Dengue FeverPhase 1/2NCT00384670
A Phase I/II Trial of a Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naïve Children
A Phase 1/2 study testing Dengue Vaccine Formulation 17 and Licensed Japanese Encephalitis (JE) Vaccine in people with Dengue Fever, run by U.S. Army Medical Research and Development Command at 1 site in Thailand.
Trial summary
To assess the safety, reactogenicity and immunogenicity of two doses of the dengue vaccine in Flavi-virus antibody-naive children between 6 and 9 years of age. Read more about this study
- Who is it for?
- Ages 6 to 10 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue Fever
- What is being tested?
- Dengue Vaccine Formulation 17 and Licensed Japanese Encephalitis (JE) Vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteThailand
- Study dates
- Aug 2003to May 2004
- 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 6 to 10 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- A male or female child six to nine years of age (greater than or equal to 6 years of age and less than 10 years of age) at the time of the first vaccination.
- Free of obvious health problems as established by medical history and physical examination before entering into the study.
- Seronegative by HAI and screening PRNT for antibodies to dengue types 1-4 and Japanese Encephalitis (JE) virus
- Written informed consents by the parent of the subject for screening and enrollment into the study.
Who cannot join
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose or planned administration during the study (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
- 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 dengue vaccine dose or planned use during the study period.
- Planned administration of a vaccine not foreseen by the study protocol and within 30 days prior or after any dengue/JE vaccine administration.
- Any current medical condition determined to be serious by the investigator (e.g. seizures)
- History of chronic headaches or a first order family member (parent or sibling) with a history of chronic headaches
- Abnormal clinical laboratory screening test result (based on normal values set by the laboratory) that is deemed clinically significant by the investigator or Medical Monitor (including seropositivity for HBsAg or anti-HCV)
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- Previous vaccination against yellow fever virus, JEV, or tick-borne encephalitis virus (TBE) or existence of any flavivirus antibody
- Any suspected or confirmed immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
- Family history of a congenital or hereditary immunodeficiency
- Acute illness at time of enrollment (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 without fever, i.e., oral temperature <37.5°C.
- Administration of immunoglobulins and/or blood products within 6 months prior to study entry or planned administration during the study period
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccines (including neomycin, streptomycin, gentamicin, amikacin, tobramycin, kanamycin and bacitracin; allergy to dogs or monkeys or hypersensitivity to proteins of rodent or neural origin or to thimerosal, allergy to porcine gelatin)
- Child whose parent has no easy access to a fixed or mobile telephone
- Plans to move from Bangkok during the first 8.5 months after initial vaccination
- Parental illiteracy.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Department of Pediatrics, Pharamongkutklao Hospital
Bangkok, 10400
About this study
To assess the safety, reactogenicity and immunogenicity of two doses of the dengue vaccine in Flavi-virus antibody-naive children between 6 and 9 years of age.
Read the detailed description
This study was a Phase I/II, open-label trial with one treatment group; 7, healthy, flavivirus naïve children between the ages of 6 and 7 years residing in Bangkok, Thailand. Seronegative status was determined by measuring neutralizing (N) antibody titers to dengue 1-4 and JE virus (JE) using hemagglutination inhibition (HAI) (1st) and PRNT (2nd) assays. Titers <10 and <10, respectively, were considered negative. Enrolled children received two doses of tetravalent dengue vaccine at study months 0 and 6, and two doses of JE vaccine (study benefit) at study months 7 and 7.5. Enrolled children attended 20 study visits, received 4 injections, and 7 venipunctures (one additional blood sample for screening). In the acute period (1 month) following vaccination, safety was assessed using symptom diary cards and clinical and laboratory evaluations. Viremia was measured 10 days post dengue vaccination. Solicited and unsolicited adverse events were assessed for 30 days following each dengue vaccination. Serious adverse events were assessed throughout the study period. In the case of illness, investigators would complete additional clinical and virologic evaluations. Dengue vaccine immunogenicity was assessed 30 days following each dengue vaccination using the PRNT50 assay. The According to Protocol (ATP) cohort was determined by evaluating the occurrence of intermittent natural dengue infection using ELISA IgM/IgG titer ratios. A long-term follow-up of dengue vaccine recipients is described in a separate protocol (Dengue-005 protocol).
- Conditions
- Dengue Fever
- Being tested
- Dengue Vaccine Formulation 17, Licensed Japanese Encephalitis (JE) Vaccine
- Keywords
- dengue, vaccine
- Medical subject headings
- Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dengue Vaccine Formulation 17Biological
Also called F17
Tetravalent live attenuated DEN vaccine candidate. Containing dengue serotypes 1,2, and 3 vaccines produced at the Salk Institute and dengue serotype 4 produced at the WRAIR Pilot Bioproduction Facility. Dosage 1 mL administered via injection at Day 0 and Day 60.
Licensed Japanese Encephalitis (JE) VaccineBiological
Also called JE
Produced by the Thailand GPO using a Beijing strain of JE in liquid form; dosed at 0.5 mL ot 7 and 7.5 months.
| Study group | Role | What they receive |
|---|---|---|
| Dengue and Japanese Encephalitis vaccine | Experimental | 1 mL subcutaneous injection Dengue Vaccine Formulation 17 on Day 0 and Day 60. 0.5 mL subcutaneous injection Licensed Japanese Encephalitis (JE) Vaccine on months 7 and 7.5. Receives: Biological: Dengue Vaccine Formulation 17; Biological: Licensed Japanese Encephalitis (JE) Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Solicited Adverse Events Within 21 Days After the First Dose of Dengue Vaccine.
Number of solicited general symptoms within the 21-day follow-up after dengue dose 1 (total vaccinated cohort).
Measured: 21 days
Secondary outcomes (6)
Number of Unsolicited Adverse Events Within 30 Days After Each Dose of Dengue Vaccine
Number of subjects with unsolicited symptoms classified by MedDRA Primary System Organ Class and Preferred Term, within 30 days after dengue vaccine (total vaccinated cohort)
Measured: 30 days
Number of Solicited Adverse Events for 21 Days (0-20) After the Second Dose of Dengue Vaccine
Number of solicited general symptoms within the 21-day follow-up of dengue dose 2 vaccine dose (total vaccinated cohort)
Measured: 21 Days (0-20) After the Second Dose of Dengue Vaccine
Percentage of Individuals With Neutralizing Antibody (Seroconversion) to Japanese Encephalitis (JE) and 4 Dengue Types, 30 Days After the Second Dose of JE Vaccine.
Percentage of individuals with ≥ 10 dilution (DIL) for neutralizing (N) Ig to DEN-1, N Ig to DEN-2, N Ig to DEN-3, N Ig to DEN-4, and N Ig to Japanese encephalitis (JE) vaccine antibody titers.
Measured: 30 days after the second dose of JE vaccine
Neutralizing Antibody (GMT) to JE and 4 Dengue Types, 30 Days After the Second Dose of JE Vaccine.
Geometric mean titers (GMT) for neutralizing (N) Ig to DEN-1, N Ig to DEN-2, N Ig to DEN-3, N Ig to DEN-4, and N Ig to JE vaccine antibody titers.
Measured: Approximately Day 225 and Day 255
Number of Solicited Symptoms 7 Days (0-6) After First Dose of Japanese Encephalitis (JE) Vaccine.
Number of solicited general symptoms within the 7-day follow-up after the first dose of Japanese encephalitis (JE) vaccine doses (total vaccinated cohort)
Measured: Approximately Day 225 and Day 255
Number of Solicited Symptoms 7 Days (0-6) After Second Dose of Japanese Encephalitis (JE) Vaccine.
Number of solicited general symptoms within the 7-day follow-up after the second dose of Japanese encephalitis (JE) vaccine doses (total vaccinated cohort)
Measured: Approximately Day 225 and Day 255
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2006 (estimated)
- Study startAug 2003
- Primary completionMay 2004
- Study completionMay 2004
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 Dengue FeverStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- MAJ Stephen J Thomas, MD, Principal investigator, Department of Virology USAMC-AFRIMSSriluck Simasathien, MD, Principal investigator, Phramongkutklao College of Medicine and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00384670
- Sponsor's protocol ID
- WRAIR 1048
- Other IDs
- HSRRB#A-12189, GSK Dengue-003
- Status last verified
- Jan 2014
- First submitted
- 4 Oct 2006
- Last updated
- 24 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Simasathien S, Thomas SJ, Watanaveeradej V, Nisalak A, Barberousse C, Innis BL, Sun W, Putnak JR, Eckels KH, Hutagalung Y, Gibbons RV, Zhang C, De La Barrera R, Jarman RG, Chawachalasai W, Mammen MP Jr. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus naive children. Am J Trop Med Hyg. 2008 Mar;78(3):426-33.
PubMed 18337339
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of a Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naïve Children
- ClinicalTrials.gov ID
- NCT00384670
- Acronym / sponsor ID
- WRAIR 1048
- Conditions
- Dengue Fever
- Keywords
- dengue, vaccine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- GlaxoSmithKline
- Study start
- Aug 2003
- Primary completion
- May 2004 (actual)
- Study completion
- May 2004 (actual)
- First posted
- 6 Oct 2006 (estimated)
- Results
- Posted 24 Feb 2014
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 safety, reactogenicity and immunogenicity of two doses of the dengue vaccine in Flavi-virus antibody-naive children between 6 and 9 years of age.
Detailed description
This study was a Phase I/II, open-label trial with one treatment group; 7, healthy, flavivirus naïve children between the ages of 6 and 7 years residing in Bangkok, Thailand. Seronegative status was determined by measuring neutralizing (N) antibody titers to dengue 1-4 and JE virus (JE) using hemagglutination inhibition (HAI) (1st) and PRNT (2nd) assays. Titers <10 and <10, respectively, were considered negative. Enrolled children received two doses of tetravalent dengue vaccine at study months 0 and 6, and two doses of JE vaccine (study benefit) at study months 7 and 7.5. Enrolled children attended 20 study visits, received 4 injections, and 7 venipunctures (one additional blood sample for screening). In the acute period (1 month) following vaccination, safety was assessed using symptom diary cards and clinical and laboratory evaluations. Viremia was measured 10 days post dengue vaccination. Solicited and unsolicited adverse events were assessed for 30 days following each dengue vaccination. Serious adverse events were assessed throughout the study period. In the case of illness, investigators would complete additional clinical and virologic evaluations. Dengue vaccine immunogenicity was assessed 30 days following each dengue vaccination using the PRNT50 assay. The According to Protocol (ATP) cohort was determined by evaluating the occurrence of intermittent natural dengue infection using ELISA IgM/IgG titer ratios. A long-term follow-up of dengue vaccine recipients is described in a separate protocol (Dengue-005 protocol).
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dengue and Japanese Encephalitis vaccine | Experimental | Biological: Dengue Vaccine Formulation 17, Biological: Licensed Japanese Encephalitis (JE) Vaccine1 mL subcutaneous injection Dengue Vaccine Formulation 17 on Day 0 and Day 60. 0.5 mL subcutaneous injection Licensed Japanese Encephalitis (JE) Vaccine on months 7 and 7.5. |
Who may qualify
- Ages
- 6 to 10 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- A male or female child six to nine years of age (greater than or equal to 6 years of age and less than 10 years of age) at the time of the first vaccination.
- Free of obvious health problems as established by medical history and physical examination before entering into the study.
- Seronegative by HAI and screening PRNT for antibodies to dengue types 1-4 and Japanese Encephalitis (JE) virus
- Written informed consents by the parent of the subject for screening and enrollment into the study.
Key exclusion criteria (15 listed)
- Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose or planned administration during the study (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
- 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 dengue vaccine dose or planned use during the study period.
- Planned administration of a vaccine not foreseen by the study protocol and within 30 days prior or after any dengue/JE vaccine administration.
- Any current medical condition determined to be serious by the investigator (e.g. seizures)
- History of chronic headaches or a first order family member (parent or sibling) with a history of chronic headaches
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 |
|---|---|---|
| Dengue Vaccine Formulation 17Also: F17Tetravalent live attenuated DEN vaccine candidate. Containing dengue serotypes 1,2, and 3 vaccines produced at the Salk Institute and dengue serotype 4 produced at the WRAIR Pilot Bioproduction Facility. Dosage 1 mL administered via injection at Day 0 and Day 60. | Biological | Dengue and Japanese Encephalitis vaccine |
| Licensed Japanese Encephalitis (JE) VaccineAlso: JEProduced by the Thailand GPO using a Beijing strain of JE in liquid form; dosed at 0.5 mL ot 7 and 7.5 months. | Biological | Dengue and Japanese Encephalitis vaccine |
Primary outcome
Number of Solicited Adverse Events Within 21 Days After the First Dose of Dengue Vaccine.
Time frame: 21 days
Number of solicited general symptoms within the 21-day follow-up after dengue dose 1 (total vaccinated cohort).
6 secondary outcomes
Number of Unsolicited Adverse Events Within 30 Days After Each Dose of Dengue Vaccine
Time frame: 30 days
Number of Solicited Adverse Events for 21 Days (0-20) After the Second Dose of Dengue Vaccine
Time frame: 21 Days (0-20) After the Second Dose of Dengue Vaccine
Percentage of Individuals With Neutralizing Antibody (Seroconversion) to Japanese Encephalitis (JE) and 4 Dengue Types, 30 Days After the Second Dose of JE Vaccine.
Time frame: 30 days after the second dose of JE vaccine
Neutralizing Antibody (GMT) to JE and 4 Dengue Types, 30 Days After the Second Dose of JE Vaccine.
Time frame: Approximately Day 225 and Day 255
Number of Solicited Symptoms 7 Days (0-6) After First Dose of Japanese Encephalitis (JE) Vaccine.
Time frame: Approximately Day 225 and Day 255
Number of Solicited Symptoms 7 Days (0-6) After Second Dose of Japanese Encephalitis (JE) Vaccine.
Time frame: Approximately Day 225 and Day 255
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 18337339Simasathien S, Thomas SJ, Watanaveeradej V, Nisalak A, Barberousse C, Innis BL, Sun W, Putnak JR, Eckels KH, Hutagalung Y, Gibbons RV, Zhang C, De La Barrera R, Jarman RG, Chawachalasai W, Mammen MP Jr. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus naive children. Am J Trop Med Hyg. 2008 Mar;78(3):426-33.
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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.
MAJ Stephen J Thomas, MD principal investigator
Department of Virology USAMC-AFRIMS
Sriluck Simasathien, MD principal investigator
Phramongkutklao College of Medicine and Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dengue Vaccine Formulation 17 and Licensed Japanese Encephalitis (JE) Vaccine in people with Dengue Fever, run by U.S. Army Medical Research and Development Command at 1 site in Thailand.
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 4 inclusion and 15 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 24 Feb 2014. 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 24 Feb 2014). 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?
Number of Solicited Adverse Events Within 21 Days After the First Dose of Dengue Vaccine. (time frame: 21 days). 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 NCT00384670, 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 24 Feb 2014.