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

• Sponsor: Allergan (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03091439
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 3.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Osteomyelitis	Drug: Dalbavancin; Drug: Standard of Care	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 15, 2017
• Actual Primary Completion Date: Aug 31, 2017
• Actual Study Completion Date: Aug 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dalbavancin Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Drug: Dalbavancin; Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.; Other Names: Dalvance® Xydalba™
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.	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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

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)

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Midway Immunology and Research Center	Fort Pierce	Florida	United States	34982

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Urania Rappo, MD, Allergan

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 17, 2017

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT03091439
• Other Study ID Numbers: 3026-201-008
• First Posted: Mar 27, 2017
• Last Update Posted: Sep 26, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Allergan: Osteomyelitis; dalbavancin; antibiotic
• Additional relevant MeSH terms: Osteomyelitis; Dalbavancin

Study Results

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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Period Title: Overall Study
STARTED	1	0
COMPLETED	0	0
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Dalbavancin	Standard of Care	Total
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Sex: Female, Male () []
Female
Male
Race (NIH/OMB) () []
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	1	0
Cure	1 Infinity	0 NaN
Failure	0 NaN	0 NaN
Indeterminate	0 NaN	0 NaN

2. Secondary Outcome

Title	Number of Participants With Clinical Improvement at Day 28 in the Modified Intent-to-Treat (mITT) Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	1	0
Count of Participants [Participants]	1 Infinity

3. Secondary Outcome

Title	Number of Participants With Clinical Improvement at Day 28 in the CE Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	1	0
Count of Participants [Participants]	1 Infinity	0 NaN

4. Secondary Outcome

Title	Number of Participants With Clinical Response at Day 42 in the mITT Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	1	0
Cure	1 Infinity	0 NaN
Failure	0 NaN	0 NaN
Indeterminate	0 NaN	0 NaN

5. Secondary Outcome

Title	Number of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	0	0

6. Secondary Outcome

Title	Number of Participants With Clinical Response at Day 180 in the mITT and CE Populations
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	0	0

7. Secondary Outcome

Title	Number of Participants With Clinical Response at Day 365 in the mITT and CE Populations
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	0	0

8. Secondary Outcome

Title	Number of Participants With Clinical Response by Pathogen at Day 42 in the CE Population
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	0	0

9. Secondary Outcome

Title	Number of Participants With Clinical Response by Pathogen at Day 180 in the CE Population
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dalbavancin	Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.	Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
Measure Participants	0	0

Adverse Events

Time Frame	Baseline to last visit (Up to Day 108)
Adverse Event Reporting Description	No participants were enrolled in the SOC arm.
Arm/Group Title	Dalbavancin		Standard of Care
Arm/Group Description	Participants received Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and on Day 8.		Participants received an antibiotic consistent with standard of care (SOC) for osteomyelitis based on Investigator judgment. The duration of treatment was 4-6 weeks.
All Cause Mortality
	Dalbavancin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)
Serious Adverse Events
	Dalbavancin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Dalbavancin		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review.