Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Patients With Osteomyelitis

Phase 2

Terminated

Conditions: Osteomyelitis

Interventions: Drug: Standard of Care
Drug: Dalbavancin

Registration Number: NCT03091439

Lead Sponsor: Allergan

Brief Summary: This clinical study will be a multi-center, randomized, open-label, active-controlled, parallel-group study comparing dalbavancin to standard of care (SOC) therapy in osteomyelitis.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

A diagnosis of osteomyelitis (first episode) defined by:
Pain or point tenderness upon palpation or probing to bone
Plain radiograph or Magnetic resonance imaging (MRI) consistent with osteomyelitis (indistinctly marginated edema-like pattern of bone marrow hypointensity on unenhanced T1-weighted sequences, hyperintensity on fat-saturated T2-weighted and Short tau inversion recovery (STIR) sequences and/or abnormal enhancement on gadolinium-enhanced fat-saturated T2-weighted sequences, with or without visible periostitis or cortical bone destruction) OR Gram-positive cocci documented on a baseline Gram-stain from a bone specimen
Elevated C-reactive protein (CRP) (low sensitivity) above the upper limit of normal (ULN) (reference range for low sensitivity CRP is 3-10 mg/L)
Subjects must be willing and able, if discharged from the hospital, to return to the hospital or a designated clinic for scheduled visits, treatment, laboratory tests, and other outpatient procedures as required by the protocol.

Exclusion Criteria

Treatment with an investigational drug within 30 days preceding the first dose of investigational product.
Receipt of > 24 hours of potentially effective IV antibacterial therapy for osteomyelitis within 96 hours of randomization, unless the pathogen isolated was documented to be Methicillin-resistant Staphylococcus aureus (MRSA) that was resistant to the administered antibiotic.
A prior episode of osteomyelitis, or a failed course of therapy for osteomyelitis.
Infection associated with a burn wound, with a sacral decubitus ulcer, or with multiple sites of osteomyelitis.
Septic arthritis that is non-contiguous to osteomyelitis, as diagnosed by isolation of a pathogen from synovial fluid culture.
Immunosuppression/immune deficiency
Evidence of Gram-negative bacteria by Gram stain in the absence of Gram-positive organisms.
Gram-negative bacteremia
Patients with concomitant endocarditis, necrotizing fasciitis, or prosthetic material at the site of infection at the time of study initiation.
Infection due to an organism known prior to study entry to not be susceptible to dalbavancin (dalbavancin mean inhibitory concentration [MIC] > 0.25 μg/mL) or vancomycin (vancomycin MIC > 2 μg/mL).
Concomitant systemic antibacterial therapy for Gram-positive infections (eg, rifampin, gentamicin).
Known or suspected hypersensitivity to glycopeptide antibiotics.
Patients with a rapidly fatal illness, who are not expected to survive for 3 months.
Pregnant or nursing females; positive urine (or serum) pregnancy test at Screening (pre-menopausal females only) or after admission (prior to dosing)
Sexually active females of childbearing potential who are unwilling or unable to use an acceptable method of contraception from at least the first dose of study drug until the last pregnancy test.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment will be 4-6 weeks.
Dalbavancin	Dalbavancin	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population	Day 42	Clinical response can be either cure, failure, or indeterminate. Cure was defined as recovery without need for additional antibiotic therapy. Failure was defined as the requirement of additional antibiotic therapy, new purulence, amputation due to progression of infection, requiring \> 6 weeks of treatment in the SOC arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency. The number of participants in each response category is reported.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Improvement at Day 28 in the Modified Intent-to-Treat (mITT) Population	Baseline (Day 0) to Day 28	Clinical improvement was based on an assessment of pain and/or point tenderness compared to Baseline and assessment of inflammation as measured by C-reactive Protein (CRP). Clinical improvement was defined as no worsening of pain from Baseline, if present, and improvement in inflammation.
Number of Participants With Clinical Improvement at Day 28 in the CE Population	Baseline (Day 0) to Day 28	Clinical improvement was based on an assessment of pain and/or point tenderness compared to Baseline and assessment of inflammation as measured by C-reactive Protein (CRP). Clinical improvement was defined as no worsening of pain from Baseline, if present, and improvement in inflammation.
Number of Participants With Clinical Response at Day 42 in the mITT Population	Day 42	Clinical response can be either cure, failure, or indeterminate. Cure was defined as recovery without need for additional antibiotic therapy. Failure was defined as the requirement of additional antibiotic therapy, new purulence, amputation due to progression of infection, requiring \> 6 weeks of treatment in the SOC arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency.
Number of Participants With Clinical Response at Day 180 in the mITT and CE Populations	Day 180	Clinical response can be either cure, failure, or indeterminate. Cure was defined as recovery without need for additional antibiotic therapy. Failure was defined as the requirement of additional antibiotic therapy, new purulence, amputation due to progression of infection, requiring \> 6 weeks of treatment in the SOC arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency.
Number of Participants With Clinical Response at Day 365 in the mITT and CE Populations	Day 365	Clinical response can be either cure, failure, or indeterminate. Cure was defined as recovery without need for additional antibiotic therapy. Failure was defined as the requirement of additional antibiotic therapy, new purulence, amputation due to progression of infection, requiring \> 6 weeks of treatment in the SOC arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency.
Number of Participants With Clinical Response by Pathogen at Day 180 in the CE Population	Day 180	Clinical response can be either cure, failure, or indeterminate. Cure was defined as recovery without need for additional antibiotic therapy. Failure was defined as the requirement of additional antibiotic therapy, new purulence, amputation due to progression of infection, requiring \> 6 weeks of treatment in the SOC arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency.
Number of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population	Day 42	Clinical response can be either cure, failure, or indeterminate. Cure was defined as recovery without need for additional antibiotic therapy. Failure was defined as the requirement of additional antibiotic therapy, new purulence, amputation due to progression of infection, requiring \> 6 weeks of treatment in the SOC arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency.
Number of Participants With Clinical Response by Pathogen at Day 42 in the CE Population	Day 42	Clinical response can be either cure, failure, or indeterminate. Cure was defined as recovery without need for additional antibiotic therapy. Failure was defined as the requirement of additional antibiotic therapy, new purulence, amputation due to progression of infection, requiring \> 6 weeks of treatment in the SOC arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency.