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Clinical Trial Results:
A Phase 3, Multicenter, Open-Label, Randomized, Comparator Controlled Trial of the Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric Subjects with Acute Bacterial Skin and Skin Structure Infections

Summary
EudraCT number	2014-005281-30
Trial protocol	LV LT ES BG GR PL
Global end of trial date	01 Jan 2024

Results information
Results version number	v1(current)
This version publication date	11 Jul 2024
First version publication date	11 Jul 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

DUR001-306

ISRCTN number

US NCT number

NCT02814916

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation address

AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB

Public contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Scientific contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000016-PIP01-09

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Jan 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Jan 2024

Was the trial ended prematurely?

Main objective of the trial

To determine the safety and descriptive efficacy of dalbavancin for the treatment of acute bacterial skin and skin structure infections in children, aged birth to 17 years (inclusive), known or suspected to be caused by susceptible Gram-positive organisms, including methicillin-resistant strains of Staphylococcus aureus.

Protection of trial subjects

In order to enroll in the trial, a signed and dated informed consent document indicating that the legally acceptable representative or the participant’s parent(s)/legal guardian(s)) had been informed of all pertinent aspects of the trial was obtained. If required by the local IRB/IEC, a child assent was to be obtained, as applicable.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Mar 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 84

Country: Number of subjects enrolled

Georgia: 71

Country: Number of subjects enrolled

Greece: 4

Country: Number of subjects enrolled

Guatemala: 6

Country: Number of subjects enrolled

Latvia: 3

Country: Number of subjects enrolled

Mexico: 3

Country: Number of subjects enrolled

Panama: 2

Country: Number of subjects enrolled

South Africa: 10

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

Ukraine: 5

Country: Number of subjects enrolled

United States: 8

Worldwide total number of subjects

199

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

105

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Eligible participants from birth to 17 years of age with acute bacterial skin and skin structure infection (ABSSSI) known or suspected to be caused by susceptible Gram-positive organisms, including methicillin-resistant strains of Staphylococcus aureus were to be enrolled. Cohort 5 participants may have presented with suspected or confirmed sepsis.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Dalbavancin Single-dose

Arm description

Participants received dalbavancin administered intravenously as follows: birth to < 3 months old and 3 months to < 6 years old: 22.5 mg/kg (maximum 1500 mg) on Day 1; ≥ 6 years to 17 years old (inclusive): 18 mg/kg (maximum 1500 mg) on Day 1. Participants aged birth to < 3 months were not randomized; all received dalbavancin single-dose.

Arm type

Experimental

Investigational medicinal product name

Dalbavancin

Investigational medicinal product code

Other name

Xydalba

Pharmaceutical forms

Powder for concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Dalbavancin was administered intravenously over 30 (± 5) minutes.

Dalbavancin Two-dose

Arm description

Participants received dalbavancin administered intravenously as follows: 3 months to < 6 years old: 15 mg/kg (maximum 1000 mg) on Day 1, and 7.5 mg/kg (maximum 500 mg) on Day 8; ≥6 years to 17 years old (inclusive): 12 mg/kg (maximum 1000 mg) on Day 1, and 6 mg/kg (maximum 500 mg) on Day 8.

Arm type

Experimental

Investigational medicinal product name

Dalbavancin

Investigational medicinal product code

Other name

Xydalba

Pharmaceutical forms

Powder for concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Dalbavancin was administered intravenously over 30 (± 5) minutes.

Comparator

Arm description

Participants 3 mos to < 6 yrs old and ≥ 6 yrs to 17 yrs old received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a 4000 mg total daily dose; or oxacillin 30 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs; or flucloxacillin 50 mg/kg/dose, infused over 60 (± 10) mins every 6 (± 1) hrs, not to exceed a 2000 mg total daily dose. Vancomycin was to be taken for methicillin-resistant Gram-positive infections. Based on local practice patterns/approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. At investigator’s discretion, after 72 hrs of IV therapy, those on oxacillin or flucloxacillin could switch to oral cefadroxil (dose for infants/children: 15 mg/kg/dose every 12 hrs, max 2 g/day; dose for adolescents: 500-1000 mg every 12 hrs), and if infection with methicillin-resistant S. aureus was confirmed, those on vancomycin were allowed to switch to oral clindamycin 10 mg/kg every 8 hrs.

Arm type

Active comparator

Investigational medicinal product name

Vancomycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Vancomycin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Investigational medicinal product name

Oxacillin

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Oxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Investigational medicinal product name

Flucloxacillin

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection/infusion

Routes of administration

Intravenous use

Dosage and administration details

Flucloxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.

Investigational medicinal product name

Cefadroxil

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, Oral suspension

Routes of administration

Oral use

Dosage and administration details

Cefadroxil was administered orally every 12 hours.

Investigational medicinal product name

Clindamycin

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, Oral suspension

Routes of administration

Oral use

Dosage and administration details

Clindamycin was administered orally every 8 hours.

Number of subjects in period 1	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Started	91	78	30
Completed	91	74	30
Not completed	0	4	0
Other, not specified	-	1	-
Withdrawal of consent	-	2	-
Lost to follow-up	-	1	-

Baseline characteristics

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Reporting group title

Dalbavancin Single-dose

Reporting group description

Reporting group title

Dalbavancin Two-dose

Reporting group description

Reporting group title

Comparator

Reporting group description

Reporting group values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator	Total
Number of subjects	91	78	30	199
Age categorical
Units: Subjects
Birth to < 3 months (Cohort 5)	10	0	0	10
3 months to < 2 years old (Cohort 4)	9	8	3	20
2 years to < 6 years old (Cohort 3)	18	17	10	45
6 years to < 12 years old (Cohort 2)	25	24	11	60
12 years to 17 years old (Cohort 1)	29	29	6	64
Age continuous
Units: years
arithmetic mean (standard deviation)	7.591 ( 5.4767 )	8.898 ( 4.9271 )	6.775 ( 4.2048 )	-
Gender categorical
Units: Subjects
Female	38	25	12	75
Male	53	53	18	124
Ethnicity
Units: Subjects
Hispanic or Latino	6	7	1	14
Not Hispanic or Latino	85	71	29	185
Race
Units: Subjects
American Indian or Alaska Native	5	1	1	7
Asian	1	1	0	2
Black or African American	4	6	0	10
Native Hawaiian or Other Pacific Islander	0	0	0	0
White	78	69	29	176
Multiple	3	1	0	4

End points

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Reporting group title

Dalbavancin Single-dose

Reporting group description

Reporting group title

Dalbavancin Two-dose

Reporting group description

Reporting group title

Comparator

Reporting group description

Subject analysis set title

Birth to < 3 months of age (Cohort 5)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants aged birth to < 3 months

Subject analysis set title

3 months to < 2 years old (Cohort 4)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants aged 3 months to < 2 years old

Subject analysis set title

2 years to < 6 years old (Cohort 3)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants aged 2 years to < 6 years old

Subject analysis set title

6 years to < 12 years old (Cohort 2)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants aged 6 years to < 12 years old

Subject analysis set title

12 years to 17 years old (Cohort 1)

Subject analysis set type

Intention-to-treat

Subject analysis set description

Participants aged 12 years to 17 years old

Primary: Shift from Baseline in Distortion Product Otoacoustic Emission at TOC Visit

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End point title

Shift from Baseline in Distortion Product Otoacoustic Emission at TOC Visit ^[1]

End point description

Audiologic testing was to be conducted in at least 20 children < 12 years old, of which at least 9 children were < 2 years old. Audiologic testing conducted on infants (< 12 months old) included: evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra and ipsilateral acoustic reflex thresholds) and (optional) threshold auditory brainstem responses. For the older children, testing included evoked otoacoustic emissions testing, acoustic immittance measures (tympanometry and contra ipsilateral acoustic reflex thresholds), and age appropriate behavioral audiologic threshold assessment. Participants with an abnormal audiologic assessment at Day 28 (± 2 days) that exceeded, by a clinically significant margin, any abnormality observed in the Baseline assessment, were considered to have an abnormal audiologic assessment.

End point type

Primary

End point timeframe

Baseline, Day 28 (± 2 days)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive data are summarized for this end point per protocol.

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	2 ^[2]	0 ^[3]	1 ^[4]
Units: participants
Baseline & TOC normal	2		1
Baseline normal & TOC abnormal	0		0
Baseline abnormal & TOC normal	0		0
Baseline & TOC abnormal	0		0

Notes
[2] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values
[3] - Not calculable/estimable due to zero participants with available data
[4] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values

No statistical analyses for this end point

Primary: Shift from Baseline in Auditory Brainstem Response Test at TOC Visit

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End point title

Shift from Baseline in Auditory Brainstem Response Test at TOC Visit ^[5]

End point description

End point type

Primary

End point timeframe

Baseline, Day 28 (± 2 days)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive data are summarized for this end point per protocol.

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	1 ^[6]	0 ^[7]	0 ^[8]
Units: participants
Baseline & TOC normal	1
Baseline normal & TOC abnormal	0
Baseline abnormal & TOC normal	0
Baseline & TOC abnormal	0

Notes
[6] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values
[7] - Not calculable/estimable due to zero participants with available data
[8] - Not calculable/estimable due to zero participants with available data

No statistical analyses for this end point

Primary: Shift from Baseline in Acoustic Immittance Test at TOC Visit

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End point title

Shift from Baseline in Acoustic Immittance Test at TOC Visit ^[9]

End point description

End point type

Primary

End point timeframe

Baseline, Day 28 (± 2 days)

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive data are summarized for this end point per protocol.

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	8 ^[10]	4 ^[11]	3 ^[12]
Units: participants
Baseline & TOC normal	8	4	3
Baseline normal & TOC abnormal	0	0	0
Baseline abnormal & TOC normal	0	0	0
Baseline & TOC abnormal	0	0	0

Notes
[10] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values
[11] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values
[12] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values

No statistical analyses for this end point

Primary: Shift from Baseline in Behavioral Audiometric Valuation at TOC Visit

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End point title

Shift from Baseline in Behavioral Audiometric Valuation at TOC Visit ^[13]

End point description

End point type

Primary

End point timeframe

Baseline, Day 28 (± 2 days)

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive data are summarized for this end point per protocol.

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	8 ^[14]	5 ^[15]	4 ^[16]
Units: participants
Baseline & TOC normal	8	5	4
Baseline normal & TOC abnormal	0	0	0
Baseline abnormal & TOC normal	0	0	0
Baseline & TOC abnormal	0	0	0

Notes
[14] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values
[15] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values
[16] - Participants who received at least 1 dose of study drug and had baseline and postbaseline values

No statistical analyses for this end point

Primary: Shift from Baseline in Clostridium Difficile (CD) and Vancomycin-resistant Enterococci (VRE) at TOC Visit

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End point title

Shift from Baseline in Clostridium Difficile (CD) and Vancomycin-resistant Enterococci (VRE) at TOC Visit ^[17]

End point description

Bowel flora was evaluated in participants from birth to < 2 years of age by performing polymerase chain reaction (PCR) analysis for Clostridium difficile (C diff) and culture for vancomycin-resistant enterococci (VRE) on a stool specimen or rectal swab. Samples were analyzed at Baseline and at the Test of Cure (TOC) visit.

End point type

Primary

End point timeframe

Baseline, Day 28 (± 2 days)

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive data are summarized for this end point per protocol.

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	19 ^[18]	8 ^[19]	3 ^[20]
Units: participants
C diff Baseline & TOC positive	1	0	0
C diff Baseline positive & TOC negative	3	1	0
C diff Baseline positive & TOC missing	2	1	0
C diff Baseline negative & TOC positive	0	0	0
C diff Baseline & TOC negative	10	4	1
C diff Baseline negative & TOC missing	1	1	0
C diff Baseline missing & TOC positive	0	0	0
C diff Baseline missing & TOC negative	2	0	1
C diff Baseline & TOC missing	0	1	1
VRE Baseline & TOC positive	1	0	0
VRE Baseline positive & TOC negative	0	0	0
VRE Baseline positive & TOC missing	0	1	0
VRE Baseline negative & TOC positive	0	0	0
VRE Baseline & TOC negative	15	5	0
VRE Baseline negative & TOC missing	1	2	2
VRE Baseline missing & TOC positive	1	0	0
VRE Baseline missing & TOC negative	1	0	1
VRE Baseline & TOC missing	0	0	0

Notes
[18] - Participants aged birth to < 2 years who received at least 1 dose of study drug
[19] - Participants aged birth to < 2 years who received at least 1 dose of study drug
[20] - Participants aged birth to < 2 years who received at least 1 dose of study drug

No statistical analyses for this end point

Secondary: Clinical Response at 48-72 hours

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End point title

Clinical Response at 48-72 hours

End point description

Clinical response defined as ≥ 20% reduction in lesion size compared to Baseline in Cohorts 1-4; cessation of increase in lesion size and decreased erythema or tenderness compared to Baseline with no appearance of new lesions in those with ABSSSI in Cohort 5; and improvement of at least one abnormal clinical and laboratory parameter related to sepsis in those diagnosed with sepsis in Cohort 5. To be considered a clinical responder, participants must have been alive and not have received rescue therapy. Presented for the modified intent-to-treat (mITT) population: all participants who received at least one dose of study drug and had a diagnosis of ABSSSI (or a suspected or confirmed sepsis for those in Cohort 5) not known to be caused exclusively by a Gram-negative organism.

End point type

Secondary

End point timeframe

Baseline, 48-72 hours

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	85 ^[21]	74 ^[22]	29 ^[23]
Units: percentage of participants
number (not applicable)
Clinical Responder	96.5	98.6	89.7
Clinical Non-Responder	3.5	1.4	10.3

Notes
[21] - Participants in the mITT population with non-missing analysis values at the visit
[22] - Participants in the mITT population with non-missing analysis values at the visit
[23] - Participants in the mITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Clinical Response at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)

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End point title

Clinical Response at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)

End point description

Cure: Resolution of clinical signs and symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study. Improvement: For Cohorts 1-4 and Cohort 5 with ABSSSI, reduction in severity of ≥ 2, but not all CSSI, when compared with Baseline. For Cohort 5 with sepsis, reduction in severity of ≥ 1 abnormal clinical and laboratory parameter related to sepsis, when compared with Baseline. For Cohorts 1-4, no additional antibacterial Tx required for disease under study. For Cohort 5, no rescue antibiotics required after ≥ 48 hours of start of study Tx. Failure: Persistence or progression of Baseline CSSI after 48 hours of Tx OR development of new findings consistent with active infection. Unknown: Extenuating circumstances precluding classification to Cure, Improvement, or Failure. Presented for the modified intent-to-treat (mITT) population.

End point type

Secondary

End point timeframe

Baseline, Day 14 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	84 ^[24]	73 ^[25]	29 ^[26]
Units: percentage of participants
number (not applicable)
Clinical Cure	92.9	93.2	100
Improvement	6.0	5.5	0
Clinical Failure	1.2	1.4	0
Unknown	0	0	0

Notes
[24] - Participants in the mITT population with non-missing analysis values at the visit
[25] - Participants in the mITT population with non-missing analysis values at the visit
[26] - Participants in the mITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Clinical Response at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)

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End point title

Clinical Response at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)

End point description

Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant’s isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥ 48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment. Presented for the modified intent-to-treat (mITT) population: all participants who received ≥1 dose of study drug and had a diagnosis of ABSSSI (or a suspected or confirmed sepsis for those in Cohort 5) not known to be caused exclusively by a Gram-negative organism.

End point type

Secondary

End point timeframe

Baseline, Day 14 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	84 ^[27]	74 ^[28]	30 ^[29]
Units: percentage of participants
number (not applicable)
Cure	90.5	91.9	100
Improvement	7.1	5.4	0
Failure	2.4	2.7	0
Unknown	0	0	0

Notes
[27] - Participants in the mITT population with non-missing analysis values at the visit
[28] - Participants in the mITT population with non-missing analysis values at the visit
[29] - Participants in the mITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Clinical Response at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)

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End point title

Clinical Response at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)

End point description

End point type

Secondary

End point timeframe

Baseline, Day 28 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	83 ^[30]	73 ^[31]	30 ^[32]
Units: percentage of participants
number (not applicable)
Clinical Cure	98.8	98.6	100
Clinical Failure	1.2	1.4	0
Unknown	0	0	0

Notes
[30] - Participants in the mITT population with non-missing analysis values at the visit
[31] - Participants in the mITT population with non-missing analysis values at the visit
[32] - Participants in the mITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Clinical Response at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)

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End point title

Clinical Response at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)

End point description

End point type

Secondary

End point timeframe

Baseline, Day 28 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	83 ^[33]	74 ^[34]	30 ^[35]
Units: percentage of participants
number (not applicable)
Cure	95.2	97.3	100
Failure	2.4	2.7	0
Unknown	2.4	0	0

Notes
[33] - Participants in the mITT population with non-missing analysis values at the visit
[34] - Participants in the mITT population with non-missing analysis values at the visit
[35] - Participants in the mITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Clinical Response at the Follow-Up Visit (Investigator Assessment of Clinical Outcome)

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End point title

Clinical Response at the Follow-Up Visit (Investigator Assessment of Clinical Outcome)

End point description

End point type

Secondary

End point timeframe

Baseline, Day 54 (± 7 days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	85 ^[36]	73 ^[37]	30 ^[38]
Units: percentage of participants
number (not applicable)
Clinical Cure	97.6	97.3	100
Clinical Failure	1.2	1.4	0
Unknown	1.2	1.4	0

Notes
[36] - Participants in the mITT population with non-missing analysis values at the visit
[37] - Participants in the mITT population with non-missing analysis values at the visit
[38] - Participants in the mITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Clinical Response at the Follow-Up Visit (Clinical Response by Sponsor)

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End point title

Clinical Response at the Follow-Up Visit (Clinical Response by Sponsor)

End point description

End point type

Secondary

End point timeframe

Baseline, Day 54 (± 7 days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	84 ^[39]	73 ^[40]	30 ^[41]
Units: percentage of participants
number (not applicable)
Cure	96.4	97.3	100
Failure	2.4	2.7	0
Unknown	1.2	0	0

Notes
[39] - Participants in the mITT population with non-missing analysis values at the visit
[40] - Participants in the mITT population with non-missing analysis values at the visit
[41] - Participants in the mITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Clinical Response by Baseline Pathogen at 48-72 hours (Clinical Response by Sponsor)

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End point title

Clinical Response by Baseline Pathogen at 48-72 hours (Clinical Response by Sponsor)

End point description

Clinical response defined as ≥ 20% reduction in lesion size compared to Baseline in Cohorts 1-4; cessation of increase in lesion size and decreased erythema or tenderness compared to Baseline with no appearance of new lesions in those with ABSSSI in Cohort 5; and improvement of at least one abnormal clinical and laboratory parameter related to sepsis in those diagnosed with sepsis in Cohort 5. To be considered a clinical responder, participants must have been alive and not have received rescue therapy. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline. In the table below, 99999 =not calculable/estimable due to zero participants analyzed.

End point type

Secondary

End point timeframe

Baseline, 48-72 hours

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[42]	55 ^[43]	18 ^[44]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA),Clinical Responder(N=2,4,0)	100	100	99999
S. aureus (MRSA),Clinical Non-Responder(N=2,4,0)	0	0	99999
S. aureus (MSSA),Clinical Responder(N=47,44,14)	97.9	95.5	85.7
S. aureus (MSSA),Clinical Non-Responder(N=47,44,14	2.1	2.3	7.1
S. aureus (MSSA),Missing(N=47,44,14)	0	2.3	7.1
S. agalactiae, Clinical Responder(N=0,1,0)	99999	100	99999
S. agalactiae, Clinical Non-Responder(N=0,1,0)	99999	0	99999
S. anginosus, Clinical Responder(N=1,0,0)	100	99999	99999
S. anginosus, Clinical Non-Responder(N=1,0,0)	0	99999	99999
S. constellatus, Clinical Responder(N=0,1,0)	99999	100	99999
S. constellatus, Clinical Non-Responder(N=0,1,0)	99999	0	99999
S. intermedius, Clinical Responder(N=0,1,0)	99999	100	99999
S. intermedius, Clinical Non-Responder(N=0,1,0)	99999	0	99999
S. pyogenes, Clinical Responder(N=5,4,3)	80	75	100
S. pyogenes, Clinical Non-Responder(N=5,4,3)	20	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Clinical Responder(N=2,2,0)	100	100	99999
E. faecalis, Clinical Non-Responder(N=2,2,0)	0	0	99999

Notes
[42] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[43] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[44] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)

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End point title

Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)

End point description

Cure: Resolution of clinical signs/symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study. Improvement: Cohorts 1-4 and Cohort 5 with ABSSSI: reduction in severity of ≥2, but not all CSSI, when compared to Baseline. Cohort 5 with sepsis: reduction in severity of ≥1 abnormal clinical/laboratory parameter related to sepsis, when compared to Baseline. Cohorts 1-4: no additional antibacterial Tx required for disease under study. Cohort 5: no rescue antibiotics required after ≥48 hrs of start of study Tx. Failure: Persistence/progression of Baseline CSSI after 48 hrs of Tx OR development of new findings consistent with active infection. Unknown: Extenuating circumstances precluding classification to Cure, Improvement, or Failure. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.

End point type

Secondary

End point timeframe

Baseline, Day 14 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[45]	55 ^[46]	18 ^[47]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA),Clinical Cure(N=2,4,0)	100	75	99999
S. aureus (MRSA),Improvement(N=2,4,0)	0	0	99999
S. aureus (MRSA),Clinical Failure(N=2,4,0)	0	0	99999
S. aureus (MRSA),Unknown(N=2,4,0)	0	0	99999
S. aureus (MRSA),Missing(N=2,4,0)	0	25	99999
S. aureus (MSSA),Clinical Cure(N=47,44,14)	91.5	86.4	100
S. aureus (MSSA),Improvement(N=47,44,14)	4.3	4.5	0
S. aureus (MSSA),Clinical Failure(N=47,44,14)	2.1	2.3	0
S. aureus (MSSA),Unknown(N=47,44,14)	0	0	0
S. aureus (MSSA),Missing(N=47,44,14)	2.1	6.8	0
S. agalactiae, Clinical Cure(N=0,1,0)	99999	100	99999
S. agalactiae, Improvement(N=0,1,0)	99999	0	99999
S. agalactiae, Clinical Failure(N=0,1,0)	99999	0	99999
S. agalactiae, Unknown(N=0,1,0)	99999	0	99999
S. anginosus, Clinical Cure(N=1,0,0)	100	99999	99999
S. anginosus, Improvement(N=1,0,0)	0	99999	99999
S. anginosus, Clinical Failure(N=1,0,0)	0	99999	99999
S. anginosus, Unknown(N=1,0,0)	0	99999	99999
S. constellatus, Clinical Cure(N=0,1,0)	99999	100	99999
S. constellatus, Improvement(N=0,1,0)	99999	0	99999
S. constellatus, Clinical Failure(N=0,1,0)	99999	0	99999
S. constellatus, Unknown(N=0,1,0)	99999	0	99999
S. intermedius, Clinical Cure(N=0,1,0)	99999	100	99999
S. intermedius, Improvement(N=0,1,0)	99999	0	99999
S. intermedius, Clinical Failure(N=0,1,0)	99999	0	99999
S. intermedius, Unknown(N=0,1,0)	99999	0	99999
S. pyogenes, Clinical Cure(N=5,4,3)	80	50	100
S. pyogenes, Improvement(N=5,4,3)	0	25	0
S. pyogenes, Clinical Failure(N=5,4,3)	20	0	0
S. pyogenes, Unknown(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Clinical Cure(N=2,2,0)	100	100	99999
E. faecalis, Improvement(N=2,2,0)	0	0	99999
E. faecalis, Clinical Failure(N=2,2,0)	0	0	99999
E. faecalis, Unknown(N=2,2,0)	0	0	99999

Notes
[45] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[46] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[47] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)

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End point title

Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)

End point description

Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant’s isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline. In table below, 99999 =not calculable/estimable due to zero participants analyzed.

End point type

Secondary

End point timeframe

Baseline, Day 14 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[48]	55 ^[49]	18 ^[50]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA),Cure(N=2,4,0)	100	75	99999
S. aureus (MRSA),Improvement(N=2,4,0)	0	0	99999
S. aureus (MRSA),Failure(N=2,4,0)	0	25	99999
S. aureus (MRSA),Unknown(N=2,4,0)	0	0	99999
S. aureus (MSSA),Cure(N=47,44,14)	91.5	86.4	100
S. aureus (MSSA),Improvement(N=47,44,14)	4.3	4.5	0
S. aureus (MSSA),Failure(N=47,44,14)	2.1	4.5	0
S. aureus (MSSA),Unknown(N=47,44,14)	0	0	0
S. aureus (MSSA),Missing(N=47,44,14)	2.1	4.5	0
S. agalactiae, Cure(N=0,1,0)	99999	100	99999
S. agalactiae, Improvement(N=0,1,0)	99999	0	99999
S. agalactiae, Failure(N=0,1,0)	99999	0	99999
S. agalactiae, Unknown(N=0,1,0)	99999	0	99999
S. anginosus, Cure(N=1,0,0)	100	99999	99999
S. anginosus, Improvement(N=1,0,0)	0	99999	99999
S. anginosus, Failure(N=1,0,0)	0	99999	99999
S. anginosus, Unknown(N=1,0,0)	0	99999	99999
S. constellatus, Cure(N=0,1,0)	99999	100	99999
S. constellatus, Improvement(N=0,1,0)	99999	0	99999
S. constellatus, Failure(N=0,1,0)	99999	0	99999
S. constellatus, Unknown(N=0,1,0)	99999	0	99999
S. intermedius, Cure(N=0,1,0)	99999	100	99999
S. intermedius, Improvement(N=0,1,0)	99999	0	99999
S. intermedius, Failure(N=0,1,0)	99999	0	99999
S. intermedius, Unknown(N=0,1,0)	99999	0	99999
S. pyogenes, Cure(N=5,4,3)	80	50	100
S. pyogenes, Improvement(N=5,4,3)	0	25	0
S. pyogenes, Failure(N=5,4,3)	20	0	0
S. pyogenes, Unknown(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Cure(N=2,2,0)	100	100	99999
E. faecalis, Improvement(N=2,2,0)	0	0	99999
E. faecalis, Failure(N=2,2,0)	0	0	99999
E. faecalis, Unknown(N=2,2,0)	0	0	99999

Notes
[48] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[49] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[50] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)

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End point title

Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)

End point description

Cure: Resolution of clinical signs and symptoms of infection (CSSI) compared to Baseline. No additional antibacterial Tx required for disease under study. Failure: Persistence or progression of Baseline CSSI after 48 hours of Tx OR development of new findings consistent with active infection. Unknown: Extenuating circumstances precluding classification to Cure or Failure. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline. In the table below, 99999 =not calculable/estimable due to zero participants analyzed.

End point type

Secondary

End point timeframe

Baseline, Day 28 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[51]	55 ^[52]	18 ^[53]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA),Clinical Cure(N=2,4,0)	100	75	99999
S. aureus (MRSA),Clinical Failure(N=2,4,0)	0	0	99999
S. aureus (MRSA),Unknown(N=2,4,0)	0	0	99999
S. aureus (MRSA),Missing(N=2,4,0)	0	25	99999
S. aureus (MSSA),Clinical Cure(N=47,44,14)	95.7	90.9	100
S. aureus (MSSA),Clinical Failure(N=47,44,14)	2.1	2.3	0
S. aureus (MSSA),Unknown(N=47,44,14)	0	0	0
S. aureus (MSSA),Missing(N=47,44,14)	2.2	6.8	0
S. agalactiae, Clinical Cure(N=0,1,0)	99999	100	99999
S. agalactiae, Clinical Failure(N=0,1,0)	99999	0	99999
S. agalactiae, Unknown(N=0,1,0)	99999	0	99999
S. anginosus, Clinical Cure(N=1,0,0)	100	99999	99999
S. anginosus, Clinical Failure(N=1,0,0)	0	99999	99999
S. anginosus, Unknown(N=1,0,0)	0	99999	99999
S. constellatus, Clinical Cure(N=0,1,0)	99999	100	99999
S. constellatus, Clinical Failure(N=0,1,0)	99999	0	99999
S. constellatus, Unknown(N=0,1,0)	99999	0	99999
S. intermedius, Clinical Cure(N=0,1,0)	99999	100	99999
S. intermedius, Clinical Failure(N=0,1,0)	99999	0	99999
S. intermedius, Unknown(N=0,1,0)	99999	0	99999
S. pyogenes, Clinical Cure(N=5,4,3)	80	75	100
S. pyogenes, Clinical Failure(N=5,4,3)	20	0	0
S. pyogenes, Unknown(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Clinical Cure(N=2,2,0)	100	100	99999
E. faecalis, Clinical Failure(N=2,2,0)	0	0	99999
E. faecalis, Unknown(N=2,2,0)	0	0	99999

Notes
[51] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[52] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[53] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)

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End point title

Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)

End point description

Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant’s isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline. In table below, 99999 =not calculable/estimable due to zero participants analyzed.

End point type

Secondary

End point timeframe

Baseline, Day 28 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[54]	55 ^[55]	18 ^[56]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA),Cure(N=2,4,0)	100	75	99999
S. aureus (MRSA),Failure(N=2,4,0)	0	25	99999
S. aureus (MRSA),Unknown(N=2,4,0)	0	0	99999
S. aureus (MSSA),Cure(N=47,44,14)	91.5	90.9	100
S. aureus (MSSA),Failure(N=47,44,14)	2.1	4.5	0
S. aureus (MSSA),Unknown(N=47,44,14)	4.3	0	0
S. aureus (MSSA),Missing(N=47,44,14)	2.1	4.5	0
S. agalactiae, Cure(N=0,1,0)	99999	100	99999
S. agalactiae, Failure(N=0,1,0)	99999	0	99999
S. agalactiae, Unknown(N=0,1,0)	99999	0	99999
S. anginosus, Cure(N=1,0,0)	100	99999	99999
S. anginosus, Failure(N=1,0,0)	0	99999	99999
S. anginosus, Unknown(N=1,0,0)	0	99999	99999
S. constellatus, Cure(N=0,1,0)	99999	100	99999
S. constellatus, Failure(N=0,1,0)	99999	0	99999
S. constellatus, Unknown(N=0,1,0)	99999	0	99999
S. intermedius, Cure(N=0,1,0)	99999	100	99999
S. intermedius, Failure(N=0,1,0)	99999	0	99999
S. intermedius, Unknown(N=0,1,0)	99999	0	99999
S. pyogenes, Cure(N=5,4,3)	80	75	100
S. pyogenes, Failure(N=5,4,3)	20	0	0
S. pyogenes, Unknown(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Cure(N=2,2,0)	100	100	99999
E. faecalis, Failure(N=2,2,0)	0	0	99999
E. faecalis, Unknown(N=2,2,0)	0	0	99999

Notes
[54] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[55] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[56] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Clinical Response by Baseline Pathogen at the Follow-up Visit (Investigator Assessment of Clinical Outcome)

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End point title

Clinical Response by Baseline Pathogen at the Follow-up Visit (Investigator Assessment of Clinical Outcome)

End point description

End point type

Secondary

End point timeframe

Baseline, Day 54 (± 7 days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[57]	55 ^[58]	18 ^[59]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA),Clinical Cure(N=2,4,0)	50	50	99999
S. aureus (MRSA),Clinical Failure(N=2,4,0)	0	0	99999
S. aureus (MRSA),Unknown(N=2,4,0)	50	25	99999
S. aureus (MRSA),Missing(N=2,4,0)	0	25	99999
S. aureus (MSSA),Clinical Cure(N=47,44,14)	95.7	88.6	100
S. aureus (MSSA),Clinical Failure(N=47,44,14)	2.1	2.3	0
S. aureus (MSSA),Unknown(N=47,44,14)	2.1	0	0
S. aureus (MSSA),Missing(N=47,44,14)	0	9.1	0
S. agalactiae, Clinical Cure(N=0,1,0)	99999	100	99999
S. agalactiae, Clinical Failure(N=0,1,0)	99999	0	99999
S. agalactiae, Unknown(N=0,1,0)	99999	0	99999
S. anginosus, Clinical Cure(N=1,0,0)	100	99999	99999
S. anginosus, Clinical Failure(N=1,0,0)	0	99999	99999
S. anginosus, Unknown(N=1,0,0)	0	99999	99999
S. constellatus, Clinical Cure(N=0,1,0)	99999	100	99999
S. constellatus, Clinical Failure(N=0,1,0)	99999	0	99999
S. constellatus, Unknown(N=0,1,0)	99999	0	99999
S. intermedius, Clinical Cure(N=0,1,0)	99999	100	99999
S. intermedius, Clinical Failure(N=0,1,0)	99999	0	99999
S. intermedius, Unknown(N=0,1,0)	99999	0	99999
S. pyogenes, Clinical Cure(N=5,4,3)	80	75	100
S. pyogenes, Clinical Failure(N=5,4,3)	20	0	0
S. pyogenes, Unknown(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Clinical Cure(n=2,2,0)	100	100	99999
E. faecalis, Clinical Failure(n=2,2,0)	0	0	99999
E. faecalis, Unknown(n=2,2,0)	0	0	99999

Notes
[57] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[58] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[59] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Clinical Response by Baseline Pathogen at the Follow-up Visit (Clinical Response by Sponsor)

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End point title

Clinical Response by Baseline Pathogen at the Follow-up Visit (Clinical Response by Sponsor)

End point description

Definitions used for the Sponsor assessment were the same as those used for the Investigator assessment. The occurrence of any of the following conditions resulted in reassignment by the Sponsor to clinical failure: 1) assessment of clinical failure at a previous time point, 2) Cohorts 1-4: receipt of concomitant antibiotic with activity against participant’s isolate of disease under study prior to evaluation time point; Cohort 5: receipt of rescue therapy (additional antibiotic therapy initiated ≥48 hrs after study drug start), 3) unplanned surgical procedure (e.g., incision and drainage of abscess, major debridement, amputation) for non-improving or worsening infection after 72 hrs of study drug treatment. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline. In table below, 99999 =not calculable/estimable due to zero participants analyzed.

End point type

Secondary

End point timeframe

Baseline, Day 54 (± 7 days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[60]	55 ^[61]	18 ^[62]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA),Cure(N=2,4,0)	50	50	99999
S. aureus (MRSA),Failure(N=2,4,0)	0	25	99999
S. aureus (MRSA),Unknown(N=2,4,0)	0	0	99999
S. aureus (MRSA),Missing(N=2,4,0)	50	25	99999
S. aureus (MSSA),Cure(N=47,44,14)	93.6	88.6	100
S. aureus (MSSA),Failure(N=47,44,14)	2.1	4.5	0
S. aureus (MSSA),Unknown(N=47,44,14)	2.1	0	0
S. aureus (MSSA),Missing(N=47,44,14)	2.1	6.8	0
S. agalactiae, Cure(N=0,1,0)	99999	100	99999
S. agalactiae, Failure(N=0,1,0)	99999	0	99999
S. agalactiae, Unknown(N=0,1,0)	99999	0	99999
S. anginosus, Cure(N=1,0,0)	100	99999	99999
S. anginosus, Failure(N=1,0,0)	0	99999	99999
S. anginosus, Unknown(N=1,0,0)	0	99999	99999
S. constellatus, Cure(N=0,1,0)	99999	100	99999
S. constellatus, Failure(N=0,1,0)	99999	0	99999
S. constellatus, Unknown(N=0,1,0)	99999	0	99999
S. intermedius, Cure(N=0,1,0)	99999	100	99999
S. intermedius, Failure(N=0,1,0)	99999	0	99999
S. intermedius, Unknown(N=0,1,0)	99999	0	99999
S. pyogenes, Cure(N=5,4,3)	80	75	100
S. pyogenes, Failure(N=5,4,3)	20	0	0
S. pyogenes, Unknown(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Cure(N=2,2,0)	100	100	99999
E. faecalis, Failure(N=2,2,0)	0	0	99999
E. faecalis, Unknown(N=2,2,0)	0	0	99999

Notes
[60] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[61] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[62] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: All-cause Mortality at the Test of Cure (TOC) Visit Among Cohort 5 Participants

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End point title

All-cause Mortality at the Test of Cure (TOC) Visit Among Cohort 5 Participants

End point description

All-cause mortality was determined for the participants in Cohort 5 (birth to < 3 months) at the Test of Cure visit.

End point type

Secondary

End point timeframe

Day 28 (± 2 Days)

End point values	Birth to < 3 months of age (Cohort 5)
Number of subjects analysed	10 ^[63]
Units: participants	0

Notes
[63] - All participants in the ITT population

No statistical analyses for this end point

Secondary: Concentration of Dalbavancin in Plasma

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End point title

Concentration of Dalbavancin in Plasma

End point description

The population pharmacokinetic (PK) profile of dalbavancin was assessed using a sparse sampling approach. Plasma PK samples were collected from participants receiving dalbavancin treatment (single-dose and two-dose arms) at 30 minutes and at 2 hours (Day 1), at 48-72 hours (Day 3-4), at 168 ± 24 hours (Day 8 ± 1), and at 312 ± 48 hours and analyzed for dalbavancin concentration.

End point type

Secondary

End point timeframe

30 min (end of infusion on Day 1); 2 hrs after start of IV (Day 1); and 48-72 hrs, 168 hrs, and 312 hrs after start of IV

End point values	Birth to < 3 months of age (Cohort 5)	3 months to < 2 years old (Cohort 4)	2 years to < 6 years old (Cohort 3)	6 years to < 12 years old (Cohort 2)	12 years to 17 years old (Cohort 1)
Number of subjects analysed	10 ^[64]	16 ^[65]	34 ^[66]	49 ^[67]	58 ^[68]
Units: µg/mL
geometric mean (geometric coefficient of variation)
30 min (end of infusion) (n=10, 15, 33, 49, 58)	212.43 ( 23.32 )	268.02 ( 44.90 )	219.45 ( 66.72 )	211.30 ( 34.26 )	233.58 ( 46.44 )
2 hrs after start of IV (n=10, 15, 34, 49, 58)	133.83 ( 24.66 )	196.51 ( 53.44 )	149.28 ( 43.40 )	165.75 ( 37.46 )	162.54 ( 36.85 )
48-72 hrs after start of IV (n=10, 16, 33, 49, 57)	53.53 ( 24.48 )	61.32 ( 40.08 )	56.68 ( 46.25 )	56.93 ( 39.79 )	60.92 ( 28.68 )
168 hrs after start of IV (n=10, 13, 31, 49, 57)	16.89 ( 35.12 )	28.80 ( 119.04 )	24.10 ( 80.90 )	26.25 ( 51.38 )	31.41 ( 31.24 )
312 hrs after start of IV (n=10, 12, 30, 47, 56)	4.94 ( 47.91 )	15.24 ( 47.97 )	12.74 ( 45.62 )	15.35 ( 39.40 )	20.75 ( 37.71 )

Notes
[64] - All subjects in the ITT population who received at least 1 dose of study drug with available data
[65] - All subjects in the ITT population who received at least 1 dose of study drug with available data
[66] - All subjects in the ITT population who received at least 1 dose of study drug with available data
[67] - All subjects in the ITT population who received at least 1 dose of study drug with available data
[68] - All subjects in the ITT population who received at least 1 dose of study drug with available data

No statistical analyses for this end point

Secondary: Microbiological Response at 48-72 Hours

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End point title

Microbiological Response at 48-72 Hours

End point description

Eradication: Source specimen demonstrated absence of the original Baseline pathogen. Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical responder. Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen. Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical non-responder. Indeterminate: Source specimen was not available to culture and the participant’s clinical response was unknown or missing. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.

End point type

Secondary

End point timeframe

Baseline, 48-72 hours

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[69]	54 ^[70]	18 ^[71]
Units: percentage of participants
number (not applicable)
Eradication	0	1.9	0
Presumed eradication	98.1	94.4	88.9
Persistence	0	1.9	0
Presumed persistence	1.9	1.9	5.6
Indeterminate	0	0	5.6

Notes
[69] - Participants in the microITT population with non-missing analysis values at the visit
[70] - Participants in the microITT population with non-missing analysis values at the visit
[71] - Participants in the microITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Microbiological Response at the End of Treatment (EOT) Visit

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End point title

Microbiological Response at the End of Treatment (EOT) Visit

End point description

Eradication: Source specimen demonstrated absence of the original Baseline pathogen. Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure or improvement. Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen. Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure. Indeterminate: Source specimen was not available to culture and the participant’s clinical response was unknown or missing. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.

End point type

Secondary

End point timeframe

Baseline, Day 14 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[72]	54 ^[73]	18 ^[74]
Units: percentage of participants
number (not applicable)
Eradication	0	1.9	0
Presumed eradication	96.2	92.6	100
Persistence	0	1.9	0
Presumed persistence	1.9	1.9	0
Indeterminate	1.9	1.9	0

Notes
[72] - Participants in the microITT population with non-missing analysis values at the visit
[73] - Participants in the microITT population with non-missing analysis values at the visit
[74] - Participants in the microITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Microbiological Response at the Test of Cure (TOC) Visit

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End point title

Microbiological Response at the Test of Cure (TOC) Visit

End point description

Eradication: Source specimen demonstrated absence of the original Baseline pathogen. Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure. Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen. Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure. Indeterminate: Source specimen was not available to culture and the participant’s clinical response was unknown or missing. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.

End point type

Secondary

End point timeframe

Baseline, Day 28 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[75]	54 ^[76]	18 ^[77]
Units: percentage of participants
number (not applicable)
Eradication	0	1.9	0
Presumed eradication	92.3	92.6	100
Persistence	0	0	0
Presumed persistence	1.9	3.7	0
Indeterminate	5.8	1.9	0

Notes
[75] - Participants in the microITT population with non-missing analysis values at the visit
[76] - Participants in the microITT population with non-missing analysis values at the visit
[77] - Participants in the microITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Microbiological Response at the Follow-Up Visit

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End point title

Microbiological Response at the Follow-Up Visit

End point description

Eradication: Source specimen demonstrated absence of the original Baseline pathogen. Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure. Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen. Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure. Indeterminate: Source specimen was not available to culture and the participant’s clinical response was unknown or missing. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline.

End point type

Secondary

End point timeframe

Baseline, Day 54 (± 7 days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[78]	54 ^[79]	18 ^[80]
Units: percentage of participants
number (not applicable)
Eradication	0	1.9	0
Presumed eradication	94.2	88.9	100
Persistence	0	0	0
Presumed persistence	1.9	3.7	0
Indeterminate	3.8	5.6	0

Notes
[78] - Participants in the microITT population with non-missing analysis values at the visit
[79] - Participants in the microITT population with non-missing analysis values at the visit
[80] - Participants in the microITT population with non-missing analysis values at the visit

No statistical analyses for this end point

Secondary: Microbiological Response at 48-72 Hours by Baseline Gram-positive Pathogen

Top of page

End point title

Microbiological Response at 48-72 Hours by Baseline Gram-positive Pathogen

End point description

End point type

Secondary

End point timeframe

Baseline, 48-72 hours

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[81]	55 ^[82]	18 ^[83]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA), Eradication(N=2,4,0)	0	0	99999
S. aureus (MRSA), Presumed eradication(N=2,4,0)	100	100	99999
S. aureus (MRSA), Persistence(N=2,4,0)	0	0	99999
S. aureus (MRSA), Presumed persistence(N=2,4,0)	0	0	99999
S. aureus (MRSA), Indeterminate(N=2,4,0)	0	0	99999
S. aureus (MSSA), Eradication(N=47,44,14)	0	2.3	0
S. aureus (MSSA), Presumed eradication(N=47,44,14)	97.9	90.9	85.7
S. aureus (MSSA), Persistence(N=47,44,14)	0	2.3	0
S. aureus (MSSA), Presumed persistence(N=47,44,14)	2.1	2.3	7.1
S. aureus (MSSA), Indeterminate(N=47,44,14)	0	0	7.1
S. aureus (MSSA), Missing(N=47,44,14)	0	2.3	0
S. agalactiae, Eradication(N=0,1,0)	99999	0	99999
S. agalactiae, Presumed eradication(N=0,1,0)	99999	100	99999
S. agalactiae, Persistence(N=0,1,0)	99999	0	99999
S. agalactiae, Presumed persistence(N=0,1,0)	99999	0	99999
S. agalactiae, Indeterminate(N=0,1,0)	99999	0	99999
S. anginosus, Eradication(N=1,0,0)	0	99999	99999
S. anginosus, Presumed eradication(N=1,0,0)	100	99999	99999
S. anginosus, Persistence(N=1,0,0)	0	99999	99999
S. anginosus, Presumed persistence(N=1,0,0)	0	99999	99999
S. anginosus, Indeterminate(N=1,0,0)	0	99999	99999
S. constellatus, Eradication(N=0,1,0)	99999	0	99999
S. constellatus, Presumed eradication(N=0,1,0)	99999	100	99999
S. constellatus, Persistence(N=0,1,0)	99999	0	99999
S. constellatus, Presumed persistence(N=0,1,0)	99999	0	99999
S. constellatus, Indeterminate(N=0,1,0)	99999	0	99999
S. intermedius, Eradication(N=0,1,0)	99999	0	99999
S. intermedius, Presumed eradication(N=0,1,0)	99999	100	99999
S. intermedius, Persistence(N=0,1,0)	99999	0	99999
S. intermedius, Presumed persistence(N=0,1,0)	99999	0	99999
S. intermedius, Indeterminate(N=0,1,0)	99999	0	99999
S. mitis/oralis, Eradication(N=1,1,1)	0	0	0
S. mitis/oralis, Presumed eradication(N=1,1,1)	100	100	100
S. mitis/oralis, Persistence(N=1,1,1)	0	0	0
S. mitis/oralis, Presumed persistence(N=1,1,1)	0	0	0
S. mitis/oralis, Indeterminate(N=1,1,1)	0	0	0
S. pyogenes, Eradication(N=5,4,3)	0	0	0
S. pyogenes, Presumed eradication(N=5,4,3)	80	75	100
S. pyogenes, Persistence(N=5,4,3)	0	0	0
S. pyogenes, Presumed persistence (N=5,4,3)	20	0	0
S. pyogenes, Indeterminate(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Eradication(N=2,2,0)	0	0	99999
E. faecalis, Presumed eradication(N=2,2,0)	100	100	99999
E. faecalis, Persistence(N=2,2,0)	0	0	99999
E. faecalis, Presumed persistence(N=2,2,0)	0	0	99999
E. faecalis, Indeterminate(N=2,2,0)	0	0	99999
E. hirae, Eradication(N=1,0,0)	0	99999	99999
E. hirae, Presumed eradication(N=1,0,0)	100	99999	99999
E. hirae, Persistence(N=1,0,0)	0	99999	99999
E. hirae, Presumed persistence(N=1,0,0)	0	99999	99999
E. hirae, Indeterminate(N=1,0,0)	0	99999	99999
G. morbillorum, Eradication(N=1,0,0)	0	99999	99999
G. morbillorum, Presumed eradication(N=1,0,0)	100	99999	99999
G. morbillorum, Persistence(N=1,0,0)	0	99999	99999
G. morbillorum, Presumed persistence(N=1,0,0)	0	99999	99999
G. morbillorum, Indeterminate(N=1,0,0)	0	99999	99999
L. lactis, Eradication(N=1,0,0)	0	99999	99999
L. lactis, Presumed eradication(N=1,0,0)	100	99999	99999
L. lactis, Persistence(N=1,0,0)	0	99999	99999
L. lactis, Presumed persistence(N=1,0,0)	0	99999	99999
L. lactis, Indeterminate (N=1,0,0)	0	99999	99999

Notes
[81] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[82] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[83] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Microbiological Response at the End of Treatment (EOT) Visit by Baseline Gram-positive Pathogen

Top of page

End point title

Microbiological Response at the End of Treatment (EOT) Visit by Baseline Gram-positive Pathogen

End point description

Eradication: Source specimen demonstrated absence of the original Baseline pathogen. Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure or improvement. Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen. Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure. Indeterminate: Source specimen was not available to culture and the participant’s clinical response was unknown or missing. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline. In the table below, 99999 =not calculable/estimable due to zero participants analyzed.

End point type

Secondary

End point timeframe

Baseline, Day 14 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[84]	55 ^[85]	18 ^[86]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA), Eradication(N=2,4,0)	0	0	99999
S. aureus (MRSA), Presumed eradication(N=2,4,0)	100	75	99999
S. aureus (MRSA), Persistence(N=2,4,0)	0	0	99999
S. aureus (MRSA), Presumed persistence(N=2,4,0)	0	25	99999
S. aureus (MRSA), Indeterminate(N=2,4,0)	0	0	99999
S. aureus (MSSA), Eradication(N=47,44,14)	0	2.3	0
S. aureus (MSSA), Presumed eradication(N=47,44,14)	95.7	88.6	100
S. aureus (MSSA), Persistence(N=47,44,14)	0	2.3	0
S. aureus (MSSA), Presumed persistence(N=47,44,14)	2.1	2.3	0
S. aureus (MSSA), Indeterminate(N=47,44,14)	2.1	2.3	0
S. aureus (MSSA), Missing(N=47,44,14)	0	2.3	0
S. agalactiae, Eradication(N=0,1,0)	99999	0	99999
S. agalactiae, Presumed eradication(N=0,1,0)	99999	100	99999
S. agalactiae, Persistence(N=0,1,0)	99999	0	99999
S. agalactiae, Presumed persistence(N=0,1,0)	99999	0	99999
S. agalactiae, Indeterminate(N=0,1,0)	99999	0	99999
S. anginosus, Eradication(N=1,0,0)	0	99999	99999
S. anginosus, Presumed eradication(N=1,0,0)	100	99999	99999
S. anginosus, Persistence(N=1,0,0)	0	99999	99999
S. anginosus, Presumed persistence(N=1,0,0)	0	99999	99999
S. anginosus, Indeterminate(N=1,0,0)	0	99999	99999
S. constellatus, Eradication(N=0,1,0)	99999	0	99999
S. constellatus, Presumed eradication(N=0,1,0)	99999	100	99999
S. constellatus, Persistence(N=0,1,0)	99999	0	99999
S. constellatus, Presumed persistence(N=0,1,0)	99999	0	99999
S. constellatus, Indeterminate(N=0,1,0)	99999	0	99999
S. intermedius, Eradication(N=0,1,0)	99999	0	99999
S. intermedius, Presumed eradication(N=0,1,0)	99999	100	99999
S. intermedius, Persistence(N=0,1,0)	99999	0	99999
S. intermedius, Presumed persistence(N=0,1,0)	99999	0	99999
S. intermedius, Indeterminate(N=0,1,0)	99999	0	99999
S. mitis/oralis, Eradication(N=1,1,1)	0	0	0
S. mitis/oralis, Presumed eradication(N=1,1,1)	100	100	100
S. mitis/oralis, Persistence(N=1,1,1)	0	0	0
S. mitis/oralis, Presumed persistence(N=1,1,1)	0	0	0
S. mitis/oralis, Indeterminate(N=1,1,1)	0	0	0
S. pyogenes, Eradication(N=5,4,3)	0	0	0
S. pyogenes, Presumed eradication(N=5,4,3)	80	75	100
S. pyogenes, Persistence(N=5,4,3)	0	0	0
S. pyogenes, Presumed persistence (N=5,4,3)	20	0	0
S. pyogenes, Indeterminate(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Eradication(N=2,2,0)	0	0	99999
E. faecalis, Presumed eradication(N=2,2,0)	100	100	99999
E. faecalis, Persistence(N=2,2,0)	0	0	99999
E. faecalis, Presumed persistence(N=2,2,0)	0	0	99999
E. faecalis, Indeterminate(N=2,2,0)	0	0	99999
E. hirae, Eradication(N=1,0,0)	0	99999	99999
E. hirae, Presumed eradication(N=1,0,0)	0	99999	99999
E. hirae, Persistence(N=1,0,0)	0	99999	99999
E. hirae, Presumed persistence(N=1,0,0)	0	99999	99999
E. hirae, Indeterminate(N=1,0,0)	100	99999	99999
G. morbillorum, Eradication(N=1,0,0)	0	99999	99999
G. morbillorum, Presumed eradication(N=1,0,0)	100	99999	99999
G. morbillorum, Persistence(N=1,0,0)	0	99999	99999
G. morbillorum, Presumed persistence(N=1,0,0)	0	99999	99999
G. morbillorum, Indeterminate(N=1,0,0)	0	99999	99999
L. lactis, Eradication(N=1,0,0)	0	99999	99999
L. lactis, Presumed eradication(N=1,0,0)	100	99999	99999
L. lactis, Persistence(N=1,0,0)	0	99999	99999
L. lactis, Presumed persistence(N=1,0,0)	0	99999	99999
L. lactis, Indeterminate (N=1,0,0)	0	99999	99999

Notes
[84] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[85] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[86] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Microbiological Response at the Test of Cure (TOC) Visit by Baseline Gram-positive Pathogen

Top of page

End point title

Microbiological Response at the Test of Cure (TOC) Visit by Baseline Gram-positive Pathogen

End point description

Eradication: Source specimen demonstrated absence of the original Baseline pathogen. Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure. Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen. Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure. Indeterminate: Source specimen was not available to culture and the participant’s clinical response was unknown or missing. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline. In the table below, 99999 =not calculable/estimable due to zero participants analyzed.

End point type

Secondary

End point timeframe

Baseline, Day 28 (± 2 Days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[87]	55 ^[88]	18 ^[89]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA), Eradication(N=2,4,0)	0	0	99999
S. aureus (MRSA), Presumed eradication(N=2,4,0)	100	75	99999
S. aureus (MRSA), Persistence(N=2,4,0)	0	0	99999
S. aureus (MRSA), Presumed persistence(N=2,4,0)	0	25	99999
S. aureus (MRSA), Indeterminate(N=2,4,0)	0	0	99999
S. aureus (MSSA), Eradication(N=47,44,14)	0	2.3	0
S. aureus (MSSA), Presumed eradication(N=47,44,14)	91.5	88.6	100
S. aureus (MSSA), Persistence(N=47,44,14)	0	0	0
S. aureus (MSSA), Presumed persistence(N=47,44,14)	2.1	4.5	0
S. aureus (MSSA), Indeterminate(N=47,44,14)	6.4	2.3	0
S. aureus (MSSA), Missing(N=47,44,14)	0	2.3	0
S. agalactiae, Eradication(N=0,1,0)	99999	0	99999
S. agalactiae, Presumed eradication(N=0,1,0)	99999	100	99999
S. agalactiae, Persistence(N=0,1,0)	99999	0	99999
S. agalactiae, Presumed persistence(N=0,1,0)	99999	0	99999
S. agalactiae, Indeterminate(N=0,1,0)	99999	0	99999
S. anginosus, Eradication(N=1,0,0)	0	99999	99999
S. anginosus, Presumed eradication(N=1,0,0)	100	99999	99999
S. anginosus, Persistence(N=1,0,0)	0	99999	99999
S. anginosus, Presumed persistence(N=1,0,0)	0	99999	99999
S. anginosus, Indeterminate(N=1,0,0)	0	99999	99999
S. constellatus, Eradication(N=0,1,0)	99999	0	99999
S. constellatus, Presumed eradication(N=0,1,0)	99999	100	99999
S. constellatus, Persistence(N=0,1,0)	99999	0	99999
S. constellatus, Presumed persistence(N=0,1,0)	99999	0	99999
S. constellatus, Indeterminate(N=0,1,0)	99999	0	99999
S. intermedius, Eradication(N=0,1,0)	99999	0	99999
S. intermedius, Presumed eradication(N=0,1,0)	99999	100	99999
S. intermedius, Persistence(N=0,1,0)	99999	0	99999
S. intermedius, Presumed persistence(N=0,1,0)	99999	0	99999
S. intermedius, Indeterminate(N=0,1,0)	99999	0	99999
S. mitis/oralis, Eradication(N=1,1,1)	0	0	0
S. mitis/oralis, Presumed eradication(N=1,1,1)	100	100	100
S. mitis/oralis, Persistence(N=1,1,1)	0	0	0
S. mitis/oralis, Presumed persistence(N=1,1,1)	0	0	0
S. mitis/oralis, Indeterminate(N=1,1,1)	0	0	0
S. pyogenes, Eradication(N=5,4,3)	0	0	0
S. pyogenes, Presumed eradication(N=5,4,3)	80	75	100
S. pyogenes, Persistence(N=5,4,3)	0	0	0
S. pyogenes, Presumed persistence (N=5,4,3)	20	0	0
S. pyogenes, Indeterminate(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Eradication(N=2,2,0)	0	0	99999
E. faecalis, Presumed eradication(N=2,2,0)	100	100	99999
E. faecalis, Persistence(N=2,2,0)	0	0	99999
E. faecalis, Presumed persistence(N=2,2,0)	0	0	99999
E. faecalis, Indeterminate(N=2,2,0)	0	0	99999
E. hirae, Eradication(N=1,0,0)	0	99999	99999
E. hirae, Presumed eradication(N=1,0,0)	100	99999	99999
E. hirae, Persistence(N=1,0,0)	0	99999	99999
E. hirae, Presumed persistence(N=1,0,0)	0	99999	99999
E. hirae, Indeterminate(N=1,0,0)	0	99999	99999
G. morbillorum, Eradication(N=1,0,0)	0	99999	99999
G. morbillorum, Presumed eradication(N=1,0,0)	100	99999	99999
G. morbillorum, Persistence(N=1,0,0)	0	99999	99999
G. morbillorum, Presumed persistence(N=1,0,0)	0	99999	99999
G. morbillorum, Indeterminate(N=1,0,0)	0	99999	99999
L. lactis, Eradication(N=1,0,0)	0	99999	99999
L. lactis, Presumed eradication(N=1,0,0)	100	99999	99999
L. lactis, Persistence(N=1,0,0)	0	99999	99999
L. lactis, Presumed persistence(N=1,0,0)	0	99999	99999
L. lactis, Indeterminate (N=1,0,0)	0	99999	99999

Notes
[87] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[88] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[89] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Secondary: Microbiological Response at the Follow-Up Visit by Baseline Gram-positive Pathogen

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End point title

Microbiological Response at the Follow-Up Visit by Baseline Gram-positive Pathogen

End point description

Eradication: Source specimen demonstrated absence of the original Baseline pathogen. Presumed eradication: Source specimen was not available to culture and the participant was assessed as a clinical cure. Persistence: Source specimen demonstrated continued presence of the original Baseline pathogen. Presumed persistence: Source specimen was not available to culture and the participant was assessed as a clinical failure. Indeterminate: Source specimen was not available to culture and the participant’s clinical response was unknown or missing. Presented for the microbiological intent-to-treat (microITT) population: all randomized (or enrolled in Cohort 5) participants who had at least 1 Gram-positive pathogen isolated at Baseline. In the table below, 99999 =not calculable/estimable due to zero participants analyzed.

End point type

Secondary

End point timeframe

Baseline, Day 54 (± 7 days)

End point values	Dalbavancin Single-dose	Dalbavancin Two-dose	Comparator
Number of subjects analysed	52 ^[90]	55 ^[91]	18 ^[92]
Units: percentage of participants
number (not applicable)
S. aureus (MRSA), Eradication(N=2,4,0)	0	0	99999
S. aureus (MRSA), Presumed eradication(N=2,4,0)	50	50	99999
S. aureus (MRSA), Persistence(N=2,4,0)	0	0	99999
S. aureus (MRSA), Presumed persistence(N=2,4,0)	0	25	99999
S. aureus (MRSA), Indeterminate(N=2,4,0)	50	25	99999
S. aureus (MSSA), Eradication(N=47,44,14)	0	2.3	0
S. aureus (MSSA), Presumed eradication(N=47,44,14)	93.6	86.4	100
S. aureus (MSSA), Persistence(N=47,44,14)	0	0	0
S. aureus (MSSA), Presumed persistence(N=47,44,14)	2.1	4.5	0
S. aureus (MSSA), Indeterminate(N=47,44,14)	4.3	4.5	0
S. aureus (MSSA), Missing(N=47,44,14)	0	2.3	0
S. agalactiae, Eradication(N=0,1,0)	99999	0	99999
S. agalactiae, Presumed eradication(N=0,1,0)	99999	100	99999
S. agalactiae, Persistence(N=0,1,0)	99999	0	99999
S. agalactiae, Presumed persistence(N=0,1,0)	99999	0	99999
S. agalactiae, Indeterminate(N=0,1,0)	99999	0	99999
S. anginosus, Eradication(N=1,0,0)	0	99999	99999
S. anginosus, Presumed eradication(N=1,0,0)	100	99999	99999
S. anginosus, Persistence(N=1,0,0)	0	99999	99999
S. anginosus, Presumed persistence(N=1,0,0)	0	99999	99999
S. anginosus, Indeterminate(N=1,0,0)	0	99999	99999
S. constellatus, Eradication(N=0,1,0)	99999	0	99999
S. constellatus, Presumed eradication(N=0,1,0)	99999	100	99999
S. constellatus, Persistence(N=0,1,0)	99999	0	99999
S. constellatus, Presumed persistence(N=0,1,0)	99999	0	99999
S. constellatus, Indeterminate(N=0,1,0)	99999	0	99999
S. intermedius, Eradication(N=0,1,0)	99999	0	99999
S. intermedius, Presumed eradication(N=0,1,0)	99999	100	99999
S. intermedius, Persistence(N=0,1,0)	99999	0	99999
S. intermedius, Presumed persistence(N=0,1,0)	99999	0	99999
S. intermedius, Indeterminate(N=0,1,0)	99999	0	99999
S. mitis/oralis, Eradication(N=1,1,1)	0	0	0
S. mitis/oralis, Presumed eradication(N=1,1,1)	100	100	100
S. mitis/oralis, Persistence(N=1,1,1)	0	0	0
S. mitis/oralis, Presumed persistence(N=1,1,1)	0	0	0
S. mitis/oralis, Indeterminate(N=1,1,1)	0	0	0
S. pyogenes, Eradication(N=5,4,3)	0	0	0
S. pyogenes, Presumed eradication(N=5,4,3)	80	75	100
S. pyogenes, Persistence(N=5,4,3)	0	0	0
S. pyogenes, Presumed persistence (N=5,4,3)	20	0	0
S. pyogenes, Indeterminate(N=5,4,3)	0	0	0
S. pyogenes, Missing(N=5,4,3)	0	25	0
E. faecalis, Eradication(N=2,2,0)	0	0	99999
E. faecalis, Presumed eradication(N=2,2,0)	100	100	99999
E. faecalis, Persistence(N=2,2,0)	0	0	99999
E. faecalis, Presumed persistence(N=2,2,0)	0	0	99999
E. faecalis, Indeterminate(N=2,2,0)	0	0	99999
E. hirae, Eradication(N=1,0,0)	0	99999	99999
E. hirae, Presumed eradication(N=1,0,0)	100	99999	99999
E. hirae, Persistence(N=1,0,0)	0	99999	99999
E. hirae, Presumed persistence(N=1,0,0)	0	99999	99999
E. hirae, Indeterminate(N=1,0,0)	0	99999	99999
G. morbillorum, Eradication(N=1,0,0)	0	99999	99999
G. morbillorum, Presumed eradication(N=1,0,0)	100	99999	99999
G. morbillorum, Persistence(N=1,0,0)	0	99999	99999
G. morbillorum, Presumed persistence(N=1,0,0)	0	99999	99999
G. morbillorum, Indeterminate(N=1,0,0)	0	99999	99999
L. lactis, Eradication(N=1,0,0)	0	99999	99999
L. lactis, Presumed eradication(N=1,0,0)	100	99999	99999
L. lactis, Persistence(N=1,0,0)	0	99999	99999
L. lactis, Presumed persistence(N=1,0,0)	0	99999	99999
L. lactis, Indeterminate (N=1,0,0)	0	99999	99999

Notes
[90] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[91] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen
[92] - Ns presented in table rows are # of subjects in microITT population with specified baseline pathogen

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All-cause mortality and adverse events were collected from the time informed consent was signed through the Final Visit. Median time on follow-up was 54.0 days for Dalbavancin Single-dose and Dalbavancin Two-dose groups and 54.5 days for Comparator group.

Adverse event reporting additional description

Adverse events were analyzed in the safety population which is defined as all participants in the ITT population who received at least 1 dose of study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

Dalbavancin Single-dose

Reporting group description

Reporting group title

Comparator

Reporting group description

Participants 3 months to < 6 years old and ≥6 years to 17 years old (inclusive) who were randomized to the comparator arm received a 10-14 day course of either vancomycin 10 to 15 mg/kg/dose, not to exceed a total daily dose of 4000 mg; or oxacillin 30 mg/kg/dose or flucloxacillin 50 mg/kg/dose, not to exceed a total daily dose of 2000 mg. Based on local practice patterns and approvals for clinical use in the pediatric population, oxacillin or flucloxacillin were supplied as an IV comparator. Those on oxacillin or flucloxacillin were permitted to switch to oral cefadroxil (dose for infants and children: 15 mg/kg/dose every 12 hours, maximum 2 g/day; dose for adolescents: 500-1000 mg every 12 hours), and if infection with methicillin-resistant S. aureus was documented, they were allowed to switch from IV vancomycin to oral therapy with clindamycin 10 mg/kg every 8 hours at the discretion of the investigator after at least 72 hours of IV therapy.

Reporting group title

Dalbavancin Two-dose

Reporting group description

Serious adverse events	Dalbavancin Single-dose	Comparator	Dalbavancin Two-dose
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 91 (3.30%)	0 / 30 (0.00%)	0 / 78 (0.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Nervous system disorders
FEBRILE CONVULSION
subjects affected / exposed	1 / 91 (1.10%)	0 / 30 (0.00%)	0 / 78 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
ABSCESS BACTERIAL
subjects affected / exposed	1 / 91 (1.10%)	0 / 30 (0.00%)	0 / 78 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OSTEOMYELITIS BACTERIAL
subjects affected / exposed	1 / 91 (1.10%)	0 / 30 (0.00%)	0 / 78 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Dalbavancin Single-dose	Comparator	Dalbavancin Two-dose
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 91 (1.10%)	1 / 30 (3.33%)	5 / 78 (6.41%)
Injury, poisoning and procedural complications
ANAEMIA POSTOPERATIVE
subjects affected / exposed	0 / 91 (0.00%)	1 / 30 (3.33%)	1 / 78 (1.28%)
occurrences all number	0	1	1
General disorders and administration site conditions
PYREXIA
subjects affected / exposed	0 / 91 (0.00%)	0 / 30 (0.00%)	2 / 78 (2.56%)
occurrences all number	0	0	2
Gastrointestinal disorders
VOMITING
subjects affected / exposed	0 / 91 (0.00%)	0 / 30 (0.00%)	2 / 78 (2.56%)
occurrences all number	0	0	2
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	0 / 91 (0.00%)	0 / 30 (0.00%)	2 / 78 (2.56%)
occurrences all number	0	0	2
Infections and infestations
NASOPHARYNGITIS
subjects affected / exposed	1 / 91 (1.10%)	1 / 30 (3.33%)	0 / 78 (0.00%)
occurrences all number	2	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

26 Feb 2015

Amendment 1 An additional arm was added to include a single dose of IV dalbavancin in addition to the 2-dose regimen. The randomization to dalbavancin (2-dose regimens) and comparator was changed to 1:1:1. The dose rationale for dalbavancin was added. PK sampling was added for the dalbavancin arms.

02 Mar 2016

Amendment 2 A sparse PK sampling design was recommended by regulatory authorities and was added as a secondary objective/endpoint. Oral clindamycin was added to the list of comparator options to allow for an oral switch from IV vancomycin. The number of participants in each treatment group and age cohort was defined to ensure sufficient numbers of participants were evaluated across the age groups and treatment arms. Inclusion and exclusion criteria were modified and clarified. The dalbavancin doses were updated to take into account different age groups to ensure expected exposures were achieved based on PK modelling and the dose rationale was updated. Audiology testing was added.

13 Jun 2016

Amendment 3 The starting dose for comparator vancomycin was adjusted from 10 mg/kg/dose to 10 to 15 mg/kg/dose to more closely match global practice patterns for vancomycin dosing in pediatrics. In addition, several changes were made to minimize blood collection in this pediatric population.

09 Mar 2017

Amendment 4 Since local rates of clindamycin-resistant MRSA were high at some sites, the option for an alternative comparator regimen was added (If an alternate comparator regimen was indicated by local susceptibility patterns, this had to be discussed with the medical monitor). Clarification was provided to explain that hematology, serum chemistry, and pregnancy testing should be conducted locally at baseline if not already collected per standard of care. Bicarbonate testing was extended to include children < 2 years and < 12 kg. Wording relating to pregnancies in the partners of male participants was removed.

27 Jun 2017

Amendment 5 A fifth cohort, Cohort 5 (birth to < 3 months of age), was added. The randomization scheme was modified, inclusion and exclusion criteria were modified, and Hy’s law criteria were included. These changes were agreed with the FDA.

26 Apr 2018

Amendment 6 Changes reflected revisions needed for Global Regulatory alignment in addition to recent feedback from the European Medicines Agency. There were further updates to the Cohort 5-based target population, recruitment initiation schedule, dosing, and assessments and outcome measures, the method of creatinine clearance evaluation in participants was changed, and expected enrolment numbers for participants with MRSA infections were removed.

29 Mar 2022

Amendment 7 The main change is to allow flexibility for the sites to use local laboratory for the collection of safety laboratory assessments, in an effort to reduce the volume of blood drawn for participants. In May 2020, AbbVie Inc. acquired Allergan, Inc. Allergan remains the sponsor (a subsidiary of AbbVie). The SAE reporting information has been changed to reflect the new ownership, i.e., Allergan to AbbVie.

18 Nov 2022

Amendment 8 The main change is that safety laboratory testing after eligibility and the peripheral blood culture are no longer required by protocol. Data from clinical laboratory tests and peripheral blood cultures performed as standard of care during the study will be collected. In May 2020, Allergan plc. was acquired by AbbVie (Allergan Sales, LLC and Allergan Ltd is a wholly owned subsidiary of AbbVie Inc.). In April 2022, AbbVie became the Sponsor of study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Multicenter, Open-Label, Randomized, Comparator Controlled Trial of the Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric Subjects with Acute Bacterial Skin and Skin Structure Infections

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Shift from Baseline in Distortion Product Otoacoustic Emission at TOC Visit

Primary: Shift from Baseline in Distortion Product Otoacoustic Emission at TOC Visit

Primary: Shift from Baseline in Auditory Brainstem Response Test at TOC Visit

Primary: Shift from Baseline in Auditory Brainstem Response Test at TOC Visit

Primary: Shift from Baseline in Acoustic Immittance Test at TOC Visit

Primary: Shift from Baseline in Acoustic Immittance Test at TOC Visit

Primary: Shift from Baseline in Behavioral Audiometric Valuation at TOC Visit

Primary: Shift from Baseline in Behavioral Audiometric Valuation at TOC Visit

Primary: Shift from Baseline in Clostridium Difficile (CD) and Vancomycin-resistant Enterococci (VRE) at TOC Visit

Primary: Shift from Baseline in Clostridium Difficile (CD) and Vancomycin-resistant Enterococci (VRE) at TOC Visit

Secondary: Clinical Response at 48-72 hours

Secondary: Clinical Response at 48-72 hours

Secondary: Clinical Response at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)

Secondary: Clinical Response at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)

Secondary: Clinical Response at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)

Secondary: Clinical Response at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)

Secondary: Clinical Response at the Follow-Up Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response at the Follow-Up Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response at the Follow-Up Visit (Clinical Response by Sponsor)

Secondary: Clinical Response at the Follow-Up Visit (Clinical Response by Sponsor)

Secondary: Clinical Response by Baseline Pathogen at 48-72 hours (Clinical Response by Sponsor)

Secondary: Clinical Response by Baseline Pathogen at 48-72 hours (Clinical Response by Sponsor)

Secondary: Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)

Secondary: Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)

Secondary: Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)

Secondary: Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)

Secondary: Clinical Response by Baseline Pathogen at the Follow-up Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response by Baseline Pathogen at the Follow-up Visit (Investigator Assessment of Clinical Outcome)

Secondary: Clinical Response by Baseline Pathogen at the Follow-up Visit (Clinical Response by Sponsor)

Secondary: Clinical Response by Baseline Pathogen at the Follow-up Visit (Clinical Response by Sponsor)

Secondary: All-cause Mortality at the Test of Cure (TOC) Visit Among Cohort 5 Participants

Secondary: All-cause Mortality at the Test of Cure (TOC) Visit Among Cohort 5 Participants

Secondary: Concentration of Dalbavancin in Plasma

Secondary: Concentration of Dalbavancin in Plasma

Secondary: Microbiological Response at 48-72 Hours

Secondary: Microbiological Response at 48-72 Hours

Secondary: Microbiological Response at the End of Treatment (EOT) Visit

Secondary: Microbiological Response at the End of Treatment (EOT) Visit

Secondary: Microbiological Response at the Test of Cure (TOC) Visit

Secondary: Microbiological Response at the Test of Cure (TOC) Visit

Secondary: Microbiological Response at the Follow-Up Visit

Secondary: Microbiological Response at the Follow-Up Visit

Secondary: Microbiological Response at 48-72 Hours by Baseline Gram-positive Pathogen

Secondary: Microbiological Response at 48-72 Hours by Baseline Gram-positive Pathogen

Secondary: Microbiological Response at the End of Treatment (EOT) Visit by Baseline Gram-positive Pathogen

Secondary: Microbiological Response at the End of Treatment (EOT) Visit by Baseline Gram-positive Pathogen

Secondary: Microbiological Response at the Test of Cure (TOC) Visit by Baseline Gram-positive Pathogen

Secondary: Microbiological Response at the Test of Cure (TOC) Visit by Baseline Gram-positive Pathogen

Secondary: Microbiological Response at the Follow-Up Visit by Baseline Gram-positive Pathogen

Secondary: Microbiological Response at the Follow-Up Visit by Baseline Gram-positive Pathogen

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Multicenter, Open-Label, Randomized, Comparator Controlled Trial of the Safety and Efficacy of Dalbavancin versus Active Comparator in Pediatric Subjects with Acute Bacterial Skin and Skin Structure Infections