DenguePhase 2NCT00239577

A Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults

A Phase 2 study testing Live attenuated tetravalent dengue vaccine in people with Dengue, run by GlaxoSmithKline at 1 site in United States.

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

This descriptive study will evaluate the safety and immunogenicity of 5 different formulations of the WRAIR dengue vaccine compared to a placebo. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Dengue
What is being tested?: Live attenuated tetravalent dengue vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 86 participants
Where: 1 siteUnited States
Study dates: 5 Apr 2006to 19 Jun 2007
Phase: Phase 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 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male or female adult 18-45 years at the time of vaccination
Free of obvious health problems as established by medical history and physical examination before entering into the study
Written informed consent obtained from the subject
Able to read the Subject Information Sheet and Consent Form
Subjects who the investigator believes can and will comply with the requirements of the protocol
Females must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions as defined in the protocol for 30 days prior to vaccination, have a negative pregnancy test within 48 hours prior to vaccination and must agree to continue such precautions for 60 days after completion of the vaccination series

Who cannot join

History of:
recurrent migraine headache
any neurological or behavioral disorder or seizures
drug abuse or alcohol consumption (more than 2 drinks per day)
allergic disease/reaction likely to be exacerbated by vaccine
urticaria related to mosquito bites requiring medical attention

Show all 16Show fewer

Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect
Any confirmed or suspected immunosuppressive or immunodeficient condition;
Seropositive for HBsAg, anti-HCV or anti-HIV
Acute disease at the time of enrollment
Chronic hepatomegaly or splenomegaly
Use of any investigational or non-registered drug or vaccine within 30 days preceding study or planned use
Planned administration of a vaccine not foreseen by the study protocol 30 days ±each vaccine dose
Planned move during study
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs or administration of immunoglobulins and/or blood products, within 90 days preceding the first dose or planned administration during the study period
Any chronic systemic drug therapy to be continued during the study period

Trial locations and contacts

1 site in 1 country.

United States1 site

GSK Investigational Site
Silver Spring, Maryland, 20910

Other trials in United States

About this study

Official title: Observer-blind, Single Center, Controlled Study of 2 Doses of Various Formulations of the WRAIR Live Attenuated Tetravalent Dengue Vaccine Compared to a Placebo Control, Administered on a 0-6-month Schedule, to Healthy Adults

This descriptive study will evaluate the safety and immunogenicity of 5 different formulations of the WRAIR dengue vaccine compared to a placebo.

Read the detailed description

Subjects will be randomized into one of 6 groups. One group will receive a placebo vaccine and the others will receive one of 5 different dengue vaccine formations. Each subject will receive two doses six months apart. Study subjects who elect to participate in a mosquito transmissibility component of the study will undergo mosquito feedings during each of the two assigned follow-up visits after vaccine dose 1. All subjects will have 11 venipunctures during 11 visits (i.e., screening plus 10 study visits) over a period of nine months.

Conditions: Dengue
Being tested: Live attenuated tetravalent dengue vaccine, Placebo
Keywords: Dengue infection
Medical subject headings: Dengue

What participants receive

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

Live attenuated tetravalent dengue vaccineBiological
Live attenuated tetravalent dengue vaccine
PlaceboBiological
Placebo

Study groups in NCT00239577
Study group	Role	What they receive
DENGUE FORMULATION 17A GROUP	Experimental	Healthy male or female subjects, between and including 18-45 years of age, who received two doses of Dengue vaccine Formulation 17a, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6. Receives: Biological: Live attenuated tetravalent dengue vaccine
DENGUE FORMULATION 17B GROUP	Experimental	Healthy male or female subjects, between and including 18-45 years of age, who received two primary doses of Dengue vaccine Formulation 17b, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6, and one booster dose approximately 5-12 months after the second dose. Receives: Biological: Live attenuated tetravalent dengue vaccine
DENGUE FORMULATION 19 GROUP	Experimental	Healthy male or female subjects, between and including 18-45 years of age, who received two primary doses of Dengue vaccine Formulation 19, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6 and one booster dose approximately 5-12 months after the second dose. Receives: Biological: Live attenuated tetravalent dengue vaccine
PLACEBO GROUP	Placebo comparator	Healthy male or female subjects, between and including 18-45 years of age, who received two doses of Placebo, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6. Receives: Biological: Placebo

What is being measured

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

Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Measured: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were abdominal pain, arthralgia, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, muscle aches, nausea, pain behind the eyes, photophobia, pruritus, rash and vomiting. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Measured: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
Titers for DEN-1, DEN-2, DEN-3 and DEN-4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum.
Measured: At 30 days (Month 7) after Dose 2 of the study vaccine
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
Titers for DEN-1, DEN-2, DEN-3 and DEN-4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum. Not primed = Not primed by MN50; Primed = Primed by MN50. Primed subject is a subject with neutralizing antibody titer ≥ 10 ED50 at pre-vaccination for at least one DEN type. Not primed subject is a subject with neutralizing antibody titer <10 ED50 for any DEN type at pre-vaccination.
Measured: At 5 to 12 months post-Dose 2 of the study vaccine
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
Titers for DEN 1, DEN 2, DEN 3 and DEN 4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum. Not primed = Not primed by MN50; Primed = Primed by MN50. Primed subject is a subject with neutralizing antibody titer ≥ 10 ED50 at pre-vaccination for at least one DEN type. Not primed subject is a subject with neutralizing antibody titer <10 ED50 for any DEN type at pre-vaccination.
Measured: At Month 1 post-booster dose of the study vaccine

Secondary outcomes (25)

Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Measured: During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were abdominal pain, arthralgia, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, muscle aches, nausea, pain behind the eyes, photophobia, pruritus, rash and vomiting. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Measured: During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Measured: During the 21-day (Days 0-20) follow-up after each dose of the study vaccine
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were abdominal pain, arthralgia, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, muscle aches, nausea, pain behind the eyes, photophobia, pruritus, rash and vomiting. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Measured: During the 21-day (Days 0-20) follow-up after each dose of the study vaccine
Number of Subjects With Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Measured: During the 31-day (Days 0-30) follow-up after any study vaccine dose
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: During the whole primary phase of the study (from Day 0 up to Month 9)
Number of Subjects With Alert Values for Safety Laboratory Determinations
Among assessed haematological and biochemical parameters were: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), hematocrit (HC), absolute neutrophil count (NEU) and platelet count (Platelet).
Measured: During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7)
Number of Subjects With Abnormal Findings at Dengue Physical Examination
The abnormal findings at Dengue physical examination included: Rash, Generalized Rash, Skin Hemorrhage, Conjunctival Hemorrhage, Conjunctival Injection, Mucosal Hemorrhage, Lymphadenopathy, Generalized Lymphadenopathy, Hepatomegaly and Splenomegaly. Rash involved < 50% of the body surface; Generalized rash involved at least 50% of the body surface. Generalized lymphadenopathy was defined as palpable lymph nodes in four or more of the following locations: cervical, axillary, inguinal or other, with right and left sides considered as separate locations.
Measured: During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses
Number of Subjects With Suspected and Confirmed Dengue
The number of subjects with suspected and confirmed Dengue post-vaccination.
Measured: During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses
Number of Subjects With Measurable Dengue Viremia
The number of subjects with measurable dengue viremia at specified timepoints. Negative = Genome equivalent (GEQ)/µL result is equal to zero; Undetermined = GEQ/µL result is below limit of detection (LOD); Positive = GEQ/µL result is ≥ LOD.
Measured: During the 31-day (Days 0-30) follow-up after each vaccine dose
Number of Subjects With Safety Laboratory Determinations Outside the Normal Ranges
Among assessed haematological and biochemical parameters were: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), hematocrit (HC), absolute neutrophil count (NEU) and platelet count (Platelet). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Measured: During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7)
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
Titers for DEN-1, DEN-2, DEN-3 and DEN-4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum.
Measured: At Month 0 and Month 1
Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype
Assay cut-off values were greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum.
Measured: At Months 0, 1 and 7
Number of Subjects With Antibody Titers Above the Assay Cut-off Value (Tetravalent Response) for All Dengue Serotypes
The antibody titers and pre-vaccination status were determined by MN50 with a cut-off value equal to 1:10.
Measured: At Months 1 and 7
Number of Subjects With Sero-response to Each DEN Type
Sero-response defined as: For initially seronegative subjects (antibody titer < 10 ED50 for neutralizing antibodies to DEN 1, DEN 2, DEN 3, DEN 4 prior to vaccination), antibody titer ≥ 10 ED50 at post-vaccination; For initially seropositive subjects (antibody titer ≥ 10 ED50 for neutralizing antibodies to DEN 1, DEN 2, DEN 3, DEN 4 prior to vaccination), antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer.
Measured: At Months 1 and 7
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Measured: During the 21-day (Days 0-20) follow-up after the study vaccine booster dose
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were abdominal pain, arthralgia, fatigue, fever [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, muscle aches, nausea, pain behind the eyes, photophobia, pruritus, rash and vomiting. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = oral fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Measured: During the 21-day (Days 0-20) follow-up after the study vaccine booster dose
Number of Subjects With Any, Grade 3 and Related Unsolicited AEs
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Measured: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Number of Subjects With SAEs
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: During the whole booster phase of the study (from pre-vaccination up to Month 6 post-vaccination with the booster dose)
Number of Subjects With Hematological and Biochemical Determinations Within and Outside the Normal Ranges
Among assessed haematological and biochemical parameters were: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), hematocrit (HC), absolute neutrophil count (NEU) and platelet count (Platelet). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Note: No blood sample was taken for these laboratory tests at Month 6 post-booster vaccination.
Measured: At each booster phase visit [pre-booster vaccination (PRE), study Visit 12 post-booster vaccination (Days 2, 5, 8 or 12) (FU1), study Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) (FU2) and at Months 1 and 6 post-booster vaccination]
Number of Subjects With Alert Values for Safety Laboratory Determinations
Among assessed haematological and biochemical parameters were: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), hematocrit (HC), absolute neutrophil count (NEU) and platelet count (Platelet).
Measured: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Number of Subjects With Abnormal Findings at Dengue Physical Examination
The abnormal findings at Dengue physical examination included: Conjunctival hemorrhage, Conjunctival injection, Generalized lymphadenopathy, Generalized rash, Hepatomegaly, Lymphadenopathy, Mucosal hemorrhage, Rash, Skin hemorrhage and Splenomegaly. Rash involved < 50% of the body surface; Generalized rash involved at least 50% of the body surface. Generalized lymphadenopathy was defined as palpable lymph nodes in four or more of the following locations: cervical, axillary, inguinal or other, with right and left sides considered as separate locations. Note: Results only available during the 31-day follow-up period (Month 1) after the booster dose, instead of at each booster phase visit [pre-vaccination, study Visit 12 post-booster vaccination (Days 2, 5, 8 or 12), Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) and at Months 1 and 6 post-booster vaccination].
Measured: At Month 1 post-booster vaccination
Number of Subjects With Suspected and Confirmed Dengue
The number of subjects with suspected and confirmed Dengue post-booster vaccination.
Measured: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Number of Subjects With Measurable Dengue Viremia
The number of subjects with measurable dengue viremia at specified timepoints.
Measured: At study Visit 12 (Days 2, 5, 8 or 12) (FU1), study Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) (FU2) and at study Visit 14 (Month 1 post-booster vaccination)
Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype
Assay cut-off values were greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum. Not primed = Not primed by MN50; Primed = Primed by MN50. Primed subject is a subject with neutralizing antibody titer ≥ 10 ED50 at pre-vaccination for at least one DEN type. Not primed subject is a subject with neutralizing antibody titer <10 ED50 for any DEN type at pre-vaccination.
Measured: Before (PRE) and one month after the booster vaccination (Month 1)

Timeline

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

5 Apr 200619 Jun 2007

First posted17 Oct 2005 (estimated)
Study start5 Apr 2006
Primary completion19 Jun 2007
Study completion19 Jun 2007

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.
Other trials for DengueStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
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 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Enrolment: 86 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00239577
Sponsor's protocol ID: 103996
Status last verified: Feb 2019
First submitted: 13 Oct 2005
Last updated: 19 Feb 2019
Results posted: Yes, on ClinicalTrials.gov

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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A Study to Evaluate V181 Dengue Vaccine in Healthy Participants 2 to 17 Years of Age (V181-005/MOBILIZE-1)
Healthy
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Phase 1 Challenge Study Using rDEN2delta30-7169 to Evaluate Host-Pathogen Interactions in Primary, Homotypic, and Heterotypic Dengue Virus Infection
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 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Observer-blind, Single Center, Controlled Study of 2 Doses of Various Formulations of the WRAIR Live Attenuated Tetravalent Dengue Vaccine Compared to a Placebo Control, Administered on a 0-6-month Schedule, to Healthy Adults
ClinicalTrials.gov ID: NCT00239577
Acronym / sponsor ID: 103996
Conditions: Dengue
Keywords: Dengue infection
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 86 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 5 Apr 2006 (actual)
Primary completion: 19 Jun 2007 (actual)
Study completion: 19 Jun 2007 (actual)
First posted: 17 Oct 2005 (estimated)
Results: Posted 19 Feb 2019

Clinical summary

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

This descriptive study will evaluate the safety and immunogenicity of 5 different formulations of the WRAIR dengue vaccine compared to a placebo.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Number of arms: 4

Arm	Type	Receives
DENGUE FORMULATION 17A GROUP	Experimental	Biological: Live attenuated tetravalent dengue vaccineHealthy male or female subjects, between and including 18-45 years of age, who received two doses of Dengue vaccine Formulation 17a, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6.
DENGUE FORMULATION 17B GROUP	Experimental	Biological: Live attenuated tetravalent dengue vaccineHealthy male or female subjects, between and including 18-45 years of age, who received two primary doses of Dengue vaccine Formulation 17b, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6, and one booster dose approximately 5-12 months after the second dose.
DENGUE FORMULATION 19 GROUP	Experimental	Biological: Live attenuated tetravalent dengue vaccineHealthy male or female subjects, between and including 18-45 years of age, who received two primary doses of Dengue vaccine Formulation 19, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6 and one booster dose approximately 5-12 months after the second dose.
PLACEBO GROUP	Placebo comparator	Biological: PlaceboHealthy male or female subjects, between and including 18-45 years of age, who received two doses of Placebo, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Healthy male or female adult 18-45 years at the time of vaccination
Free of obvious health problems as established by medical history and physical examination before entering into the study
Written informed consent obtained from the subject
Able to read the Subject Information Sheet and Consent Form
Subjects who the investigator believes can and will comply with the requirements of the protocol

Key exclusion criteria (16 listed)

recurrent migraine headache
any neurological or behavioral disorder or seizures
drug abuse or alcohol consumption (more than 2 drinks per day)
allergic disease/reaction likely to be exacerbated by vaccine
urticaria related to mosquito bites requiring medical attention

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
Live attenuated tetravalent dengue vaccineLive attenuated tetravalent dengue vaccine	Biological	DENGUE FORMULATION 17A GROUP, DENGUE FORMULATION 17B GROUP, DENGUE FORMULATION 19 GROUP
PlaceboPlacebo	Biological	PLACEBO GROUP

Primary outcome

Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Assessed solicited general symptoms were abdominal pain, arthralgia, fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache, muscle aches, nausea, pain behind the eyes, photophobia, pruritus, rash and vomiting. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
Time frame: At 30 days (Month 7) after Dose 2 of the study vaccine
Titers for DEN-1, DEN-2, DEN-3 and DEN-4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum.
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
Time frame: At 5 to 12 months post-Dose 2 of the study vaccine
Titers for DEN-1, DEN-2, DEN-3 and DEN-4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum. Not primed = Not primed by MN50; Primed = Primed by MN50. Primed subject is a subject with neutralizing antibody titer ≥ 10 ED50 at pre-vaccination for at least one DEN type. Not primed subject is a subject with neutralizing antibody titer <10 ED50 for any DEN type at pre-vaccination.
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
Time frame: At Month 1 post-booster dose of the study vaccine
Titers for DEN 1, DEN 2, DEN 3 and DEN 4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum. Not primed = Not primed by MN50; Primed = Primed by MN50. Primed subject is a subject with neutralizing antibody titer ≥ 10 ED50 at pre-vaccination for at least one DEN type. Not primed subject is a subject with neutralizing antibody titer <10 ED50 for any DEN type at pre-vaccination.

25 secondary outcomes

Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 21-day (Days 0-20) follow-up after each dose of the study vaccine
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 21-day (Days 0-20) follow-up after each dose of the study vaccine
Number of Subjects With Unsolicited Adverse Events (AEs)
Time frame: During the 31-day (Days 0-30) follow-up after any study vaccine dose
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: During the whole primary phase of the study (from Day 0 up to Month 9)
Number of Subjects With Alert Values for Safety Laboratory Determinations
Time frame: During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7)
Number of Subjects With Abnormal Findings at Dengue Physical Examination
Time frame: During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses
Number of Subjects With Suspected and Confirmed Dengue
Time frame: During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses
Number of Subjects With Measurable Dengue Viremia
Time frame: During the 31-day (Days 0-30) follow-up after each vaccine dose
Number of Subjects With Safety Laboratory Determinations Outside the Normal Ranges
Time frame: During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7)
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
Time frame: At Month 0 and Month 1
Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype
Time frame: At Months 0, 1 and 7
Number of Subjects With Antibody Titers Above the Assay Cut-off Value (Tetravalent Response) for All Dengue Serotypes
Time frame: At Months 1 and 7
Number of Subjects With Sero-response to Each DEN Type
Time frame: At Months 1 and 7
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time frame: During the 21-day (Days 0-20) follow-up after the study vaccine booster dose
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time frame: During the 21-day (Days 0-20) follow-up after the study vaccine booster dose
Number of Subjects With Any, Grade 3 and Related Unsolicited AEs
Time frame: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Number of Subjects With SAEs
Time frame: During the whole booster phase of the study (from pre-vaccination up to Month 6 post-vaccination with the booster dose)
Number of Subjects With Hematological and Biochemical Determinations Within and Outside the Normal Ranges
Time frame: At each booster phase visit [pre-booster vaccination (PRE), study Visit 12 post-booster vaccination (Days 2, 5, 8 or 12) (FU1), study Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) (FU2) and at Months 1 and 6 post-booster vaccination]
Number of Subjects With Alert Values for Safety Laboratory Determinations
Time frame: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Number of Subjects With Abnormal Findings at Dengue Physical Examination
Time frame: At Month 1 post-booster vaccination
Number of Subjects With Suspected and Confirmed Dengue
Time frame: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Number of Subjects With Measurable Dengue Viremia
Time frame: At study Visit 12 (Days 2, 5, 8 or 12) (FU1), study Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) (FU2) and at study Visit 14 (Month 1 post-booster vaccination)
Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype
Time frame: Before (PRE) and one month after the booster vaccination (Month 1)

Results and safety

Results posted to the registry on 19 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dengue Formulation 17a Group	22	17
Dengue Formulation 17b Group	22	19
Dengue Formulation 19 Group	21	18
Placebo Group	21	21

Primary outcome: Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Time frame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine. Count of participants. Unit: Participants

Measure	Dengue Formulation 17a Group n = 22	Dengue Formulation 17b Group n = 22	Dengue Formulation 19 Group n = 21	Placebo Group n = 21
Any Pain	7	2	4	5
Grade 3 Pain	0	0	0	1
Any Redness	8	3	4	4
Grade 3 Redness	1	1	0	0
Any Swelling	6	4	5	2
Grade 3 Swelling	0	1	1	1

Population analysed: The analysis was performed on the Primary Total Vaccinated Cohort, which included all vaccinated subjects (with at least one vaccine administration documented) for whom data were available.

Primary outcome: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Time frame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine. Count of participants. Unit: Participants

Measure	Dengue Formulation 17a Group n = 22	Dengue Formulation 17b Group n = 22	Dengue Formulation 19 Group n = 21	Placebo Group n = 21
Any Abdominal pain	0	3	3	4
Grade 3 Abdominal pain	0	0	1	0
Related Abdominal pain	0	2	2	3
Any Arthralgia	5	2	2	3
Grade 3 Arthralgia	0	0	0	1
Related Arthralgia	4	2	2	2
Any Fatigue	8	5	5	7
Grade 3 Fatigue	0	0	1	1

Primary outcome: Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4

Time frame: At 30 days (Month 7) after Dose 2 of the study vaccine. Geometric mean (95% Confidence Interval). Unit: ED50

Measure	Dengue Formulation 17a Group n = 16	Dengue Formulation 17b Group n = 18	Dengue Formulation 19 Group n = 15	Placebo Group n = 19
DEN-1	241 (81 to 719)	83 (25 to 273)	204 (69 to 603)	7 (4 to 14)
DEN-2	691 (407 to 1175)	223 (76 to 656)	342 (123 to 954)	6 (4 to 10)
DEN-3	94 (28 to 321)	55 (17 to 177)	96 (30 to 309)	6 (4 to 10)
DEN-4	350 (85 to 1439)	91 (27 to 305)	84 (24 to 294)	6 (4 to 8)

Population analysed: The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Primary outcome: Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status

Time frame: At 5 to 12 months post-Dose 2 of the study vaccine. Geometric mean (95% Confidence Interval). Unit: ED50

Measure	Dengue Formulation 17b Group n = 6	Dengue Formulation 19 Group n = 7
DEN-1, Not primed	15 (4 to 57)	35 (6 to 187)
DEN-1, Primed	521 (40 to 6785)	2430 (2430 to 2430)
DEN-2, Not primed	33 (5 to 203)	30 (6 to 158)
DEN-2, Primed	346 (0 to 97683203)	673 (10 to 46541)
DEN-3, Not primed	7 (3 to 20)	12 (4 to 38)
DEN-3, Primed	426 (0 to 785070000000000)	1413 (1165 to 1715)
DEN-4, Not primed	29 (2 to 521)	23 (3 to 168)
DEN-4, Primed	123 (0 to 15158843)	766 (1 to 959438)

Population analysed: The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects who completed the primary vaccination course, who had received the booster dose according to their random assignment and for whom data concerning immunogenicity outcome measures were available.

25 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited local and general symptoms: during the 21-day (Days 0-20) follow up period after primary vaccination; Unsolicited AEs: during the 31-day (Days 0-30) follow up period after primary vaccination; SAEs: throughout the whole study period (from Day 0 up to Month 6 post-booster vaccination).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dengue Formulation 17a Group	0 of 22 (0%)	20 of 22 (90.9%)	0 of 22
Dengue Formulation 17b Group	1 of 22 (4.5%)	19 of 22 (86.4%)	0 of 22
Dengue Formulation 19 Group	1 of 21 (4.8%)	18 of 21 (85.7%)	0 of 21
Placebo Group	1 of 21 (4.8%)	16 of 21 (76.2%)	0 of 21

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

GSK Clinical Trials study director

GlaxoSmithKline

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Live attenuated tetravalent dengue vaccine in people with Dengue, run by GlaxoSmithKline at 1 site in United States.

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 6 inclusion and 16 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 Feb 2019. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

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 Feb 2019). 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 Subjects With Any and Grade 3 Solicited Local Symptoms (time frame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine). 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 NCT00239577.

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 Feb 2019.