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

• Sponsor: Durata Therapeutics Inc., an affiliate of Allergan plc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02685033
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Actual Duration (Months): 20.9
• Patients Per Site Per Month: 3.8

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Osteomyelitis	Drug: Dalbavancin; Drug: Comparator	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 15, 2016
• Actual Primary Completion Date: Dec 12, 2017
• Actual Study Completion Date: Dec 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Dalbavancin; Other Names: Dalvance® Xydalba™
Active Comparator: Standard of Care Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.	Drug: Comparator

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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

1. 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]).

2. 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]).

3. 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).

4. 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).

5. 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).

6. 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).

7. 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).

8. 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).

9. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Allergan Investigative Site 001	Cherkasy		Ukraine	18009

Sponsors and Collaborators

• Durata Therapeutics Inc., an affiliate of Allergan plc

Investigators

• Study Director: Urania Rappo, MD, MS, PharmD, Allergan

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 16, 2018
• Study Protocol - Jun 23, 2015

More Information

Publications

None provided.

• Responsible Party: Durata Therapeutics Inc., an affiliate of Allergan plc
• ClinicalTrials.gov Identifier: NCT02685033
• Other Study ID Numbers: DAL-MD-04
• First Posted: Feb 18, 2016
• Last Update Posted: Jan 4, 2019
• Last Verified: Dec 1, 2018

• 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
• Keywords provided by Durata Therapeutics Inc., an affiliate of Allergan plc: Osteomyelitis; dalbavancin; antibiotic
• Additional relevant MeSH terms: Osteomyelitis; Dalbavancin

Study Results

Participant Flow

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Period Title: Overall Study
STARTED	70	10
COMPLETED	67	8
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Dalbavancin	Standard of Care	Total
Arm/Group 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.	Total of all reporting groups
Overall Participants	70	10	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.2 (13.3)	54.4 (15.3)	49.8 (13.6)
Sex: Female, Male (Count of Participants)
Female	11 15.7%	5 50%	16 20%
Male	59 84.3%	5 50%	64 80%
Race/Ethnicity, Customized (Count of Participants)
White	70 100%	10 100%	80 100%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	70 100%	10 100%	80 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

CE-D42 population included all modified intent-to-treat (mITT) participants who met specific conditions for evaluability at Day 42 (D42).

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	67	8
Clinical Cure	97.0 138.6%	87.5 875%
Clinical Failure	0.0 0%	12.5 125%
Indeterminate	3.0 4.3%	0.0 0%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population included all ITT participants who received any amount of 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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	67	8
Number (95% Confidence Interval) [percentage of participants]	94.0 134.3%	62.5 625%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

CE-D21 population included all mITT (modified intent-to-treat) participants who met specific conditions for evaluability at Day 21 (D21).

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	67	8
Number (95% Confidence Interval) [percentage of participants]	94.0 134.3%	62.5 625%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population included all ITT participants who received any amount of 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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	67	8
Clinical Cure	97.0 138.6%	87.5 875%
Clinical Failure	0.0 0%	12.5 125%
Indeterminate	3.0 4.3%	0.0 0%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Micro-mITT population included mITT participants with a Gram-positive pathogen isolated from blood and/or bone specimen. Participants whose cultures included both a Gram-positive and a Gram-negative pathogen are included.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	62	8
Clinical Cure	96.8 138.3%	87.5 875%
Clinical Failure	0.0 0%	12.5 125%
Indeterminate	3.2 4.6%	0.0 0%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population included all ITT participants who received any amount of 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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	67	8
Clinical Cure	94.0 134.3%	87.5 875%
Clinical Failure	3.0 4.3%	0.0 0%
Indeterminate	3.0 4.3%	12.5 125%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

CE-D180 population included all mITT participants who met specific conditions for evaluability at Day 180 (D180).

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	66	8
Clinical Cure	95.5 136.4%	87.5 875%
Clinical Failure	1.5 2.1%	0.0 0%
Indeterminate	3.0 4.3%	12.5 125%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

mITT population included all ITT participants who received any amount of 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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	67	8
Clinical Cure	94.0 134.3%	87.5 875%
Clinical Failure	3.0 4.3%	0 0%
Indeterminate	3.0 4.3%	12.5 125%

9. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

CE-D365 population included all mITT participants who met specific conditions for evaluability at Day 365 (D365).

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	66	8
Clinical Cure	95.5 136.4%	87.5 875%
Clinical Failure	1.5 2.1%	0 0%
Indeterminate	3.0 4.3%	12.5 125%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

CE-D42 population included all mITT participants who met specific conditions for evaluability at Day 42 (D42). Includes participants who had baseline pathogens. Participants who had more than one pathogen at Baseline were counted in each category.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	62	8
Staphylococcus aureus	41 58.6%	5 50%
Staphylococcus epidermidis	6 8.6%	2 20%
Staphylococcus haemolyticus	3 4.3%
Staphylococcus pasteuri	1 1.4%
Staphylococcus hominis	1 1.4%
Staphylococcus simulans	1 1.4%
Enterococcus faecalis	7 10%	1 10%
Enterococcus faecium	1 1.4%
Streptococcus agalactiae	1 1.4%	1 10%
Streptococcus dysgalactiae	1 1.4%
Streptococcus pyogenes	1 1.4%
Corynebacterium striatum	2 2.9%	1 10%
Aerococcus viridans	1 1.4%
Globicatella species	1 1.4%
Micrococcus luteus	1 1.4%
Peptoniphilus harei	2 2.9%
Anaerococcus prevotii	1 1.4%
Finegoldia magna	1 1.4%
Peptostrep. anaerobius	1 1.4%
Escherichia coli	3 4.3%
Klebsiella pneumoniae	2 2.9%	1 10%
Pseudomonas aeruginosa	2 2.9%	0 0%
Enterobacter cloacae complex	2 2.9%
Morganella morganii	2 2.9%
Proteus mirabilis	1 1.4%	1 10%
Raoultella planticola	1 1.4%	0 0%
Serratia marcescens	0 0%
Escherichia hermannii	1 1.4%
Pluralibacter gergoviae	1 1.4%
Acinetobacter calcoaceticus	1 1.4%
Bacteroides fragilis	2 2.9%
Bacteroides thetaiotaomicron	1 1.4%
Bacteroides vulgatus	1 1.4%
Porphyromonas asaccharolytica	2 2.9%
Prevotella melaninogenica	2 2.9%
Prevotella disiens	1 1.4%
Prevotella intermedia	1 1.4%
Prevotella species	1 1.4%

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

CE-D180 population included all mITT participants who met specific conditions for evaluability at Day 180 (D180). Includes participants who had baseline pathogens. Participants who had more than one pathogen at Baseline were counted in each category.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group 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.
Measure Participants	61	8
Staphylococcus aureus	39 55.7%	5 50%
Staphylococcus epidermidis	6 8.6%	2 20%
Staphylococcus haemolyticus	3 4.3%
Staphylococcus pasteuri	1 1.4%
Staphylococcus hominis	1 1.4%
Staphylococcus simulans	1 1.4%
Enterococcus faecalis	7 10%	0 0%
Enterococcus faecium	1 1.4%
Streptococcus agalactiae	1 1.4%	1 10%
Streptococcus dysgalactiae	1 1.4%
Streptococcus pyogenes	1 1.4%
Corynebacterium striatum	2 2.9%	1 10%
Aerococcus viridans	1 1.4%
Globicatella species	1 1.4%
Micrococcus luteus	1 1.4%
Peptoniphilus harei	2 2.9%
Anaerococcus prevotii	1 1.4%
Finegoldia magna	1 1.4%
Peptostrep. anaerobius	1 1.4%
Escherichia coli	3 4.3%
Klebsiella pneumoniae	2 2.9%	1 10%
Pseudomonas aeruginosa	2 2.9%	1 10%
Enterobacter cloacae complex	2 2.9%
Morganella morganii	2 2.9%
Proteus mirabilis	1 1.4%	1 10%
Raoultella planticola	1 1.4%	1 10%
Serratia marcescens	1 1.4%
Escherichia hermannii	1 1.4%
Pluralibacter gergoviae	1 1.4%
Acinetobacter calcoaceticus	1 1.4%
Bacteroides fragilis	2 2.9%
Bacteroides thetaiotaomicron	1 1.4%
Bacteroides vulgatus	1 1.4%
Porphyromonas asaccharolytica	2 2.9%
Prevotella melaninogenica	2 2.9%
Prevotella disiens	1 1.4%
Prevotella intermedia	1 1.4%
Prevotella species	1 1.4%

Adverse Events

Time Frame	From Baseline (Day 0) to Day 365
Arm/Group Title	Dalbavancin		Standard of Care
Arm/Group 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.
All Cause Mortality
	Dalbavancin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/70 (1.4%)		0/10 (0%)
Serious Adverse Events
	Dalbavancin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/70 (2.9%)		0/10 (0%)
Cardiac disorders
Cardiac failure acute	1/70 (1.4%)	1	0/10 (0%)	0
Injury, poisoning and procedural complications
Inflammation of wound	1/70 (1.4%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Dalbavancin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI agrees that the first results publication shall be made in conjunction with a joint multi-center publication. If the multi-center publication is not submitted within 12 months after conclusion of the study at all sites, or if the sponsor confirms not to publish the results, the PI may publish the results from the institution subject to terms of the clinical trial agreement. The publication must be sent to Sponsor at least 60 days before the intended submission date for reference and comment.