Osteomyelitis
Conditions
Keywords
Osteomyelitis, dalbavancin, antibiotic
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.
Interventions
DRUGDalbavancin
Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.
DRUGStandard of Care
Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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. |
| 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 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. |
Countries
United States
Participant flow
Recruitment details
Although this was a planned multi-center study, the study was terminated and only one investigative site in the United States enrolled a participant.
Participants by arm
| Arm | Count |
|---|---|
| Dalbavancin Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8. | 0 |
| Standard of Care Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks. | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study Terminated by the Sponsor | 1 | 0 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population
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.
Time frame: Day 42
Population: CE population included all participants in the mITT Population who received ≥ 1 dose of dalbavancin or ≥ 2 weeks of comparator and ≤ 1 dose of another (non-study) systemic antibiotic with activity against the causative organism for an indication other than osteomyelitis. No participants were enrolled in the SOC arm.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dalbavancin | Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Failure | 0 Participants |
| Dalbavancin | Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Cure | 1 Participants |
| Dalbavancin | Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Indeterminate | 0 Participants |
| Standard of Care | Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Failure | 0 Participants |
| Standard of Care | Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Cure | 0 Participants |
| Standard of Care | Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Indeterminate | 0 Participants |
Secondary
Number of Participants With Clinical Improvement at Day 28 in the CE Population
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.
Time frame: Baseline (Day 0) to Day 28
Population: CE population included all participants in the mITT Population who received ≥ 1 dose of dalbavancin or ≥ 2 weeks of comparator and ≤ 1 dose of another (non-study) systemic antibiotic with activity against the causative organism for an indication other than osteomyelitis. No participants were enrolled in the SOC arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dalbavancin | Number of Participants With Clinical Improvement at Day 28 in the CE Population | 1 Participants |
| Standard of Care | Number of Participants With Clinical Improvement at Day 28 in the CE Population | 0 Participants |
Secondary
Number of Participants With Clinical Improvement at Day 28 in the Modified Intent-to-Treat (mITT) Population
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.
Time frame: Baseline (Day 0) to Day 28
Population: mITT population including all randomized participants who received randomized medication and met criteria for known or suspected Gram-positive osteomyelitis. Participants from whom only a Gram-negative pathogen was isolated from blood and/or bone culture were excluded. No participants were enrolled in the SOC arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dalbavancin | Number of Participants With Clinical Improvement at Day 28 in the Modified Intent-to-Treat (mITT) Population | 1 Participants |
Secondary
Number of Participants With Clinical Response at Day 180 in the mITT and CE Populations
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.
Time frame: Day 180
Population: Due to early termination of the study prior to the Day 180 visit, the participant enrolled did not have data collected for this visit, but did have an early termination visit prior to Day 180.
Secondary
Number of Participants With Clinical Response at Day 365 in the mITT and CE Populations
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.
Time frame: Day 365
Population: Due to early termination of the study prior to the Day 180 visit, the participant enrolled did not have data collected for the visits at Day 180 or Day 365, but did have an early termination visit prior to Day 180.
Secondary
Number of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population
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.
Time frame: Day 42
Population: micro-mITT included participants in the mITT Population with a Gram-positive pathogen isolated from blood and/or bone specimen. No participants met criteria for the micro-mITT population.
Secondary
Number of Participants With Clinical Response at Day 42 in the mITT Population
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.
Time frame: Day 42
Population: mITT population included all randomized participants who received randomized medication and met the criteria for known or suspected Gram-positive osteomyelitis. Participants from whom only a Gram-negative pathogen was isolated from blood and/or bone culture were excluded. No participants were enrolled in the SOC arm.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dalbavancin | Number of Participants With Clinical Response at Day 42 in the mITT Population | Cure | 1 Participants |
| Dalbavancin | Number of Participants With Clinical Response at Day 42 in the mITT Population | Failure | 0 Participants |
| Dalbavancin | Number of Participants With Clinical Response at Day 42 in the mITT Population | Indeterminate | 0 Participants |
| Standard of Care | Number of Participants With Clinical Response at Day 42 in the mITT Population | Cure | 0 Participants |
| Standard of Care | Number of Participants With Clinical Response at Day 42 in the mITT Population | Failure | 0 Participants |
| Standard of Care | Number of Participants With Clinical Response at Day 42 in the mITT Population | Indeterminate | 0 Participants |
Secondary
Number of Participants With Clinical Response by Pathogen at Day 180 in the CE Population
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.
Time frame: Day 180
Population: There were no pathogens identified in this study; the participant enrolled had no pathogens detected on blood culture, and the optional bone biopsy was not performed.
Secondary
Number of Participants With Clinical Response by Pathogen at Day 42 in the CE Population
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.
Time frame: Day 42
Population: There were no pathogens identified in this study; the participant enrolled had no pathogens detected on blood culture, and the optional bone biopsy was not performed.