Clinical Trials Register

Summary
EudraCT Number:	2009-011466-29
Sponsor's Protocol Code Number:	CXA 101-03
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-10-12
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2009-011466-29

A.3

Full title of the trial

A Multicenter, Double-blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA 101 and Intravenous Ceftazidime in Complicated Urinary Tract Infectionb, Including Pyelonephritis

A.3.2

Name or abbreviated title of the trial where available

CXA-101-03

A.4.1

Sponsor's protocol code number

CXA 101-03

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

not available

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Calixa Therapeutics 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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	CXA-101
D.3.2	Product code	CXA-101
D.3.4	Pharmaceutical form	Powder for infusion*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	936111-69-2
D.3.9.2	Current sponsor code	CXA-101
D.3.9.3	Other descriptive name	FR264205
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	1000
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Fortum, 1g
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmitthkline Export Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Poland
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	Ceftazidime
D.3.4	Pharmaceutical form	Powder for infusion*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	CEFTAZIDIME
D.3.9.1	CAS number	72558-82-8
D.3.9.2	Current sponsor code	Ceftazidime
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	1000
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Complicated Urinary Tract Infection, including Pyelonephritis

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10037596
E.1.2	Term	Pyelonephritis

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10046571
E.1.2	Term	Urinary tract infection

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10054088
E.1.2	Term	Urinary tract infection bacterial

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10062279
E.1.2	Term	Urinary tract infection pseudomonal

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Determine the microbiological response at 6 to 9 days after treatment in subjects with complicated Urinary Tract Infection (cUTI) including pyelonephritis following a 7- to 10-day treatment regimen

E.2.2

Secondary objectives of the trial

-Evaluate the safety of CXA 101 in subjects with cUTI including pyelonephritis;
-Determine the clinical response at 6 to 9 days after treatment in subjects with cUTI including pyelonephritis following a 7- to 10-day treatment regimen;
- Evaluate the population plasma PK profile in subjects with cUTI.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects are each required to meet the following inclusion criteria:
1. Males and females 18 to 90 years of age, inclusive. Females of childbearing potential must have a documented negative serum pregnancy test and be using a highly effective method of birth control.

2. Pyuria (white blood cell [WBC] count > 10/µL in unspun urine or ≥ 10 per high power field in spun urine)

3. Clinical signs and/or symptoms of cUTI, either of:
a. Pyelonephritis, as indicated by both of the following:
i. Fever (oral temperature ≥ 37.8°C);
ii. Flank pain or costovertebral angle tenderness;
OR
b. Complicated lower UTI, as indicated by both of the following:
i. At least one of the following new or worsening symptoms:
• Dysuria;
• Frequency;
• Suprapubic pain;
• Urgency.
ii. At least one of the following complicating factors:
• Male gender;
• Current bladder instrumentation or indwelling urinary catheter that is expected to be removed during the course of IV study drug administration;
• Obstructive uropathy that is expected to be medically or surgically treated during the course of IV study drug administration;
• Urogenital surgery within 7 days preceding administration of the first dose of study drug;
• Functional or anatomical abnormality of the urogenital tract including anatomic malformations or neurogenic bladder with voiding disturbance of at least 100 mL residual urine.

4. Have a pretreatment baseline urine culture specimen obtained within two calendar days before the start of administration of the first dose of study drug
NOTE: Subjects may be enrolled in this study and start IV study drug therapy before the Investigator knows the results of the baseline urine culture.

5. Require IV antibacterial therapy for the treatment of the presumed cUTI

6. Provide written informed consent.

E.4

Principal exclusion criteria

Subjects must each NOT meet any of the following exclusion criteria:
1. Documented history of any hypersensitivity or allergic reaction to any β-lactam antibacterial

2. Concomitant infection requiring systemic antibacterial therapy in addition to IV study drug therapy at the time of randomization. Drugs with only gram-positive activity (e.g. vancomycin, linezolid) are allowed

3. Receipt of any amount of potentially therapeutic antibacterial therapy after collection of the pretreatment baseline urine culture and before administration of the first dose of study drug

4. Receipt of more than one dose of a potentially therapeutic antibacterial agent for the treatment of the current UTI within 96 hours before obtaining the study- qualifying pretreatment baseline urine NOTE: Subjects receiving UTI prophylaxis are eligible to enroll if all other eligibility criteria are met, including obtaining a study-qualifying pretreatment baseline urine culture (see Section 7.3)

5. Intractable infection anticipated to require more than 10 days of study drug therapy

6. Complete, permanent obstruction of the urinary tract

7. Confirmed (at time of randomization) fungal urinary tract infection (with ≥ 103 fungal CFU/mL)

8. Permanent indwelling bladder catheter or instrumentation including nephrostomy

9. Suspected or confirmed perinephric or intrarenal abscess

10. Suspected or confirmed prostatitis

11. Known ileal loop or vesico-ureteral reflux

12. Moderate or severe impairment of renal function including a estimated CrCl < 50 mL/min, requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/h urine output over 24 hours)

13. Current urinary catheter that will not be removed or anticipation of placement of an indwelling urinary catheter that will not be removed during the course of IV study drug administration. (Intermittent straight catheterization after the IV study drug administration period is acceptable)

14. Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the subject or the quality of study data

15. Any rapidly progressing disease or immediately life-threatening illness including acute hepatic failure, respiratory failure, and septic shock

16. Immunocompromising condition, including known infection with human immunodeficiency virus (HIV), AIDS, hematological malignancy, or bone marrow transplantation, or immunosuppressive therapy including cancer chemotherapy, medications for prevention of organ transplantation rejection, or the administration of corticosteroids equivalent to or greater than 40 mg of prednisone per day administered for more than 14 days preceding randomization

17. One or more of the following laboratory abnormalities in baseline specimens: AST, ALT, or alkaline phosphatase level greater than 3 times the upper limit of normal (ULN), total bilirubin greater than 2 times ULN, absolute neutrophil count less than 1000/μL, platelet count less than 50,000/μL, or hematocrit less than 25%

18. Clinically significant abnormality in baseline ECG

19. Participation within the last 30 days in any clinical study of an investigational product

20. Previous participation in any study of CXA 101\

21. Women who are pregnant or nursing

E.5 End points

E.5.1

Primary end point(s)

The primary outcome measure is the per-subject microbiological response at the Test of Cure (TOC) visit in the microbiologically evaluable (ME) and microbiological modified intent-to-treat (mMITT) populations.

The Intent-to-Treat (ITT) Population will consist of all randomized subjects

The Modified Intent-to-Treat Population (MITT) Population is the same as the ITT Population and consists of all randomized subjects who receive any amount of study drug.

The Microbiological Modified Intent-to-treat (mMITT) Population will be a subset of the MITT Population and include subjects who have at least one acceptable causative pathogen from a study-qualifying pretreatment baseline urine specimen or a blood culture.

The ME Population will be a subset of the mMITT Population and will include subjects who meet all the following conditions:
• Met the minimal disease criteria (defined by inclusion criterion 2);
• Had no protocol deviation likely to impact the microbiological outcome, including receiving a confounding non-study antibacterial agent. A confounding nonstudy antibacterial agent is one, with potential activity against the subject’s baseline uropathogen and that was given systemically at any time from the time of the study-qualifying baseline culture through the TOC visit.
• Received an appropriate duration of study drug therapy or was classified as an evaluable microbiologic failure after completing at least 3 days of study drug therapy;
• Had an interpretable urine culture at the TOC visit. Urine cultures that were repeated within 7 days of the TOC visit because of contamination of the original specimen are acceptable.
• Attended the TOC visit 6 to 9 days after EOT or subject was classified as a microbiological failure before the TOC visit

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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.8.3

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

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 visit of the last subject undergoing the trial

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.1.3

Elderly (>=65 years)

Yes

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

120

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)

Late follow-up vists 21-28 days after last administration of study drug
Adversse events are followed until resolved or stable

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

2009-11-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-11-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-03-11

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