Clinical trial NCT05599295: Study to Evaluate the Safety and Tolerability of Single-Dose Intravenous (IV) Oritavancin
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Bacterial Skin and Skin Structure Infection
Lead sponsor: Melinta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-31
Enrollment: 200
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

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   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.

Primary outcomes:
measure: Safety Assessments
timeFrame: 28 Days
Secondary outcomes:
measure: Test of Cure
timeFrame: Day 28
measure: Clinical Outcome Assessments
timeFrame: EoT Day 14; ToC Day 28
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Lom
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment- Sveti Nikolay Chudotvoretz - LOM EOOD
state: Montana
city: Gabrovo
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment Dr Tota Venkova
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti Georgi EAD-66 Peshtersko Shosse blvd
city: Ruse
country: Bulgaria
facility: University Multiprofile Hospital For Active Treatment Kanev AD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD
city: Athens
country: Greece
facility: Aghia Sophia' Children's General Hospital of Athens
state: Attiki
city: Chaidari
country: Greece
facility: Attikon University General Hospital
state: Attiki
city: Thessaloniki
country: Greece
facility: Ippokratio General Hospital of Thessaloniki
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital of Thessaloniki
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
state: Daugavpils Aprinkis
city: Liepaja
country: Latvia
facility: Regional Hospital of Liepaja
state: Liepajas Aprinkis
city: Riga
country: Latvia
facility: Children's Clinical University Hospital
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno klinikos
state: Kauno Apskritis
city: Klaipeda
country: Lithuania
facility: Klaipeda Children Hospital
state: Klaipedos Apskritis
city: Warszawa
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka - PIN
state: Mazowieckie
city: Alcabideche
country: Portugal
facility: Hospital de Cascais
state: Lisboa
city: Braga
country: Portugal
facility: Hospital de Braga
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental, EPE - Hospital São Francisco Xavier
city: Lisboa
country: Portugal
facility: Hospital CUF Descobertas
city: Timisoara
country: Romania
facility: Louis Turcanu Emergency Clinical Hospital for Children
state: Timis
city: Brașov
country: Romania
facility: Brasov Children Clinical Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu - PIN
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
Study officials:
References: