Clinical Trials Register

Summary
EudraCT Number:	2019-001401-25
Sponsor's Protocol Code Number:	QHD00012
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-07-24
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

Finland - Fimea

A.2

EudraCT number

2019-001401-25

A.3

Full title of the trial

Relative Effectiveness of a High-Dose Quadrivalent Influenza Vaccine versus a Standard-Dose Quadrivalent Influenza Vaccine in Subjects 65 Years of Age and Older

A.3.1

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

Study to Evaluate the Effectiveness of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD) in Adults 65 Years of Age and Older

A.4.1

Sponsor's protocol code number

QHD00012

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1217-2654

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	Sanofi Pasteur 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	Sanofi Pasteur
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi Pasteur
B.5.2	Functional name of contact point	Stéphanie Pepin
B.5.3	Address:
B.5.3.1	Street Address	1541 avenue Marcel Mérieux
B.5.3.2	Town/ city	Marcy l'Etoile
B.5.3.3	Post code	69280
B.5.3.4	Country	France
B.5.4	Telephone number	+33437 37 5850
B.5.6	E-mail	Stephanie.Pepin@sanofi.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	Efluelda
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	quadrivalent influenza vaccine high dose
D.3.2	Product code	522
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLUENZA VACCINE (SPLIT VIRION, INACTIVATED)
D.3.9.3	Other descriptive name	A/H1N1-like strain
D.3.9.4	EV Substance Code	SUB12066MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	60
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLUENZA VACCINE (SPLIT VIRION, INACTIVATED)
D.3.9.3	Other descriptive name	A/H3N2 -like strain
D.3.9.4	EV Substance Code	SUB12066MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	60
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLUENZA VACCINE (SPLIT VIRION, INACTIVATED)
D.3.9.3	Other descriptive name	B/Victoria Lineage
D.3.9.4	EV Substance Code	SUB12066MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	60
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLUENZA VACCINE (SPLIT VIRION, INACTIVATED)
D.3.9.3	Other descriptive name	B/Yamagata Lineage
D.3.9.4	EV Substance Code	SUB12066MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
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.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	VaxigripTetra
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur Europe
D.2.1.2	Country which granted the Marketing Authorisation	Finland
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	VaxigripTetra
D.3.2	Product code	J07BB
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLUENZA VACCINE (SPLIT VIRION, INACTIVATED)
D.3.9.3	Other descriptive name	A/H1N1-like strain
D.3.9.4	EV Substance Code	SUB12066MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLUENZA VACCINE (SPLIT VIRION, INACTIVATED)
D.3.9.3	Other descriptive name	A/H3N2-like strain
D.3.9.4	EV Substance Code	SUB12066MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLUENZA VACCINE (SPLIT VIRION, INACTIVATED)
D.3.9.3	Other descriptive name	B/Victoria Lineage
D.3.9.4	EV Substance Code	SUB12066MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLUENZA VACCINE (SPLIT VIRION, INACTIVATED)
D.3.9.3	Other descriptive name	B/Yamagata Lineage
D.3.9.4	EV Substance Code	SUB12066MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	15
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

Prevention of influenza infection in adults from 65 years of age and older

E.1.1.1

Medical condition in easily understood language

Active immunisation of adults from 65 years of age and older against
influenza infection

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10022000
E.1.2	Term	Influenza
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

To demonstrate the superior relative effectiveness of QIV-HD as compared to QIV-SD among persons 65 years of age and older for the prevention of cardiovascular and/or respiratory hospitalizations

E.2.2

Secondary objectives of the trial

- To assess the clinical relative effectiveness of QIV-HD as compared to QIV-SD in prevention of:
inpatient hospitalization for selected circulatory and respiratory causes
death, either all-cause or cardiovascular or respiratory causes
inpatient hospitalization (using primary and secondary discharge diagnoses)
inpatient hospitalization (using admission diagnoses)
hospital emergency room visits
primary care visits to physician
or
- major acute cardiovascular events (MACE)
- To assess the characteristics of inpatient hospitalization or hospital emergency room visits or primary care visits to physician by QIV-HD and QIV-SD groups
- To describe the clinical relative effectivenes of QIV-HD as compared to QIV-SD:
- by age group and by group with specific comorbidities
- for different periods of observation
To describe all serious adverse events (SAEs) (including adverse event of special interest [AESIs]) for all subjects in both QIV-HD and QIV-SD groups

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Aged 65 years or older on the day of inclusion ("65 years" means from the day of the 65th birthday)

E.4

Principal exclusion criteria

- Participation at the time of study enrollment (or in the 4 weeks [28 days] preceding the study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
- Previous vaccination against influenza (in the preceding 6 months) with either the study vaccines or another vaccine
- Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances

E.5 End points

E.5.1

Primary end point(s)

1 - Number of unscheduled cardiovascular or respiratory inpatient hospitalizations
First occurrence of an unscheduled cardiovascular or respiratory inpatient hospitalization will be considered

2 - Number of inpatient hospitalizations with primary discharge diagnosis (for circulatory and respiratory systems diseases only)
Inpatient hospitalizations with primary discharge diagnosis (using International Classification of Diseases, Tenth Revision [ICD-10] codes) for the following diseases will be considered:
- Diseases of the circulatory system
- Diseases of the respiratory system

E.5.1.1

Timepoint(s) of evaluation of this end point

[1] , [2] : From 14 days after vaccination to 31 May of the year following
the vaccination

E.5.2

Secondary end point(s)

1 - Number of inpatient hospitalizations with primary discharge diagnosis
Inpatient hospitalization with primary discharge diagnosis (using ICD-10 codes) for the following diseases will be considered:

- Diseases of the respiratory system
- Diseases of the circulatory system
- Pneumonia
- Heart failure
- Acute myocardial infarction
- Atrial Fibrillation
- Stroke
- Influenza and pneumonia

2 - Number of deaths
Death all-cause and based on the diseases listed in first secondary endpoint will be considered

3 - Number of inpatient hospitalizations with primary and secondary admission and discharge diagnoses
Inpatient hospitalization with primary discharge and second admission discharge diagnosis based on the diseases listed in first secondary endpoint will be considered

4 - Number of hospital emergency room visits
Hospital emergency room visits based on the diseases listed in first secondary endpoint will be considered

5 - Number of acute primary care visits to physician
Acute primary care visits to physician based on the diseases listed in first secondary endpoint (using ICD-10 or corresponding International Classification of Primary Care 2nd edition [ICPC-2] codes) will be considered

6 - Number of major acute cardiovascular events (MACE)
First occurrence of the following MACE (using ICD-10 codes) will be considered:
- Ischemic heart diseases
- Non-fatal myocardial infarction
- Fatal or non-fatal stroke based
- Unstable angina

7 - Number of unscheduled cardiovascular or respiratory inpatient hospitalizations or hospital emergency room visits or primary care visits to physician
For all occurrences of selected outcomes the following characterization will be described:
- Onset of event
- Duration of event

8 - Number of participants reporting listed serious adverse events (SAEs)
Number of serious adverse reactions (SARs), adverse event of special interest (AESI)s, and all fatal cases occuring throughout the study will be considered

9 - Number of participants reporting non-fatal SAEs
Non-fatal SAEs occuring up to 6 months after vaccination will be considered

E.5.2.1

Timepoint(s) of evaluation of this end point

[1], [2], [3], [4], [5], [6], [7] : From 14 days after vaccination to 31 May of the year following the vaccination
[8] : From Day 0 (post-vaccination) up to 11 months (post-vaccination)
[9] : From Day 0 (post-vaccination) up to 6 months (post-vaccination)

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

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

Effectiveness

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

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

modified double blind

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

140

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

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

End of Year 3 data collection period (approximately 11 months after Year 3 vaccination).

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)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

121000

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

121000

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)

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

2019-09-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-07

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-04-01

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