A Phase 3 interventional study of Dalbavancin and Vancomycin in Methicillin-Resistant Staphylococcus Aureus, Bacterial Infections and Staphylococcal Skin Infections, sponsored by AbbVie. Completed at 84 sites in 20 countries. Open to participants aged 0 Years to 17 Years. Per ClinicalTrials.gov, last updated 2024-09-19.
Sponsored by AbbVie · Phase 3, Interventional, and Treatment
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.
Major cutaneous abscess characterized as a collection of pus within the dermis or deeper that is accompanied by erythema, edema and/or induration which i. requires surgical incision and drainage, and ii. is associated with cellulitis such that the total affected area involves at least 35 cm2 of erythema, or total affected area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR iii. alternatively, involves the central face and is associated with an area of erythema of at least 15 cm2 b. Surgical site or traumatic wound infection characterized by purulent drainage with surrounding erythema, edema and/or induration which occurred within 30 days after the trauma or surgery and is associated with cellulitis such that: i. the total affected area involves at least 35 cm2 of erythema, or total affected area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, involves the central face and is associated with an affected area of at least 15 cm2 c. Cellulitis, defined as a diffuse skin infection characterized by spreading areas of erythema, edema and/or induration and: i. is associated with erythema that involves at least 35 cm2 of surface area, or surface area of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, cellulitis of the central face that is associated with an affected area of at least 15 cm2 5. In addition to the requirement for erythema, all patients are required to have at least two (2) of the following signs of ABSSSI: a. Purulent drainage/discharge b. Fluctuance c. Heat/localized warmth d. Tenderness to palpation e. Swelling/induration
In patients age birth to \< 3 months, each patient must meet the following inclusion criteria to be enrolled in this study.
A clinical picture compatible with an ABSSSI suspected or confirmed to be caused by Gram-positive bacteria, including MRSA.
OR
Suspected or confirmed sepsis including any of the following clinical criteria:
In addition, patients must meet at least one of the following laboratory criteria:
a. White blood cell count ≤4.0 × 10\^9/L OR ≥20.0 × 10\^9/L b, Immature to total neutrophil ratio >0.2 c. Platelet count ≤100 × 10\^9/L d. C-reactive protein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL e. Hyperglycemia OR Hypoglycemia f. Metabolic acidosis
Infections must be of sufficient severity to merit hospitalization and parenteral antibiotic therapy. These infections may include:
Exclusion Criteria:
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.
Drug: Dalbavancin
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.
Drug: Dalbavancin
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.
Drug: Vancomycin · Drug: Oxacillin · Drug: Flucloxacillin · Drug: Cefadroxil · Drug: Clindamycin
Dalbavancin was administered intravenously over 30 (± 5) minutes.
Also known as: Xydalba
Vancomycin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.
Oxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.
Flucloxacillin was administered intravenously over 60 (± 10) minutes every 6 (± 1) hours.
Cefadroxil was administered orally every 12 hours.
Clindamycin was administered orally every 8 hours.
Shift From Baseline in Distortion Product Otoacoustic Emission at TOC Visit
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.
Time frame: Baseline, Day 28 (± 2 days)
Shift From Baseline in Auditory Brainstem Response Test at TOC Visit
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.
Time frame: Baseline, Day 28 (± 2 days)
Shift From Baseline in Acoustic Immittance Test at TOC Visit
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.
Time frame: Baseline, Day 28 (± 2 days)
Shift From Baseline in Behavioral Audiometric Valuation at TOC Visit
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.
Time frame: Baseline, Day 28 (± 2 days)
Shift From Baseline in Clostridium Difficile (CD) and Vancomycin-resistant Enterococci (VRE) at TOC Visit
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.
Time frame: Baseline, Day 28 (± 2 days)
Clinical Response at 48-72 Hours
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.
Time frame: Baseline, 48-72 hours
Clinical Response at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)
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.
Time frame: Baseline, Day 14 (± 2 Days)
Clinical Response at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)
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.
Time frame: Baseline, Day 14 (± 2 Days)
Clinical Response at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)
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 modified intent-to-treat (mITT) population.
Time frame: Baseline, Day 28 (± 2 Days)
Clinical Response at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)
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.
Time frame: Baseline, Day 28 (± 2 Days)
Clinical Response at the Follow-Up Visit (Investigator Assessment of Clinical Outcome)
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 modified intent-to-treat (mITT) population
Time frame: Baseline, Day 54 (± 7 days)
Clinical Response at the Follow-Up Visit (Clinical Response by Sponsor)
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.
Time frame: Baseline, Day 54 (± 7 days)
Clinical Response by Baseline Pathogen at 48-72 Hours (Clinical Response by Sponsor)
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.
Time frame: Baseline, 48-72 hours
Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Investigator Assessment of Clinical Outcome)
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.
Time frame: Baseline, Day 14 (± 2 Days)
Clinical Response by Baseline Pathogen at the End of Treatment (EOT) Visit (Clinical Response by Sponsor)
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.
Time frame: Baseline, Day 14 (± 2 Days)
Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Investigator Assessment of Clinical Outcome)
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.
Time frame: Baseline, Day 28 (± 2 Days)
Clinical Response by Baseline Pathogen at the Test of Cure (TOC) Visit (Clinical Response by Sponsor)
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.
Time frame: Baseline, Day 28 (± 2 Days)
Clinical Response by Baseline Pathogen at the Follow-up Visit (Investigator Assessment of Clinical Outcome)
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.
Time frame: Baseline, Day 54 (± 7 days)
Clinical Response by Baseline Pathogen at the Follow-up Visit (Clinical Response by Sponsor)
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.
Time frame: Baseline, Day 54 (± 7 days)
Microbiological Response at 48-72 Hours
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.
Time frame: Baseline, 48-72 hours
Microbiological Response at the End of Treatment (EOT) Visit
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.
Time frame: Baseline, Day 14 (± 2 Days)
Microbiological Response at the Test of Cure (TOC) Visit
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.
Time frame: Baseline, Day 28 (± 2 Days)
Microbiological Response at the Follow-Up Visit
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.
Time frame: Baseline, Day 54 (± 7 days)
Microbiological Response at 48-72 Hours by Baseline Gram-positive Pathogen
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.
Time frame: Baseline, 48-72 hours
Microbiological Response at the End of Treatment (EOT) Visit by Baseline Gram-positive Pathogen
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.
Time frame: Baseline, Day 14 (± 2 Days)
Microbiological Response at the Test of Cure (TOC) Visit by Baseline Gram-positive Pathogen
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.
Time frame: Baseline, Day 28 (± 2 Days)
Microbiological Response at the Follow-Up Visit by Baseline Gram-positive Pathogen
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.
Time frame: Baseline, Day 54 (± 7 days)
All-cause Mortality at the Test of Cure (TOC) Visit Among Cohort 5 Participants
All-cause mortality was determined for the participants in Cohort 5 (birth to \< 3 months) at the Test of Cure visit.
Time frame: Day 28 (± 2 Days)
Concentration of Dalbavancin in Plasma
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.
Time frame: 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
| Milestone | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Started | 91 | 78 | 30 |
| Completed | 91 | 74 | 30 |
| Not completed | 0 | 4 | 0 |
| Withdrew: Withdrawal of consent | 0 | 2 | 0 |
| Withdrew: Lost to follow-up | 0 | 1 | 0 |
| Withdrew: Other, not specified | 0 | 1 | 0 |
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.
| Participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Baseline & TOC normal | 2 | — | 1 |
| Baseline normal & TOC abnormal | 0 | — | 0 |
| Baseline abnormal & TOC normal | 0 | — | 0 |
| Baseline & TOC abnormal | 0 | — | 0 |
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.
| Participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Baseline & TOC normal | 1 | — | — |
| Baseline normal & TOC abnormal | 0 | — | — |
| Baseline abnormal & TOC normal | 0 | — | — |
| Baseline & TOC abnormal | 0 | — | — |
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.
| Participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| 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 |
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.
| Participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| 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 |
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.
| Participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| 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 negative & 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 missing & 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 negative & 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 missing & TOC missing | 0 | 0 | 0 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Clinical Responder | 96.5 | 98.6 | 89.7 |
| Clinical Non-Responder | 3.5 | 1.4 | 10.3 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Clinical Cure | 92.9 | 93.2 | 100 |
| Improvement | 6.0 | 5.5 | 0 |
| Clinical Failure | 1.2 | 1.4 | 0 |
| Unknown | 0 | 0 | 0 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Cure | 90.5 | 91.9 | 100 |
| Improvement | 7.1 | 5.4 | 0 |
| Failure | 2.4 | 2.7 | 0 |
| Unknown | 0 | 0 | 0 |
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 modified intent-to-treat (mITT) population.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Clinical Cure | 98.8 | 98.6 | 100 |
| Clinical Failure | 1.2 | 1.4 | 0 |
| Unknown | 0 | 0 | 0 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Cure | 95.2 | 97.3 | 100 |
| Failure | 2.4 | 2.7 | 0 |
| Unknown | 2.4 | 0 | 0 |
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 modified intent-to-treat (mITT) population
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Clinical Cure | 97.6 | 97.3 | 100 |
| Clinical Failure | 1.2 | 1.4 | 0 |
| Unknown | 1.2 | 1.4 | 0 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| Cure | 96.4 | 97.3 | 100 |
| Failure | 2.4 | 2.7 | 0 |
| Unknown | 1.2 | 0 | 0 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA),Clinical Responder | 100 | 100 | — |
| S. aureus (MRSA),Clinical Non-Responder | 0 | 0 | — |
| S. aureus (MSSA),Clinical Responder | 97.9 | 95.5 | 85.7 |
| S. aureus (MSSA),Clinical Non-Responder | 2.1 | 2.3 | 7.1 |
| S. aureus (MSSA),Missing | 0 | 2.3 | 7.1 |
| S. agalactiae, Clinical Responder | — | 100 | — |
| S. agalactiae, Clinical Non-Responder | — | 0 | — |
| S. anginosus, Clinical Responder | 100 | — | — |
| S. anginosus, Clinical Non-Responder | 0 | — | — |
| S. constellatus, Clinical Responder | — | 100 | — |
| S. constellatus, Clinical Non-Responder | — | 0 | — |
| S. intermedius, Clinical Responder | — | 100 | — |
| S. intermedius, Clinical Non-Responder | — | 0 | — |
| S. pyogenes, Clinical Responder | 80 | 75 | 100 |
| S. pyogenes, Clinical Non-Responder | 20 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Clinical Responder | 100 | 100 | — |
| E. faecalis, Clinical Non-Responder | 0 | 0 | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA),Clinical Cure | 100 | 75 | — |
| S. aureus (MRSA),Improvement | 0 | 0 | — |
| S. aureus (MRSA),Clinical Failure | 0 | 0 | — |
| S. aureus (MRSA),Unknown | 0 | 0 | — |
| S. aureus (MRSA),Missing | 0 | 25 | — |
| S. aureus (MSSA),Clinical Cure | 91.5 | 86.4 | 100 |
| S. aureus (MSSA),Improvement | 4.3 | 4.5 | 0 |
| S. aureus (MSSA),Clinical Failure | 2.1 | 2.3 | 0 |
| S. aureus (MSSA),Unknown | 0 | 0 | 0 |
| S. aureus (MSSA),Missing | 2.1 | 6.8 | 0 |
| S. agalactiae, Clinical Cure | — | 100 | — |
| S. agalactiae, Improvement | — | 0 | — |
| S. agalactiae, Clinical Failure | — | 0 | — |
| S. agalactiae, Unknown | — | 0 | — |
| S. anginosus, Clinical Cure | 100 | — | — |
| S. anginosus, Improvement | 0 | — | — |
| S. anginosus, Clinical Failure | 0 | — | — |
| S. anginosus, Unknown | 0 | — | — |
| S. constellatus, Clinical Cure | — | 100 | — |
| S. constellatus, Improvement | — | 0 | — |
| S. constellatus, Clinical Failure | — | 0 | — |
| S. constellatus, Unknown | — | 0 | — |
| S. intermedius, Clinical Cure | — | 100 | — |
| S. intermedius, Improvement | — | 0 | — |
| S. intermedius, Clinical Failure | — | 0 | — |
| S. intermedius, Unknown | — | 0 | — |
| S. pyogenes, Clinical Cure | 80 | 50 | 100 |
| S. pyogenes, Improvement | 0 | 25 | 0 |
| S. pyogenes, Clinical Failure | 20 | 0 | 0 |
| S. pyogenes, Unknown | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Clinical Cure | 100 | 100 | — |
| E. faecalis, Improvement | 0 | 0 | — |
| E. faecalis, Clinical Failure | 0 | 0 | — |
| E. faecalis, Unknown | 0 | 0 | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA),Cure | 100 | 75 | — |
| S. aureus (MRSA),Improvement | 0 | 0 | — |
| S. aureus (MRSA),Failure | 0 | 25 | — |
| S. aureus (MRSA),Unknown | 0 | 0 | — |
| S. aureus (MSSA),Cure | 91.5 | 86.4 | 100 |
| S. aureus (MSSA),Improvement | 4.3 | 4.5 | 0 |
| S. aureus (MSSA),Failure | 2.1 | 4.5 | 0 |
| S. aureus (MSSA),Unknown | 0 | 0 | 0 |
| S. aureus (MSSA),Missing | 2.1 | 4.5 | 0 |
| S. agalactiae, Cure | — | 100 | — |
| S. agalactiae, Improvement | — | 0 | — |
| S. agalactiae, Failure | — | 0 | — |
| S. agalactiae, Unknown | — | 0 | — |
| S. anginosus, Cure | 100 | — | — |
| S. anginosus, Improvement | 0 | — | — |
| S. anginosus, Failure | 0 | — | — |
| S. anginosus, Unknown | 0 | — | — |
| S. constellatus, Cure | — | 100 | — |
| S. constellatus, Improvement | — | 0 | — |
| S. constellatus, Failure | — | 0 | — |
| S. constellatus, Unknown | — | 0 | — |
| S. intermedius, Cure | — | 100 | — |
| S. intermedius, Improvement | — | 0 | — |
| S. intermedius, Failure | — | 0 | — |
| S. intermedius, Unknown | — | 0 | — |
| S. pyogenes, Cure | 80 | 50 | 100 |
| S. pyogenes, Improvement | 0 | 25 | 0 |
| S. pyogenes, Failure | 20 | 0 | 0 |
| S. pyogenes, Unknown | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Cure | 100 | 100 | — |
| E. faecalis, Improvement | 0 | 0 | — |
| E. faecalis, Failure | 0 | 0 | — |
| E. faecalis, Unknown | 0 | 0 | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA),Clinical Cure | 100 | 75 | — |
| S. aureus (MRSA),Clinical Failure | 0 | 0 | — |
| S. aureus (MRSA),Unknown | 0 | 0 | — |
| S. aureus (MRSA),Missing | 0 | 25 | — |
| S. aureus (MSSA),Clinical Cure | 95.7 | 90.9 | 100 |
| S. aureus (MSSA),Clinical Failure | 2.1 | 2.3 | 0 |
| S. aureus (MSSA),Unknown | 0 | 0 | 0 |
| S. aureus (MSSA),Missing | 2.2 | 6.8 | 0 |
| S. agalactiae, Clinical Cure | — | 100 | — |
| S. agalactiae, Clinical Failure | — | 0 | — |
| S. agalactiae, Unknown | — | 0 | — |
| S. anginosus, Clinical Cure | 100 | — | — |
| S. anginosus, Clinical Failure | 0 | — | — |
| S. anginosus, Unknown | 0 | — | — |
| S. constellatus, Clinical Cure | — | 100 | — |
| S. constellatus, Clinical Failure | — | 0 | — |
| S. constellatus, Unknown | — | 0 | — |
| S. intermedius, Clinical Cure | — | 100 | — |
| S. intermedius, Clinical Failure | — | 0 | — |
| S. intermedius, Unknown | — | 0 | — |
| S. pyogenes, Clinical Cure | 80 | 75 | 100 |
| S. pyogenes, Clinical Failure | 20 | 0 | 0 |
| S. pyogenes, Unknown | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Clinical Cure | 100 | 100 | — |
| E. faecalis, Clinical Failure | 0 | 0 | — |
| E. faecalis, Unknown | 0 | 0 | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA),Cure | 100 | 75 | — |
| S. aureus (MRSA),Failure | 0 | 25 | — |
| S. aureus (MRSA),Unknown | 0 | 0 | — |
| S. aureus (MSSA),Cure | 91.5 | 90.9 | 100 |
| S. aureus (MSSA),Failure | 2.1 | 4.5 | 0 |
| S. aureus (MSSA),Unknown | 4.3 | 0 | 0 |
| S. aureus (MSSA),Missing | 2.1 | 4.5 | 0 |
| S. agalactiae, Cure | — | 100 | — |
| S. agalactiae, Failure | — | 0 | — |
| S. agalactiae, Unknown | — | 0 | — |
| S. anginosus, Cure | 100 | — | — |
| S. anginosus, Failure | 0 | — | — |
| S. anginosus, Unknown | 0 | — | — |
| S. constellatus, Cure | — | 100 | — |
| S. constellatus, Failure | — | 0 | — |
| S. constellatus, Unknown | — | 0 | — |
| S. intermedius, Cure | — | 100 | — |
| S. intermedius, Failure | — | 0 | — |
| S. intermedius, Unknown | — | 0 | — |
| S. pyogenes, Cure | 80 | 75 | 100 |
| S. pyogenes, Failure | 20 | 0 | 0 |
| S. pyogenes, Unknown | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Cure | 100 | 100 | — |
| E. faecalis, Failure | 0 | 0 | — |
| E. faecalis, Unknown | 0 | 0 | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA),Clinical Cure | 50 | 50 | — |
| S. aureus (MRSA),Clinical Failure | 0 | 0 | — |
| S. aureus (MRSA),Unknown | 50 | 25 | — |
| S. aureus (MRSA),Missing | 0 | 25 | — |
| S. aureus (MSSA),Clinical Cure | 95.7 | 88.6 | 100 |
| S. aureus (MSSA),Clinical Failure | 2.1 | 2.3 | 0 |
| S. aureus (MSSA),Unknown | 2.1 | 0 | 0 |
| S. aureus (MSSA),Missing | 0 | 9.1 | 0 |
| S. agalactiae, Clinical Cure | — | 100 | — |
| S. agalactiae, Clinical Failure | — | 0 | — |
| S. agalactiae, Unknown | — | 0 | — |
| S. anginosus, Clinical Cure | 100 | — | — |
| S. anginosus, Clinical Failure | 0 | — | — |
| S. anginosus, Unknown | 0 | — | — |
| S. constellatus, Clinical Cure | — | 100 | — |
| S. constellatus, Clinical Failure | — | 0 | — |
| S. constellatus, Unknown | — | 0 | — |
| S. intermedius, Clinical Cure | — | 100 | — |
| S. intermedius, Clinical Failure | — | 0 | — |
| S. intermedius, Unknown | — | 0 | — |
| S. pyogenes, Clinical Cure | 80 | 75 | 100 |
| S. pyogenes, Clinical Failure | 20 | 0 | 0 |
| S. pyogenes, Unknown | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Clinical Cure | 100 | 100 | — |
| E. faecalis, Clinical Failure | 0 | 0 | — |
| E. faecalis, Unknown | 0 | 0 | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA),Cure | 50 | 50 | — |
| S. aureus (MRSA),Failure | 0 | 25 | — |
| S. aureus (MRSA),Unknown | 0 | 0 | — |
| S. aureus (MRSA),Missing | 50 | 25 | — |
| S. aureus (MSSA),Cure | 93.6 | 88.6 | 100 |
| S. aureus (MSSA),Failure | 2.1 | 4.5 | 0 |
| S. aureus (MSSA),Unknown | 2.1 | 0 | 0 |
| S. aureus (MSSA),Missing | 2.1 | 6.8 | 0 |
| S. agalactiae, Cure | — | 100 | — |
| S. agalactiae, Failure | — | 0 | — |
| S. agalactiae, Unknown | — | 0 | — |
| S. anginosus, Cure | 100 | — | — |
| S. anginosus, Failure | 0 | — | — |
| S. anginosus, Unknown | 0 | — | — |
| S. constellatus, Cure | — | 100 | — |
| S. constellatus, Failure | — | 0 | — |
| S. constellatus, Unknown | — | 0 | — |
| S. intermedius, Cure | — | 100 | — |
| S. intermedius, Failure | — | 0 | — |
| S. intermedius, Unknown | — | 0 | — |
| S. pyogenes, Cure | 80 | 75 | 100 |
| S. pyogenes, Failure | 20 | 0 | 0 |
| S. pyogenes, Unknown | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Cure | 100 | 100 | — |
| E. faecalis, Failure | 0 | 0 | — |
| E. faecalis, Unknown | 0 | 0 | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| 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 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| 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 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| 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 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| 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 |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA), Eradication | 0 | 0 | — |
| S. aureus (MRSA), Presumed eradication | 100 | 100 | — |
| S. aureus (MRSA), Persistence | 0 | 0 | — |
| S. aureus (MRSA), Presumed persistence | 0 | 0 | — |
| S. aureus (MRSA), Indeterminate | 0 | 0 | — |
| S. aureus (MSSA), Eradication | 0 | 2.3 | 0 |
| S. aureus (MSSA), Presumed eradication | 97.9 | 90.9 | 85.7 |
| S. aureus (MSSA), Persistence | 0 | 2.3 | 0 |
| S. aureus (MSSA), Presumed persistence | 2.1 | 2.3 | 7.1 |
| S. aureus (MSSA), Indeterminate | 0 | 0 | 7.1 |
| S. aureus (MSSA), Missing | 0 | 2.3 | 0 |
| S. agalactiae, Eradication | — | 0 | — |
| S. agalactiae, Presumed eradication | — | 100 | — |
| S. agalactiae, Persistence | — | 0 | — |
| S. agalactiae, Presumed persistence | — | 0 | — |
| S. agalactiae, Indeterminate | — | 0 | — |
| S. anginosus, Eradication | 0 | — | — |
| S. anginosus, Presumed eradication | 100 | — | — |
| S. anginosus, Persistence | 0 | — | — |
| S. anginosus, Presumed persistence | 0 | — | — |
| S. anginosus, Indeterminate | 0 | — | — |
| S. constellatus, Eradication | — | 0 | — |
| S. constellatus, Presumed eradication | — | 100 | — |
| S. constellatus, Persistence | — | 0 | — |
| S. constellatus, Presumed persistence | — | 0 | — |
| S. constellatus, Indeterminate | — | 0 | — |
| S. intermedius, Eradication | — | 0 | — |
| S. intermedius, Presumed eradication | — | 100 | — |
| S. intermedius, Persistence | — | 0 | — |
| S. intermedius, Presumed persistence | — | 0 | — |
| S. intermedius, Indeterminate | — | 0 | — |
| S. mitis/oralis, Eradication | 0 | 0 | 0 |
| S. mitis/oralis, Presumed eradication | 100 | 100 | 100 |
| S. mitis/oralis, Persistence | 0 | 0 | 0 |
| S. mitis/oralis, Presumed persistence | 0 | 0 | 0 |
| S. mitis/oralis, Indeterminate | 0 | 0 | 0 |
| S. pyogenes, Eradication | 0 | 0 | 0 |
| S. pyogenes, Presumed eradication | 80 | 75 | 100 |
| S. pyogenes, Persistence | 0 | 0 | 0 |
| S. pyogenes, Presumed persistence | 20 | 0 | 0 |
| S. pyogenes, Indeterminate | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Eradication | 0 | 0 | — |
| E. faecalis, Presumed eradication | 100 | 100 | — |
| E. faecalis, Persistence | 0 | 0 | — |
| E. faecalis, Presumed persistence | 0 | 0 | — |
| E. faecalis, Indeterminate | 0 | 0 | — |
| E. hirae, Eradication | 0 | — | — |
| E. hirae, Presumed eradication | 100 | — | — |
| E. hirae, Persistence | 0 | — | — |
| E. hirae, Presumed persistence | 0 | — | — |
| E. hirae, Indeterminate | 0 | — | — |
| G. morbillorum, Eradication | 0 | — | — |
| G. morbillorum, Presumed eradication | 100 | — | — |
| G. morbillorum, Persistence | 0 | — | — |
| G. morbillorum, Presumed persistence | 0 | — | — |
| G. morbillorum, Indeterminate | 0 | — | — |
| L. lactis, Eradication | 0 | — | — |
| L. lactis, Presumed eradication | 100 | — | — |
| L. lactis, Persistence | 0 | — | — |
| L. lactis, Presumed persistence | 0 | — | — |
| L. lactis, Indeterminate | 0 | — | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA), Eradication | 0 | 0 | — |
| S. aureus (MRSA), Presumed eradication | 100 | 75 | — |
| S. aureus (MRSA), Persistence | 0 | 0 | — |
| S. aureus (MRSA), Presumed persistence | 0 | 25 | — |
| S. aureus (MRSA), Indeterminate | 0 | 0 | — |
| S. aureus (MSSA), Eradication | 0 | 2.3 | 0 |
| S. aureus (MSSA), Presumed eradication | 95.7 | 88.6 | 100 |
| S. aureus (MSSA), Persistence | 0 | 2.3 | 0 |
| S. aureus (MSSA), Presumed persistence | 2.1 | 2.3 | 0 |
| S. aureus (MSSA), Indeterminate | 2.1 | 2.3 | 0 |
| S. aureus (MSSA), Missing | 0 | 2.3 | 0 |
| S. agalactiae, Eradication | — | 0 | — |
| S. agalactiae, Presumed eradication | — | 100 | — |
| S. agalactiae, Persistence | — | 0 | — |
| S. agalactiae, Presumed persistence | — | 0 | — |
| S. agalactiae, Indeterminate | — | 0 | — |
| S. anginosus, Eradication | 0 | — | — |
| S. anginosus, Presumed eradication | 100 | — | — |
| S. anginosus, Persistence | 0 | — | — |
| S. anginosus, Presumed persistence | 0 | — | — |
| S. anginosus, Indeterminate | 0 | — | — |
| S. constellatus, Eradication | — | 0 | — |
| S. constellatus, Presumed eradication | — | 100 | — |
| S. constellatus, Persistence | — | 0 | — |
| S. constellatus, Presumed persistence | — | 0 | — |
| S. constellatus, Indeterminate | — | 0 | — |
| S. intermedius, Eradication | — | 0 | — |
| S. intermedius, Presumed eradication | — | 100 | — |
| S. intermedius, Persistence | — | 0 | — |
| S. intermedius, Presumed persistence | — | 0 | — |
| S. intermedius, Indeterminate | — | 0 | — |
| S. mitis/oralis, Eradication | 0 | 0 | 0 |
| S. mitis/oralis, Presumed eradication | 100 | 100 | 100 |
| S. mitis/oralis, Persistence | 0 | 0 | 0 |
| S. mitis/oralis, Presumed persistence | 0 | 0 | 0 |
| S. mitis/oralis, Indeterminate | 0 | 0 | 0 |
| S. pyogenes, Eradication | 0 | 0 | 0 |
| S. pyogenes, Presumed eradication | 80 | 75 | 100 |
| S. pyogenes, Persistence | 0 | 0 | 0 |
| S. pyogenes, Presumed persistence | 20 | 0 | 0 |
| S. pyogenes, Indeterminate | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Eradication | 0 | 0 | — |
| E. faecalis, Presumed eradication | 100 | 100 | — |
| E. faecalis, Persistence | 0 | 0 | — |
| E. faecalis, Presumed persistence | 0 | 0 | — |
| E. faecalis, Indeterminate | 0 | 0 | — |
| E. hirae, Eradication | 0 | — | — |
| E. hirae, Presumed eradication | 0 | — | — |
| E. hirae, Persistence | 0 | — | — |
| E. hirae, Presumed persistence | 0 | — | — |
| E. hirae, Indeterminate | 100 | — | — |
| G. morbillorum, Eradication | 0 | — | — |
| G. morbillorum, Presumed eradication | 100 | — | — |
| G. morbillorum, Persistence | 0 | — | — |
| G. morbillorum, Presumed persistence | 0 | — | — |
| G. morbillorum, Indeterminate | 0 | — | — |
| L. lactis, Eradication | 0 | — | — |
| L. lactis, Presumed eradication | 100 | — | — |
| L. lactis, Persistence | 0 | — | — |
| L. lactis, Presumed persistence | 0 | — | — |
| L. lactis, Indeterminate | 0 | — | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA), Eradication | 0 | 0 | — |
| S. aureus (MRSA), Presumed eradication | 100 | 75 | — |
| S. aureus (MRSA), Persistence | 0 | 0 | — |
| S. aureus (MRSA), Presumed persistence | 0 | 25 | — |
| S. aureus (MRSA), Indeterminate | 0 | 0 | — |
| S. aureus (MSSA), Eradication | 0 | 2.3 | 0 |
| S. aureus (MSSA), Presumed eradication | 91.5 | 88.6 | 100 |
| S. aureus (MSSA), Persistence | 0 | 0 | 0 |
| S. aureus (MSSA), Presumed persistence | 2.1 | 4.5 | 0 |
| S. aureus (MSSA), Indeterminate | 6.4 | 2.3 | 0 |
| S. aureus (MSSA), Missing | 0 | 2.3 | 0 |
| S. agalactiae, Eradication | — | 0 | — |
| S. agalactiae, Presumed eradication | — | 100 | — |
| S. agalactiae, Persistence | — | 0 | — |
| S. agalactiae, Presumed persistence | — | 0 | — |
| S. agalactiae, Indeterminate | — | 0 | — |
| S. anginosus, Eradication | 0 | — | — |
| S. anginosus, Presumed eradication | 100 | — | — |
| S. anginosus, Persistence | 0 | — | — |
| S. anginosus, Presumed persistence | 0 | — | — |
| S. anginosus, Indeterminate | 0 | — | — |
| S. constellatus, Eradication | — | 0 | — |
| S. constellatus, Presumed eradication | — | 100 | — |
| S. constellatus, Persistence | — | 0 | — |
| S. constellatus, Presumed persistence | — | 0 | — |
| S. constellatus, Indeterminate | — | 0 | — |
| S. intermedius, Eradication | — | 0 | — |
| S. intermedius, Presumed eradication | — | 100 | — |
| S. intermedius, Persistence | — | 0 | — |
| S. intermedius, Presumed persistence | — | 0 | — |
| S. intermedius, Indeterminate | — | 0 | — |
| S. mitis/oralis, Eradication | 0 | 0 | 0 |
| S. mitis/oralis, Presumed eradication | 100 | 100 | 100 |
| S. mitis/oralis, Persistence | 0 | 0 | 0 |
| S. mitis/oralis, Presumed persistence | 0 | 0 | 0 |
| S. mitis/oralis, Indeterminate | 0 | 0 | 0 |
| S. pyogenes, Eradication | 0 | 0 | 0 |
| S. pyogenes, Presumed eradication | 80 | 75 | 100 |
| S. pyogenes, Persistence | 0 | 0 | 0 |
| S. pyogenes, Presumed persistence | 20 | 0 | 0 |
| S. pyogenes, Indeterminate | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Eradication | 0 | 0 | — |
| E. faecalis, Presumed eradication | 100 | 100 | — |
| E. faecalis, Persistence | 0 | 0 | — |
| E. faecalis, Presumed persistence | 0 | 0 | — |
| E. faecalis, Indeterminate | 0 | 0 | — |
| E. hirae, Eradication | 0 | — | — |
| E. hirae, Presumed eradication | 100 | — | — |
| E. hirae, Persistence | 0 | — | — |
| E. hirae, Presumed persistence | 0 | — | — |
| E. hirae, Indeterminate | 0 | — | — |
| G. morbillorum, Eradication | 0 | — | — |
| G. morbillorum, Presumed eradication | 100 | — | — |
| G. morbillorum, Persistence | 0 | — | — |
| G. morbillorum, Presumed persistence | 0 | — | — |
| G. morbillorum, Indeterminate | 0 | — | — |
| L. lactis, Eradication | 0 | — | — |
| L. lactis, Presumed eradication | 100 | — | — |
| L. lactis, Persistence | 0 | — | — |
| L. lactis, Presumed persistence | 0 | — | — |
| L. lactis, Indeterminate | 0 | — | — |
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.
| percentage of participants | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| S. aureus (MRSA), Eradication | 0 | 0 | — |
| S. aureus (MRSA), Presumed eradication | 50 | 50 | — |
| S. aureus (MRSA), Persistence | 0 | 0 | — |
| S. aureus (MRSA), Presumed persistence | 0 | 25 | — |
| S. aureus (MRSA), Indeterminate | 50 | 25 | — |
| S. aureus (MSSA), Eradication | 0 | 2.3 | 0 |
| S. aureus (MSSA), Presumed eradication | 93.6 | 86.4 | 100 |
| S. aureus (MSSA), Persistence | 0 | 0 | 0 |
| S. aureus (MSSA), Presumed persistence | 2.1 | 4.5 | 0 |
| S. aureus (MSSA), Indeterminate | 4.3 | 4.5 | 0 |
| S. aureus (MSSA), Missing | 0 | 2.3 | 0 |
| S. agalactiae, Eradication | — | 0 | — |
| S. agalactiae, Presumed eradication | — | 100 | — |
| S. agalactiae, Persistence | — | 0 | — |
| S. agalactiae, Presumed persistence | — | 0 | — |
| S. agalactiae, Indeterminate | — | 0 | — |
| S. anginosus, Eradication | 0 | — | — |
| S. anginosus, Presumed eradication | 100 | — | — |
| S. anginosus, Persistence | 0 | — | — |
| S. anginosus, Presumed persistence | 0 | — | — |
| S. anginosus, Indeterminate | 0 | — | — |
| S. constellatus, Eradication | — | 0 | — |
| S. constellatus, Presumed eradication | — | 100 | — |
| S. constellatus, Persistence | — | 0 | — |
| S. constellatus, Presumed persistence | — | 0 | — |
| S. constellatus, Indeterminate | — | 0 | — |
| S. intermedius, Eradication | — | 0 | — |
| S. intermedius, Presumed eradication | — | 100 | — |
| S. intermedius, Persistence | — | 0 | — |
| S. intermedius, Presumed persistence | — | 0 | — |
| S. intermedius, Indeterminate | — | 0 | — |
| S. mitis/oralis, Eradication | 0 | 0 | 0 |
| S. mitis/oralis, Presumed eradication | 100 | 100 | 100 |
| S. mitis/oralis, Persistence | 0 | 0 | 0 |
| S. mitis/oralis, Presumed persistence | 0 | 0 | 0 |
| S. mitis/oralis, Indeterminate | 0 | 0 | 0 |
| S. pyogenes, Eradication | 0 | 0 | 0 |
| S. pyogenes, Presumed eradication | 80 | 75 | 100 |
| S. pyogenes, Persistence | 0 | 0 | 0 |
| S. pyogenes, Presumed persistence | 20 | 0 | 0 |
| S. pyogenes, Indeterminate | 0 | 0 | 0 |
| S. pyogenes, Missing | 0 | 25 | 0 |
| E. faecalis, Eradication | 0 | 0 | — |
| E. faecalis, Presumed eradication | 100 | 100 | — |
| E. faecalis, Persistence | 0 | 0 | — |
| E. faecalis, Presumed persistence | 0 | 0 | — |
| E. faecalis, Indeterminate | 0 | 0 | — |
| E. hirae, Eradication | 0 | — | — |
| E. hirae, Presumed eradication | 100 | — | — |
| E. hirae, Persistence | 0 | — | — |
| E. hirae, Presumed persistence | 0 | — | — |
| E. hirae, Indeterminate | 0 | — | — |
| G. morbillorum, Eradication | 0 | — | — |
| G. morbillorum, Presumed eradication | 100 | — | — |
| G. morbillorum, Persistence | 0 | — | — |
| G. morbillorum, Presumed persistence | 0 | — | — |
| G. morbillorum, Indeterminate | 0 | — | — |
| L. lactis, Eradication | 0 | — | — |
| L. lactis, Presumed eradication | 100 | — | — |
| L. lactis, Persistence | 0 | — | — |
| L. lactis, Presumed persistence | 0 | — | — |
| L. lactis, Indeterminate | 0 | — | — |
All-cause mortality was determined for the participants in Cohort 5 (birth to \< 3 months) at the Test of Cure visit.
| Participants | Birth to < 3 Months of Age (Cohort 5) |
|---|---|
| All-cause Mortality at the Test of Cure (TOC) Visit Among Cohort 5 Participants | 0 |
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.
| µg/mL | Birth to < 3 Months of Age (Cohort 5) | 3 Months to < 2 Years Old (Cohort 4) | 2 Years to < 6 Years Old (Cohort 3) | Participants Aged 6 Years to < 12 Years Old | 12 Years to 17 Years Old (Cohort 1) |
|---|---|---|---|---|---|
| 30 min (end of infusion) | 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 | 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 | 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 | 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 | 4.94 ± 47.91 | 15.24 ± 47.97 | 12.74 ± 45.62 | 15.35 ± 39.40 | 20.75 ± 37.71 |
Collected over 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 the Dalbavancin Single-dose and Dalbavancin Two-dose groups and 54.5 days for the Comparator group.. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dalbavancin Single-dose | 0/91 (0%) | 3/91 (3.3%) | 1/91 (1.1%) |
| Dalbavancin Two-dose | 0/78 (0%) | 0/78 (0%) | 5/78 (6.4%) |
| Comparator | 0/30 (0%) | 0/30 (0%) | 1/30 (3.3%) |
| Event | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| ABSCESS BACTERIALInfections and infestations | 1/91 | 0/78 | 0/30 |
| OSTEOMYELITIS BACTERIALInfections and infestations | 1/91 | 0/78 | 0/30 |
| FEBRILE CONVULSIONNervous system disorders | 1/91 | 0/78 | 0/30 |
| Event | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator |
|---|---|---|---|
| NASOPHARYNGITISInfections and infestations | 1/91 | 0/78 | 1/30 |
| ANAEMIA POSTOPERATIVEInjury, poisoning and procedural complications | 0/91 | 1/78 | 1/30 |
| VOMITINGGastrointestinal disorders | 0/91 | 2/78 | 0/30 |
| PYREXIAGeneral disorders | 0/91 | 2/78 | 0/30 |
| COUGHRespiratory, thoracic and mediastinal disorders | 0/91 | 2/78 | 0/30 |
Safety population: all participants in the ITT population who received at least 1 dose of study drug
| Age, Continuous(years) | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator | Total |
|---|---|---|---|---|
| Mean | 7.591 ± 5.4767 | 8.898 ± 4.9271 | 6.775 ± 4.2048 | 7.980 ± 5.1270 |
| Age, Customized(Participants) | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator | Total |
|---|---|---|---|---|
| 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 |
| Sex: Female, Male(Participants) | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator | Total |
|---|---|---|---|---|
| Female | 38 | 25 | 12 | 75 |
| Male | 53 | 53 | 18 | 124 |
| Ethnicity (NIH/OMB)(Participants) | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator | Total |
|---|---|---|---|---|
| Hispanic or Latino | 6 | 7 | 1 | 14 |
| Not Hispanic or Latino | 85 | 71 | 29 | 185 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Dalbavancin Single-dose | Dalbavancin Two-dose | Comparator | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 5 | 1 | 1 | 7 |
| Asian | 1 | 1 | 0 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 4 | 6 | 0 | 10 |
| White | 78 | 69 | 29 | 176 |
| More than one race | 3 | 1 | 0 | 4 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
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