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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Melinta Therapeutics LLC

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

2 May 2023 → 20 Nov 2025

Decision date (initial)

2024-12-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Melinta Therapeutics, LLC

External identifiers

EU CT number

2024-516385-10-00

EudraCT number

2022-001297-63

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacokinetic, Dose response, Efficacy

To evaluate the safety and tolerability of single-dose IV oritavancin (ORBACTIV and KIMYRSA) in pediatric subjects with Acute ABSSSI

Secondary objectives 2

1. • To evaluate the PK profile of single-dose IV oritavancin (ORBACTIV and KIMYRSA) in pediatric subjects with ABSSSI
2. • To evaluate the clinical outcome of single-dose IV oritavancin (ORBACTIV and KIMYRSA) in pediatric subjects with ABSSSI

Conditions and MedDRA coding

Acute Bacterial Skin and Skin Structure Infections

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Subjects must meet all the following criteria to be eligible for the study: 1. Male or female 3 months to <12 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): a. 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 b. Cellulitis/erysipelas: a diffuse skin infection characterized by spreading areas of erythema, edema, and/or induration c. 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: a. Purulent drainage or discharge b. Erythema (>1 cm beyond edge of wound or abscess) c. Fluctuance d. Heat or localized warmth e. Edema/induration f. Pain or tenderness to palpation AND at least one of the following signs of systemic inflammation: a. Proximal lymph node swelling and tenderness b. Increased temperature (>38.0°C [>100.4°F]) c. Decreased temperature (<36.0°C [<96.8°F]) d. Decreased white blood cell (WBC) count (<4000/mm3) or increased WBC count (>12,000mm3) e. Bandemia >10% f. 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 2

1. Subjects who meet any of the following exclusion criteria at screening will not be enrolled in the study: 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: a. Infection suspected or documented to be caused solely by gramnegative pathogens (e.g., human or animal bite, injury contaminated with fresh or saltwater, external malignant otitis), fungi, or viruses b. Wound infection (surgical or traumatic) or abscess with only gram-negative pathogens c. Concomitant infection at another site, not including a secondary ABSSSI lesion (e.g., septic arthritis, endocarditis, osteomyelitis). d. Infected burn e. Primary infection superimposed on a pre-existing skin disease with associated inflammatory changes, e.g., atopic dermatitis, eczema f. 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) g. 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 ab-solute neutrophil count (ANC) <500 cells/mm3 10. Subjects with severe renal impairment as an eGFR < 30 ml/min/1.73m2 when using the updated bedside Schwartz formula. For subjects under 1 year of age, severe renal impairment is defined as serum creatinine ≥ 2 times the 97.5th percentile creatinine for age, converted to mg/dL, from Table 10 OR requirement for dialysis. If you have a subject under 1 year of age with renal impairment, please consult with the Medical Monitor before enrollment (see Appendix 3). 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 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.
2. 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 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety assessment of ORBACTIV and KIMYRSA in pediatric populations

Secondary endpoints 1

1. All-cause mortality assessed at the Time of Cure (ToC) visit

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Melinta Therapeutics LLC

Sponsor organisation

Melinta Therapeutics LLC

Address

389 Interpace Parkway Suite 450

City

Parsippany

Postcode

07054-1132

Country

United States

Scientific contact point

Organisation

Melinta Therapeutics LLC

Contact name

Michael Paul

Public contact point

Organisation

Melinta Therapeutics LLC

Contact name

Michael Paul

Third parties 1

Locations

8 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 197 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications