Clinical Trials Register

Summary
EudraCT Number:	2018-003980-77
Sponsor's Protocol Code Number:	DEN-315
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-12-13
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

Expand All Collapse All

A. Protocol Information

A.2

EudraCT number

2018-003980-77

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Investigate the Immunogenicity and Safety of Subcutaneous Administration of a Tetravalent Dengue Vaccine Candidate in Healthy Adolescent Subjects in Non-Endemic Area(s) for Dengue

A.3.1

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

Trial to Investigate Immunogenicity and Safety of TDV in Healthy Children in Non-Endemic Area(s)

A.4.1

Sponsor's protocol code number

DEN-315

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03341637

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1192-7827

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/180/2017

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Takeda Vaccines, 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	Takeda Vaccines, 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	Takeda Vaccines, Inc.
B.5.2	Functional name of contact point	Shibadas Biswal
B.5.3	Address:
B.5.3.1	Street Address	40 Landsdowne Street
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	MA 02139
B.5.3.4	Country	United States
B.5.4	Telephone number	+6568089724

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	Tetravalent Dengue Vaccine Candidate (TDV)
D.3.2	Product code	TAK-003
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TDV CHIMERIC DENGUE VIRUS SEROTYPE 1
D.3.9.2	Current sponsor code	TDV-1
D.3.9.3	Other descriptive name	TDV CHIMERIC DENGUE VIRUS SEROTYPE 1 (TDV-1)
D.3.9.4	EV Substance Code	SUB188351
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/ml plaque forming unit(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	25178
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TDV DENGUE VIRUS SEROTYPE 2
D.3.9.2	Current sponsor code	TDV-2
D.3.9.3	Other descriptive name	TDV DENGUE VIRUS SEROTYPE 2 (TDV-2)
D.3.9.4	EV Substance Code	SUB188352
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/ml plaque forming unit(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	7962
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TDV CHIMERIC DENGUE VIRUS SEROTYPE 3
D.3.9.2	Current sponsor code	TDV-3
D.3.9.3	Other descriptive name	TDV CHIMERIC DENGUE VIRUS SEROTYPE 3 (TDV-3)
D.3.9.4	EV Substance Code	SUB188353
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/ml plaque forming unit(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	100236
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TDV CHIMERIC DENGUE VIRUS SEROTYPE 4
D.3.9.2	Current sponsor code	TDV-4
D.3.9.3	Other descriptive name	TDV CHIMERIC DENGUE VIRUS SEROTYPE 4 (TDV-4)
D.3.9.4	EV Substance Code	SUB188354
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/ml plaque forming unit(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	399052
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	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

The purpose of this study is to describe the neutralizing antibody response against each dengue serotype at 1 month post second dose of TDV or placebo in dengue-naive adolescent participants.

E.1.1.1

Medical condition in easily understood language

Dengue fever is caused by infection with dengue virus, a RNA virus that occurs as 4 recognized serotypes: DENV-1, -2, -3, or -4. These viruses are transmitted from human to human by mosquitoes.

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10012312
E.1.2	Term	Dengue fever virus infection
E.1.2	System Organ Class	100000004862

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 describe the neutralizing antibody response against each dengue serotype at 1 month post second dose of TDV or placebo in dengue-naive adolescent subjects.

E.2.2

Secondary objectives of the trial

Immunogenicity:
• To describe the persistence of the immune response at 6 months post second dose of TDV or placebo in dengue-naive adolescent subjects.
• To describe the seropositivity rates for all dengue serotypes at 1 month and 6 months post second dose of TDV or placebo in dengue-naive adolescent subjects, where seropositivity is defined as a reciprocal neutralizing titer ≥10.

Safety:
• To describe the safety profile following a first and second dose of TDV or placebo at Day 1
(Month 0 [M0]) and Day 90 (Month 3 [M3]), respectively.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The subject is aged 12 to 17 years, inclusive.
2. Individuals who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and the clinical judgment of the Investigator.
3. The subject/the subject’s legally authorized representative (LAR) signs and dates a written, informed consent/assent form and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements. Assent is obtained from the subject where required.
4. Individuals who can comply with trial procedures and are available for the duration of follow-up.

E.4

Principal exclusion criteria

1. Individuals with an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination (consider whether applicable as an exclusion criterion or criterion for delay, see Section 7.3).
2. Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccines or placebo).
3. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the subject’s ability to participate in the trial.
4. Individuals with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).
5. Individuals with history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose additional risk to the subject due to participation in the trial.
6. Known or suspected impairment/alteration of immune function, including:
a.Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (M0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
b.Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥ 2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (M0).
c. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
d.Receipt of immunostimulants within 60 days prior to Day 1 (M0).
e. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within
6 months prior to Day 1 (M0).
f. Human immunodeficiency virus (HIV) infection or HIV-related disease.
g.Genetic immunodeficiency.
7. Abnormalities of splenic or thymic function.
8. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
9. Individuals with any serious chronic or progressive disease according to judgment of the Investigator (eg, neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
10. Individuals with body mass index (BMI) greater than or equal to 35 kg/m2 (=weight in kg/[height in meters2]).
11. Individuals participating in any clinical trial with another investigational product 30 days prior to Day 1 (M0) or intent to participate in another clinical trial at any time during the conduct of this trial.
12. Individuals who received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of trial vaccine administration.
13. Individuals involved in the trial conduct or their first degree relatives.
14. Individuals with history of substance or alcohol abuse within the past 2 years.
15. Female subjects who are pregnant or breastfeeding.
16. Females of childbearing potential who are sexually active, and who have not used any of the acceptable contraceptive methods for at least 2 months prior to Day 1 (M0).
a. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy.
b. Acceptable birth control methods are defined as one or more of the following:
i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).
ii. Barrier method (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.
iii. Intrauterine device.
iv. Monogamous relationship with vasectomized partner (partner must have been vasectomized for at least 6 months prior to Day 1 [M0]).
Other contraceptive methods may be considered in agreement with the Sponsor and will be approved by the appropriate ethics committee.
17. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks after the last dose of trial vaccine (Day 90 [M3]). In addition, they must be advised not to donate ova during this period.
18. Any positive or indeterminate pregnancy test.
19. Previous and planned vaccination (during the trial conduct), against any flaviviruses including dengue, yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.
20. Previous participation in any clinical trial of a dengue or other flavivirus (eg, West Nile [WN] virus) candidate vaccine, except for subjects who received placebo in those trials.
21. Subjects with documented or suspected disease caused by a flavivirus such as dengue, Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.

E.5 End points

E.5.1

Primary end point(s)

Geometric mean titers (GMT) of neutralizing antibodies (microneutralization test 50% [MNT50]) for each of the 4 dengue serotypes at 1 month post second dose (Day 120 [Month 4 (M4)]).

E.5.1.1

Timepoint(s) of evaluation of this end point

Time Frame: 1 month post second dose (Day 120)

E.5.2

Secondary end point(s)

Immunogenicity:
• GMTs of neutralizing antibodies (MNT50) for each of the 4 dengue serotypes at 6 months post second dose (Day 270 [M9]).
• Seropositivity rates (% of subjects seropositive) for each of the 4 dengue serotypes at 1 month and 6 months post second dose (Day 120 [M4]) and Day 270 [M9], respectively).
• Seropositivity rates (% of subjects seropositive) for multiple (2, 3, or 4) dengue serotypes at 1 month and 6 months post second dose (Day 120 [M4]) and Day 270 [M9], respectively).
Note: Seropositivity is defined as a reciprocal neutralizing titer ≥10.

Safety:
• Frequency and severity of solicited local (injection site) adverse events (AE) for 7 days (day of vaccination+6 subsequent days) and solicited systemic AEs for 14 days (day of vaccination+13 subsequent days) after each TDV/placebo dose on Day 1 (M0) and Day 90 (M3).
• Percentage of subjects with any unsolicited AEs for 28 days (day of vaccination+27 subsequent days) after each TDV/placebo dose on Day 1 (M0) and Day 90 (M3).
• Percentage of subjects with medically attended AEs (MAAE) and serious adverse events (SAE) throughout the trial.

E.5.2.1

Timepoint(s) of evaluation of this end point

Multiple time points occurring as stated in Section E.5.2

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

Immunogenicity

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

Yes

E.8.1.5

Parallel group

Yes

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.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Mexico

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

400

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

400

F.1.2

Adults (18-64 years)

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children between 12 and 17 years of age.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

400

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

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Mexico

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