A Study of Two Doses of WRAIR Dengue Vaccine Administered Six Months Apart to Healthy Adults and Children
Primary Purpose
Dengue Fever, Dengue Hemorrhagic Fever, Dengue Shock Syndrome
Status
Completed
Phase
Phase 2
Locations
Puerto Rico
Study Type
Interventional
Intervention
Placebo
T-DEN-Post-Transfection F17
T-DEN-Post-Transfection F19
Sponsored by
About this trial
This is an interventional prevention trial for Dengue Fever focused on measuring Dengue, Virus, Live-attenuated, Vaccine, Dengue viral infection, Dengue Vaccine
Eligibility Criteria
Inclusion Criteria:>
- Subjects who the investigator believes that they and/or their parents/guardians can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study.>
- A healthy male or non-pregnant female between 12 months (mths) and 50 years (yrs) 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;>
- For children: 23mths of age, full compliance with the United States Advisory Committee on Immunization Practices (U.S. ACIP) recommended childhood immunization schedule;>
- Written informed consent obtained from the subject or a parent/guardian and assent for subjects 7-20 yrs of age;>
- If the subject is female, she must be of non-childbearing potential, i.e. either pre-menarcheal, surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (i.e. intrauterine contraceptive device; condom and spermicide combination, oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) for 30 days (dys) prior to vaccination, have a negative pregnancy test within 48 hrs prior to vaccination and must agree to continue such precautions for 60 dys after completion of the vaccination series. Any child who begins menarche during the study period must follow the same precautions listed above, from menarche until 60 dys after the second vaccine dose.>
Exclusion Criteria:>
- Pregnant or lactating female;>
- Female planning to become pregnant or planning to discontinue abstinence or contraceptive precautions;>
- History of any neurological or behavioral disorder or seizures, with the exception of a single febrile seizure in childhood; >
- History of allergic disease/reaction likely to be exacerbated by any component of the vaccine;>
- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect, as determined by physical examination or laboratory tests;>
- Any confirmed or suspected immunosuppressive or immunodeficient condition;>
- Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever); note that vaccine can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., equivalent to an oral temperature <37.5°C/<99.5°F.>
- Chronic hepatomegaly, right upper quadrant abdominal pain or tenderness;>
- Chronic splenomegaly, left upper quadrant abdominal pain or tenderness;>
- Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 dys preceding the first dose of study vaccine/placebo or planned use during the study period;>
- Planned administration of a vaccine not foreseen by the study protocol during the period starting from 30 dys before each dose of the study vaccine and ending 30 dys after; with the exception of standard infant and children "inactivated" vaccines or the inactivated influenza vaccine administered to adults or children; >
- A planned move to a location that will prohibit participating in the trial for the 12 mth duration;>
- Chronic administration (defined as more than 14 dys) of immunosuppressants or other immune-modifying drugs within 90 dys preceding the first dose or planned administration during the study period. For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed;>
- Administration of immunoglobulins and/or blood products within 90 dys preceding the first dose or planned administration during the study period;>
- Hypertension;>
- Chest pain, palpitations, dizziness, shortness of breath unrelated to asthma, arrhythmias or friction rubs;>
- Any chronic systemic drug therapy to be continued during the study period (except for vitamin/mineral supplements, routine treatment for gastro-esophageal reflux);>
- Potential adult volunteers, or parents of potential child volunteers, who do not have easy access to a fixed or mobile telephone;>
- History of chronic alcohol consumption and/or drug abuse.
Sites / Locations
- San Juan Batista Medical School
- Private Practice
- St Luke's Memorial Hospital
- Caparra Internal Medicine Research Center
- Private Practice
- RCMI Clinical Research Center
- Torre Medica San Vicente de Paul
- Clinical Research PR
- Centro de Neumologia Pediatricia
- Private Practice
- Dept Pediatria, Esc. De Medicina
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
T-DEN-Post-Transfection F17
T-DEN-Post-Transfection F19
Placebo
Arm Description
Post-Transfection F17, full dose
Post-Transfection F19, full dose
Control
Outcomes
Primary Outcome Measures
Safety: Incidence of All and Grade 3 Solicited Local Symptoms
Incidence of all and grade 3 (prevents normal, everyday activities) solicited local and general symptoms within the 21-day follow-up period (Total vaccinated cohort)
Safety: Summary of Unsolicited Adverse Events Within the 31-day Post-vaccination Period
Summary of unsolicited Adverse Events within the 31-day post-vaccination period by age group (total vaccinated cohort)
Safety: Occurrence of Serious Adverse Events (SAEs)
Summary of SAEs, 6 months + 30 day follow-up period after last vaccine dose
Secondary Outcome Measures
Incidence of Suspected and Laboratory Confirmed Dengue
Incidence of suspected and confirmed dengue reported during the 31-day (Days 0-30) post-vaccination period and after the 31-day period
GMTs for Antibody Titer Above the Assay Cut Off to Each DEN Serotype for Unprimed and Primed Subjects
Comparison of F17 and F19 formulations in terms of GMTs at month 7 (one month post dose 2) for each DEN type, -unprimed and primed subjects
Percent of Subjects With Neut. Antibody Titer Above the Assay Cut-off to All Dengue Serotypes
Monovalent, bivalent, trivalent and tetravalent response for DEN neut. antibodies for unprimed and primed subjects
Percent of Subjects With Neut. Sero-response to Each DEN Serotype
Seropositivity rates for DEN neut. antibodies for unprimed and primed subjects
Vaccine Response to DEN Antibody at Post Dose 1, Month 3
Vaccine response for DEN-1, DEN-2, DEN-3 and DEN-4 antibody
S- = seronegative subjects (antibody titer <10 ED50 for DEN-1, 2, 3, and 4 prior to vaccination; S+ = Seropositive subjects (antibody titer >10 ED50 for DEN-1, 2, 3 and 4 prior to vaccination; Total = subjects either seropositive or seronegative at pre-vaccination
Vaccine response defined as: For initially seronegative subjects, antibody titer >10 ED50 at PI(M3) and for initially seropositive subjects: antibody titer at PI(m3) >4 fold the pre-vaccination antibody titer
Vaccine Response to DEN Antibody at Post Dose 2, Month 7
Vaccine response for DEN-1, DEN2, DEN-3, DEN-4 antibody at post dose 2, month 7
Full Information
NCT ID
NCT00468858
First Posted
May 1, 2007
Last Updated
June 5, 2017
Sponsor
U.S. Army Medical Research and Development Command
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT00468858
Brief Title
A Study of Two Doses of WRAIR Dengue Vaccine Administered Six Months Apart to Healthy Adults and Children
Official Title
Phase II, Randomized, Double-blind, Placebo-controlled Study of Two Doses of WRAIR Live Attenuated Tetravalent Dengue Vaccine Formulations, Administered Six Months Apart, to Healthy Adults and Children
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
April 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
U.S. Army Medical Research and Development Command
Collaborators
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and effectiveness of two different formulations of an investigational dengue vaccine (T-DEN) against a placebo vaccine when two doses are given six months apart to adults and children.
Detailed Description
In this study, children and adults at multiple sites in Puerto Rico will be randomly allocated to receive one of two T-DEN formulations or placebo. Subjects will be stratified by age group (a specific number of subjects in each of 4 age groups [12 months to 50 years of age] will be enrolled). The study includes 6 scheduled visits and 4 scheduled venipunctures. Safety follow-up for dengue may require unscheduled visits and venipunctures.> Multiple DEN virus serotypes are endemic in Puerto Rico and all residents are considered to be at risk for dengue. The results of this phase II study will provide a basis for identifying the vaccine formulations which elicit neutralizing antibodies to all four dengue virus serotypes in a high proportion of vaccine recipients. The most immunogenic and well tolerated candidate formulation identified in this study will be considered for advancement to phase III development.>
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue Fever, Dengue Hemorrhagic Fever, Dengue Shock Syndrome
Keywords
Dengue, Virus, Live-attenuated, Vaccine, Dengue viral infection, Dengue Vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
636 (Actual)
8. Arms, Groups, and Interventions
Arm Title
T-DEN-Post-Transfection F17
Arm Type
Experimental
Arm Description
Post-Transfection F17, full dose
Arm Title
T-DEN-Post-Transfection F19
Arm Type
Experimental
Arm Description
Post-Transfection F19, full dose
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Control
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Lyophilized, single dose vials and sterile water for
> injection; 0.5 mL dose; Vaccination schedule: 0, 6 months
Intervention Type
Biological
Intervention Name(s)
T-DEN-Post-Transfection F17
Intervention Description
Lyophilized, single dose vials and sterile water for injection; 0.5 mL dose at 0 and 6 months
Intervention Type
Biological
Intervention Name(s)
T-DEN-Post-Transfection F19
Intervention Description
Lyophilized, single dose vials and sterile water for injection; 0.5 mL dose at 0 and 6 months
Primary Outcome Measure Information:
Title
Safety: Incidence of All and Grade 3 Solicited Local Symptoms
Description
Incidence of all and grade 3 (prevents normal, everyday activities) solicited local and general symptoms within the 21-day follow-up period (Total vaccinated cohort)
Time Frame
Within 21 days (days 0-20) f/up period after each vaccine dose
Title
Safety: Summary of Unsolicited Adverse Events Within the 31-day Post-vaccination Period
Description
Summary of unsolicited Adverse Events within the 31-day post-vaccination period by age group (total vaccinated cohort)
Time Frame
Within the 31-day (days 0-30) follow-up period after each vaccine dose
Title
Safety: Occurrence of Serious Adverse Events (SAEs)
Description
Summary of SAEs, 6 months + 30 day follow-up period after last vaccine dose
Time Frame
6 months + 30 day follow-up period after last vaccine dose
Secondary Outcome Measure Information:
Title
Incidence of Suspected and Laboratory Confirmed Dengue
Description
Incidence of suspected and confirmed dengue reported during the 31-day (Days 0-30) post-vaccination period and after the 31-day period
Time Frame
31-day (days 0-30) post-vaccination period and after 31-day period
Title
GMTs for Antibody Titer Above the Assay Cut Off to Each DEN Serotype for Unprimed and Primed Subjects
Description
Comparison of F17 and F19 formulations in terms of GMTs at month 7 (one month post dose 2) for each DEN type, -unprimed and primed subjects
Time Frame
at month 7 (one month post dose 2)
Title
Percent of Subjects With Neut. Antibody Titer Above the Assay Cut-off to All Dengue Serotypes
Description
Monovalent, bivalent, trivalent and tetravalent response for DEN neut. antibodies for unprimed and primed subjects
Time Frame
Pre-vaccination, at post dose 1, months 3 and 6 and post dose 2, month 7
Title
Percent of Subjects With Neut. Sero-response to Each DEN Serotype
Description
Seropositivity rates for DEN neut. antibodies for unprimed and primed subjects
Time Frame
Pre-accination, at post dose 1, months 3 and 6 and post dose 2, month 7
Title
Vaccine Response to DEN Antibody at Post Dose 1, Month 3
Description
Vaccine response for DEN-1, DEN-2, DEN-3 and DEN-4 antibody
S- = seronegative subjects (antibody titer <10 ED50 for DEN-1, 2, 3, and 4 prior to vaccination; S+ = Seropositive subjects (antibody titer >10 ED50 for DEN-1, 2, 3 and 4 prior to vaccination; Total = subjects either seropositive or seronegative at pre-vaccination
Vaccine response defined as: For initially seronegative subjects, antibody titer >10 ED50 at PI(M3) and for initially seropositive subjects: antibody titer at PI(m3) >4 fold the pre-vaccination antibody titer
Time Frame
at month 3, post dose 1
Title
Vaccine Response to DEN Antibody at Post Dose 2, Month 7
Description
Vaccine response for DEN-1, DEN2, DEN-3, DEN-4 antibody at post dose 2, month 7
Time Frame
at month 7, post dose 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:>
Subjects who the investigator believes that they and/or their parents/guardians can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study.>
A healthy male or non-pregnant female between 12 months (mths) and 50 years (yrs) 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;>
For children: 23mths of age, full compliance with the United States Advisory Committee on Immunization Practices (U.S. ACIP) recommended childhood immunization schedule;>
Written informed consent obtained from the subject or a parent/guardian and assent for subjects 7-20 yrs of age;>
If the subject is female, she must be of non-childbearing potential, i.e. either pre-menarcheal, surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (i.e. intrauterine contraceptive device; condom and spermicide combination, oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) for 30 days (dys) prior to vaccination, have a negative pregnancy test within 48 hrs prior to vaccination and must agree to continue such precautions for 60 dys after completion of the vaccination series. Any child who begins menarche during the study period must follow the same precautions listed above, from menarche until 60 dys after the second vaccine dose.>
Exclusion Criteria:>
Pregnant or lactating female;>
Female planning to become pregnant or planning to discontinue abstinence or contraceptive precautions;>
History of any neurological or behavioral disorder or seizures, with the exception of a single febrile seizure in childhood; >
History of allergic disease/reaction likely to be exacerbated by any component of the vaccine;>
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect, as determined by physical examination or laboratory tests;>
Any confirmed or suspected immunosuppressive or immunodeficient condition;>
Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever); note that vaccine can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., equivalent to an oral temperature <37.5°C/<99.5°F.>
Chronic hepatomegaly, right upper quadrant abdominal pain or tenderness;>
Chronic splenomegaly, left upper quadrant abdominal pain or tenderness;>
Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 dys preceding the first dose of study vaccine/placebo or planned use during the study period;>
Planned administration of a vaccine not foreseen by the study protocol during the period starting from 30 dys before each dose of the study vaccine and ending 30 dys after; with the exception of standard infant and children "inactivated" vaccines or the inactivated influenza vaccine administered to adults or children; >
A planned move to a location that will prohibit participating in the trial for the 12 mth duration;>
Chronic administration (defined as more than 14 dys) of immunosuppressants or other immune-modifying drugs within 90 dys preceding the first dose or planned administration during the study period. For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed;>
Administration of immunoglobulins and/or blood products within 90 dys preceding the first dose or planned administration during the study period;>
Hypertension;>
Chest pain, palpitations, dizziness, shortness of breath unrelated to asthma, arrhythmias or friction rubs;>
Any chronic systemic drug therapy to be continued during the study period (except for vitamin/mineral supplements, routine treatment for gastro-esophageal reflux);>
Potential adult volunteers, or parents of potential child volunteers, who do not have easy access to a fixed or mobile telephone;>
History of chronic alcohol consumption and/or drug abuse.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jorge Bertran-Pasarell, MD
Organizational Affiliation
Dept Medicina Interna Seccion Enfermedades Infecciosas
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Clemente Diaz-Perez, MD
Organizational Affiliation
University of PR
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ines O. Esquilin-Rivera, MD
Organizational Affiliation
University of PR
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Evelyn Matta-Fontanet, MD
Organizational Affiliation
Caparra Internal Medicine Research Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Domingo Chardon-Feliciano, MD
Organizational Affiliation
Ponce School of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Javier Morales-Ramirez, MD
Organizational Affiliation
Clinical Research PR
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Luis Rodriguez-Carrasquillo, MD
Organizational Affiliation
Private Practice, PR
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jose Rodriguez-Santana, MD
Organizational Affiliation
Centro de Neumologia pediatrica
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Miguel Sosa-Padilla, MD
Organizational Affiliation
Private Practice PR
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jose Tavarez-Valle, MD
Organizational Affiliation
Private Practice, PR
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alberto Santiago-Cornier, MD
Organizational Affiliation
Department of Molecular Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anna Quintero, MD
Organizational Affiliation
San Juan Batista Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
San Juan Batista Medical School
City
Caguas
ZIP/Postal Code
00725
Country
Puerto Rico
Facility Name
Private Practice
City
Carolina
ZIP/Postal Code
00983
Country
Puerto Rico
Facility Name
St Luke's Memorial Hospital
City
Ponce
ZIP/Postal Code
00733
Country
Puerto Rico
Facility Name
Caparra Internal Medicine Research Center
City
Rio Grande
ZIP/Postal Code
00745
Country
Puerto Rico
Facility Name
Private Practice
City
Rio Piedras
ZIP/Postal Code
00926
Country
Puerto Rico
Facility Name
RCMI Clinical Research Center
City
Rio Piedras
ZIP/Postal Code
00935
Country
Puerto Rico
Facility Name
Torre Medica San Vicente de Paul
City
San German
ZIP/Postal Code
00683
Country
Puerto Rico
Facility Name
Clinical Research PR
City
San Juan
ZIP/Postal Code
00909-1711
Country
Puerto Rico
Facility Name
Centro de Neumologia Pediatricia
City
San Juan
ZIP/Postal Code
00917
Country
Puerto Rico
Facility Name
Private Practice
City
San Juan
ZIP/Postal Code
00921
Country
Puerto Rico
Facility Name
Dept Pediatria, Esc. De Medicina
City
San Juan
ZIP/Postal Code
00936-5067
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
GlaxoSmithKline
Citations:
PubMed Identifier
26175027
Citation
Bauer K, Esquilin IO, Cornier AS, Thomas SJ, Quintero Del Rio AI, Bertran-Pasarell J, Morales Ramirez JO, Diaz C, Carlo S, Eckels KH, Tournay E, Toussaint JF, De La Barrera R, Fernandez S, Lyons A, Sun W, Innis BL. A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico. Am J Trop Med Hyg. 2015 Sep;93(3):441-453. doi: 10.4269/ajtmh.14-0625. Epub 2015 Jul 14.
Results Reference
derived
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A Study of Two Doses of WRAIR Dengue Vaccine Administered Six Months Apart to Healthy Adults and Children
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