Clinical Trials Register

Summary
EudraCT Number:	2007-004018-15
Sponsor's Protocol Code Number:	V710-003
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2007-11-19
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

Sweden - MPA

A.2

EudraCT number

2007-004018-15

A.3

Full title of the trial

A Randomized, Multicenter, Double-Blind, Group-Sequential Study to Evaluate the Efficacy, Immunogenicity, and Safety of a Single Dose of Merck 0657nI Staphylococcus aureus Vaccine (V710) in Adult Patients Scheduled for Cardiothoracic Surgery.

A.3.1

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

A Study to Evaluate Staphylococcus aureus Vaccine (V710) in Adult Patients Scheduled for Cardiothoracic Surgery.

A.3.2

Name or abbreviated title of the trial where available

V710 Cardiothoracic Surgery Efficacy, Immunogenicity, and Safety Study

A.4.1

Sponsor's protocol code number

V710-003

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	Merck Sharp & Dohme (Sweden) AB
B.1.3.4	Country	Sweden
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	Merck & Co., Inc.
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	Merck Sharp & Dohme (Sweden) AB
B.5.2	Functional name of contact point	Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Box 7125
B.5.3.2	Town/ city	Sollentuna
B.5.3.3	Post code	192 07
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+468578 135 00
B.5.5	Fax number	+468754 15 00
B.5.6	E-mail	lotta.jonsson@merck.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	Staphylococcus aureus Recombinant Surface Protein
D.3.2	Product code	V710
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	V710
D.3.9.3	Other descriptive name	staph aureus vaccine
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
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	Injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Staphylococcus aureus bacteremia
Staphylococcus aureus mediastinitis

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	10058887
E.1.2	Term	Staphylococcus aureus bacteremia
E.1.2	System Organ Class	10021881 - Infections and infestations

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	10066413
E.1.2	Term	Staphylococcus aureus mediastinitis
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

(1) Primary Efficacy Objective: To demonstrate that a single dose of V710 administered prior to cardiothoracic surgery will reduce the proportion of adult patients who acquire S. aureus bacteremia and/or S. aureus deep sternal wound infections through postoperative Day 90. For this study, a
S. aureus deep sternal wound infection includes S. aureus mediastinitis or a S. aureus deep incisional surgical-site infection involving the sternal wound.
(2) Primary Safety Objective: To evaluate the safety profile of a single dose of V710 administered to adult patients prior to cardiothoracic surgery.

E.2.2

Secondary objectives of the trial

(1) Secondary Efficacy Objective: To demonstrate that a single dose of V710 administered prior to cardiothoracic surgery will reduce the proportion of adult patients who acquire any invasive S. aureus infection through postoperative Day 90.
(2) Secondary Efficacy Objective: To demonstrate that a single dose of V710 administered prior to cardiothoracic surgery will reduce the proportion of adult patients who acquire any S. aureus surgical-site infection through postoperative Day 90.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is 18 years of age or greater.
2. Patient is scheduled to undergo cardiothoracic surgery involving a full median sternotomy (not including cardiac transplantation surgery) within 14 to 60 days postvaccination.
3. Female patients of reproductive potential are required to have a negative urine or serum pregnancy test immediately prior to study vaccination. Female patients of reproductive potential must have been using an acceptable form of birth control for two weeks prior to enrollment, and agree to use an acceptable method of birth control for one month postvaccination. Acceptable methods of birth control include use of hormonal contraceptives, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, tubal ligation, condoms, or abstinence.

E.4

Principal exclusion criteria

1. Patient developed an invasive S. aureus infection (e.g., bacteremia, endocarditis, pneumonia, mediastinitis, osteomyelitis, etc.) in the three months prior to study entry.
2. Patient’s underlying condition is sufficiently unstable so that there is a realistic (>50%) possibility that cardiothoracic surgery will be necessary within the 10 days following study entry/vaccination.
3. Patient is planning to undergo cardiac transplantation surgery or sternal debridement to remedy an infection resulting from a prior cardiothoracic surgery.
4. Patient has received any other investigational S. aureus vaccine or any investigational S. aureus antibodies within the 12 months prior to study entry.
5. Patient has a temperature of ≥100.4ºF (≥38.0ºC), oral equivalent, within 48 hours prior to study vaccination.
6. Patient was administered any immunoglobulin within 90 days prior to study vaccination or is scheduled to receive such products at any time through postoperative Day 90.
7. Patient has a known or suspected impairment of immunologic function including, but not limited to, the following conditions: autoimmune disease, moderate/severe hepatic insufficiency or cirrhosis, renal failure or insufficiency (on hemodialysis or peritoneal dialysis), immunoglobulin deficiency, or other congenital or acquired immunodeficiency, including HIV/AIDS.
8. Patient is currently pregnant or breastfeeding, or planning to conceive at any time throughout the duration of the study (through postoperative Day 90).
9. Patient has a medical condition in which the expected survival is less than 90 days.

E.5 End points

E.5.1

Primary end point(s)

(1) The primary efficacy endpoint is the proportion of patients with evidence of S. aureus bacteremia and/or S. aureus deep sternal wound infections at any time through postoperative Day 90. These primary endpoints will be defined as follows:
S. aureus Bacteremia: A case of S. aureus bacteremia will be defined as ≥1 positive blood culture for S. aureus (regardless of the presence of clinical symptoms).
S. aureus Deep Sternal Wound Infection: For this study, a S. aureus deep sternal wound infection includes S. aureus mediastinitis or a S. aureus deep incisional surgical-site infection involving the sternal wound. Each is defined separately below:
A case of S. aureus mediastinitis will be defined as any infection that meets one of the following two criteria:
 A positive S. aureus culture from mediastinal tissue or fluid obtained during a surgical operation or needle aspiration; or
 Patient meets the following 2 criteria:
1. Purulent discharge from the mediastinal area (i.e., from mediastinal fluid or tissue and not only from more anterior sites [including skin, subcutaneous tissue, fascial layer, or muscle layer]) positive on culture for S. aureus, and
2. At least one of the following signs or symptoms with no other recognized cause:
- Fever (>38ºC [or >100.4ºF]),
- Chest pain,
- Sternal instability, or
- Radiographic evidence on either chest X-ray/CT of mediastinal widening.
A case of S. aureus deep incisional surgical-site infection of the sternal wound will be defined as any infection that meets the following 2 criteria:
 S. aureus organisms isolated from an aseptically obtained culture of deep soft tissue (involving the fascial or muscle layers) but not from mediastinal tissue or fluid, and
 The patient has at least one of the following:
1. Purulent drainage from the deep incision (from fascial or muscle layers, but not from mediastinal space);
2. The sternal wound spontaneously dehisces or is deliberately opened by the surgeon;
3. The patient has at least one of the following signs or symptoms: fever (>38° C or >100.4ºF), chest pain, or chest tenderness; or
An abscess or other evidence of infection involving the fascial or muscle layers is found on direct examination, during reoperation, or by histopathologic or radiologic examination (a stitch abscess, which is defined as minimal inflammation and discharge confined to the point of suture penetration, or other abscesses anterior to the fascial layers do not qualify).
(2) The primary safety endpoint will be based on the proportion of vaccine-related serious adverse experiences observed throughout the course of the study (through postoperative Day 90) in each vaccination group.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

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

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

Yes

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

The end of the trial is based on the accruement of 76 cases of the primary efficacy endpoint (S. aureus bacteremia and/or S. aureus deep sternal wound infections [DSWI]), or upon demonstration of vaccine futility or early efficacy success at any of the three prespecified interim analyses, as described in the protocol.

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	No
F.1.1.1	In Utero	Information not present in EudraCT
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	Information not present in EudraCT
F.1.1.3	Newborns (0-27 days)	Information not present in EudraCT
F.1.1.4	Infants and toddlers (28 days-23 months)	Information not present in EudraCT
F.1.1.5	Children (2-11years)	Information not present in EudraCT
F.1.1.6	Adolescents (12-17 years)	Information not present in EudraCT
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	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	Yes
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	Yes
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	110
F.4.2	For a multinational trial
F.4.2.1	In the EEA	1420
F.4.2.2	In the whole clinical trial	15000

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

2008-01-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-12-19

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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