Back to resultsA Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults
Primary Purpose
Dengue
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Live attenuated tetravalent dengue vaccine
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Dengue focused on measuring Dengue infection
Eligibility Criteria
Inclusion: 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 Exclusion: 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 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
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
DENGUE FORMULATION 17A GROUP
DENGUE FORMULATION 17B GROUP
DENGUE FORMULATION 19 GROUP
PLACEBO GROUP
Arm Description
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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).
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.
Number of Subjects With Suspected and Confirmed Dengue
The number of subjects with suspected and confirmed Dengue post-vaccination.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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].
Number of Subjects With Suspected and Confirmed Dengue
The number of subjects with suspected and confirmed Dengue post-booster vaccination.
Number of Subjects With Measurable Dengue Viremia
The number of subjects with measurable dengue viremia at specified timepoints.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00239577
Brief Title
A Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
April 5, 2006 (Actual)
Primary Completion Date
June 19, 2007 (Actual)
Study Completion Date
June 19, 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
This descriptive study will evaluate the safety and immunogenicity of 5 different formulations of the WRAIR dengue vaccine compared to a placebo.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue
Keywords
Dengue infection
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DENGUE FORMULATION 17A GROUP
Arm Type
Experimental
Arm Description
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.
Arm Title
DENGUE FORMULATION 17B GROUP
Arm Type
Experimental
Arm Description
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.
Arm Title
DENGUE FORMULATION 19 GROUP
Arm Type
Experimental
Arm Description
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.
Arm Title
PLACEBO GROUP
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Live attenuated tetravalent dengue vaccine
Intervention Description
Live attenuated tetravalent dengue vaccine
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description
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.
Time Frame
During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Title
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description
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.
Time Frame
During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Title
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
Description
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.
Time Frame
At 30 days (Month 7) after Dose 2 of the study vaccine
Title
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
Description
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.
Time Frame
At 5 to 12 months post-Dose 2 of the study vaccine
Title
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
Description
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.
Time Frame
At Month 1 post-booster dose of the study vaccine
Secondary Outcome Measure Information:
Title
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description
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.
Time Frame
During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine
Title
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description
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.
Time Frame
During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine
Title
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description
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.
Time Frame
During the 21-day (Days 0-20) follow-up after each dose of the study vaccine
Title
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description
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.
Time Frame
During the 21-day (Days 0-20) follow-up after each dose of the study vaccine
Title
Number of Subjects With Unsolicited Adverse Events (AEs)
Description
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.
Time Frame
During the 31-day (Days 0-30) follow-up after any study vaccine dose
Title
Number of Subjects With Serious Adverse Events (SAEs)
Description
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame
During the whole primary phase of the study (from Day 0 up to Month 9)
Title
Number of Subjects With Alert Values for Safety Laboratory Determinations
Description
Among assessed haematological and biochemical parameters were: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), hematocrit (HC), absolute neutrophil count (NEU) and platelet count (Platelet).
Time Frame
During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7)
Title
Number of Subjects With Abnormal Findings at Dengue Physical Examination
Description
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.
Time Frame
During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses
Title
Number of Subjects With Suspected and Confirmed Dengue
Description
The number of subjects with suspected and confirmed Dengue post-vaccination.
Time Frame
During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses
Title
Number of Subjects With Measurable Dengue Viremia
Description
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.
Time Frame
During the 31-day (Days 0-30) follow-up after each vaccine dose
Title
Number of Subjects With Safety Laboratory Determinations Outside the Normal Ranges
Description
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.
Time Frame
During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7)
Title
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
Description
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.
Time Frame
At Month 0 and Month 1
Title
Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype
Description
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.
Time Frame
At Months 0, 1 and 7
Title
Number of Subjects With Antibody Titers Above the Assay Cut-off Value (Tetravalent Response) for All Dengue Serotypes
Description
The antibody titers and pre-vaccination status were determined by MN50 with a cut-off value equal to 1:10.
Time Frame
At Months 1 and 7
Title
Number of Subjects With Sero-response to Each DEN Type
Description
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.
Time Frame
At Months 1 and 7
Title
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description
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.
Time Frame
During the 21-day (Days 0-20) follow-up after the study vaccine booster dose
Title
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description
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.
Time Frame
During the 21-day (Days 0-20) follow-up after the study vaccine booster dose
Title
Number of Subjects With Any, Grade 3 and Related Unsolicited AEs
Description
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.
Time Frame
During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Title
Number of Subjects With SAEs
Description
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame
During the whole booster phase of the study (from pre-vaccination up to Month 6 post-vaccination with the booster dose)
Title
Number of Subjects With Hematological and Biochemical Determinations Within and Outside the Normal Ranges
Description
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.
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]
Title
Number of Subjects With Alert Values for Safety Laboratory Determinations
Description
Among assessed haematological and biochemical parameters were: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), hematocrit (HC), absolute neutrophil count (NEU) and platelet count (Platelet).
Time Frame
During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Title
Number of Subjects With Abnormal Findings at Dengue Physical Examination
Description
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].
Time Frame
At Month 1 post-booster vaccination
Title
Number of Subjects With Suspected and Confirmed Dengue
Description
The number of subjects with suspected and confirmed Dengue post-booster vaccination.
Time Frame
During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
Title
Number of Subjects With Measurable Dengue Viremia
Description
The number of subjects with measurable dengue viremia at specified timepoints.
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)
Title
Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype
Description
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.
Time Frame
Before (PRE) and one month after the booster vaccination (Month 1)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion:
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
Exclusion:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Silver Spring
State/Province
Maryland
ZIP/Postal Code
20910
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults
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