Clinical Trials Register

Summary
EudraCT Number:	2011-001333-17
Sponsor's Protocol Code Number:	V59_53
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-06-08
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

Germany - PEI

A.2

EudraCT number

2011-001333-17

A.3

Full title of the trial

A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Immunogenicity of Combined Hepatitis A/B Vaccine when Administered Concomitantly with Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Adults

A.3.1

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

Study to evaluate the immunogenicity and safety of Twinrix, Engerix-B and Havrix when administered with Menveo.

A.4.1

Sponsor's protocol code number

V59_53

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	Novartis Vaccines and Diagnostics S.r.l.
B.1.3.4	Country	Italy
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	Novartis Vaccines and Diagnostics S.r.l.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Vaccines and Diagnostics S.r.l.
B.5.2	Functional name of contact point	Regulatory Affairs Manager
B.5.3	Address:
B.5.3.1	Street Address	Via Fiorentina 1
B.5.3.2	Town/ city	Siena
B.5.3.3	Post code	53100
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390577245421
B.5.5	Fax number	+390577243048
B.5.6	E-mail	dario.de_angelis@novartis.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	Menveo
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Vaccines and Diagnostics S.r.l.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Novartis MenACWY Conjugate Vaccine
D.3.4	Pharmaceutical form	Powder and solution for solution for 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.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	MenA-CRM
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	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	MenC-CRM
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	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	MenW-CRM
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	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	MenY-CRM
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	5
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

To Evaluate the Safety and Immunogenicity of Combined Hepatitis A/B Vaccine when Administered Concomitantly with Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Adults

E.1.1.1

Medical condition in easily understood language

To Evaluate the Safety and Immunogenicity of Twinrix, Engerix-B and Havrix when administered concomitantly with Meningococcal ACWY Conjugate Vaccine in healthy adults

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10027202
E.1.2	Term	Meningitis bacterial
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

Immunogenicity Objectives:
Primary
To establish the non-inferiority of hepatitis A/B vaccine with MenACWY-CRM as compared to hepatitis A/B vaccine without MenACWY-CRM, measured by geometric mean titers (GMTs) on day 57 in previously unvaccinated subjects or on day 29 after a booster dose in previously primed subjects.
Safety Objectives
1. To describe the safety profile of combined hepatitis A/B virus vaccine given alone or concomitantly with MenACWY-CRM.
2. To describe the safety profile of MenACWY-CRM when given alone.
Safety will be assessed for all subjects in terms of the frequency and percentage of all spontaneously reported adverse events (AEs) and serious adverse events (SAEs).

E.2.2

Secondary objectives of the trial

Immunogenicity Objectives:
Secondary
1. To assess hepatitis A and B vaccine seroprotection rates on day 57, elicited by 3 doses of hepatitis A and/or B vaccine, or on day 29 after a booster dose in previously primed subjects, given with or without MenACWY-CRM.
2. To assess seroresponse rates elicited by MenACWY-CRM on Day 29 when administered concomitantly with combined hepatitis A/B vaccine or given alone.
3. To assess the immune response of MenACWY-CRM in terms of geometric mean titers (GMTs) on day 29 when administered concomitantly with combined hepatitis A/B vaccine or given alone.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria: Female and male subjects eligible to be enrolled in this study are:
• available for all study visits,
• able to give written informed consent,
• 18 years of age or older, and
• generally in good health.

Subjects with previous vaccination against hepatitis A and/or B, determined by history (interview of the subject) and/or by review of his or her vaccination card will be eligible to participate in the study if more than 5 years have elapsed since vaccination.

E.4

Principal exclusion criteria

Exclusion Criteria:
Individuals not eligible to be enrolled in the study are those:
1. who are breastfeeding;
2. who have a previous personal history of Neisseria meningitidis, hepatitis A or hepatitis B infection;
3. who received previous immunization with any meningococcal vaccine;
4. who received previous hepatitis A and/or B vaccination, determined by history (interview of the subject) and/or by review of his or her vaccination card, if less than 5 years have elapsed since vaccination;
5. who received investigational agents or vaccines within 30 days prior to enrollment or who expect to receive an investigational agent or vaccine prior to completion of the study;
6. who received live licensed vaccines within 30 days and inactive vaccine within 15 days prior to enrollment or for whom receipt of a licensed vaccine is anticipated during the study period.
(Exception: Influenza vaccine may be administered up to 15 days prior to each study immunization and no less than 15 days after each study immunization.)
7. who experienced, within the 7 days prior to enrollment, significant acute infection (for example requiring systemic antibiotic treatment or antiviral therapy) or have experienced fever (defined as body temperature ≥ 38°C) within 3 days prior to enrollment.
8. who have any serious acute, chronic or progressive disease such as
o history of cancer
o complicated diabetes mellitus
o advanced arteriosclerotic disease
o autoimmune disease
o HIV infection or AIDS
o blood dyscrasias
o congestive heart failure
o renal failure
o severe malnutrition
(Note: Subjects with mild asthma are eligible for enrollment. Subjects with moderate or severe asthma requiring routine use of inhaled or systemic corticosteroids are not eligible for enrollment.)
9. who have epilepsy, any progressive neurological disease or history of Guillain-Barre syndrome;
10. who have a history of anaphylaxis, serious vaccine reactions, or allergy to any vaccine component, including but not limited to latex allergy and antibiotic allergy;
11. who have a known or suspected impairment/alteration of immune function, either congenital or acquired or resulting from (for example):
o receipt of immunosuppressive therapy within 30 days prior to enrollment (systemic corticosteroids administered for more than 5 days, or in a daily dose > 1 mg/kg/day prednisone or equivalent during any of 30 days prior to enrollment, or cancer chemotherapy);
o receipt of immunostimulants;
o receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 90 days prior to enrollment and for the full length of the study;
12. who are known to have a bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;
13. who have any condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
14. who are part of the study personnel or close family members of those conducting this study.

E.5 End points

E.5.1

Primary end point(s)

Immunogenicity Endpoints
Primary Endpoints
• Post immunization geometric mean concentrations (GMCs) of anti-HAV antibodies 28 days after primary or booster immunization.
• Post immunization geometric mean concentrations (GMCs) of antiHBsAg antibodies 28 days after primary or booster immunization.

Safety Endpoints
Safety will be assessed for all subjects in terms of the frequency and percentage of spontaneously reported adverse events (AEs) and serious adverse events (SAEs). SAEs will be collected from the time the subject signs the informed consent until he or she stops study participation.

E.5.1.1

Timepoint(s) of evaluation of this end point

one month

E.5.2

Secondary end point(s)

Secondary Endpoints
• Percentage of subjects with anti-HAV antibody concentration ≥ 20 mIU/mL or 33 mIU/mL, depending on which immunoassay is used, 28 days after primary or booster immunization.
• Percentage of subjects with anti-HBsAg antibody concentration ≥ 10 mIU/mL, 28 days after primary or booster immunization.
• Geometric mean titers (GMTs) of antibodies to meningococcal serogroups A, C, W and Y on day 29.
• Seroresponse rates for meningococcal serogroups A, C, W and Y on day 29. For a subject with a baseline hSBA titer < 1:4, seroresponse is defined as a post-vaccination hSBA titer ≥ 1:8; for a subject with a baseline hSBA titer ≥ 1:4, seroresponse is defined as a post-vaccination hSBA titer of at least 4 times the baseline.

E.5.2.1

Timepoint(s) of evaluation of this end point

one month

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

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)

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

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

Hepatitis A, Hepatitis B or Hepatitisa/B

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

Please refer to 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

F.1.1

Number of subjects for this age range:

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:

252

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

252

F.4.2

For a multinational trial

F.4.2.1

In the EEA

252

F.4.2.2

In the whole clinical trial

252

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)

Not Applicable

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

2011-09-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-27

P. End of Trial
P.	End of Trial Status	Completed

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