DenguePhase 1/2NCT00322049

A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Infants

A Phase 1/2 study testing Tetravalent live attenuated dengue vaccine and Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine in people with Dengue, run by U.S. Army Medical Research and Development Command at 1 site in Thailand.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 12 to 15 monthsHealthy volunteers can take part
Conditions the study is for: Dengue
What is being tested?: Tetravalent live attenuated dengue vaccine and Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 1 siteThailand
Study dates: Feb 2004to Jun 2009
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 15 months
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Male and female infants between 12 and 15 months (12 and <16 months) of age at the time of the first dengue vaccination
Free of obvious health problems as established by medical history and clinical examination before entering into the study. As a marker of nutritional status, an infant's weight to height ratio will be above the 5th percentile compared to the standards for same sex and age children cared for at Phramongkutklao Hospital, Bangkok, Thailand
Written informed consent obtained from the parent of the subject.
Amendment 8 Inclusion Criteria:
Completed the Dengue-001 study having previously received 2 doses of experimental dengue vaccine according to protocol.
Written informed consent obtained from the parent or guardian of the subject. (obtained in amendment 5)
Written informed consent obtained from the parent or guardian of the subject who agrees to their child's participation to receive a dengue booster dose and booster follow-up.

Who cannot join

Use of any investigational or non-registered drug or vaccine other than the protocol-specified vaccines within 30 days preceding the administration of the first dose of dengue/control vaccine or planned use during the study period
Administration of a registered vaccine within 30 days preceding the first study vaccination or planned administration within 30 days prior to, or 30 days after any protocol-specified vaccine administration
MMR vaccination given within 60 days prior to the first dose of dengue/control vaccine (added bullet point, or planned administration within 60 days prior to, or 30 days after any protocol-specified vaccine administration
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the study period. (For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.
Any confirmed or suspected immunosuppressive or immunodeficient condition
Any clinically significant history, including any seizures or other serious medical condition as determined by the investigator

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A first order family member (parent or sibling) with a history of chronic headaches
A first order family member (parent or sibling) with a history of a congenital or hereditary immunodeficiency
Abnormal clinical laboratory screening test results (based on normal values set by the laboratory) that are deemed clinically significant by study investigators and/or the Medical Monitor
The presence of HBsAg or antibodies against HIV or HCV at screening
Pre-existing antibody to dengue 1-4 virus serotypes or Japanese encephalitis virus (JEV) by HAI or PRNT50 at screening
Previous vaccination against yellow fever virus, JEV, tick-borne encephalitis virus (TBE), varicella virus or booster dose of Hib in the second year of life
History of varicella disease or invasive Haemophilus Influenzae B disease
Acute disease at time of enrollment (Acute illness is defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness such as diarrhea or mild upper respiratory infection with or without low-grade febrile illness, i.e., axillary temperature <37.5°C (<99.5°F).
Administration of immunoglobulins and/or blood products since birth or planned administration during the study period
Known allergic or idiosyncratic reaction to neomycin or related antibiotics (including streptomycin, gentamicin, amikacin, , tobramycin, kanamycin and bacitracin)
Allergy to dogs or monkeys or hypersensitivity to proteins of rodent or neural origin
Allergy to gelatin or hypersensitivity to thimerosal
Infant whose parent has no easy access to a fixed or mobile telephone
Parental illiteracy
Plans to leave Bangkok during the first 8.5 months after initial vaccination or definite plans to move from Bangkok during the 5 years following first dose dengue/control vaccination.
Amendment 8 Exclusion Criteria:
-Any subject with confirmed dengue hemorrhagic fever during the 2 to 3 year period before booster dose administration will not be eligible for enrollment for the booster.

Trial locations and contacts

1 site in 1 country.

Thailand1 site

USAMC-AFRIMS/Department of Pediatrics, Pharamongkutklao Hospital
Bangkok, 10400

Other trials in Thailand

About this study

The main target populations for the tetravalent live attenuated dengue virus vaccine are indigenous populations, especially infants less than 2 years old, residing in areas of the world endemic for dengue and at risk of developing dengue hemorrhagic fever (DHF). The presence of maternal dengue antibody during the first year of life makes it unlikely that a vaccine given during that time will have long-term efficacy, as the vaccine virus would likely be neutralized prior to necessary replication. Children older than 18 months may have preexisting flavivirus antibody. Therefore, vaccination of infants living in Thailand early in the second year of life (between the ages of 12 and 18 months) seems most beneficial. The aim of this trial is to evaluate the safety and immunogenicity of a two-dose schedule of a tetravalent live attenuated dengue vaccine in flavivirus antibody naïve infants beginning at 12-15 months of age.

To assess the kinetics of dengue neutralizing antibodies to each dengue virus serotype one and four years following dose 2 of dengue/control vaccination in the setting of potential wild-type dengue virus exposure.
To assess the immunogenicity, the safety and reactogenicity of a booster dose of dengue vaccine administered at Year 3 following primary vaccination.

Read the detailed description

This is a Phase I/II, randomized, observer-blind, controlled trial. Thirty-four flavivirus naïve infants will be randomized to the vaccine group and 17 infants to the control group.
Infants receive dengue vaccine at study months 0 and 6 or control vaccine (Varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both are licensed for use in Thailand.
All infants subsequently receive an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2.
Infants are monitored daily for 21 days following each dengue or control vaccination and 7 days after each JE vaccination for solicited adverse events. Unsolicited events will be recorded up to 31 days (days 0-30) after dengue/control vaccinations and each day after dose 1 of JE vaccine until the concluding study visit.
Study duration (excluding screening) is approximately 8.5 months for each subject.
Each enrollee is followed a four year period following dose 2 of dengue/control vaccination to assess for dengue-related hospitalizations and dengue antibody kinetics.
Investigators will administer a 3rd dose of tetravalent dengue vaccine to all subjects who received 2 doses of dengue vaccine (0 and 6 months) during the primary phase of the study. The 3rd dose will be administered 3 years following the primary vaccination series. Peripheral blood mononuclear cells (PBMCs) and sera will be collected at the time of dose 3, and twice again at one month and one year following dose 3 from dengue group subjects.

Investigators will address the following questions:

Is a 3rd dose of live virus tetravalent dengue vaccine safe in Thai toddlers/children?
Is a 3rd dose of live virus tetravalent dengue vaccine required in toddlers/children to induce optimal immune (neutralizing antibody, cellular mediated immunity) responses?
Is there evidence of T and B cell memory following a primary dengue vaccination series (dose 1 and 2)?
How does a 3rd dose of live virus tetravalent dengue vaccine impact B and T cell memory?

Conditions: Dengue
Being tested: Tetravalent live attenuated dengue vaccine, Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine
Keywords: Dengue, Vaccine, Thailand
Medical subject headings: Dengue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tetravalent live attenuated dengue vaccineBiological
DEN candidate vaccine: One dose of the tetravalent, live attenuated DEN vaccine candidate, F17, contains dengue serotype 1, 2, 3 and 4 vaccines. This formulation contains 50 mcg/mL neomycin base, 5.5% lactose, and 1.9 g/dL human serum albumin; for subcutaneous injection.
Infants received dengue vaccine at study months 0 and 6 or control vaccine (varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both control vaccines are licensed for use in Thailand.
All infants subsequently received an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. The licensed JE vaccine in liquid form, was dosed at 0.25 ml for subcutaneous injection.
A booster dose of DEN vaccine was given to all subjects previously vaccinated with DEN vaccine in Dengue -001. The booster dose was administered approximately 42 months after dose 2 (at the Year 3 visit).
Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccineBiological
Infants received dengue vaccine at study months 0 and 6 or control vaccine (varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both control vaccines are licensed for use in Thailand.

Study groups in NCT00322049
Study group	Role	What they receive
Cohort A: Dengue Vaccine- Full Dose (T-DEN F17 )	Experimental	Dengue vaccine at Months 0 and 6 and booster follow-up at 3 years; DEN candidate vaccine: One dose of the tetravalent, live attenuated DEN vaccine candidate, F17, contains dengue serotype 1, 2, 3 and 4 vaccines. This formulation contains 50 mcg/mL neomycin base, 5.5% lactose, and 1.9 g/dL human serum albumin; for subcutaneous injection. All infants subsequently received an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. The licensed JE vaccine in liquid form, was dosed at 0.25 ml for subcutaneous injection. Receives: Biological: Tetravalent live attenuated dengue vaccine
Cohort B: Control vaccines	Active comparator	Control vaccines: Hemophilus influenza type b (Hib) vaccine and varicella vaccine Receives: Biological: Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine
Cohort C: Dengue Vaccine - 1/10 Dose (T-DEN F17 )	Experimental	Dengue vaccine at Months 0 and 6 and booster follow-up at 3 years Receives: Biological: Tetravalent live attenuated dengue vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Local and general solicited reactogenicity using diary cards for 21 days (days 0-20) after the first dose of dengue/control vaccine
Measured: 21-day follow-up period after Dose 1
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
Assess the immunogenicity of the dengue vaccine in terms of GMTs 30 days post-Dose 2 of dengue vaccine for all four serotypes (DEN-1, 2, 3, 4 and JE (Japanese encephalitis)). Analysis of immunogenicity was performed on the ATP cohort.
Measured: 30 days post Dose 2
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2
Seronegative for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2.
Seronegative (antibody titer <10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
Measured: month 7 after dose 2
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE
Seropositivity for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2 (and 2 doses of JE).
Seronegative (antibody titer <10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
Measured: month 8.5
JE Vaccine Response
Seropositivity rates and GMTs for N lg to JEV antibodies. Pre= Pre vaccination, blood sampling prior to the first vaccine dose; PI(M1)= Post 1, month 1, blood sampling one month after dose 1 at study month 1; PI(M6)= Post 1, month 6, blood sampling 6 months after dose 1 at study month 6; PII(M7)= Post II, month 7, blood sampling one month after dose 2 at study month 7; PIV(M8.5)= Post IV, month 8.5, blood sampling after 2 doses of dengue/control and 2 doses of JE vaccines at study month 8.5
Measured: Pre-vaccination, 1, 6, 7 and 8.5 months after two doses of dengue vaccine

Secondary outcomes (2)

Incidence of Dengue Specific Symptoms
Percentage of subjects showing incidence of dengue specific symptoms during the 30-day follow-up period after vaccinations
Measured: 30-day follow-up period after dose 1 and 2
Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose
Percentage of subjects with a dengue viremia 10 days after each dose of vaccine.
RT PCR = Reverse-transcriptase polymerase chain reaction Nested PCR - Nested polymerase chain reaction
Per protocol, all participants receiving a Dengue Vaccine were combined for Dengue Viremia assessment via RT-PCR and Nested PCR
Measured: 10 days after post dose 1 and 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2004Jun 2009

First posted4 May 2006 (estimated)
Study startFeb 2004
Primary completionJun 2009
Study completionJun 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for DengueStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00322049
Sponsor's protocol ID: WRAIR 824
Other IDs: HSRRB Log A-10064, GSK CPMS7663310/001, DEN-001
Status last verified: Dec 2017
First submitted: 3 May 2006
Last updated: 19 Jan 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Undecided

Publications

Watanaveeradej V, Simasathien S, Nisalak A, Endy TP, Jarman RG, Innis BL, Thomas SJ, Gibbons RV, Hengprasert S, Samakoses R, Kerdpanich A, Vaughn DW, Putnak JR, Eckels KH, Barrera Rde L, Mammen MP Jr. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus-naive infants. Am J Trop Med Hyg. 2011 Aug;85(2):341-51. doi: 10.4269/ajtmh.2011.10-0501.
PubMed 21813857

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Healthy Volunteers, Dengue
Active, not recruiting
A Controlled Human Infection Model of Dengue
Dengue
RecruitingPhase 2/3
Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)
Dengue
RecruitingPhase 2
Adaptive Dengue Antiviral Platform Trial
Dengue, Antiviral Drugs

All Dengue trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Infants
ClinicalTrials.gov ID: NCT00322049
Acronym / sponsor ID: WRAIR 824
Conditions: Dengue
Keywords: Dengue, Vaccine, Thailand
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 51 participants (actual)
Lead sponsor: U.S. Army Medical Research and Development CommandUS federal agency
Collaborators: GlaxoSmithKline
Study start: Feb 2004
Primary completion: Jun 2009 (actual)
Study completion: Jun 2009 (actual)
First posted: 4 May 2006 (estimated)
Results: Posted 19 Jul 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To assess the kinetics of dengue neutralizing antibodies to each dengue virus serotype one and four years following dose 2 of dengue/control vaccination in the setting of potential wild-type dengue virus exposure.
To assess the immunogenicity, the safety and reactogenicity of a booster dose of dengue vaccine administered at Year 3 following primary vaccination.

Detailed description

This is a Phase I/II, randomized, observer-blind, controlled trial. Thirty-four flavivirus naïve infants will be randomized to the vaccine group and 17 infants to the control group.
Infants receive dengue vaccine at study months 0 and 6 or control vaccine (Varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both are licensed for use in Thailand.
All infants subsequently receive an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2.
Infants are monitored daily for 21 days following each dengue or control vaccination and 7 days after each JE vaccination for solicited adverse events. Unsolicited events will be recorded up to 31 days (days 0-30) after dengue/control vaccinations and each day after dose 1 of JE vaccine until the concluding study visit.
Study duration (excluding screening) is approximately 8.5 months for each subject.
Each enrollee is followed a four year period following dose 2 of dengue/control vaccination to assess for dengue-related hospitalizations and dengue antibody kinetics.
Investigators will administer a 3rd dose of tetravalent dengue vaccine to all subjects who received 2 doses of dengue vaccine (0 and 6 months) during the primary phase of the study. The 3rd dose will be administered 3 years following the primary vaccination series. Peripheral blood mononuclear cells (PBMCs) and sera will be collected at the time of dose 3, and twice again at one month and one year following dose 3 from dengue group subjects.

Investigators will address the following questions:

Is a 3rd dose of live virus tetravalent dengue vaccine safe in Thai toddlers/children?
Is a 3rd dose of live virus tetravalent dengue vaccine required in toddlers/children to induce optimal immune (neutralizing antibody, cellular mediated immunity) responses?
Is there evidence of T and B cell memory following a primary dengue vaccination series (dose 1 and 2)?
How does a 3rd dose of live virus tetravalent dengue vaccine impact B and T cell memory?

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 3

Arm	Type	Receives
Cohort A: Dengue Vaccine- Full Dose (T-DEN F17 )	Experimental	Biological: Tetravalent live attenuated dengue vaccineDengue vaccine at Months 0 and 6 and booster follow-up at 3 years; DEN candidate vaccine: One dose of the tetravalent, live attenuated DEN vaccine candidate, F17, contains dengue serotype 1, 2, 3 and 4 vaccines. This formulation contains 50 mcg/mL neomycin base, 5.5% lactose, and 1.9 g/dL human serum albumin; for subcutaneous injection. All infants subsequently received an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. The licensed JE vaccine in liquid form, was dosed at 0.25 ml for subcutaneous injection.
Cohort B: Control vaccines	Active comparator	Biological: Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccineControl vaccines: Hemophilus influenza type b (Hib) vaccine and varicella vaccine
Cohort C: Dengue Vaccine - 1/10 Dose (T-DEN F17 )	Experimental	Biological: Tetravalent live attenuated dengue vaccineDengue vaccine at Months 0 and 6 and booster follow-up at 3 years

Who may qualify

Ages: 12 to 15 months
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (7 listed)

Male and female infants between 12 and 15 months (12 and <16 months) of age at the time of the first dengue vaccination
Free of obvious health problems as established by medical history and clinical examination before entering into the study. As a marker of nutritional status, an infant's weight to height ratio will be above the 5th percentile compared to the standards for same sex and age children cared for at Phramongkutklao Hospital, Bangkok, Thailand
Written informed consent obtained from the parent of the subject.
Completed the Dengue-001 study having previously received 2 doses of experimental dengue vaccine according to protocol.
Written informed consent obtained from the parent or guardian of the subject. (obtained in amendment 5)

Key exclusion criteria (23 listed)

Use of any investigational or non-registered drug or vaccine other than the protocol-specified vaccines within 30 days preceding the administration of the first dose of dengue/control vaccine or planned use during the study period
Administration of a registered vaccine within 30 days preceding the first study vaccination or planned administration within 30 days prior to, or 30 days after any protocol-specified vaccine administration
MMR vaccination given within 60 days prior to the first dose of dengue/control vaccine (added bullet point, or planned administration within 60 days prior to, or 30 days after any protocol-specified vaccine administration
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the study period. (For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.
Any confirmed or suspected immunosuppressive or immunodeficient condition

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tetravalent live attenuated dengue vaccineDEN candidate vaccine: One dose of the tetravalent, live attenuated DEN vaccine candidate, F17, contains dengue serotype 1, 2, 3 and 4 vaccines. This formulation contains 50 mcg/mL neomycin base, 5.5% lactose, and 1.9 g/dL human serum albumin; for subcutaneous injection. Infants received dengue vaccine at study months 0 and 6 or control vaccine (varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both control vaccines are licensed for use in Thailand. All infants subsequently received an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. The licensed JE vaccine in liquid form, was dosed at 0.25 ml for subcutaneous injection. A booster dose of DEN vaccine was given to all subjects previously vaccinated with DEN vaccine in Dengue -001. The booster dose was administered approximately 42 months after dose 2 (at the Year 3 visit).	Biological	Cohort A: Dengue Vaccine- Full Dose (T-DEN F17 ), Cohort C: Dengue Vaccine - 1/10 Dose (T-DEN F17 )
Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccineInfants received dengue vaccine at study months 0 and 6 or control vaccine (varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both control vaccines are licensed for use in Thailand.	Biological	Cohort B: Control vaccines

Primary outcome

Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Time frame: 21-day follow-up period after Dose 1
Local and general solicited reactogenicity using diary cards for 21 days (days 0-20) after the first dose of dengue/control vaccine
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
Time frame: 30 days post Dose 2
Assess the immunogenicity of the dengue vaccine in terms of GMTs 30 days post-Dose 2 of dengue vaccine for all four serotypes (DEN-1, 2, 3, 4 and JE (Japanese encephalitis)). Analysis of immunogenicity was performed on the ATP cohort.
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2
Time frame: month 7 after dose 2
Seronegative for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2. Seronegative (antibody titer <10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE
Time frame: month 8.5
Seropositivity for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2 (and 2 doses of JE). Seronegative (antibody titer <10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
JE Vaccine Response
Time frame: Pre-vaccination, 1, 6, 7 and 8.5 months after two doses of dengue vaccine
Seropositivity rates and GMTs for N lg to JEV antibodies. Pre= Pre vaccination, blood sampling prior to the first vaccine dose; PI(M1)= Post 1, month 1, blood sampling one month after dose 1 at study month 1; PI(M6)= Post 1, month 6, blood sampling 6 months after dose 1 at study month 6; PII(M7)= Post II, month 7, blood sampling one month after dose 2 at study month 7; PIV(M8.5)= Post IV, month 8.5, blood sampling after 2 doses of dengue/control and 2 doses of JE vaccines at study month 8.5

2 secondary outcomes

Incidence of Dengue Specific Symptoms
Time frame: 30-day follow-up period after dose 1 and 2
Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose
Time frame: 10 days after post dose 1 and 2

Results and safety

Results posted to the registry on 19 Jul 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort A - 1/10th Dose Dengue Vaccine	4	4
Cohort B - Full Dose Dengue Vaccine	10	9
Cohort C - Full Dose Dengue Vaccine	20	20
Control Group - Hib Vaccine	17	16

Primary outcome: Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.

Time frame: 21-day follow-up period after Dose 1. Number. Unit: specified events

Measure	Control Group - Hib Vaccine n = 17	Cohort A - 1/10th Dose Dengue Vaccine n = 4	Cohorts B & C - Full Dose Dengue Vaccine n = 30
Dose 1 : Pain	3	1	11
Dose 1 : Redness	1	2	21
Dose 1 : Swelling	2	1	16
Dose 2 : Pain	2	1	13
Dose 2 : Redness	3	1	13
Dose 2 : Swelling	1	1	8
Overall / dose : Pain	5	2	24
Overall / dose : Redness	4	3	34

Population analysed: Format of results is consistent with how data was presented in the Final Clinical Study Report. Combining of cohorts B and C was due to both cohorts being full dose

Primary outcome: Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine

Time frame: 30 days post Dose 2. Mean (95% Confidence Interval). Unit: titers

Measure	Control Group - Hib Vaccine n = 17	Cohort A - 1/10th Dose Dengue Vaccine n = 4	Cohorts B & C - Full Dose Dengue Vaccine n = 30
DEN-1 GMT - PI(M1)	5.0 (5.0 to 5.0)	5.0 (5.0 to 5.0)	5.2 (4.8 to 5.5)
DEN-1 GMT - PII(M7)	5.0 (5.0 to 5.0)	6.1 (3.3 to 11.4)	20.7 (11.4 to 37.7)
DEN-2 GMT - PI(M1)	5.0 (5.0 to 5.0)	8.8 (1.4 to 54.4)	13.7 (7.7 to 24.5)
DEN-2 GMT - PII(M7)	5.0 (5.0 to 5.0)	173.6 (50.1 to 601.5)	239.6 (163.6 to 351.1)
DEN-3 GMT - PI(M1)	5.0 (5.0 to 5.0)	5.0 (5.0 to 5.0)	5.0 (5.0 to 5.0)
DEN-3 GMT PII(M7)	5.0 (5.0 to 5.0)	5.0 (5.0 to 5.0)	29.2 (18.6 to 45.7)
DEN-4 GMT PI(M1)	5.0 (5.0 to 5.0)	15.7 (0.4 to 600.1)	22.5 (10.0 to 50.3)
DEN-4 GMT PII(M7)	5.0 (5.0 to 5.0)	31.9 (2.5 to 408.2)	52.5 (29.0 to 95.0)

Population analysed: GMT calculated on all subjects. Dil = Dilution; P1(M1) = blood sampling on month after dose 1, at study month 1; PII(M7) = blood sampling one month after dose 2, at study month 7; PII(M8.5) = blood sampling 2 1/2 months after dose 2, at study month 8.5. Combining of cohorts B and C was due to both cohorts being full dose

Primary outcome: Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2

Time frame: month 7 after dose 2. Mean (95% Confidence Interval). Unit: % of responders

Measure	Cohort A - 1/10th Dose Dengue Vaccine n = 4	Cohort B - Full Dose Dengue Vaccine n = 9	Cohort C - Full Dose Dengue Vaccine n = 20	Cohorts B & C - Full Dose Dengue Vaccine n = 29
N lg to DEN-1 (Dil)	25.0 (0.6 to 80.6)	88.9 (51.8 to 99.7)	40.0 (19.1 to 63.9)	55.2 (35.7 to 73.6)
N lg to DEN-2 (Dil)	100 (39.8 to 100)	100 (66.4 to 100)	100 (82.4 to 100)	100 (87.7 to 100)
N lg to DEN-3 (Dil)	0.0 (0.0 to 0.0)	100 (66.4 to 100)	80.0 (56.3 to 94.3)	86.2 (68.3 to 96.1)
N lg to DEN-4 (Dil)	75.0 (19.4 to 99.4)	100 (66.4 to 100)	94.7 (74.0 to 99.9)	96.4 (81.7 to 99.9)

Primary outcome: Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE

Time frame: month 8.5. Mean (95% Confidence Interval). Unit: % of responders

Measure	Cohort A - 1/10th Dose Dengue Vaccine n = 4	Cohort B - Full Dose Dengue Vaccine n = 9	Cohort C - Full Dose Dengue Vaccine n = 20	Cohorts B & C - Full Dose Dengue Vaccine n = 29
N lg to DEN-1 (Dil)	25.0 (0.6 to 80.6)	55.6 (21.2 to 86.3)	35.0 (15.4 to 59.2)	41.4 (23.5 to 61.1)
N lg to DEN-2 (Dil)	100 (39.8 to 100)	100 (66.4 to 100)	100 (82.4 to 100)	100 (87.7 to 100)
N lg to DEN-3 (Dil)	25.0 (0.6 to 80.6)	77.8 (40.0 to 97.2)	60.0 (36.1 to 80.9)	65.5 (45.7 to 82.1)
N lg to DEN-4 (Dil)	50.0 (6.8 to 93.2)	88.9 (51.8 to 99.7)	60.0 (36.1 to 80.9)	69.0 (49.2 to 84.7)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 8.5 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort A: Dengue Vaccine- 1/10 Dose (T-DEN F17 )	0 of 4 (0%)	4 of 4 (100%)	0 of 4
Cohort B: Full Dose (T-DEN F17 )	1 of 10 (10%)	10 of 10 (100%)	0 of 10
Cohort C: Dengue Vaccine - Full Dose (T-DEN F17 )	0 of 20 (0%)	20 of 20 (100%)	0 of 20
Control Group	3 of 17 (17.6%)	6 of 17 (35.3%)	0 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 21813857Watanaveeradej V, Simasathien S, Nisalak A, Endy TP, Jarman RG, Innis BL, Thomas SJ, Gibbons RV, Hengprasert S, Samakoses R, Kerdpanich A, Vaughn DW, Putnak JR, Eckels KH, Barrera Rde L, Mammen MP Jr. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus-naive infants. Am J Trop Med Hyg. 2011 Aug;85(2):341-51. doi: 10.4269/ajtmh.2011.10-0501.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert V. Gibbons, MD principal investigator

U.S. Army Medical Component Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS)

Veerachai Watanaveeradej, MD principal investigator

Infectious Disease Department of Pediatrics Phramongkutklao Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. (time frame: 21-day follow-up period after Dose 1). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00322049, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2018.