Back to resultsStudy on the Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Participants With Osteomyelitis
Primary Purpose
Osteomyelitis
Status
Completed
Phase
Phase 2
Locations
Ukraine
Study Type
Interventional
Intervention
Dalbavancin
Comparator
Sponsored by
About this trial
This is an interventional treatment trial for Osteomyelitis focused on measuring Osteomyelitis, dalbavancin, antibiotic
Eligibility Criteria
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.
Sites / Locations
- Allergan Investigative Site 001
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Dalbavancin
Standard of Care
Arm Description
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.
Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.
Outcomes
Primary Outcome Measures
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).
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).
Secondary Outcome Measures
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]).
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]).
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).
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).
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).
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).
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).
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).
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).
Full Information
NCT ID
NCT02685033
First Posted
February 12, 2016
Last Updated
December 11, 2018
Sponsor
Durata Therapeutics Inc., an affiliate of Allergan plc
1. Study Identification
Unique Protocol Identification Number
NCT02685033
Brief Title
Study on the Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Participants With Osteomyelitis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
March 15, 2016 (Actual)
Primary Completion Date
December 12, 2017 (Actual)
Study Completion Date
December 12, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Durata Therapeutics Inc., an affiliate of Allergan plc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteomyelitis
Keywords
Osteomyelitis, dalbavancin, antibiotic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dalbavancin
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard of Care
Arm Type
Active Comparator
Arm Description
Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Dalbavancin
Other Intervention Name(s)
Dalvance®, Xydalba™
Intervention Type
Drug
Intervention Name(s)
Comparator
Primary Outcome Measure Information:
Title
Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population
Description
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).
Time Frame
Day 42
Title
Percentage of Participants With Clinical Response at Day 365 in the CE Population
Description
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).
Time Frame
Day 365
Secondary Outcome Measure Information:
Title
Percentage of Participants With Clinical Improvement at Day 21 in the mITT Population
Description
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]).
Time Frame
Baseline to Day 21
Title
Percentage of Participants With Clinical Improvement at Day 21 in the CE Population
Description
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]).
Time Frame
Baseline to Day 21
Title
Percentage of Participants With Clinical Response at Day 42 in the mITT Population
Description
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).
Time Frame
Day 42
Title
Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population
Description
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).
Time Frame
Day 42
Title
Percentage of Participant With Clinical Response at Day 180 in the mITT Population
Description
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).
Time Frame
Day 180
Title
Percentage of Participants With Clinical Response at Day 180 in the CE Population
Description
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).
Time Frame
Day 180
Title
Percentage of Participants With Clinical Response at Day 365 in the mITT Population
Description
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).
Time Frame
Day 365
Title
Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population
Description
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).
Time Frame
Day 42
Title
Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population
Description
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).
Time Frame
Day 180
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Urania Rappo, MD, MS, PharmD
Organizational Affiliation
Allergan
Official's Role
Study Director
Facility Information:
Facility Name
Allergan Investigative Site 001
City
Cherkasy
ZIP/Postal Code
18009
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
30648126
Citation
Rappo U, Puttagunta S, Shevchenko V, Shevchenko A, Jandourek A, Gonzalez PL, Suen A, Mas Casullo V, Melnick D, Miceli R, Kovacevic M, De Bock G, Dunne MW. Dalbavancin for the Treatment of Osteomyelitis in Adult Patients: A Randomized Clinical Trial of Efficacy and Safety. Open Forum Infect Dis. 2018 Dec 10;6(1):ofy331. doi: 10.1093/ofid/ofy331. eCollection 2019 Jan.
Results Reference
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Study on the Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Participants With Osteomyelitis
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