A Phase 3, Multicenter, Open-Label, Randomized, Comparator Controlled Trial of the Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric Subjects with Acute Bacterial Skin and Skin Structure Infections

Phase 1

• Conditions: Acute bacterial skin and skin structure infection. For Cohort 5 (from birth to less than 3 months) also patients with sepsis are allowed.; MedDRA version: 20.0Level: LLTClassification code 10066412Term: Staphylococcus aureus skin infectionSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0Level: LLTClassification code 10037633Term: Pyoderma (skin infection)System Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.1Level: LLTClassification code 10040873Term: Skin infection aggravatedSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0Level: PTClassification code 10040872Term: Skin infectionSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0Level: LLTClassification code 10040875Term: Skin infection pyogenicSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0Level: LLTClassification code 10040874Term: Skin infection NOSSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.1Level: PTClassification code 10066409Term: Staphylococcal skin infectionSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0Level: PTClassification code 10040047Term: SepsisSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Body processes [G] - Microbiological Phenomena [G06]

• Registration Number: EUCTR2014-005281-30-PL
• Lead Sponsor: Allergan Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-13
• Study Completion: 2024-01-01
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 199

Inclusion Criteria

Cohort 1 to 4:
- Male or female patients 3 months -17 years of age
- A clinical picture compatible with an ABSSSI suspected or confirmed to be caused by Gram-positive bacteria, including 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)
•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:
(a)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
- 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
- Patients must be expected to survive with appropriate antibiotic therapy and appropriate supportive care throughout the study.
For Cohort 5 (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:
(a) Hypothermia (<36°C) OR fever (>38.5°C)
(b) Bradycardia OR tachycardia OR rhythm instability
(c) Hypotension OR mottled skin OR impaired peripheral perfusion
(d) Petechial rash
(e) New onset or worsening of apnea episodes OR tachypnea episodes
OR increased oxygen requirements OR requirement for ventilation support
(f) Feeding intolerance OR poor sucking OR abdominal distension
(g) Irritability
(h) Lethargy
(i) Hypotonia
3. In addition, patients must meet at least one of the following laboratory criteria:
(a) White blood cell count =4.0 × 109/L OR =20.0 × 109/L
(b) Immature to total neutrophil ratio >0.2
(c) Platelet

Exclusion Criteria

- Clinically significant renal impairment, defined as calculated creatinine clearance < 30 mL/min. Patients in Cohort 5 (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.
- Clinically significant hepatic impairment, defined as serum bilirubin or alkaline phosphatase >2X ULN for age, and/or serum AST or ALT >3X ULN for age.
- 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.
- 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.
- Patients with necrotizing fasciitis, or deep-seated infections that would require > 2 weeks of antibiotics (e.g., endocarditis, osteomyelitis or septic arthritis).
- 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.
- Venous catheter entry site infection.
- Infections involving diabetic foot ulceration, perirectal abscess or a decubitus ulcer.
- 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, intra-aortic balloon pump, left ventricular assist device, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter.
- 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.
- Patients whose skin infection is the result of having sustained full or partial thickness burns.
- Cohort 1 to 4: Patients with uncomplicated skin infections such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure. Patients in
Cohort 5 (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.
- For Cohorts 1 - 4: Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of study drug for the condition under study.
- Sickle cell anemia
- Cystic fibrosis
- Anticipated need of antibiotic therapy for longer than 14 days.
- Patients who are placed in a hyperbaric chamber as adjunctive therapy for the ABSSSI.
- More than 2 surgical interventions (defined as procedures conducted under sterile technique and typically un

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified