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

Acute Bacterial Skin and Skin Structure Infection Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05599295
• Other study ID #: ML-ORI-201
• Secondary ID: 2022-001297-63
• Status: Recruiting
• Phase: Phase 2
• Start date: June 15, 2023
• Est. completion date: January 15, 2026

Study information

• Verified date: March 2024
• Source: Melinta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 15, 2026
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Bacterial Skin and Skin Structure Infection
• Infections
• Skin Diseases, Bacterial

Intervention

Drug:
• Oritavancin
Oritavancin for IV infusion

Locations

Country	Name	City	State
Bulgaria	Multiprofile Hospital For Active Treatment Dr Tota Venkova	Gabrovo
Bulgaria	Multiprofile Hospital for Active Treatment- Sveti Nikolay Chudotvoretz - LOM EOOD	Lom	Montana
Bulgaria	University Multiprofile Hospital for Active Treatment Sveti Georgi EAD-66 Peshtersko Shosse blvd	Plovdiv
Bulgaria	University Multiprofile Hospital For Active Treatment Kanev AD	Ruse
Bulgaria	University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD	Stara Zagora
Greece	Aghia Sophia' Children's General Hospital of Athens	Athens	Attiki
Greece	Attikon University General Hospital	Chaidari	Attiki
Greece	Ippokratio General Hospital of Thessaloniki	Thessaloniki
Greece	Papageorgiou General Hospital of Thessaloniki	Thessaloniki
Latvia	Daugavpils Regional Hospital	Daugavpils	Daugavpils Aprinkis
Latvia	Regional Hospital of Liepaja	Liepaja	Liepajas Aprinkis
Latvia	Children's Clinical University Hospital	Riga
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos	Kaunas	Kauno Apskritis
Lithuania	Klaipeda Children Hospital	Klaipeda	Klaipedos Apskritis
Poland	Instytut Pomnik Centrum Zdrowia Dziecka - PIN	Warszawa	Mazowieckie
Portugal	Hospital de Cascais	Alcabideche	Lisboa
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar de Lisboa Ocidental, EPE - Hospital São Francisco Xavier	Lisboa
Portugal	Hospital CUF Descobertas	Lisboa
Romania	Brasov Children Clinical Hospital	Bra?ov
Romania	Louis Turcanu Emergency Clinical Hospital for Children	Timisoara	Timis
Spain	Hospital Sant Joan de Deu - PIN	Barcelona
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz - PPDS	Madrid
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Mount Sinai Beth Israel	New York	New York
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Melinta Therapeutics, LLC

Countries where clinical trial is conducted

United States,  Bulgaria,  Greece,  Latvia,  Lithuania,  Poland,  Portugal,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Assessments	Adverse events (AEs)	28 Days
Secondary	Test of Cure	All-cause mortality assessed at the Test of Cure visit.	Day 28
Secondary	Clinical Outcome Assessments	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