Clinical Trials Register

Summary
EudraCT Number:	2014-000419-15
Sponsor's Protocol Code Number:	DUR001-303
National Competent Authority:	Latvia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-07-04
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Latvia - SAM

A.2

EudraCT number

2014-000419-15

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

DUR001-303

A.5.4

Other Identifiers

Name:

IND Number

Number:

60,613

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Durata Therapeutics International B.V.
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Durata Therapeutics International B.V.
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Durata Therapeutics International B.V.
B.5.2	Functional name of contact point	Executive Director Clinical and Med
B.5.3	Address:
B.5.3.1	Street Address	322 E. Main St. 3rd Floor
B.5.3.2	Town/ city	Branford CT
B.5.3.3	Post code	06405
B.5.3.4	Country	United States
B.5.4	Telephone number	+1203-871-4613
B.5.5	Fax number	+1203-315-0115
B.5.6	E-mail	jbaldassarre@duratatx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Dalvance
D.2.1.1.2	Name of the Marketing Authorisation holder	Durata Therapeutics International B.V.
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dalbavancin
D.3.2	Product code	DUR001
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DALBAVANCIN
D.3.9.1	CAS number	171500-79-1
D.3.9.2	Current sponsor code	DUR001
D.3.9.4	EV Substance Code	SUB26697
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Acute Bacterial Skin and Skin Structure Infections

E.1.1.1

Medical condition in easily understood language

Acute Bacterial Skin and Skin Structure Infections

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	PT
E.1.2	Classification code	10052891
E.1.2	Term	Skin bacterial infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacokinetic sub-study 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.The PK substudy will be conducted at selected sites on a voluntary basis. It has been determined that up to 125 subjects will have pharmacokinetic samples drawn in this study.Patients enrolled in the treatment portion of the study may elect not to participate in the PK substudy.

E.3

Principal 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.

E.4

Principal 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 study drug for the condition under study.
17. Anticipated need of antibiotic therapy for longer than 14 days.
18. Patients who are placed in a hyperbaric chamber as adjunctive therapy for the abSSSI.
19. More than 2 surgical interventions (defined as procedures conducted under sterile technique and typically unable to be performed at the bedside) for the abSSSI, or patients who are expected to require more than 2 such interventions.
20. Medical conditions in which chronic inflammation may preclude assessment of clinical response to therapy even after successful treatment (e.g., chronic stasis dermatitis of the lower extremity).
21. Absolute neutrophil count < 500 cells/mm3.
22. Known or suspected human immunodeficiency virus (HIV) infected patients with a CD4 cell count < 200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count.
23. Patients with a recent bone marrow transplant (in post-transplant hospital stay).
24. Patients receiving oral steroids > 20 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation.
25. Patients with a rapidly fatal illness, who are not expected to survive for 3 months.
26. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

48-72 hours after the initiation of therapy with study medication

E.5.2

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).

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 28 (+/- 2 days).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Two dose regimen of dalbavancin (1000 mg on Day 1 followed by 500 mg on Day 8)

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Bulgaria

Croatia

Estonia

Georgia

Hungary

Latvia

Romania

Russian Federation

Serbia

South Africa

Ukraine

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LSLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

600

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

218

F.4.2.2

In the whole clinical trial

698

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Standard of care

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-07-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-04-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-03-11

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