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

Phase 2

Completed

• Conditions: Osteomyelitis
• Interventions: Drug: Comparator; Drug: Dalbavancin

• Registration Number: NCT02685033
• Lead Sponsor: Durata Therapeutics Inc., an affiliate of Allergan plc

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-02-12
• Study First Submitted QC: 2016-02-12
• Study First Posted: 2016-02-18
• Study Start: 2016-03-15
• Primary Completion: 2017-12-12
• Study Completion: 2017-12-12
• Status Verified: 2018-12
• Results First Submitted: 2018-12-11
• Results First Submitted QC: 2018-12-11
• Last Update Submitted: 2018-12-11
• Results First Posted: 2019-01-04
• Last Update Posted: 2019-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Comparator	Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.
Dalbavancin	Dalbavancin	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population	Day 42	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).
Percentage of Participants With Clinical Response at Day 365 in the CE Population	Day 365	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population	Day 42	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).
Percentage of Participants With Clinical Improvement at Day 21 in the mITT Population	Baseline to Day 21	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 \[CRP\]).
Percentage of Participants With Clinical Improvement at Day 21 in the CE Population	Baseline to Day 21	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 \[CRP\]).
Percentage of Participants With Clinical Response at Day 42 in the mITT Population	Day 42	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).
Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population	Day 42	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).
Percentage of Participants With Clinical Response at Day 180 in the CE Population	Day 180	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).
Percentage of Participant With Clinical Response at Day 180 in the mITT Population	Day 180	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).
Percentage of Participants With Clinical Response at Day 365 in the mITT Population	Day 365	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).
Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population	Day 180	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).

Trial Locations

Locations (1)

Allergan Investigative Site 001; 🇺🇦 Cherkasy, Ukraine