Clinical Trials Register

Summary
EudraCT Number:	2019-000836-24
Sponsor's Protocol Code Number:	IIV-406
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-04-30
Trial 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

Netherlands - Competent Authority

A.2

EudraCT number

2019-000836-24

A.3

Full title of the trial

Immune responses to influenza and pneumococcal conjugate vaccines in older adults compared to middle-aged adults and adults.

A.3.1

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

Immune responses to influenza and pneumococcal conjugate vaccines in older adults compared to middle-aged adults and adults.

Afweerreacties tegen influenza en pneumokokken vaccin vergeleken tussen 3 leeftijdsgroepen

A.3.2

Name or abbreviated title of the trial where available

VITAL

A.4.1

Sponsor's protocol code number

IIV-406

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	National Institute of Health and the Environment
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Innovative Medicines Initiative
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	National Institute of Health and the Environment (RIVM)
B.5.2	Functional name of contact point	VITAL studyteam
B.5.3	Address:
B.5.3.1	Street Address	Antonie van Leeuwenhoeklaan 9
B.5.3.2	Town/ city	Bilthoven
B.5.3.3	Post code	3720 MA
B.5.3.4	Country	Netherlands
B.5.6	E-mail	VITAL@rivm.nl

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	Prevenar-13
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
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.3.2	Product code	EU/1/09/590
D.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
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.IMP: 2
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.2.5	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.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
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

Healthy volunteers above 25 years of age

E.1.1.1

Medical condition in easily understood language

Healthy volunteers above 25 years of age

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

•Compare serotype-specific IgG antibody response to pneumococcal PCV13 vaccination in older adults with the response in middle-aged adults and adults one month after vaccination.
•Compare influenza vaccine strain-specific serum antibody titers in older adults with the response in middle-aged adults and adults one month after influenza vaccination.

E.2.2

Secondary objectives of the trial

3.Compare levels of QIV and PCV13 vaccin induced antibody responses and persistence over time in older adults.
4.Compare PCV13 carrier protein-specific serum antibody titers pre- and post-PCV13 vaccination in older adults with the response in middle-aged adults and adults.
5.Compare influenza vaccine–specific and PCV13 carrier protein-specific T-cell responses pre- and post-vaccination in older adults with those observed in middle- aged adults and adults.
6.Determine the impact of clinical baseline status and changes in baseline status, as a predictive marker for vaccine response and compare them between older adults, middle-aged adults and adults.
7.Determine the impact of (immunological) biomarkers status at baseline as a predictive marker for vaccine response for each subject and compare results for older adults to middle-aged adults and adults.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Be 25 years or older at the time of inclusion.
•Have received a seasonal influenza vaccination in previous season (2018-2019).
•Be capacitated.
•Have signed Informed Consent

E.4

Principal exclusion criteria

•Having had a previous pneumococcal vaccination (PCV or the 23-valent pneumococcal polysaccharide vaccine (PPV23)).
•Known or suspected allergy to any of the vaccine components or having experienced a previous severe adverse reaction to any vaccine.
•Receipt of any high-dose (≥ 20 mg of prednisone daily or equivalent) daily corticosteroids (local incl. inhaled steroids are acceptable) within 2 weeks of study entry.
•Receipt of an organ- or bone marrow transplant
•Have a (functional) asplenie.
•Receipt of chemotherapy in the last 3 years.
•Receipt of blood products or immunoglobulin, within three months of study entry.
•Known or suspected coagulation disorder that in the opinion of the investigator would contraindicate against receiving an intramuscular injection or undergo frequent blood sampling.
•Known pregnancy.
•Known to be positive for human immunodeficiency virus (HIV), and/or hepatitis C virus (HCV) and/or hepatitis B virus (HBV).

E.5 End points

E.5.1

Primary end point(s)

1.Pneumococcal serotype- specific serum IgG antibody concentrations (GMCs) pre-vaccination (T5) and one-month post (T8) PCV13 vaccination measured by bead-based multiplex immune assay.
•Influenza vaccine strain-specific serum antibody titers (GMTs) will be measured pre- vaccination (T0) and one-month post-influenza vaccination (T4) by Hemagglutinin Inhibition (HI) assay.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. 6 months and 7 months after start study
2. 1 month and 2 months after start of the study

E.5.2

Secondary end point(s)

1.Influenza strain-specific and pneumococcal serotype-specific antibody titers in serum pre- and post-vaccination: ((T1, T5, T3, T7, T4, T8, T5, T9, T10).
2.CRM197-specific serum antibody titers before (T5) and at 7 days (T7), 1 (T8), 6 (T9) and 12 (T10) months post pneumococcal vaccination
3. Influenza-specific and CRM197-specific T-cells measured by Enzyme-Linked Immunosorbent Spot (ELISPOT) in peripheral blood mononuclear cells (PBMCs) of pre- (T0; T5) and post-vaccination samples (T3, T4, T7, T8).
4. A- health status assessment will be done by questionnaires, which include demographics, the short-form (SF) 36 health assessment of quality of life that covers 8 different sections (vitality, physical functioning, pain, general health perception, physical role functioning, emotional role functioning, social role functioning and mental health), a EQ-5D QoL-assessment, socio-economic status (SES), chronic diseases and medication use (including other vaccines), level of exercise, body mass index (BMI) and life style characteristics. In addition, grip strength and blood pressure will be measured by standardized protocols.
Questionnaires and measurements will be done at 3 time points during the study at T0, T5 and T9.
A deficit accumulation index will be calculated for each subject and the subjects will be ranked based on this index.
5. Measure absolute numbers of immune cell types, a.o. lymphocytes, granulocytes and monocytes, in whole blood by Trucount (T0, T5).
Measure cell frequency, phenotype and functional capacity of immune cells by Fluorescence-Activated Cell Sorting (FACS).
Measure priming efficacy of T-cells specific for influenza or model antigens.
Measure systemic and local immune and inflammatory profiles by systems immunology, serology and molecular methods in serum, saliva and swabs. (T0, T5, T9).
Determine biomarkers, such as creatinine and cystatin C in plasma.
Determine both broad and targeted transcriptome profile at baseline (T0, T5).

E.5.2.1

Timepoint(s) of evaluation of this end point

1. month 1, 2, 6, 7, 12 and 18 after start study
2. month 6, 7, 12, 18 after start study
3. month 0, 2, 6, 7 after start study
4. month 0, 6 and 12 after start study
5. month 0, 6 and 12 after start study

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

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

immune responses after influenza and pneumococcal vaccination

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

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

Yes

E.8.1.7.1

Other trial design description

Longitudinal

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

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

LSLV

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

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:

220

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

165

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

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 2019-04-30.

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

Yes

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

385

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)

none

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

2019-04-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-19

P. End of Trial
P.	End of Trial Status	Ongoing

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