Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Children, Known or Suspected to be Caused by Susceptible Gram-positive Organisms, Including MRSA

Phase 3

Completed

• Conditions: Bacterial Infections; Methicillin-Resistant Staphylococcus Aureus; Staphylococcal Skin Infections
• Interventions: Drug: Dalbavancin; Drug: Vancomycin; Drug: Oxacillin; Drug: Flucloxacillin; Drug: Cefadroxil; Drug: Clindamycin

• Registration Number: NCT02814916
• Lead Sponsor: AbbVie

Brief Summary

To determine the safety and descriptive efficacy of dalbavancin for the treatment of acute bacterial skin and skin structure infections in children, aged birth to 17 years (inclusive), known or suspected to be caused by susceptible Gram-positive organisms, including methicillin-resistant strains of Staphylococcus aureus.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-06-08
• Study First Submitted QC: 2016-06-23
• Study First Posted: 2016-06-28
• Study Start: 2017-03-31
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-16
• Last Update Posted: 2024-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 199

Inclusion Criteria

• Male or female patients birth to 17 years (inclusive)

• A clinical picture compatible with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) suspected or confirmed to be caused by Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA).

• In addition to local signs of ABSSSI, the patient has at least one of the following:

• Fever, defined as body temperature ≥ 38.4°C (101.2°F) taken orally, ≥ 38.7°C (101.6°F) tympanically, or ≥ 39°C (102.2°F) rectally (core temperature) OR

• Leukocytosis (WBC > 10,000 mm3) or leukopenia (WBC < 2,000 mm3) or left shift of >10% band neutrophils

• Infection either involving deeper soft tissue or requiring significant surgical intervention

• Major cutaneous abscess characterized as a collection of pus within the dermis or deeper that is accompanied by erythema, edema and/or induration which i. requires surgical incision and drainage, and ii. is associated with cellulitis such that the total affected area involves at least 35 cm2 of erythema, or total affected area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR iii. alternatively, involves the central face and is associated with an area of erythema of at least 15 cm2 b. Surgical site or traumatic wound infection characterized by purulent drainage with surrounding erythema, edema and/or induration which occurred within 30 days after the trauma or surgery and is associated with cellulitis such that: i. the total affected area involves at least 35 cm2 of erythema, or total affected area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, involves the central face and is associated with an affected area of at least 15 cm2 c. Cellulitis, defined as a diffuse skin infection characterized by spreading areas of erythema, edema and/or induration and: i. is associated with erythema that involves at least 35 cm2 of surface area, or surface area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, cellulitis of the central face that is associated with an affected area of at least 15 cm2 5. In addition to the requirement for erythema, all patients are required to have at least two (2) of the following signs of ABSSSI: a. Purulent drainage/discharge b. Fluctuance c. Heat/localized warmth d. Tenderness to palpation e. Swelling/induration

  • In patients age birth to < 3 months, each patient must meet the following inclusion criteria to be enrolled in this study.

    1. Male or female patients from birth to < 3 months of age, including pre-term neonates (gestational age ≥ 32 weeks)

    2. A clinical picture compatible with an ABSSSI suspected or confirmed to be caused by Gram-positive bacteria, including MRSA.

       OR

       Suspected or confirmed sepsis including any of the following clinical criteria:

       1. Hypothermia (<36°C) OR fever (>38.5°C)
       2. Bradycardia OR tachycardia OR rhythm instability
       3. Hypotension OR mottled skin OR impaired peripheral perfusion
       4. Petechial rash
       5. New onset or worsening of apnea episodes OR tachypnea episodes OR increased oxygen requirements OR requirement for ventilation support
       6. Feeding intolerance OR poor sucking OR abdominal distension
       7. Irritability
       8. Lethargy
       9. Hypotonia

    3. In addition, patients must meet at least one of the following laboratory criteria:

       a. White blood cell count ≤4.0 × 10^9/L OR ≥20.0 × 10^9/L b, Immature to total neutrophil ratio >0.2 c. Platelet count ≤100 × 10^9/L d. C-reactive protein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL e. Hyperglycemia OR Hypoglycemia f. Metabolic acidosis

    4. Infections must be of sufficient severity to merit hospitalization and parenteral antibiotic therapy. These infections may include:

       1. Cutaneous or subcutaneous abscess
       2. Surgical site or traumatic wound infection
       3. Cellulitis, Erysipelas
       4. Omphalitis
       5. Impetigo and bullous impetigo
       6. Pustular folliculitis
       7. Scarlet fever
       8. Staphylococcal scalded skin syndrome
       9. Streptococcal toxic shock syndrome
       10. Erythematous based-erosion
       11. Other infections originating in the skin or subcutaneous tissue and associated with signs and symptoms of sepsis as defined in Inclusion Criterion 2.

    5. Patients must be expected to survive with appropriate antibiotic therapy and appropriate supportive care throughout the study.

Read More

Exclusion Criteria

1. Patients age 3 months to 17 years: Clinically significant renal impairment, defined as calculated creatinine clearance of less than 30 mL/min. (calculated by the Schwartz "bedside" formula). Patients birth to < 3 months of age: Moderate or severe renal impairment defined as serum creatinine ≥ 2 times the upper limit of normal (× ULN) for age OR urine output < 0.5 mL/kg/h (measured over at least 8 hours prior to dosing) OR requirement for dialysis.
2. Clinically significant hepatic impairment, defined as serum bilirubin or alkaline phosphatase greater than 2 times the upper limits of normal (ULN) for age, and/or serum aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal (ULN) for age.
3. Treatment with an investigational drug within 30 days preceding the first dose of study medication.
4. Patients with sustained shock defined as systolic blood pressure < 90 mm Hg in children ≥ 10 years old, < 70 mm Hg + [2 x age in years] in children 1 to <10 years, or < 70 mmHg in infants 3 to <12 months old for more than 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents to maintain blood pressure.
5. More than 24 hours of any systemic antibacterial therapy within 96 hours before randomization. EXCEPTION: Microbiological or clinical treatment failure with a systemic antibiotic other than IV study drug that was administered for at least 48 hours. Failure must be confirmed by either a microbiological laboratory report or documented worsening clinical signs or symptoms.
6. Infection due to an organism known prior to study entry to be resistant to dalbavancin (dalbavancin minimum inhibitory concentration (MIC) greater than 0.25 ug/mL) or vancomycin (vancomycin minimum inhibitory concentration (MIC) greater than 2 ug/mL).
7. Patients with necrotizing fasciitis, or deep-seated infections that would require > 2 weeks of antibiotics (e.g., endocarditis, osteomyelitis or septic arthritis).
8. Infections caused exclusively by Gram-negative bacteria (without Gram-positive bacteria present) and infections caused by fungi, whether alone or in combination with a bacterial pathogen.
9. Venous catheter entry site infection.
10. Infections involving diabetic foot ulceration, perirectal abscess or a decubitus ulcer.
11. Patient with an infected device, even if the device is removed. Examples include infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint prosthesis, implantable pacemaker or defibrillator, intraaortic balloon pump, left ventricular assist device, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter.
12. Gram-negative bacteremia, even in the presence of Gram-positive infection or Gram-positive bacteremia. Note: If a Gram-negative bacteremia develops during the study, or is subsequently found to have been present at Baseline, the patient should be removed from study treatment and receive appropriate antibiotic(s) to treat the Gram-negative bacteremia.
13. Patients whose skin infection is the result of having sustained full or partial thickness burns.
14. Patients age 3 months to 17 years, with uncomplicated skin infections such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure. Patients birth to < 3 months of age may be enrolled if they have uncomplicated skin infections of sufficient severity to require hospitalization and parenteral antibiotic therapy.
15. Patients age 3 months to 17 years: Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study.
16. Sickle cell anemia
17. Cystic fibrosis
18. Anticipated need of antibiotic therapy for longer than 14 days.
19. Patients who are placed in a hyperbaric chamber as adjunctive therapy for the ABSSSI.
20. More than 2 surgical interventions (defined as procedures conducted under sterile technique and typically unable to be performed at the bedside) for the skin infection, or patients who are expected to require more than 2 such interventions.
21. Medical conditions in which chronic inflammation may preclude assessment of clinical response to therapy even after successful treatment (e.g., chronic stasis dermatitis of the lower extremity).
22. Immunosuppression/immune deficiency, including hematologic malignancy, recent bone marrow transplant (in post-transplant hospital stay), absolute neutrophil count < 500 cells/mm3, receiving immunosuppressant drugs after organ transplantation, receiving oral steroids ≥ 20 mg prednisolone per day (or equivalent) for > 14 days prior to enrollment, and known or suspected human immunodeficiency virus (HIV) infected patients with a CD4 cell count< 200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count.
23. Known or suspected hypersensitivity to glycopeptide antibiotics, betalactam agents, aztreonam, or cephalosporins.
24. Patients with a rapidly fatal illness, who are not expected to survive for 3 months.
25. Positive urine (or serum) pregnancy test at screening (post-menarchal females only) or after admission (prior to dosing).
26. Pregnant or nursing females; sexually active females of childbearing potential who are unwilling or unable to use adequate contraceptive precautions. Female patients to have pregnancy testing are those who are at least 10 years old with menarche and/or thelarche (beginning of breast development).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dalbavancin single-dose	Dalbavancin	Participants received dalbavancin administered intravenously as follows: birth to \< 3 months old and 3 months to \< 6 years old: 22.5 mg/kg (maximum 1500 mg) on Day 1; ≥6 years to 17 years old (inclusive): 18 mg/kg (maximum 1500 mg) on Day 1. Participants aged birth to \< 3 months were not randomized; all received dalbavancin single-dose.
Comparator	Vancomycin	Participants 3 mos to \< 6 yrs old and ≥6 yrs to 17 yrs old received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a 4000 mg total daily dose; or oxacillin 30 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs; or flucloxacillin 50 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs, not to exceed a 2000 mg total daily dose. Vancomycin was to be taken for methicillin-resistant Gram-positive infections. Based on local practice patterns/approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. At investigator's discretion, after 72 hrs of IV therapy, those on oxacillin or flucloxacillin could switch to oral cefadroxil (dose for infants/children: 15 mg/kg/dose every 12 hrs, max 2 g/day; dose for adolescents: 500-1000 mg every 12 hrs), and if infection with methicillin-resistant S. aureus was confirmed, those on vancomycin were allowed to switch to oral clindamycin 10 mg/kg every 8 hrs.
Comparator	Clindamycin	Participants 3 mos to \< 6 yrs old and ≥6 yrs to 17 yrs old received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a 4000 mg total daily dose; or oxacillin 30 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs; or flucloxacillin 50 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs, not to exceed a 2000 mg total daily dose. Vancomycin was to be taken for methicillin-resistant Gram-positive infections. Based on local practice patterns/approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. At investigator's discretion, after 72 hrs of IV therapy, those on oxacillin or flucloxacillin could switch to oral cefadroxil (dose for infants/children: 15 mg/kg/dose every 12 hrs, max 2 g/day; dose for adolescents: 500-1000 mg every 12 hrs), and if infection with methicillin-resistant S. aureus was confirmed, those on vancomycin were allowed to switch to oral clindamycin 10 mg/kg every 8 hrs.
Dalbavancin two-dose	Dalbavancin	Participants received dalbavancin administered intravenously as follows: 3 months to \< 6 years old: 15 mg/kg (maximum 1000 mg) on Day 1, and 7.5 mg/kg (maximum 500 mg) on Day 8; ≥6 years to 17 years old (inclusive): 12 mg/kg (maximum 1000 mg) on Day 1, and 6 mg/kg (maximum 500 mg) on Day 8.
Comparator	Oxacillin	Participants 3 mos to \< 6 yrs old and ≥6 yrs to 17 yrs old received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a 4000 mg total daily dose; or oxacillin 30 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs; or flucloxacillin 50 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs, not to exceed a 2000 mg total daily dose. Vancomycin was to be taken for methicillin-resistant Gram-positive infections. Based on local practice patterns/approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. At investigator's discretion, after 72 hrs of IV therapy, those on oxacillin or flucloxacillin could switch to oral cefadroxil (dose for infants/children: 15 mg/kg/dose every 12 hrs, max 2 g/day; dose for adolescents: 500-1000 mg every 12 hrs), and if infection with methicillin-resistant S. aureus was confirmed, those on vancomycin were allowed to switch to oral clindamycin 10 mg/kg every 8 hrs.
Comparator	Cefadroxil	Participants 3 mos to \< 6 yrs old and ≥6 yrs to 17 yrs old received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a 4000 mg total daily dose; or oxacillin 30 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs; or flucloxacillin 50 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs, not to exceed a 2000 mg total daily dose. Vancomycin was to be taken for methicillin-resistant Gram-positive infections. Based on local practice patterns/approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. At investigator's discretion, after 72 hrs of IV therapy, those on oxacillin or flucloxacillin could switch to oral cefadroxil (dose for infants/children: 15 mg/kg/dose every 12 hrs, max 2 g/day; dose for adolescents: 500-1000 mg every 12 hrs), and if infection with methicillin-resistant S. aureus was confirmed, those on vancomycin were allowed to switch to oral clindamycin 10 mg/kg every 8 hrs.
Comparator	Flucloxacillin	Participants 3 mos to \< 6 yrs old and ≥6 yrs to 17 yrs old received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a 4000 mg total daily dose; or oxacillin 30 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs; or flucloxacillin 50 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs, not to exceed a 2000 mg total daily dose. Vancomycin was to be taken for methicillin-resistant Gram-positive infections. Based on local practice patterns/approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. At investigator's discretion, after 72 hrs of IV therapy, those on oxacillin or flucloxacillin could switch to oral cefadroxil (dose for infants/children: 15 mg/kg/dose every 12 hrs, max 2 g/day; dose for adolescents: 500-1000 mg every 12 hrs), and if infection with methicillin-resistant S. aureus was confirmed, those on vancomycin were allowed to switch to oral clindamycin 10 mg/kg every 8 hrs.

Primary Outcome Measures

Name	Time	Method
Shift From Baseline in Distortion Product Otoacoustic Emission at TOC Visit	Baseline, Day 28 (± 2 days)	Audiologic testing was to be conducted in at least 20 children \< 12 years old, of which at least 9 children were \< 2 years old. Audiologic testing conducted on infants (\< 12 months old) included: evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra and ipsilateral acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. For the older children, testing included evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra ipsilateral acoustic reflex thresholds), and age appropriate behavioral audiologic threshold assessment. Participants with an abnormal audiologic assessment at Day 28 (± 2 days) that exceeded, by a clinically significant margin, any abnormality observed in the Baseline assessment, were considered to have an abnormal audiologic assessment.
Shift From Baseline in Auditory Brainstem Response Test at TOC Visit	Baseline, Day 28 (± 2 days)	Audiologic testing was to be conducted in at least 20 children \< 12 years old, of which at least 9 children were \< 2 years old. Audiologic testing conducted on infants (\< 12 months old) included: evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra and ipsilateral acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. For the older children, testing included evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra ipsilateral acoustic reflex thresholds), and age appropriate behavioral audiologic threshold assessment. Participants with an abnormal audiologic assessment at Day 28 (± 2 days) that exceeded, by a clinically significant margin, any abnormality observed in the Baseline assessment, were considered to have an abnormal audiologic assessment.
Shift From Baseline in Acoustic Immittance Test at TOC Visit	Baseline, Day 28 (± 2 days)	Audiologic testing was to be conducted in at least 20 children \< 12 years old, of which at least 9 children were \< 2 years old. Audiologic testing conducted on infants (\< 12 months old) included: evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra and ipsilateral acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. For the older children, testing included evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra ipsilateral acoustic reflex thresholds), and age appropriate behavioral audiologic threshold assessment. Participants with an abnormal audiologic assessment at Day 28 (± 2 days) that exceeded, by a clinically significant margin, any abnormality observed in the Baseline assessment, were considered to have an abnormal audiologic assessment.
Shift From Baseline in Behavioral Audiometric Valuation at TOC Visit	Baseline, Day 28 (± 2 days)	Audiologic testing was to be conducted in at least 20 children \< 12 years old, of which at least 9 children were \< 2 years old. Audiologic testing conducted on infants (\< 12 months old) included: evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra and ipsilateral acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. For the older children, testing included evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra ipsilateral acoustic reflex thresholds), and age appropriate behavioral audiologic threshold assessment. Participants with an abnormal audiologic assessment at Day 28 (± 2 days) that exceeded, by a clinically significant margin, any abnormality observed in the Baseline assessment, were considered to have an abnormal audiologic assessment.
Shift From Baseline in Clostridium Difficile (CD) and Vancomycin-resistant Enterococci (VRE) at TOC Visit	Baseline, Day 28 (± 2 days)	Bowel flora was evaluated in participants from birth to \< 2 years of age by performing polymerase chain reaction (PCR) analysis for Clostridium difficile (C diff) and culture for vancomycin-resistant enterococci (VRE) on a stool specimen or rectal swab. Samples were analyzed at Baseline and at the Test of Cure (TOC) visit.

Secondary Outcome Measures

Name	Time	Method
Clinical Response at 48-72 Hours	Baseline, 48-72 hours	Clinical response defined as ≥20% reduction in lesion size compared to Baseline in Cohorts 1-4; cessation of increase in lesion size and decreased erythema or tenderness compared to Baseline with no appearance of new lesions in those with ABSSSI in Cohort 5; and improvement of at least one abnormal clinical and laboratory parameter related to sepsis in those diagnosed with sepsis in Cohort 5. To be considered a clinical responder, participants must have been alive and not have received rescue therapy.; Presented for the modified intent-to-treat (mITT) population: all participants who received at least one dose of study drug and had a diagnosis of ABSSSI (or a suspected or confirmed sepsis for those in Cohort 5) not known to be caused exclusively by a Gram-negative organism.
Clinical Response at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)	Baseline, Day 14 (± 2 Days)	Cure: Resolution of clinical signs and symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study.; Improvement: For Cohorts 1-4 and Cohort 5 with ABSSSI, reduction in severity of ≥2, but not all CSSI, when compared with Baseline. For Cohort 5 with sepsis, reduction in severity of ≥1 abnormal clinical and laboratory parameter related to sepsis, when compared with Baseline. For Cohorts 1-4, no additional antibacterial Tx required for disease under study. For Cohort 5, no rescue antibiotics required after ≥48 hours of start of study Tx.; Failure: Persistence or progression of Baseline CSSI after 48 hours of Tx OR development of new findings consistent with active infection.; Unknown: Extenuating circumstances precluding classification to Cure, Improvement, or Failure.; Presented for the modified intent-to-treat (mITT) population.
Clinical Response at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)	Baseline, Day 14 (± 2 Days)	Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant's isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment.; Presented for the modified intent-to-treat (mITT) population: all participants who received ≥1 dose of study drug and had a diagnosis of ABSSSI (or a suspected or confirmed sepsis for those in Cohort 5) not known to be caused exclusively by a Gram-negative organism.
Clinical Response at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)	Baseline, Day 28 (± 2 Days)	Cure: Resolution of clinical signs and symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study.; Failure: Persistence or progression of Baseline CSSI after 48 hours of Tx OR development of new findings consistent with active infection.; Unknown: Extenuating circumstances precluding classification to Cure or Failure.; Presented for the modified intent-to-treat (mITT) population.
Clinical Response at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)	Baseline, Day 28 (± 2 Days)	Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant's isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment.; Presented for the modified intent-to-treat (mITT) population: all participants who received ≥1 dose of study drug and had a diagnosis of ABSSSI (or a suspected or confirmed sepsis for those in Cohort 5) not known to be caused exclusively by a Gram-negative organism.
Clinical Response at the Follow-Up Visit (Investigator Assessment of Clinical Outcome)	Baseline, Day 54 (± 7 days)	Cure: Resolution of clinical signs and symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study.; Failure: Persistence or progression of Baseline CSSI after 48 hours of Tx OR development of new findings consistent with active infection.; Unknown: Extenuating circumstances precluding classification to Cure or Failure.; Presented for the modified intent-to-treat (mITT) population
Clinical Response at the Follow-Up Visit (Clinical Response by Sponsor)	Baseline, Day 54 (± 7 days)	Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant's isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment.; Presented for the modified intent-to-treat (mITT) population: all participants who received ≥1 dose of study drug and had a diagnosis of ABSSSI (or a suspected or confirmed sepsis for those in Cohort 5) not known to be caused exclusively by a Gram-negative organism.
Clinical Response by Baseline Pathogen at 48-72 Hours (Clinical Response by Sponsor)	Baseline, 48-72 hours	Clinical response defined as ≥20% reduction in lesion size compared to Baseline in Cohorts 1-4; cessation of increase in lesion size and decreased erythema or tenderness compared to Baseline with no appearance of new lesions in those with ABSSSI in Cohort 5; and improvement of at least one abnormal clinical and laboratory parameter related to sepsis in those diagnosed with sepsis in Cohort 5. To be considered a clinical responder, participants must have been alive and not have received rescue therapy.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)	Baseline, Day 14 (± 2 Days)	Cure: Resolution of clinical signs/symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study.; Improvement: Cohorts 1-4 and Cohort 5 with ABSSSI: reduction in severity of ≥2, but not all CSSI, when compared to Baseline. Cohort 5 with sepsis: reduction in severity of ≥1 abnormal clinical/laboratory parameter related to sepsis, when compared to Baseline. Cohorts 1-4: no additional antibacterial Tx required for disease under study. Cohort 5: no rescue antibiotics required after ≥48 hrs of start of study Tx.; Failure: Persistence/progression of Baseline CSSI after 48 hrs of Tx OR development of new findings consistent with active infection.; Unknown: Extenuating circumstances precluding classification to Cure, Improvement, or Failure.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)	Baseline, Day 14 (± 2 Days)	Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant's isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)	Baseline, Day 28 (± 2 Days)	Cure: Resolution of clinical signs and symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study.; Failure: Persistence or progression of Baseline CSSI after 48 hours of Tx OR development of new findings consistent with active infection.; Unknown: Extenuating circumstances precluding classification to Cure or Failure.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)	Baseline, Day 28 (± 2 Days)	Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant's isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Clinical Response by Baseline Pathogen at the Follow-up Visit (Investigator Assessment of Clinical Outcome)	Baseline, Day 54 (± 7 days)	Cure: Resolution of clinical signs and symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study.; Failure: Persistence or progression of Baseline CSSI after 48 hours of Tx OR development of new findings consistent with active infection.; Unknown: Extenuating circumstances precluding classification to Cure or Failure.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Clinical Response by Baseline Pathogen at the Follow-up Visit (Clinical Response by Sponsor)	Baseline, Day 54 (± 7 days)	Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant's isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Microbiological Response at 48-72 Hours	Baseline, 48-72 hours	Eradication: Source specimen demonstrated absence of the original Baseline pathogen.; Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical responder.; Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen.; Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical non-responder.; Indeterminate: Source specimen was not available to culture and the participant's clinical response was unknown or missing.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Microbiological Response at the End of Treatment (EOT) Visit	Baseline, Day 14 (± 2 Days)	Eradication: Source specimen demonstrated absence of the original Baseline pathogen.; Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure or improvement.; Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen.; Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure.; Indeterminate: Source specimen was not available to culture and the participant's clinical response was unknown or missing.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Microbiological Response at the Test of Cure (TOC) Visit	Baseline, Day 28 (± 2 Days)	Eradication: Source specimen demonstrated absence of the original Baseline pathogen.; Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure.; Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen.; Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure.; Indeterminate: Source specimen was not available to culture and the participant's clinical response was unknown or missing.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Microbiological Response at the Follow-Up Visit	Baseline, Day 54 (± 7 days)	Eradication: Source specimen demonstrated absence of the original Baseline pathogen.; Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure.; Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen.; Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure.; Indeterminate: Source specimen was not available to culture and the participant's clinical response was unknown or missing.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Microbiological Response at 48-72 Hours by Baseline Gram-positive Pathogen	Baseline, 48-72 hours	Eradication: Source specimen demonstrated absence of the original Baseline pathogen.; Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical responder.; Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen.; Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical non-responder.; Indeterminate: Source specimen was not available to culture and the participant's clinical response was unknown or missing.,; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Microbiological Response at the End of Treatment (EOT) Visit by Baseline Gram-positive Pathogen	Baseline, Day 14 (± 2 Days)	Eradication: Source specimen demonstrated absence of the original Baseline pathogen.; Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure or improvement.; Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen.; Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure.; Indeterminate: Source specimen was not available to culture and the participant's clinical response was unknown or missing.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Microbiological Response at the Test of Cure (TOC) Visit by Baseline Gram-positive Pathogen	Baseline, Day 28 (± 2 Days)	Eradication: Source specimen demonstrated absence of the original Baseline pathogen.; Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure.; Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen.; Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure.; Indeterminate: Source specimen was not available to culture and the participant's clinical response was unknown or missing.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
Microbiological Response at the Follow-Up Visit by Baseline Gram-positive Pathogen	Baseline, Day 54 (± 7 days)	Eradication: Source specimen demonstrated absence of the original Baseline pathogen.; Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure.; Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen.; Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure.; Indeterminate: Source specimen was not available to culture and the participant's clinical response was unknown or missing.; Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.
All-cause Mortality at the Test of Cure (TOC) Visit Among Cohort 5 Participants	Day 28 (± 2 Days)	All-cause mortality was determined for the participants in Cohort 5 (birth to \< 3 months) at the Test of Cure visit.
Concentration of Dalbavancin in Plasma	30 min (end of infusion on Day 1); 2 hrs after start of IV (Day 1); and 48-72 hrs, 168 hrs, and 312 hrs after start of IV	The population pharmacokinetic (PK) profile of dalbavancin was assessed using a sparse sampling approach. Plasma PK samples were collected from participants receiving dalbavancin treatment (single-dose and two-dose arms) at 30 minutes and at 2 hours (Day 1), at 48-72 hours (Day 3-4), at 168 ± 24 hours (Day 8 ± 1), and at 312 ± 48 hours and analyzed for dalbavancin concentration.

Trial Locations

Locations (84)

Klaipeda Children's Hospital /ID# 235652; 🇱🇹 Klaipeda, Lithuania

University Multiprofile Hospital for Active Treatment Deva Maria EOOD Burgas /ID# 235965; 🇧🇬 Bulgas, Bulgaria

MHAT (Multiprofile Hospital for Active Treatment) /ID# 235539; 🇧🇬 Kozloduy, Bulgaria

Valleywise Health Medical Center /ID# 234343; 🇺🇸 Phoenix, Arizona, United States

Duplicate_Children's Hospital Colorado /ID# 237622; 🇺🇸 Aurora, Colorado, United States

Global Research Holdings LLC /ID# 235747; 🇺🇸 Panama City, Florida, United States

Duplicate_Children's Mercy Hospital and Clinics /ID# 237800; 🇺🇸 Kansas City, Missouri, United States

NYU School of Medicine /ID# 236783; 🇺🇸 New York, New York, United States

Hospital de Ninos Dr. Orlando Alassia /ID# 235562; 🇦🇷 Santa Fe, Argentina

Grodno Regional Infectious Disease Hospital /ID# 235661; 🇧🇾 Grodno, Belarus

Mogilev Regional Children's Hospital /ID# 235657; 🇧🇾 Mogilev, Belarus

Vitebsk Regional Clinical Center for Children /ID# 235659; 🇧🇾 Vitebsk, Belarus

Duplicate_Hospital Pequeno Princípe /ID# 235629; 🇧🇷 Curitiba, Parana, Brazil

Duplicate_Irmandade Santa Casa de Misericórdia de Porto Alegre /ID# 235627; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

UMHAT Dr Georgi Stranski EAD /ID# 237829; 🇧🇬 Pleven, Bulgaria

UMHAT Dr Georgi Stranski EAD /ID# 237830; 🇧🇬 Pleven, Bulgaria

Medical center 1 Sevlievo /ID# 237470; 🇧🇬 Sevlievo, Bulgaria

MHATEM N.I.Pirogov Septic Surgery Clinic /ID# 235541; 🇧🇬 Sofia, Bulgaria

University Multiprofile Hospital for Active Treatment Prof. Dr. Stoyan Kirkovich /ID# 235543; 🇧🇬 Stara Zagora, Bulgaria

Hospital El Carmen de Maipú /ID# 235570; 🇨🇱 Santiago, Chile

Unidad De Investigacion Clinica Universidad De La Sabana /ID# 235566; 🇨🇴 Chia, Cundinamarca, Colombia

LTD Unimedi Kakheti Batumi Maternal and Child Healthcare Center /ID# 235643; 🇬🇪 Batumi, Georgia

LEPL Tbilisi State Medical University Givi Zhvania Academic Clinic of Pediatry /ID# 235645; 🇬🇪 Tbilisi, Georgia

LTD M. Iashvili Children's Central Hospital /ID# 235639; 🇬🇪 Tbilisi, Georgia

University General Hospital Attikon /ID# 237398; 🇬🇷 Athens, Attiki, Greece

Childrens Hospital of Penteli /ID# 235667; 🇬🇷 Athens, Greece

Hospital Valle del Sol /ID# 235569; 🇬🇹 Guatemala, Guatemala

Liepaja Regional Hospital /ID# 235650; 🇱🇻 Liepaja, Latvia

University Childrens Hospital /ID# 235648; 🇱🇻 Riga, Latvia

Hospital of Lithuanian University of Health Sciences Kaunas Clinics /ID# 236947; 🇱🇹 Kaunas, Lithuania

Duplicate_Children's Hospital Affiliate - Vilnius University Hospital Santariski /ID# 235654; 🇱🇹 Vilnius, Lithuania

Hospital Universitario Dr. Jose Eleuterio Gonzalez /ID# 237597; 🇲🇽 Monterrey, Nuevo Leon, Mexico

Hospital General Dr. Agustin O'Horan /ID# 235510; 🇲🇽 Merida, Yucatan, Mexico

Hospital Infantil de Mexico Federico Gomez /ID# 235508; 🇲🇽 Mexico City, Mexico

Wojewodzki Szpital Obserwacyjno-Zakazny im. Tadeusza Browicza /ID# 236920; 🇵🇱 Bydgoszcz, Kujawsko-pomorskie, Poland

Panstwowy Instytut Medyczny MSWiA w Warszawie /ID# 237112; 🇵🇱 Warszawa, Mazowieckie, Poland

Specjalistyczny ZOZ nad Matka i Dzieckiem w Poznaniu Oddzial Obserwacyjno /ID# 235518; 🇵🇱 Poznan, Poland

Institutul National de Boli Infectioase Prof. Dr. Matei Bals /ID# 235606; 🇷🇴 Sector 2, Bucuresti, Romania

Spitalul Clinic de Urgenta pentru Copii ?Louis Turcanu? /ID# 235608; 🇷🇴 Timisoara, Timis, Romania

Spitalul Clinic de Boli infectioase si Tropicale Dr. Victor Babes /ID# 235610; 🇷🇴 Bucuresti, Romania

Spitalul Clinic Judeatean Mures /ID# 234728; 🇷🇴 Targu Mures, Romania

Smolensk State Medical University /ID# 236996; 🇷🇺 Smolensk, Russian Federation

Stavropol State Medical University /ID# 236239; 🇷🇺 Stavropol, Russian Federation

Regional Childrens Hospital /ID# 235560; 🇷🇺 Vologda, Russian Federation

Peermed Clinical Trial Centre /ID# 235514; 🇿🇦 Kempton Park, Gauteng, South Africa

Mzansi Ethical Research Center /ID# 236480; 🇿🇦 Middelburg, Mpumalanga, South Africa

Complejo Hospitalario Universitario de Santiago /ID# 235512; 🇪🇸 Santiago de Compostela, A Coruna, Spain

Hospital Sant Joan de Deu /ID# 236797; 🇪🇸 Esplugues de Llobregat, Barcelona, Spain

Hospital Donostia /ID# 237773; 🇪🇸 Donostia, Guipuzcoa, Spain

Hospital General Universitario Gregorio Maranon /ID# 236955; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz /ID# 237775; 🇪🇸 Madrid, Spain

Dnipropetrovsk Regional children's Clinical Hospital /ID# 235558; 🇺🇦 Dnipro, Ukraine

PE PMC Acinus, Medical and Diagnostic Center /ID# 237514; 🇺🇦 Kropyvnytskyi, Ukraine

Lviv Regional Clinical Hospital /ID# 236921; 🇺🇦 Lviv, Ukraine

Ukrainian Medical Stomatological Academy - Children's City Clinical Hospital /ID# 234886; 🇺🇦 Poltava, Ukraine

Communal Nonprofit Enterprise "Central City Clinical Hospital" of Uzhhorod City /ID# 238058; 🇺🇦 Uzhhorod, Ukraine

University of South Alabama /ID# 237446; 🇺🇸 Mobile, Alabama, United States

Southbay Pharma Research /ID# 235700; 🇺🇸 La Palma, California, United States

University of California, Los Angeles /ID# 237533; 🇺🇸 Los Angeles, California, United States

Tampa General Hospital /ID# 237061; 🇺🇸 Tampa, Florida, United States

Children's Healthcare of Atlanta - Ferry Rd /ID# 237003; 🇺🇸 Atlanta, Georgia, United States

University of Maryland Medical Center /ID# 234353; 🇺🇸 Baltimore, Maryland, United States

Robert Wood Johnson Univ Hosp /ID# 237862; 🇺🇸 New Brunswick, New Jersey, United States

SUNY Upstate Medical University /ID# 236831; 🇺🇸 Syracuse, New York, United States

Duke University Medical Center /ID# 234315; 🇺🇸 Durham, North Carolina, United States

Cleveland Clinic Main Campus /ID# 237564; 🇺🇸 Cleveland, Ohio, United States

Multiprofile Hospital for Active Treatment ( UMHAT) Sveti Georgi EAD Plovdiv /ID# 235487; 🇧🇬 Plovdiv, Bulgaria

UMHAT Sveti Georgi /ID# 237026; 🇧🇬 Plovdiv, Bulgaria

UMHAT Kanev /ID# 237809; 🇧🇬 Ruse, Bulgaria

SHAT Hematologic Diseases /ID# 237915; 🇧🇬 Sofia, Bulgaria

Hospital de Ninos Dr. Roberto del Rio /ID# 235568; 🇨🇱 Independencia, Chile

Fundacion Cardioinfantil /Id# 238041; 🇨🇴 Bogota, Cundinamarca, Colombia

Hospital Universitario San Vic /ID# 238117; 🇨🇴 Medellin, Colombia

LTD Unimedi Kakheti Children New Hospital /ID# 235634; 🇬🇪 Tbilisi, Georgia

Papageorgiou General Hospital Thessaloniki /ID# 237505; 🇬🇷 Stavroupoli (Thessalonikis), Thessaloniki, Greece

General Hospital of Thessaloniki Hippokrateio /ID# 237186; 🇬🇷 Thessaloniki, Greece

Hospital Roosevelt /ID# 235520; 🇬🇹 Guatemala, Guatemala

Hospital del Centro Medico Infectology Department /ID# 235522; 🇬🇹 Guatemala, Guatemala

Daugavpils Regional Hospital /ID# 237022; 🇱🇻 Daugavpils, Latvia

Instituto Nacional de Pediatria /ID# 235506; 🇲🇽 Coyoacan, Ciudad De Mexico, Mexico

Hospital Materno Infantil José Domingo de Obaldía /ID# 235625; 🇵🇦 Chiriquí, Chiriqui, Panama

Hospital Del Niño Dr. José Renán Esquivel /ID# 235572; 🇵🇦 Panama City, Panama

Hospital Universitario y Politecnico La Fe /ID# 237086; 🇪🇸 Valencia, Spain

Ivano-Frankivsk Pediatric Regional Clinical Hospital /ID# 235556; 🇺🇦 Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine