A Phase II Trial of a WRAIR Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
Walter Reed Army Institute of Research (WRAIR)
ClinicalTrials.gov Identifier:
NCT00350337
First received: July 6, 2006
Last updated: July 16, 2008
Last verified: July 2008
  Purpose

This descriptive study will evaluate the safety and immunogenicity of 3 different formulations of the WRAIR dengue vaccine compared to a placebo.


Condition Intervention Phase
Dengue
Biological: Live attenuated tetravalent dengue vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Prevention
Official Title: Phase II, Randomized, Observer-Blind, Single Center, Controlled Study of Two Doses of Various Formulations of WRAIR Live Attenuated Tetravalent Dengue Vaccine Compared to Placebo Control Administered on 0-6-Month Schedule, to Healthy Adults

Resource links provided by NLM:


Further study details as provided by Walter Reed Army Institute of Research (WRAIR):

Primary Outcome Measures:
  • Occurrence of any, and grade 3 solicited adverse events (AEs) within 21 days follow-up after dose 1 of study vaccine;
  • N antibody (GMT) to DEN serotypes 1, 2, 3 and 4, 30 and 90 days after the last study vaccine dose

Secondary Outcome Measures:
  • Safety endpoints
  • Occurrence of any, and grade 3 solicited adverse events (AEs) within 21 days follow-up after dose 2 of study vaccine;
  • Occurrence of each type of any and grade 3 solicited AE within the 21-day solicited follow-up period after each dose;
  • Occurrence of unsolicited AEs within 31 days (days 0-30) after any study vaccine dose;
  • Occurrence of serious adverse events (SAEs) throughout the entire study period;
  • Occurrence of alert values for safety laboratory determinations within 31 days after each vaccine dose.
  • Occurrence of abnormal findings at DEN physical examination after each vaccine dose
  • Occurrence of suspected and confirmed dengue throughout the entire study period
  • Immunogenicity endpoints
  • N antibody titer above the assay cut-off, to each DEN serotype, after each dose;
  • N antibody titer above the assay cut-off, to all dengue serotypes after each dose;
  • N sero-response to each DEN serotype after each dose
  • N antibody titer to each DEN serotype after vaccine dose 1
  • Occurrence of measurable dengue viremia at specified time points following each vaccine dose.

Estimated Enrollment: 88
Study Start Date: January 2006
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Detailed Description:

Subjects will be randomized into one of 4 groups. One group will receive a placebo vaccine and the others will receive one of 3 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.

A third (booster) dose of post transfection F17 or F19 will be administered approximately 5 to 12 months after dose 2 to all subjects who received one of these formulation for their first two doses. Volunteers will return for a single visit 6 months after receiving their booster dose (long term follow-up)

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A 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 (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study;
  • If the subject is female, she must be of non-childbearing potential, i.e. either 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; oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) 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 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 drug abuse or alcohol consumption (more than 2 drinks per day);
  • History of allergic disease/reaction likely to be exacerbated by any component of the vaccine;
  • History of urticaria related to mosquito bites requiring medical attention;
  • 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;
  • Subject seropositive for HBsAg, anti-HCV or anti-HIV;
  • Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever);
  • (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., 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 days preceding the study vaccine (includes 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 days before each dose of the study vaccine and ending 30 days after;
  • A planned move to a location that will prohibit participating in the trial for 9 months after the initial vaccination;
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 90 days 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 days preceding the first dose or planned administration during the study period;
  • Any chronic systemic drug therapy to be continued during the study period (except for vitamin/mineral supplements, a single anti-hypertension medication or routine treatment for gastro-esophageal reflux).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00350337

Locations
United States, Maryland
Walter Reed Army Institute of Research
Silver Spring, Maryland, United States, 20910
Sponsors and Collaborators
Walter Reed Army Institute of Research (WRAIR)
GlaxoSmithKline
Investigators
Principal Investigator: Stephen J Thomas, MD, FACP Walter Reed Army Institute of Research (WRAIR)
  More Information

No publications provided by Walter Reed Army Institute of Research (WRAIR)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00350337     History of Changes
Other Study ID Numbers: WRAIR 1151, GSK 103996, HSRRB A-13291
Study First Received: July 6, 2006
Last Updated: July 16, 2008
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral

ClinicalTrials.gov processed this record on August 21, 2014