Clinical Trials Register

Summary
EudraCT Number:	2013-001997-18
Sponsor's Protocol Code Number:	ACHN-490-007
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-12-20
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2013-001997-18

A.3

Full title of the trial

A Phase 3, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Plazomicin Compared with Colistin in Patients with Infection due to Carbapenem-Resistant Enterobacteriaceae (CRE)

A.3.1

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

A Study of Plazomicin Compared with Colistin when combined with a second antibiotic (either meropenem or tigcycline) in the treatment of Patients with blood stream Infection (BSI) or nosocomial pneumonia due to Carbapenem-Resistant Enterobacteriaceae (CRE). Therapeutic Drug Managment (TDM) will be used to ensure that Plazomicin exposures lie within an acceptable range of the target mean steady-state area the curve
(AUC).

A.4.1

Sponsor's protocol code number

ACHN-490-007

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01970371

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	Achaogen, Inc.
B.1.3.4	Country	United States
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	Achaogen, Inc.
B.4.2	Country	United States
B.4.1	Name of organisation providing support	US Department of Health and Human Services, Biomedical Advanced Research and Development Authority (BARDA)
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Achaogen, Inc.
B.5.2	Functional name of contact point	Clinical Trials Registration Group
B.5.3	Address:
B.5.3.1	Street Address	7000 Shoreline Court, Suite 371
B.5.3.2	Town/ city	South San Francisco, CA
B.5.3.3	Post code	94080
B.5.3.4	Country	United States
B.5.4	Telephone number	+1650800-3636
B.5.5	Fax number	+1650434-3765
B.5.6	E-mail	clinical-trials@achaogen.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	No
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	Plazomicin
D.3.2	Product code	ACHN-490
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	To be determined
D.3.9.1	CAS number	1380078-95-4
D.3.9.2	Current sponsor code	ACHN-490
D.3.9.3	Other descriptive name	NO ACTIVE SUBSTANCE
D.3.9.4	EV Substance Code	SUB49728
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Colistimethate for Injection
D.2.1.1.2	Name of the Marketing Authorisation holder	X-Gen Pharmaceuticals
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	Colistimethate sodium
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLISTIMETHATE SODIUM
D.3.9.1	CAS number	8068-28-8
D.3.9.4	EV Substance Code	SUB06801MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Bloodstream infections (BSI), hospital-acquired pneumonia (HABP) and
ventilator-associated bacterial pneumonia (VABP) due to carbapenemresistant
Enterobacteriaceae (CRE)

E.1.1.1

Medical condition in easily understood language

Infection due to Carbapenem Resistant Enterobacteriaceae (CRE)

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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10018657
E.1.2	Term	Gram-negative bacterial infection NOS
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to demonstrate the superiority of plazomicin (+ meropenem or tigecycline) compared with colistin (+ meropenem or tigecycline) in the treatment of BSI, HABP, or VABP due to CRE, with respect to the primary endpoint of all-cause mortality at Day 28 or significant disease-related complications .

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are:
- to compare additional efficacy outcomes and safety of a plazomicinbased regimen with a colistin-based regimen in the treatment of BSI, HABP or VABP due to CRE
- to evaluate the PK of intravenous (IV) plazomicin in patients with CRE infection.
- to evaluate the clinical utility of TDM for plazomicin dose adjustment

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Male and female patients age 18 to 85 years, inclusive
•APACHE II score between 15 and 30, inclusive
•Positive blood (for BSI) or lower respiratory tract (for HABP/VABP)
culture that was collected ≤96 hours prior to randomization meeting any of the following criteria;
a. Direct susceptibility testing or susceptibility testing on a purified
isolate suggesting a CRE (type 2 carbapenem [any one of: meropenem, imipenem or doripenem] MIC ≥ 4 μg/mL or a disc diffusion zone ≤ 19 mm)
b. Isolation of a carbapenemase-producing member of the
Enterobacteriaceae
c. Identification of a K. pneumoniae isolate from a qualifying culture in a patient from an intensive care unit or ward where ≥50% of clinical K. pneumoniae isolates are resistant to a type 2 carbapenem
d. Identification of an Enterobacteriaceae from a qualifying culture in a patient known to be colonized (urinary, respiratory or gastrointestinal tract) or infected by a CRE in the past 6 months
•Diagnosis of BSI, HABP, or VABP; all components defining the infection at baseline must have been present within 96 hours prior to randomization

E.4

Principal exclusion criteria

•Receipt of more than 72 hours of potentially effective antibacterial
therapy prior to randomization
– Antibiotic therapy with a narrow spectrum of activity against Grampositive or anaerobic organisms is not restricted (eg, daptomycin, linezolid, metronidazole, nafcillin [or equivalent], cloxacillin, clindamycin, telavancin, teicoplanin, vancomycin, dalbavancin, oritavancin and tedizolid).
– Potentially effective antibacterial therapy is defined as the use of any antibiotic for which in vitro susceptibility testing against the index CRE isolate indicates full or intermediate susceptibility according to CLSI breakpoints (M100-S25, Performance
Standards for Anti-microbial Susceptibility Testing, January 2015).
Where CLSI breakpoints are not available, EUCAST breakpoints may be used (Clinical Breakpoints version 5.0, January 2015).
– If the study-qualifying infection occurred while the patient was
receiving antibiotics as prophylaxis or for treatment of an unrelated
infection, the antibacterial therapy will be considered ineffective
irrespective of the susceptibility profile of the study qualifying pathogen.
•Polymicrobial infections involving two or more aerobic Gram-negative pathogens (ie, not colonizers or contaminants) in the study qualifying culture, with the following exceptions:
– Up to two Enterobacteriaceae are permitted
– Polymicrobial infections involving CRE and Gram-positive or anaerobic Gram negative pathogens are permitted, provided that the infection can be treated using antibiotics permitted in Section 5.3.2.2
•Knowledge that the index CRE pathogen is resistant to colistin (MIC > 2 μg/mL) prior to randomization (including Enterobacteriaceae genera with intrinsic resistance to colistin, eg Serratia, Proteus and Providencia)
•Patients with a requirement for prohibited concomitant therapy
•Objective clinical evidence for any of the following clinical syndromes that necessitates antimicrobial therapy for greater than 14 days:
endovascular infection including endocarditis, osteomyelitis, prosthetic joint infection, meningitis and/or other central nervous system infections
•Objective clinical evidence of infectious involvement of intravascular material not intended to be removed within 4 calendar days of initial positive culture
•Receipt of high level vasopressors, defined as >0.5 μg/kg/min
norepinephrine or equivalent for > 36 hours prior to randomization or need for ≥2 vasopressors to maintain MAP ≥ 65 mm Hg despite initial adequate fluid resuscitation (30 mL/kg crystalloid or 15 mL/kg of colloid within 6 hours of onset of hypotension) OR an initial serum or blood lactate level of ≥4 mmol/L that fails to decline >10%/h over the first 8 hours of resuscitation (where lactate results are available)
•Patients in acute renal failure or on intermittent hemodialysis (IHD) at the time of screening
•HABP/VABP patients only: Known bronchial obstruction or a history of post-obstructive pneumonia, tracheobronchitis in the absence of
concurrent pneumonia, primary lung cancer or malignancies metastatic to the lung, known or suspected active tuberculosis, and currently known or suspected fungal or viral pneumonia. Patients with chronic obstructive pulmonary disease (COPD) are eligible.

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is all-cause mortality at Day 28 or
significant disease-related complications

E.5.1.1

Timepoint(s) of evaluation of this end point

28 days

E.5.2

Secondary end point(s)

Secondary efficacy parameters include all-cause mortality at day 28;
time to death through day 28; all cause mortatlity at day 28 or
significant disease related complications at end of treatment and test of cure; overall incidence of adverse events; plazomicin PK parameters; and frequency with which the use of TDM leads to a dose adjustment of
plazomicin.

E.5.2.1

Timepoint(s) of evaluation of this end point

14 and 28 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

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

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

Argentina

Brazil

Colombia

France

Germany

Greece

Israel

Italy

Korea, Republic of

Mexico

Poland

Spain

Taiwan

Turkey

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

Last follow-up call for the last patient

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:

179

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

179

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2013-12-20.

Yes

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Critically ill in an intensive care unit with a subset sedated and/or on mechanical ventilation

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

200

F.4.2.2

In the whole clinical trial

358

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)

Both of the study treatments (trial drug, plazomicin and comparator, colistin) are intended for the short term treatment of bacterial infection. If the treatment fails, the investigators are expected to use an appropriate alternative standard of care treatment.

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

2014-04-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-02-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-09-15

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials