Study to Compare the Efficacy and Safety of Single Dose Dalbavancin to a Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections

• Register: EUCTR
• Last refreshed on: 6 October 2015
• Main ID: EUCTR2014-000419-15-HR
• Date of registration: 02/12/2014
• Prospective Registration: No
• Primary sponsor: Durata Therapeutics International B.V.
• Public title: Study to Compare the Efficacy and Safety of Single Dose Dalbavancin to a Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections
• Scientific title: A Phase 3b, Double-Blind, Multicenter, Randomized Study to Compare the Efficacy and Safety of Single Dose Dalbavancin to a Two Dose Regimen of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections
• Date of first enrolment: 31/10/2014
• Target sample size: 410
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000419-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) Number of treatment arms in the trial: 2

Countries of recruitment

Bulgaria, Croatia, Estonia, Georgia, Hungary, Latvia, Lithuania, Romania, Russian Federation, Serbia, Ukraine, United States

Contacts

• Name: Executive Director Clinical and Med
• Affiliation: Durata Therapeutics International B.V.

• Name: Executive Director Clinical and Med
• Affiliation: Durata Therapeutics International B.V.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients, 18-85 years of age.
2. A personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
3. Patients having an abSSSI (suspected or confirmed to be caused by Gram-positive bacteria) defined for purposes of this study as an infection either involving deeper soft tissue or requiring significant surgical intervention:
(a) 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 75 cm2 of erythema, and
iii. is defined by a margin of erythema that is = 5 cm from the rim of induration or edema that defines the border of the abscess in all directions, or,
iv. alternatively, involves the central face and is associated with an area of erythema of at least 50 cm2 and a margin = 3 cm in all directions from the abscess rim
(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 75 cm2 of erythema, and
ii. is defined by a margin of erythema in at least one direction that is = 5 cm from the edge of the wound, or
iii. alternatively, involves the central face and is associated with an affected area of at least 50 cm2 and has a margin of erythema in at least one direction = 3 cm from the wound edge
(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 75 cm2 of surface area, or
ii. alternatively, cellulitis of the central face that is associated with an affected area of at least 50 cm2
4. 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
5. Patients must present with at least ONE of the following systemic signs of infection:
(a) An elevated body temperature ? 38?C/100.4?F as measured by the patient/caregiver or investigator within 24 hours of baseline;
(b) White blood cell count > 12,000 cells/mm3;
(c) A manually performed white blood differential count with = 10% band forms, regardless of peripheral white blood cell count.
6. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 336
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 74

Exclusion criteria:
1. Patients with a contra-indication to the administration of dalbavancin (see Section 5.4.1) such as hypersensitivity to any of the glycopeptide agents.
2. Females of child-bearing potential who are unable to take adequate contraceptive precautions, have a positive pregnancy result within 24 hours prior to study entry, are known to be pregnant, or are currently breastfeeding an infant.
3. Patients with sustained shock defined as systolic blood pressure < 90 mm Hg for more than 2 hours despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents to maintain blood pressure.
4. Participation in another study of an investigational drug or device within 30 days prior to enrollment.
5. Receipt of a systemically or topically administered antibiotic with a Gram-positive spectrum that achieves therapeutic concentrations in the serum or at the site of the abSSSI within 14 days prior to randomization. An exception is allowed for patients receiving a single dose of a short-acting (half-life = 12 hours) antibacterial drug prior to randomization; up to 25% of subjects may have received such therapy.
6. Infection due to an organism known prior to study entry to be resistant to dalbavancin or vancomycin (vancomycin MIC > 8 ?g/mL).
7. Patients with evidence of meningitis, necrotizing fasciitis, gas gangrene, gangrene, septic arthritis, osteomyelitis; endovascular infection, such as clinical and/or echocardiographic evidence of endocarditis or septic thrombophlebitis.
8. Infections caused exclusively by Gram-negative bacteria (without Gram-positive bacteria present) and infections caused by fungi, whether alone or in combination with a bacterial pathogen.
9. Venous catheter entry site infection.
10. Infections involving a diabetic foot ulceration, perirectal abscess or a decubitus ulcer.
11. Patient with an infected device, even if the device is removed. Examples include infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack, joint prosthesis, hemodialysis catheter, implantable pacemaker or defibrillator, intra-aortic balloon pump, left ventricular assist device, a peritoneal dialysis catheter, or a neurosurgical device such as a ventricular peritoneal shunt, intra-cranial pressure monitor, or epidural catheter.
12. Gram-negative bacteremia, even in the presence of Gram-positive infection or Gram-positive bacteremia. Note: If a Gram-negative bacteremia develops during the study, or is subsequently found to have been present at Baseline, the patient should be removed from study treatment and receive appropriate antibiotic(s) to treat the Gram-negative bacteremia. Such patients must have an EOT visit performed within 3 calendar days after discontinuing study medication and are required to have AEs reported through Final Visit.
13. Patients whose abSSSI is the result of having sustained full or partial thickness burns.14. Patients with an infection involving a limb with evidence of critical ischemia of an affected limb defined as any of the following criteria: absent or abnormal Doppler wave forms, toe blood pressure of < 45 mm Hg, ankle brachial index < 0.5, and/ or critical ischemia as assessed by a vascular surgeon.
15. Patients with abSSSI such as superficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only requires surgical drainage for cure.
16. Concomitant condition requiring any antibiotic therapy that would interfere with the assessment of

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acute Bacterial Skin and Skin Structure Infections
MedDRA version: 17.1 Level: PT Classification code 10052891 Term: Skin bacterial infection System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Product Name: Dalbavancin
Product Code: DUR001
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: DALBAVANCIN
CAS Number: 171500-79-1
Current Sponsor code: DUR001
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 48-72 hours after the initiation of therapy with study medication

Secondary Objective: To compare the efficacy outcomes at relevant time points as well as the safety profile of treatment with a single dose of dalbavancin 1500 mg versus the safety profile of treatment with a two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in patients with known or suspected Gram-positive abSSSI.
To compare the population PK profiles of a single dose of dalbavancin 1500 mg versus the two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in patients with acute bacterial skin and skin structure infections and to estimate and compare the PK/PD relationship of each dose regimen.

Main Objective: To compare the efficacy of treatment with a single dose of dalbavancin 1500 mg to treatment with a two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8) in patients with known or suspected Gram-positive abSSSI at 48 -72 hours after initiation of treatment.

Primary end point(s): The primary efficacy assessment will be the clinical status (success or failure) in the ITT population at 48-72 hours after initiation of therapy; The primary outcome measure for efficacy evaluation will be the percentage of patients in each treatment group who demonstrate a clinical response at 48-72 hours after the initiation of therapy with study medication, with clinical response defined as follows:
• The patient is alive;
• The patient has received no rescue therapy for abSSSI; and
• Examination of the patient’s abSSSI lesion demonstrates a decrease of =20% in lesion area (calculated as the longest length multiplied by the longest perpendicular width) relative to the baseline measurement.
For the primary efficacy evaluation, these percentages will be compared using an Intention to Treat (ITT) population comprised of all randomized subjects.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Day 28 (+/- 2 days).

Secondary end point(s): The secondary outcome measure for efficacy evaluation (Clinical Status - ) will be the percentage of patients in each treatment group who demonstrate clinical success at Day 28 (+/- 2 days).

Secondary ID(s)

DUR001-303

2014-000419-15-LV

60,613

Source(s) of Monetary Support

Durata Therapeutics International B.V.