| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| acute bacterial skin and skin structure infections (abSSSI) |
|
| E.1.1.1 | Medical condition in easily understood language |
Acute infections of the skin and nearby soft tissue known or believed to
be caused by a type of Gram positive bacteria. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10004035 |
| E.1.2 | Term | Bacterial infection due to staphylococcus aureus |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the early clinical
efficacy (after 48-72 hours of therapy) of dalbavancin to the comparator
regimen [vancomycin with the option to switch to oral linezolid
(vancomycin/linezolid)] for the treatment of patients with a suspected
or proven Gram-positive abSSSI. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
- To compare the clinical efficacy at end of treatment (EOT) of
dalbavancin to the comparator regimen.
- To compare the per-patient microbiological efficacy of dalbavancin to
the comparator regimen.
- To compare clinical efficacy by individual pathogens in the two
treatment groups.
- To compare pathogen eradication rates for individual pathogens in the
two treatment groups.
- To compare the safety and tolerability of dalbavancin to that of the
comparator regimen. |
|
| E.2.3 | Trial contains a sub-study | No |
| 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, 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 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 ≥ 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
• Purulent drainage/discharge
• Fluctuance
• Heat/localized warmth
• Tenderness to palpation
• 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. Infection severity such that a minimum of 3 days of IV therapy is appropriate for management of the abSSSI.
7. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Patient must meet all of the inclusion criteria listed above to be eligible for enrollment into the study. |
|
| E.4 | Principal exclusion criteria |
Patients presenting with any of the following will be excluded from the
study:
1.A contra-indication to the administration of dalbavancin, vancomycin,
or linezolid, such as hypersensitivity to any of the 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.Sustained shock, defined as systolic blood pressure <90 mm Hg for
more than 2 hr 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 before this study begins.
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
(Exception: patients receiving a single dose of a short-acting (half-life ≤
12 hr) antibacterial drug 3 or more days prior to randomization (e.g.,
administration of a single dose of an antibacterial drug for surgical
prophylaxis).
6.Infection due to an organism known prior to study entry to be
resistant to dalbavancin or vancomycin (vancomycin mean inhibitory
concentration (MIC) > 8 microgram/ml).
7.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 or a decubitus ulcer.
11.An infected device, even if the device is removed (eg, prosthetic
cardiac valve, vascular graft, a pacemaker battery pack, joint prosthesis,
hemodialysis catheter, implantable pacemaker or defibrillator, intraaortic
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.
13.Patient's abSSSI is the result of having sustained full or partial
thickness burns.
14.An infection involving a limb with evidence of critical ischemia of an
affected limb (ie, 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.Patient's abSSSI (ie, 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.Placement 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 (eg, chronic stasis dermatitis of the lower extremity).
21.Absolute neutrophil count <500 cells/mm3.
22.Human immunodeficiency virus (HIV) infected patients with a CD4
cell count <200 cells/mm3.
23.A recent bone marrow transplant (in post-transplant hospital stay).
24.Receiving oral steroids > 20 mg prednisolone per day (or equivalent)
or receiving immunosuppressant drugs after organ transplantation.
25.Receiving an antipyretic drug on a daily basis (eg, daily use of
naproxen) whose regimen cannot be modified during the first three daysof study drug therapy.
26.A rapidly fatal illness, who are not expected to survive for 3 months.
27.Other severe acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with study
participation or investigational product administration or may interfere
with the interpretation of study results and, in the judgment of the
investigator, would make the patient inappropriate for entry into this
study.
28. Prior participation in this study or in study DUR001-301. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary outcome measure is clinical response at 48-72 hours post
study drug initiation, as defined programmatically based on measurements of abSSSI lesion size and temperature |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| A secondary outcome is clinical status at the EOT Visit |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 68 |
| 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 | No |
| 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 |
| Czech Republic |
| Estonia |
| Hungary |
| Israel |
| Japan |
| Korea, Republic of |
| Latvia |
| Lithuania |
| Romania |
| Russian Federation |
| Slovakia |
| Taiwan |
| 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
|
| Please refer to protocol section 13 |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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