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

March 4, 2024 updated by: Melinta Therapeutics, LLC

A Multicenter, Open-Label, Evaluator-Blinded, Randomized Study to Evaluate the Safety and Tolerability of Single-Dose IV Oritavancin vs SoC for the Treatment of Pediatric Subjects With Acute Bacterial Skin and Skin Structure Infections

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Bulgaria
      • Gabrovo, Bulgaria, 5300
        • Recruiting
        • Multiprofile Hospital For Active Treatment Dr Tota Venkova
        • Principal Investigator:
          • Svetla Pashova-Mihova
        • Contact:
      • Plovdiv, Bulgaria, 4000
        • Recruiting
        • University Multiprofile Hospital for Active Treatment Sveti Georgi EAD-66 Peshtersko Shosse blvd
        • Principal Investigator:
          • Penka Stefanova, MD, PhD
        • Contact:
      • Ruse, Bulgaria, 7002
        • Recruiting
        • University Multiprofile Hospital For Active Treatment Kanev AD
        • Principal Investigator:
          • Simeon Simeonov, MD
        • Contact:
      • Sofia, Bulgaria, 1606
        • Recruiting
        • University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
        • Principal Investigator:
          • Yavor Pukalski
        • Contact:
      • Stara Zagora, Bulgaria, 6003
        • Recruiting
        • University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD
        • Contact:
        • Principal Investigator:
          • Krasimira Atanasova-Georgieva
    • Montana
      • Lom, Montana, Bulgaria, 3600
        • Recruiting
        • Multiprofile Hospital for Active Treatment- Sveti Nikolay Chudotvoretz - LOM EOOD
        • Principal Investigator:
          • Chavdar Antonov, MD
        • Contact:
  • Greece
      • Thessaloniki, Greece, 56429
        • Recruiting
        • Papageorgiou General Hospital of Thessaloniki
        • Principal Investigator:
          • Efimia Papadopoulou Alataki, MD
        • Contact:
          • Efimia Papadopoulou Alataki
          • Phone Number: +302313323901
          • Email: papadoef@auth.gr
      • Thessaloniki, Greece, 546 42
        • Recruiting
        • Ippokratio General Hospital of Thessaloniki
        • Principal Investigator:
          • Emmanuel Roilides, MD
        • Contact:
    • Attiki
      • Athens, Attiki, Greece, 115 27
        • Recruiting
        • Aghia Sophia' Children's General Hospital of Athens
        • Principal Investigator:
          • Vana Spoulou, MD
        • Contact:
      • Chaidari, Attiki, Greece, 124 62
        • Recruiting
        • Attikon University General Hospital
        • Principal Investigator:
          • Vassiliki Papaevangelou, MD
        • Contact:
  • Latvia
      • Riga, Latvia, LV-1004
        • Recruiting
        • Children's Clinical University Hospital
        • Principal Investigator:
          • Ainars Gilis, MD
        • Contact:
    • Daugavpils Aprinkis
      • Daugavpils, Daugavpils Aprinkis, Latvia, LV-5417
        • Recruiting
        • Daugavpils Regional Hospital
        • Principal Investigator:
          • Vladimirs Oleinikovs, MD
        • Contact:
    • Liepajas Aprinkis
      • Liepaja, Liepajas Aprinkis, Latvia, LV-3414
        • Recruiting
        • Regional Hospital of Liepaja
        • Principal Investigator:
          • Marija Kraule, MD
        • Contact:
  • Lithuania
    • Kauno Apskritis
      • Kaunas, Kauno Apskritis, Lithuania, LT-50009
        • Recruiting
        • Hospital of Lithuanian University of Health Sciences Kauno Klinikos
        • Principal Investigator:
          • Dalius Malcius, MD, PhD
        • Contact:
    • Klaipedos Apskritis
      • Klaipeda, Klaipedos Apskritis, Lithuania, 92140
        • Recruiting
        • Klaipeda Children Hospital
        • Principal Investigator:
          • Raimondas Latvys, MD
        • Contact:
  • Poland
    • Mazowieckie
      • Warszawa, Mazowieckie, Poland, 04-736
        • Recruiting
        • Instytut Pomnik Centrum Zdrowia Dziecka - PIN
        • Principal Investigator:
          • Malgorzata Mikaszewska - Sokolewicz
        • Contact:
  • Portugal
      • Braga, Portugal, 4710-243
      • Lisboa, Portugal, 1998-018
        • Recruiting
        • Hospital CUF Descobertas
        • Principal Investigator:
          • Merlin Mcmillan
        • Contact:
      • Lisboa, Portugal, 1449-005
        • Recruiting
        • Centro Hospitalar de Lisboa Ocidental, EPE - Hospital São Francisco Xavier
        • Principal Investigator:
          • Inês Belo
        • Contact:
    • Lisboa
      • Alcabideche, Lisboa, Portugal, 2755-009
  • Romania
      • Brașov, Romania, 500063
        • Recruiting
        • Brasov Children Clinical Hospital
        • Principal Investigator:
          • Iuliu Muntean, MD
        • Contact:
    • Timis
      • Timisoara, Timis, Romania, 300011
        • Recruiting
        • Louis Turcanu Emergency Clinical Hospital for Children
        • Principal Investigator:
          • Vlad David, MD, PhD
        • Contact:
  • Spain
      • Barcelona, Spain, 8035
        • Recruiting
        • Hospital Universitario Vall d'Hebron - PPDS
        • Principal Investigator:
          • Pere Soler Palacin, MD, PhD
        • Contact:
      • Barcelona, Spain, 8950
        • Recruiting
        • Hospital Sant Joan de Deu - PIN
        • Principal Investigator:
          • Claudia Fortuny Guasch, MD
        • Contact:
      • Madrid, Spain, 28041
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Principal Investigator:
          • Daniel Blazquez, MD
        • Contact:
      • Madrid, Spain, 28046
        • Recruiting
        • Hospital Universitario La Paz - PPDS
        • Principal Investigator:
          • Cristina Calvo Rey, MD
        • Contact:
  • United States
    • Florida
      • Tampa, Florida, United States, 33606
        • Recruiting
        • Tampa General Hospital
        • Principal Investigator:
          • Claudia Espinosa, MD, MSc
        • Contact:
    • New York
      • New York, New York, United States, 10003-2925
        • Recruiting
        • Mount Sinai Beth Israel
        • Contact:
        • Principal Investigator:
          • Czer Lim, MD
    • Ohio
      • Columbus, Ohio, United States, 43205-2664

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 17 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female, 3 months to <18 years of age at randomization

  2. Diagnosis of at least one of the following ABSSSI infections (known or suspected to be caused by a gram-positive pathogen):

    1. 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 induration
    2. Cellulitis/erysipelas: a diffuse skin infection characterized by spreading areas of erythema, edema, and/or induration
    3. Major 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 induration

  3. ABSSSI must present with at least two of the following signs and symptoms:

    1. Purulent drainage or discharge
    2. Erythema (>1 cm beyond edge of wound or abscess)
    3. Fluctuance
    4. Heat or localized warmth
    5. Edema/induration
    6. Pain or tenderness to palpation AND at least one of the following signs of systemic inflammation:
    1. Proximal lymph node swelling and tenderness
    2. Increased temperature (>38.0°C [>100.4°F])
    3. Decreased temperature (<36.0°C [<96.8°F])
    4. Decreased white blood count (WBC) (<4000/mm3) or increased WBC (>12,000mm3)
    5. Bandemia >10%
    6. C-reactive protein (CRP) >upper limit of normal (ULN)
  4. 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:

  1. Subjects who have received more than 72 hours of effective antibacterial drug therapy for treatment of the current episode of ABSSSI
  2. Subjects who have received a glycopeptide antibiotic (e.g., vancomycin, telavancin, teicoplanin) within 24 hours of randomization
  3. Subjects who have received dalbavancin within 45 days prior to randomization
  4. Subjects who have been treated with oritavancin within the last 50 days
  5. Subjects with infection suspected to be associated with a device or implant
  6. Subjects with septic shock or hemodynamic instability

  7. Subjects with ABSSSI due to, or associated with any of the following:

    1. 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 viruses
    2. Wound infection (surgical or traumatic) or abscess with only gram-negative pathogens
    3. Concomitant infection at another site, not including a secondary ABSSSI lesion (e.g., septic arthritis, endocarditis, osteomyelitis).
    4. Infected burn
    5. Primary infection superimposed on a pre-existing skin disease with associated inflammatory changes, e.g., atopic dermatitis, eczema
    6. Any 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)
    7. 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)
  8. Subjects currently receiving chronic systemic immunosuppressive therapy
  9. Subjects with neutropenia, defined as absolute neutrophil count (ANC) <500 cells/mm3

  10. Creatinine 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 boys

  11. Menstruating females with a positive result for the urine or serum human chorionic gonadotropin (HCG) test administered at screening
  12. Females 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 period
  13. Subjects 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 excipients
  14. Subjects 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)]
  15. Subjects receiving treatment with an investigational medicinal product or investigational device within 3 months before enrollment or during the study
  16. Subjects 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)
  17. Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x ULN or total bilirubin ≥2x ULN.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Orbactiv
ORBACTIV is infused at 15mg/kg over 3 hours for all subjects not to exceed a dose of 1200mg.
Drug: Oritavancin
Oritavancin for IV infusion
Experimental: Kimyrsa
  • KIMYRSA is infused at 15mg/kg over 1 hour for subjects ≥12 years old and weighing >40 kg not to exceed a dose of 1200mg.
  • KIMYRSA is infused at 15mg/kg over 3 hours in subjects <12 years old or weighing ≤40 kg.
Drug: Oritavancin
Oritavancin for IV infusion
Active Comparator: Standard of Care

The following SoC medications below will be administered via IV infusion, per the package insert, and according to local rules and regulations. SoC medications cannot be used in combination with one another.

  • Vancomycin
  • Teicoplanin
  • Clindamycin
  • Daptomycin
  • Semi-synthetic penicillins (e.g., nafcillin, oxacillin, cloxacillin)
  • Cefazolin
  • Ceftaroline
Drug: Oritavancin
Oritavancin for IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Assessments
Time Frame: 28 Days
Adverse events (AEs)
28 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Test of Cure
Time Frame: Day 28
All-cause mortality assessed at the Test of Cure visit.
Day 28
Clinical Outcome Assessments
Time Frame: EoT Day 14; ToC Day 28

Clinical Outcome Definitions: Clinical response of Cure or failure at End of Treatment visit and Test of Cure visit.

Cure

  • Complete or nearly complete resolution of baseline signs and symptoms of the primary infection, including absence of fever
  • No further treatment with antibiotics required for the primary infection

Failure

  • Use of additional antibiotic treatment for the primary infection prior to the visit (other than for gram-negative coverage, when given according to this protocol)
  • Worsening signs and symptoms (either assessed by the investigational site or reported by the subject or subject's caregivers) of the primary infection >72 hours from the start of Study Drug treatment.
  • Lost to Follow-up or other extenuating circumstance where the subject cannot be adequately assessed
EoT Day 14; ToC Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Melinta Therapeutics, LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2023

Primary Completion (Estimated)

June 15, 2025

Study Completion (Estimated)

January 15, 2026

Study Registration Dates

First Submitted

October 20, 2022

First Submitted That Met QC Criteria

October 25, 2022

First Posted (Actual)

October 31, 2022

Study Record Updates

Last Update Posted (Estimated)

March 5, 2024

Last Update Submitted That Met QC Criteria

March 4, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML-ORI-201
  • 2022-001297-63 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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