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A Study of Two Doses of WRAIR Dengue Vaccine Administered Six Months Apart to Healthy Adults and Children

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00468858
First Posted: May 3, 2007
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
  Purpose
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.

Condition Intervention Phase
Dengue Fever Dengue Hemorrhagic Fever Dengue Shock Syndrome Other: Placebo Biological: T-DEN-Post-Transfection F17 Biological: T-DEN-Post-Transfection F19 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Safety: Incidence of All and Grade 3 Solicited Local Symptoms [ Time Frame: Within 21 days (days 0-20) f/up period after each vaccine dose ]
    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 [ Time Frame: Within the 31-day (days 0-30) follow-up period after each vaccine dose ]
    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) [ Time Frame: 6 months + 30 day follow-up period after last vaccine dose ]
    Summary of SAEs, 6 months + 30 day follow-up period after last vaccine dose


Secondary Outcome Measures:
  • Incidence of Suspected and Laboratory Confirmed Dengue [ Time Frame: 31-day (days 0-30) post-vaccination period and after 31-day period ]
    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 [ Time Frame: at month 7 (one month post dose 2) ]
    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 [ Time Frame: Pre-vaccination, at post dose 1, months 3 and 6 and post dose 2, month 7 ]
    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 [ Time Frame: Pre-accination, at post dose 1, months 3 and 6 and post dose 2, month 7 ]
    Seropositivity rates for DEN neut. antibodies for unprimed and primed subjects

  • Vaccine Response to DEN Antibody at Post Dose 1, Month 3 [ Time Frame: at month 3, post dose 1 ]

    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 [ Time Frame: at month 7, post dose 2 ]
    Vaccine response for DEN-1, DEN2, DEN-3, DEN-4 antibody at post dose 2, month 7


Enrollment: 636
Study Start Date: July 2007
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T-DEN-Post-Transfection F17
Post-Transfection F17, full dose
Biological: T-DEN-Post-Transfection F17
Lyophilized, single dose vials and sterile water for injection; 0.5 mL dose at 0 and 6 months
Experimental: T-DEN-Post-Transfection F19
Post-Transfection F19, full dose
Biological: T-DEN-Post-Transfection F19
Lyophilized, single dose vials and sterile water for injection; 0.5 mL dose at 0 and 6 months
Placebo Comparator: Placebo
Control
Other: Placebo

Lyophilized, single dose vials and sterile water for

> injection; 0.5 mL dose; Vaccination schedule: 0, 6 months


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.

>

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Months to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00468858


Locations
Puerto Rico
San Juan Batista Medical School
Caguas, Puerto Rico, 00725
Private Practice
Carolina, Puerto Rico, 00983
St Luke's Memorial Hospital
Ponce, Puerto Rico, 00733
Caparra Internal Medicine Research Center
Rio Grande, Puerto Rico, 00745
Private Practice
Rio Piedras, Puerto Rico, 00926
RCMI Clinical Research Center
Rio Piedras, Puerto Rico, 00935
Torre Medica San Vicente de Paul
San German, Puerto Rico, 00683
Clinical Research PR
San Juan, Puerto Rico, 00909-1711
Centro de Neumologia Pediatricia
San Juan, Puerto Rico, 00917
Private Practice
San Juan, Puerto Rico, 00921
Dept Pediatria, Esc. De Medicina
San Juan, Puerto Rico, 00936-5067
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
GlaxoSmithKline
Investigators
Principal Investigator: Jorge Bertran-Pasarell, MD Dept Medicina Interna Seccion Enfermedades Infecciosas
Principal Investigator: Clemente Diaz-Perez, MD University of PR
Principal Investigator: Ines O. Esquilin-Rivera, MD University of PR
Principal Investigator: Evelyn Matta-Fontanet, MD Caparra Internal Medicine Research Center
Principal Investigator: Domingo Chardon-Feliciano, MD Ponce School of Medicine
Principal Investigator: Javier Morales-Ramirez, MD Clinical Research PR
Principal Investigator: Luis Rodriguez-Carrasquillo, MD Private Practice, PR
Principal Investigator: Jose Rodriguez-Santana, MD Centro de Neumologia pediatrica
Principal Investigator: Miguel Sosa-Padilla, MD Private Practice PR
Principal Investigator: Jose Tavarez-Valle, MD Private Practice, PR
Principal Investigator: Alberto Santiago-Cornier, MD Department of Molecular Medicine
Principal Investigator: Anna Quintero, MD San Juan Batista Medical School
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT00468858     History of Changes
Other Study ID Numbers: A-14040
WIRB number 20070071 ( Other Identifier: Western Institutional Review Boards (WIRB) )
106405 ( Other Identifier: GSK )
T-DEN-003 ( Other Identifier: MRMC/WRAIR )
First Submitted: May 1, 2007
First Posted: May 3, 2007
Results First Submitted: February 8, 2017
Results First Posted: June 6, 2017
Last Update Posted: July 2, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: GlaxoSmithKline

Keywords provided by U.S. Army Medical Research and Materiel Command:
Dengue
Virus
Live-attenuated
Vaccine
Dengue viral infection
Dengue Vaccine

Additional relevant MeSH terms:
Dengue
Severe Dengue
Fever
Hemorrhagic Fevers, Viral
Shock
Body Temperature Changes
Signs and Symptoms
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Pathologic Processes
Vaccines
Immunologic Factors
Physiological Effects of Drugs