard treatments. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The efficacy of the clinical trial will be assessed through the evaluation of safety and tolerability of single-dose intravenous **oritavancin** (ORBACTIV and KIMYRSA) compared to standard of care treatments in pediatric subjects with acute bacterial skin and skin structure infections (ABSSSI). The primary endpoint focuses on the safety assessment of ORBACTIV and KIMYRSA in the pediatric population. Secondary endpoints include the assessment of all-cause mortality at the Time of Cure (ToC) visit. The trial is designed as a multicenter, open-label, evaluator-blinded, randomized study. The trial will involve pediatric subjects aged 3 months to less than 18 years, diagnosed with ABSSSI infections suspected to be caused by gram-positive pathogens. The study will monitor the presence of specific signs and symptoms of ABSSSI, such as purulent drainage, erythema, and systemic inflammation indicators like increased or decreased temperature and white blood cell count. The trial is set to conclude by June 30, 2025, with recruitment having started on June 1, 2023.