AHOM: Dalbavancin vs Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis

Sponsor

Durata Therapeutics International BV (an Affiliate of Actavis, Inc.) (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02344511

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

Dalbavancin for Pediatric Osteomyelitis

Condition or Disease	Intervention/Treatment	Phase
Osteomyelitis	Drug: Dalbavancin Drug: cefazolin, nafcillin, oxacillin or vancomycin	Phase 3

Detailed Description

A Phase 3, Multicenter, Double-Blind, Randomized, Comparator Controlled Trial of the Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric Subjects with Acute Hematogenous Osteomyelitis of the Long Bones Known or Suspected to be due to Gram-Positive Organisms.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Multicenter, Double-Blind, Randomized, Comparator Controlled Trial of the Safety and Efficacy of Dalbavancin Versus Active Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis of the Long Bones Known or Suspected to be Due to Gram-Positive Organisms

Study Start Date :

Mar 1, 2016

Anticipated Primary Completion Date :

Oct 1, 2018

Anticipated Study Completion Date :

Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dalbavancin Patients with Creatine Clearance (CrCl) greater than 30 mL/min and patients receiving regular hemodialysis or peritoneal dialysis will receive 15 mg/kg Intravenous (IV) dalbavancin over 30 (+/- 5) minutes on Day 1 and on Day 8, not to exceed 1500 mg per administration in children at least 12 years and not to exceed 1000 mg per administration in children less than 12 years of age. • Patients with CrCl < 30 mL/min who are not receiving regular hemodialysis or peritoneal dialysis will receive 10 mg/kg IV dalbavancin over 30 (+/- 5) minutes on Day 1 and on Day 8, not to exceed 1000 mg per administration in children at least 12 years and not to exceed 750 mg per administration in children less than 12 years of age. Additionally, subjects randomized to the dalbavancin group will receive an IV placebo infusion at times corresponding to comparator group dosage times for the first eight days.	Drug: Dalbavancin Drug Other Names: Dalvance
Active Comparator: 4 Comparators cefazolin, oxacillin, nafcillin or vancomycin according to the commercial label Patients with normal renal function will receive either vancomycin 15 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour) not to exceed a daily total dose of 4000 mg, with dose adjustment based on local standard of care to achieve serum trough concentrations of 10 μg/mL to 20 μg/mL; or cefazolin 25 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour); or nafcillin or oxacillin 50 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour).	Drug: cefazolin, nafcillin, oxacillin or vancomycin Standard of Care

Arm

Intervention/Treatment

Experimental: Dalbavancin

Patients with Creatine Clearance (CrCl) greater than 30 mL/min and patients receiving regular hemodialysis or peritoneal dialysis will receive 15 mg/kg Intravenous (IV) dalbavancin over 30 (+/- 5) minutes on Day 1 and on Day 8, not to exceed 1500 mg per administration in children at least 12 years and not to exceed 1000 mg per administration in children less than 12 years of age. • Patients with CrCl < 30 mL/min who are not receiving regular hemodialysis or peritoneal dialysis will receive 10 mg/kg IV dalbavancin over 30 (+/- 5) minutes on Day 1 and on Day 8, not to exceed 1000 mg per administration in children at least 12 years and not to exceed 750 mg per administration in children less than 12 years of age. Additionally, subjects randomized to the dalbavancin group will receive an IV placebo infusion at times corresponding to comparator group dosage times for the first eight days.

Drug: Dalbavancin

Drug

Other Names:

Dalvance

Active Comparator: 4 Comparators

cefazolin, oxacillin, nafcillin or vancomycin according to the commercial label Patients with normal renal function will receive either vancomycin 15 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour) not to exceed a daily total dose of 4000 mg, with dose adjustment based on local standard of care to achieve serum trough concentrations of 10 μg/mL to 20 μg/mL; or cefazolin 25 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour); or nafcillin or oxacillin 50 mg/kg/dose, infused over 60 (+/- 10) minutes, every 6 hours (+/- 1 hour).

Drug: cefazolin, nafcillin, oxacillin or vancomycin

Standard of Care

Outcome Measures

Primary Outcome Measures

Number of patients with clinical improvement at Day 8 [Day 8]

Secondary Outcome Measures

Number of clinical responders [Day 8]
Average reduction in C-reactive Protein (CRP) relative to the highest value [Day 8]
Number of clinical responders by pathogen [Day 8]
Number of Participants with Adverse Events [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female 2-16 yrs
diagnosis of Acute Hematogenous Osteomyelitis (AHOM) of the long bones (ulna, radius, femur, tibia) defined by the following clinical signs and symptoms (< 2 weeks in duration; multiple sites of infection within long bones):
Limb abnormality: Pain, point tenderness upon palpation, motion restriction, loss of function
Magnetic resonance imaging (MRI) -OR- Gram-positive cocci documented on a Gram-stain from a bone specimen or from blood cultures.
Elevated C-Reactive Protein (CRP)
informed consent
willing and able to comply with the study protocol
Life Expectancy with appropriate antibiotic therapy and thru study duration

Exclusion Criteria:

Treatment with an investigational drug within 30 days preceding the first dose of study medication.
Receipt of > 24 hours of potentially effective intravenous antibacterial therapy for AHOM within 96 hours before randomization, unless the pathogen isolated was documented to be Methicillin resistant Staphylococcus aureus (MRSA) that was resistant to the administered antibiotic.
Evidence of subacute or chronic osteomyelitis including: symptoms > 2 weeks in duration
AHOM of non-long bones (e.g., pelvis or spine).
Extraosseous findings such as: subperiosteal abscess, pyomyositis, venous thrombosis, or pulmonary embolism.
Previous history of septic arthritis or osteomyelitis.
Major trauma, open-fracture, puncture wound of the foot, post-operative osteomyelitis, foreign body in or adjacent to affected bone or joint, or other iatrogenic bone or joint infections present at the site of infection.
Septic arthritis that is non-contiguous to osteomyelitis
Immunosuppression/immune deficiency
Evidence of Gram-negative bacteria by gram stain in the absence of Gram-positive organisms; fungus or mycobacteria at baseline.
Gram-negative bacteremia, even in the presence of gram-positive infection or gram-positive bacteremia.
A history of oral ulcers preceding the onset of musculoskeletal findings, recent gastrointestinal surgery (within 2 months)
Infection due to an organism known prior to study entry to be not susceptible to dalbavancin (dalbavancin mean inhibitory concentration > 0.12 µg/mL) or vancomycin (vancomycin mean inhibitory concentration (MIC) > 2 μg/mL).
Concomitant systemic antibacterial therapy for Gram-positive infections (eg. Rifampin, gentamicin).
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.
hypersensitivity to glycopeptide antibiotics.
not expected to survive for 3 months.
Positive urine (or serum) pregnancy test
Women of Child Bearing Potential who are unwilling or unable to use adequate contraceptive precautions.
Other severe acute or chronic medical or psychiatric condition would make the patient inappropriate for entry into this study.
Unwilling or unable to follow study procedures.