Efficacy and Safety of Dalbavancin Compared to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients With Complicated Bacteremia or Infective Endocarditis

• Sponsor: Allergan
• Information provided by (Responsible Party): Allergan

Tracking Information

• First Submitted Date: May 9, 2017
• First Posted Date: May 11, 2017
• Results First Submitted Date: August 8, 2018
• Results First Posted Date: September 10, 2018
• Last Update Posted Date: September 10, 2018
• Actual Study Start Date: May 12, 2017
• Actual Primary Completion Date: August 4, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 8, 2018)

Number of Participants With Clinical Response at Day 84 in the Intent-to Treat (ITT) Population [ Time Frame: Day 84 ]

Clinical response was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. Failure was defined as: ongoing signs and symptoms considered by the investigator to be related to complicated bacteremia or IE requiring additional antibacterial therapy or unplanned valve replacement, recurrent bacteremia, death during the study period up to Day 84 or discontinuation of the study medication due to an adverse event.

Original Primary Outcome Measures (submitted: May 9, 2017)

Clinical response at Day 84 in the ITT population [ Time Frame: At Day 84 ]

Clinical response can be either success or failure. Success is defined as recovery without need for additional antibiotic therapy. Failure is defined as:

• requirement of additional antibiotic therapy
• recurrent bacteremia
• death up to Day 84
• discontinuation of study drug due to adverse event (AE)

• Change History: Complete list of historical versions of study NCT03148756 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: August 8, 2018)

• Percentage of Participants With Clinical Outcome of Success at Day 42 in the ITT Population [ Time Frame: Day 42 ]
  Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
• Percentage of Participants With Clinical Outcome of Success at Day 42 in the Clinically Evaluable (CE) Population [ Time Frame: Day 42 ]
  Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
• Number of Participants With Day 84 Mortality in the Safety Population [ Time Frame: Day 84 ]
  Day 84 mortality was measured by the number of deaths up to Day 84.
• Percentage of Participants With Clinical Outcome of Success at Day 84 in the CE Population [ Time Frame: Day 84 ]
  Clinical outcome was either success or failure/relapse. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
• Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the ITT Population [ Time Frame: Day 42 ]
  Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
• Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the ITT Population [ Time Frame: Day 84 ]
  Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
• Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the CE Population [ Time Frame: Day 42 ]
  Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
• Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the CE Population [ Time Frame: Day 84 ]
  Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
• Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the ITT Population [ Time Frame: Day 42 ]
  Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures.
• Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the ITT Population [ Time Frame: Day 84 ]
  Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures.
• Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the CE Population [ Time Frame: Day 42 ]
  Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures.
• Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the CE Population [ Time Frame: Day 84 ]
  Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures.

Original Secondary Outcome Measures (submitted: May 9, 2017)

• Clinical outcome at Day 42 in the ITT and the CE populations [ Time Frame: At Day 42 ]
  Clinical outcome can be either Success or Failure. Success is defined as recovery without need for additional antibiotic therapy. Failure is defined as:

  • requirement of additional antibiotic therapy
  • recurrent bacteremia
  • death up to Day 42
• Day 84 mortality in the safety population [ Time Frame: At Day 84 ]
  Day 84 mortality is measured by the number of deaths up to Day 84.
• Clinical outcome at Day 84 in the CE population [ Time Frame: At Day 84 ]
  Clinical outcome can be either Success or Failure/Relapse. Success is defined as recovery without need for additional antibiotic therapy. Failure/Relapse is defined as:

  • requirement of additional antibiotic therapy
  • new signs and symptoms after recovery at Day 42
  • recurrent bacteremia
  • patient considered as clinical failure at Day 42
  • death up to Day 84
• Clinical outcome by pathogen at Day 42 and Day 84 in the ITT and CE populations [ Time Frame: At Day 42 and Day 84 ]
  Clinical outcome by pathogen at Day 42 can be either Success or Failure. Success is defined as recovery without need for additional antibiotic therapy. Failure is defined as:

  • requirement of additional antibiotic therapy
  • recurrent bacteremia
  • death up to Day 42

  Clinical outcome by pathogen at Day 84 can be either Success or Failure/Relapse. Success is defined as recovery without need for additional antibiotic therapy. Failure/Relapse is defined as:

  • requirement of additional antibiotic therapy
  • new signs and symptoms after recovery at Day 42
  • recurrent bacteremia
  • patient defined as clinical failure at Day 42
  • death up to Day 84
• Microbiologic outcome by pathogen at Day 42 and Day 84 in the ITT and CE populations [ Time Frame: At Day 42 and Day 84 ]
  Microbiological outcome can be either Microbiologic Success or Microbiologic Failure. Microbiologic Success is defined as no further growth of baseline pathogen from blood cultures. Microbiologic Failure is defined as:

  • further growth of baseline pathogen from 2 consecutive blood cultures leading to the discontinuation of study drug
  • isolation of the baseline pathogen from 2 consecutive blood cultures after initial clinical improvement (relapse)

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

Descriptive Information

• Brief Title: Efficacy and Safety of Dalbavancin Compared to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients With Complicated Bacteremia or Infective Endocarditis
• Official Title: Phase 2, Open-Label, Randomized, Multicenter Study to Compare the Efficacy and Safety of Dalbavancin to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients With Complicated Bacteremia or Documented Infective Endocarditis
• Brief Summary: This study will compare dalbavancin to standard of care (SOC) antibiotic therapy for the completion of therapy in patients with complicated bacteremia or infective endocarditis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Endocarditis
• Bacteremia

Intervention

• Drug: Dalbavancin
  Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1, and on Day 8.
• Drug: Standard of Care
  Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.

Study Arms

• Experimental: Dalbavancin
  Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1, and on Day 8.
  Intervention: Drug: Dalbavancin
• Active Comparator: Standard of Care
  Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.
  Intervention: Drug: Standard of Care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 20, 2017): 2
• Original Estimated Enrollment (submitted: May 9, 2017): 150
• Actual Study Completion Date: August 4, 2017
• Actual Primary Completion Date: August 4, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• A diagnosis of complicated bacteremia or infective endocarditis
• Gram-positive bacteremia at screening with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) or Streptococci
• Treatment with standard of care antibiotics for 72 hours (h) - 10 days
• Defervescence for at least 24h and clearance of bacteremia from screening pathogen.

Exclusion Criteria:

• Embolic events
• History of prosthetic valve surgery, cardiac device or prosthetic joint
• Left-sided endocarditis due to Staphylococcus aureus (S. aureus)
• Large mobile vegetations (>10 mm) on mitral valves
• Perivalvular abscess
• Uncomplicated bacteremia due to S. aureus
• Gram-negative bacteria or fungi in blood cultures
• Heart failure associated with infective endocarditis [Left Ventricular Ejection Fraction (LVEF) <40%]
• Intravascular material or removable infection source not intended to be removed within 4 days postrandomization
• Planned valve replacement surgery within 3 days of randomization
• Refractory shock, significant hepatic insufficiency or severe leukopenia [Absolute Neutrophil Count (ANC) < 500 cells/mm^3]
• Known osteomyelitis
• Hypersensitivity to dalbavancin or other drugs in glycopeptide class
• Infection with enterococci, coagulase-negative staphylococci, or with organism not susceptible to dalbavancin or vancomycin
• Immunosuppression/immune deficiency
• Concomitant systemic antibacterial therapy for gram-positive infection other than that allowed in protocol
• Pregnant or nursing females.

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
• Removed Location Countries: Korea, Republic of, Singapore, Taiwan, United Kingdom

Administrative Information

• NCT Number: NCT03148756
• Other Study ID Numbers: DAL-MD-09
• Has Data Monitoring Committee: Yes

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