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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

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ClinicalTrials.gov Identifier: NCT02814916
Recruitment Status : Recruiting
First Posted : June 28, 2016
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Durata Therapeutics Inc., an affiliate of Allergan plc

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 3 months to 17 years, known or suspected to be caused by susceptible Gram-positive organisms, including methicillin-resistant strains of Staphylococcus aureus.

Condition or disease Intervention/treatment Phase
Methicillin-Resistant Staphylococcus Aureus Bacterial Infections Staphylococcal Skin Infections Drug: Dalbavancin single dose Drug: Dalbavancin two dose Drug: Comparator Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 188 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 30, 2017
Estimated Primary Completion Date : October 25, 2019
Estimated Study Completion Date : October 25, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Dalbavancin

Arm Intervention/treatment
Experimental: dalbavancin, single dose Drug: Dalbavancin single dose

Dalbavancin, weight-adjusted dose, up to 1500mg. Intravenous (IV) administration.

Aztreonam may be administered at randomization for presumed co-infection with a Gram-negative pathogen and could be discontinued if a Gram-negative pathogen is not documented by culture. For suspected anaerobic pathogens, metronidazole oral/IV may be used.


Experimental: dalbavancin, two dose Drug: Dalbavancin two dose

Dalbavancin, weight-adjusted dose, up to 1000mg. Intravenous (IV) administration, with second dalbavancin weight-adjusted dose, up to 500mg.

Aztreonam may be administered at randomization for presumed co-infection with a Gram-negative pathogen and could be discontinued if a Gram-negative pathogen is not documented by culture. For suspected anaerobic pathogens, metronidazole oral/IV may be used.


Active Comparator: Comparator Drug: Comparator

Course of either vancomycin not to exceed a total daily dose of 4000 mg;or oxacillin; or flucloxacillin not to exceed a total daily dose of 2000 mg. Intravenous (IV) administration. Possible oral switch after at least 72 hours from oxacillin or flucloxacillin to oral cefadroxil, or from IV vancomycin to oral clindamycin (for MRSA).

Aztreonam may be administered at randomization for presumed co-infection with a Gram-negative pathogen and could be discontinued if a Gram-negative pathogen is not documented by culture. For suspected anaerobic pathogens, metronidazole oral/IV may be used.

Additional comparator drugs may be used, if an alternate comparator regimen is indicated by local susceptibility patterns.





Primary Outcome Measures :
  1. Number of patients with abnormal audiologic assessment [ Time Frame: Baseline to Visit 5 (Day 26 to Day 30) ]
    Audiologic testing will be conducted in at least 30 children less than 12 years old and will include evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra and ipsilateral acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. Patients with an abnormal audiologic assessment at Day 28 (plus or minus 2 days) that exceeds, by a clinically significant margin, any abnormality observed in the Baseline assessment, will be considered to have an abnormal audiologic assessment

  2. Change in number of patients with the presence of either Clostridium difficile (CD), vancomycin-resistant enterococci (VRE), or both CD and VRE in bowel flora [ Time Frame: Baseline to Visit 5 (Day 26 to Day 30) ]
    Evaluated in patients 3 months of age to < 2 years of age, by performing polymerase chain reaction (PCR) for Clostridium difficile (C diff) and culture for vancomycin-resistant enterococci (VRE) on a stool specimen or rectal swab.


Secondary Outcome Measures :
  1. Clinical response [ Time Frame: Baseline to Visit 2 (48 to 72 hours) ]
    Defined as greater than 20% reduction in lesion size compared to baseline

  2. Clinical response evaluated at the end of treatment (EOT) visit: Cure [ Time Frame: Baseline and Visit 4 (Day 12 to Day 16). ]
    Clinical response of Cure will be defined as resolution of the clinical signs and symptoms of infection, when compared to baseline. No additional antibacterial treatment is required for disease under study.

  3. Clinical response evaluated at the end of treatment (EOT) visit: Improvement [ Time Frame: Baseline and Visit 4 (Day 12 to Day 16). ]
    Clinical response of Improvement will be defined as a reduction in severity of two or more, but not all, clinical signs and symptoms of infection, when compared with baseline. No additional antibacterial treatment is required for disease under study. This outcome category will only be used at the EOT evaluation.

  4. Clinical response evaluated at the end of treatment (EOT) visit: Failure [ Time Frame: Baseline and Visit 4 (Day 12 to Day 16). ]
    Clinical response of Failure will be defined as persistence or progression of baseline clinical signs and symptoms of infection after at least 2 days (48 hours) of treatment OR development of new clinical findings consistent with active infection.

  5. Clinical response evaluated at the end of treatment (EOT) visit: Unknown [ Time Frame: Baseline and Visit 4 (Day 12 to Day 16). ]
    Clinical response of Unknown will be defined as extenuating circumstances precluding classification to Cure, Improvement or Failure

  6. Clinical response evaluated at the test of cure visit: Cure [ Time Frame: Baseline and Visit 5 (Day 26 to Day 30). ]
    Clinical response of Cure will be defined as resolution of the clinical signs and symptoms of infection, when compared to baseline. No additional antibacterial treatment is required for disease under study.

  7. Clinical response evaluated at the test of cure visit: Failure [ Time Frame: Baseline and Visit 5 (Day 26 to Day 30). ]
    Clinical response of Failure will be defined as persistence or progression of baseline clinical signs and symptoms of infection after at least 2 days (48 hours) of treatment OR development of new clinical findings consistent with active infection.

  8. Clinical response evaluated at the test of cure visit: Unknown [ Time Frame: Baseline and Visit 5 (Day 26 to Day 30). ]
    Clinical response of Unknown will be defined as extenuating circumstances precluding classification to Cure or Failure

  9. Clinical response evaluated at follow-up visit: Cure [ Time Frame: Baseline and Visit 6 (Day 47 to Day 61) ]
    Clinical response of Cure will be defined as resolution of the clinical signs and symptoms of infection, when compared to baseline. No additional antibacterial treatment is required for disease under study.

  10. Clinical response evaluated at follow-up visit: Failure [ Time Frame: Baseline and Visit 6 (Day 47 to Day 61) ]
    Clinical response of Failure will be defined as persistence or progression of baseline clinical signs and symptoms of infection after at least 2 days (48 hours) of treatment OR development of new clinical findings consistent with active infection.

  11. Clinical response evaluated at follow-up visit: Unknown [ Time Frame: Baseline and Visit 6 (Day 47 to Day 61) ]
    Clinical response of Unknown will be defined as extenuating circumstances precluding classification to Cure or Failure

  12. Presence of baseline pathogen after treatment [ Time Frame: Baseline to Visit 6 (up to Day 61) ]
    Direct demonstration of eradication or persistence of the causative organism



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Ages Eligible for Study:   3 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    1. 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
    2. 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:

    1. Major cutaneous abscess characterized as a collection of pus within the dermis or deeper that is accompanied by erythema, edema and/or induration which:

      1. requires surgical incision and drainage, and
      2. 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
      3. alternatively, involves the central face and is associated with an area of erythema of at least 15 cm2
    2. 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
    3. 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:

    1. Purulent drainage/discharge
    2. Fluctuance
    3. Heat/localized warmth
    4. Tenderness to palpation
    5. Swelling/induration

Exclusion Criteria:

  • Clinically significant renal impairment, defined as calculated creatinine clearance of less than 30 mL/min.
  • 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.
  • Treatment with an investigational drug within 30 days preceding the first dose of study medication.
  • 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.
  • Receipt of a systemically or topically administered antibiotic with a Gram-positive spectrum that achieves therapeutic concentrations in the serum or at the site of the skin infection within 14 days prior to randomization. An exception is allowed for patients receiving a single dose of a short-acting (half-life ≤ 12 hours) antibacterial drug prior to randomization.
  • 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).
  • 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.
  • Patients with uncomplicated skin infections such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure.
  • 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 unable to be performed at the bedside) for the skin infection, or patients who are expected to require more than 2 such interventions.
  • 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).
  • 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.
  • Known or suspected hypersensitivity to glycopeptide antibiotics, beta-lactam agents, aztreonam, or cephalosporins.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02814916


Contacts
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Contact: Clinical Trial Registries Team 877-277-8566 IR-CTRegistration@allergan.com

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Sponsors and Collaborators
Durata Therapeutics Inc., an affiliate of Allergan plc
Investigators
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Study Director: Urania Rappo, MD Allergan plc

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Responsible Party: Durata Therapeutics Inc., an affiliate of Allergan plc
ClinicalTrials.gov Identifier: NCT02814916     History of Changes
Other Study ID Numbers: DUR001-306
2014-005281-30 ( EudraCT Number )
First Posted: June 28, 2016    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Durata Therapeutics Inc., an affiliate of Allergan plc:
Acute Bacterial Skin and Skin Structure Infection (ABSSSI)

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Bacterial Infections
Staphylococcal Infections
Cellulitis
Skin Diseases, Infectious
Skin Diseases, Bacterial
Staphylococcal Skin Infections
Gram-Positive Bacterial Infections
Suppuration
Connective Tissue Diseases
Inflammation
Pathologic Processes
Skin Diseases
Dalbavancin
Teicoplanin
Anti-Bacterial Agents
Anti-Infective Agents