Study on the Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Participants With Osteomyelitis

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

Official Title
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A Phase 2, Single-center, Open-label, Randomized, Comparator-controlled Trial of the Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Patients With Osteomyelitis Known or Suspected to be Due to Gram-Positive Organisms

Conditions
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Osteomyelitis

Intervention / Treatment
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* Drug: Dalbavancin
* Drug: Comparator


Participation Criteria
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Eligibility Criteria
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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) Participants 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] > 0.12 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dalbavancin<br>Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and Day 8. If creatinine clearance was < 30 milliliters per minute (mL/min) and participant was not receiving regular hemodialysis or peritoneal dialysis, dalbavancin dose was decreased to 1000 mg. | Drug: Dalbavancin<br> <br> * Other names: Xydalba™;|
| Active Comparator: Standard of Care<br>Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks. | Drug: Comparator<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 42 | 
| Percentage of Participants With Clinical Response at Day 365 in the CE Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Improvement at Day 21 in the mITT Population | Clinical improvement was defined as no worsening of pain from baseline, if present (subjective pain and/or point tenderness), and improvement in inflammation (as measured by C-reactive protein [CRP]). | Baseline to Day 21 | 
| Percentage of Participants With Clinical Improvement at Day 21 in the CE Population | Clinical improvement was defined as no worsening of pain from baseline, if present (subjective pain and/or point tenderness), and improvement in inflammation (as measured by C-reactive protein [CRP]). | Baseline to Day 21 | 
| Percentage of Participants With Clinical Response at Day 42 in the mITT Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 42 | 
| Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 42 | 
| Percentage of Participant With Clinical Response at Day 180 in the mITT Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 180 | 
| Percentage of Participants With Clinical Response at Day 180 in the CE Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 180 | 
| Percentage of Participants With Clinical Response at Day 365 in the mITT Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 365 | 
| Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 42 | 
| Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring >6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). | Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteomyelitis, dalbavancin, antibiotic