| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Acute Bacterial Skin and Skin Structure Infections | |
| E.1.1.1 | Medical condition in easily understood language | | Bacterial infection of the skin and associated tissues. | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | To evaluate the safety and tolerability of single-dose IV oritavancin (ORBACTIV and KIMYRSA) relative to Standard of Care (SoC) treatments in pediatric subjects with Acute ABSSSI. | |
| E.2.2 | Secondary objectives of the trial | To evaluate the Clinical Response of single-dose IV oritavancin (ORBACTIV and KIMYRSA) relative to SoC treatments in pediatric subjects with ABSSSI
To evaluate the pharmacokinetic (PK) profile of single-dose IV oritavancin (ORBACTIV and KIMYRSA) in pediatric subjects with ABSSSI | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Male or female, 3 months to <18 years of age at screening
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 count (WBC) (<4000/mm3) or increased WBC (>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. | |
| E.4 | Principal 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:
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 body site, from bacteria that is different from gram-positive bacteria causing the ABSSSI lesion (e.g., septic arthritis, endocarditis, osteomyelitis). Secondary infections due to the same gram-positive bacteria are eligible to be enrolled in
this study).
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 a glomerular filtration rate 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). Subjects under 1 year of age with renal impairment require, consultation
with the Sponsor 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, from the time of 1st dose until 50 days after the last dose of protocol defined study medication.
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. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | Safety assessment of ORBACTIV and KIMYRSA in pediatric populations. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | | Data will be analyzed by treatment group using the following parameters: laboratory results, vital signs, adverse events (AEs), physical examinations, and concomitant medication use. | |
| E.5.2 | Secondary end point(s) | All-cause mortality assessed at the Time of Cure (ToC) visit
| |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | o Clinical Response of Cure, Failure, or Unknown at EoT Visit
o Clinical Response of Cure, Failure, or Unknown at ToC Visit | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description | |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 | The trial involves single site in the Member State concerned | No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | United States | | Belgium | | Bulgaria | | Greece | | Latvia | | Lithuania | | Poland | | Portugal | | Romania | | Spain | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 3 |
