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

• ClinicalTrials.gov Identifier: NCT03091439
• Recruitment Status: Terminated
• First Posted: March 27, 2017
• Results First Posted: September 26, 2018
• Last Update Posted: September 26, 2018
• Sponsor: Allergan
• Information provided by (Responsible Party): Allergan

Tracking Information

• First Submitted Date: March 21, 2017
• First Posted Date: March 27, 2017
• Results First Submitted Date: August 27, 2018
• Results First Posted Date: September 26, 2018
• Last Update Posted Date: September 26, 2018
• Actual Study Start Date: May 15, 2017
• Actual Primary Completion Date: August 31, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2018)

Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population [ Time Frame: 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.

Original Primary Outcome Measures (submitted: March 21, 2017)

Clinical response in the Clinically Evaluable (CE) population [ Time Frame: At Day 42 ]

Clinical response can be either cure, failure, or indeterminate: Cure is defined as recovery without need for additional antibiotic therapy. Failure is defined as: ○ Requirement of additional antibiotic therapy Indeterminate is defined as:

• Lost to follow-up
• Amputation due to vascular insufficiency

Current Secondary Outcome Measures (submitted: August 27, 2018)

• Number of Participants With Clinical Improvement at Day 28 in the Modified Intent-to-Treat (mITT) Population [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: March 21, 2017)

• Clinical improvement in the modified intent-to-treat (mITT) and CE Populations [ Time Frame: From Baseline (Day 0) to Day 28 ]
  Clinical improvement at Day 28 is defined as no worsening of pain from baseline, if present, and improvement in inflammation
• Clinical response in the mITT and microbiological modified intent-to-treat (micro-mITT) Populations [ Time Frame: At Day 42 ]
  Clinical response can be either cure, failure, or indeterminate: Cure is defined as recovery without need for additional antibiotic therapy. Failure is defined as: ○ Requirement of additional antibiotic therapy Indeterminate is defined as:

  • Lost to follow-up
  • Amputation due to vascular insufficiency
• Clinical response at Day 180 in the mITT and CE Populations [ Time Frame: At Day 180 ]
  Clinical response can be either cure, failure, or indeterminate: Cure is defined as recovery without need for additional antibiotic therapy. Failure is defined as: ○ Requirement of additional antibiotic therapy Indeterminate is defined as:

  • Lost to follow-up
  • Amputation due to vascular insufficiency
• Clinical response at Day 365 in the mITT and CE Populations [ Time Frame: At Day 365 ]
  Clinical response can be either cure, failure, or indeterminate: Cure is defined as recovery without need for additional antibiotic therapy. Failure is defined as: ○ Requirement of additional antibiotic therapy Indeterminate is defined as:

  • Lost to follow-up
  • Amputation due to vascular insufficiency
• Clinical response by pathogen at Day 42 in the CE Population [ Time Frame: At Day 42 ]
  Clinical response can be either cure, failure, or indeterminate: Cure is defined as recovery without need for additional antibiotic therapy. Failure is defined as: ○ Requirement of additional antibiotic therapy Indeterminate is defined as:

  • Lost to follow-up
  • Amputation due to vascular insufficiency
• Clinical response by pathogen at Day 180 in the CE Population [ Time Frame: At Day 180 ]
  Clinical response can be either cure, failure, or indeterminate: Cure is defined as recovery without need for additional antibiotic therapy. Failure is defined as: ○ Requirement of additional antibiotic therapy Indeterminate is defined as:

  • Lost to follow-up
  • Amputation due to vascular insufficiency

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Dalbavancin Versus Active Comparator in Adult Patients With Osteomyelitis
• Official Title: A Phase 2, Multicenter, 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Osteomyelitis

Intervention

• Drug: Dalbavancin
  Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.
  Other Names:

  • Dalvance®
  • Xydalba™
• Drug: 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.

Study Arms

• Experimental: Dalbavancin
  Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.
  Intervention: Drug: Dalbavancin
• Active Comparator: 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.
  Intervention: Drug: Standard of Care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 18, 2017): 1
• Original Estimated Enrollment (submitted: March 21, 2017): 100
• Actual Study Completion Date: August 31, 2017
• Actual Primary Completion Date: August 31, 2017 (Final data collection date for primary outcome measure)

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)
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03091439
• Other Study ID Numbers: 3026-201-008
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Allergan
• Study Sponsor: Allergan
• Collaborators: Not Provided

Investigators

• Study Director: Urania Rappo, MD; Allergan

• PRS Account: Allergan
• Verification Date: August 2018