Clinical trial NCT01084291: Evaluation of the Safety and Immune Response to an Investigational Dengue Type 1 Vaccine
Official title: A Phase I Evaluation of the Safety and Immunogenicity of the rDEN1∆30 Dengue Serotype 1 Vaccine Given at a Single Dose of 101 PFU in Healthy Flavivirus-naïve Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dengue Virus
Keywords: Vaccine
Dengue Hemorrhagic Fever
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2010-03-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Dengue viruses can cause dengue fever and other serious health conditions, primarily affecting people living in tropical regions of the world. There are four types of dengue virus, and infection with one does not offer protection against the others. This study will test whether a vaccine developed to prevent infection with dengue virus type 1 (DEN1) causes a response in people's immune system and is safe.

Detailed description: The dengue virus causes approximately 50 million cases of dengue fever and 1.5 million cases of the more severe diseases dengue hemorrhagic fever (DHS) and dengue shock syndrome (DSS) every year. There are four subtypes of the virus, and infection with one offers no protection from infection by the others. In fact, most cases of DHS and DSS occur in people infected by more than one subtype. In areas of the world where multiple subtypes of dengue are common, vaccines must be developed against each of the subtypes of dengue virus. This study will examine the safety and immune response of an investigational vaccine for preventing infection with DEN1.

Participation in this study will last about 6 weeks. Participants will be randomly assigned to be injected with either the investigational study vaccine or a placebo. Participants will have a five in six chance of receiving the vaccine. The first study visit will take place on the vaccination day, on which participants will undergo a physical examination, blood draw, and pregnancy test, and then receive the vaccine. Participants will be given a thermometer and temperature card, and be told to record their temperature three times per day for 16 days after vaccination. Participants will come to follow-up visits every other day for the 16 days after vaccination, and then 3, 4, and 6 weeks after vaccination (Days 21, 28, and 42). Assessments completed during these visits will include a questionnaire about how the participant is feeling, pregnancy test, review of temperature cards, blood draw, and physical exam. Blood drawn will be analyzed to check participants' health, determine the amount of vaccine and antibodies in the blood, test markers in white blood cells and genes, and look for proteins that are important for fighting dengue infection.

Eligibility criteria: Inclusion Criteria:

* In good general health as determined by physical examination, laboratory screening, and review of medical history
* Available for the duration of the study, including approximately 6 weeks post-vaccination
* Female participants of childbearing potential must be willing to use effective contraception for the duration of the trial

Exclusion Criteria:

* Currently breast-feeding or pregnant
* Exhibits evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
* Presence of a behavioral, cognitive, or psychiatric disease that affects the ability of the participant to understand and cooperate with the requirements of the study protocol
* Has screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), ALT, and serum creatinine, as defined in this protocol
* Presence of any condition that would jeopardize the safety or rights of the participant or would render the participant unable to comply with the protocol
* Significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by participant history
* History of a severe allergic reaction or anaphylaxis
* Severe asthma (emergency room visit or hospitalization within the last 6 months)
* Presence of HIV infection, determined by screening and confirmatory assays
* Presence of hepatitis C virus (HCV) infection, determined by screening and confirmatory assays
* Presence of hepatitis B virus (HBV) infection, determined by hepatitis B surface antigen (HBsAg) screening
* Presence of any known immunodeficiency syndrome
* Uses anticoagulant medications
* Has used corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 42 days prior to or following vaccination. An immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg prednisone equivalent per day for greater than or equal to 14 days.
* Has received a live vaccine within 28 days or a killed vaccine within 14 days prior to vaccination or anticipated receipt of any vaccine during the 42 days following vaccination
* Has no spleen
* Received blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 42 days following vaccination
* History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus)
* Has received a flavivirus vaccine (licensed or experimental)
* Anticipates receipt of any investigational agent in the 42 days before or after vaccination
* Participant has definite plans to travel to a dengue endemic area during the study

Primary outcomes:
measure: Frequency of vaccine-related adverse events (AEs), as classified by both severity and seriousness, through active and passive surveillance
timeFrame: Measured throughout study
measure: Immunogenicity to dengue virus subtype one (DEN1), as assessed by neutralizing antibody titers
timeFrame: Measured 4 and 6 weeks after vaccination
Secondary outcomes:
measure: Frequency, quantity, and duration of viremia following vaccination
timeFrame: Measured every other day after vaccination for 16 days, and on Days 21, 28, and 42
measure: Number of vaccinees infected with DEN1, defined as recovery of vaccine virus from the blood or serum of a participant and/or by seroconversion to DEN1
timeFrame: Measured at study completion
measure: Comparison of the infectivity rates, safety, and immunogenicity of a single dose of DEN1 vaccine to those rates of previous clinical trials
timeFrame: Measured at study completion
Other outcomes:
Locations:
city: Burlington
country: United States
facility: Fletcher Allen Health Care (FAHC) General Clinical Research Center (GCRC)
state: Vermont
city: Burlington
country: United States
facility: University of Vermont Vaccine Testing Center
state: Vermont
Study officials:
affiliation: CIR, Johns Hopkins University
name: Anna Durbin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Vermont
name: Beth Kirkpatrick, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring;19(1):10-32. doi: 10.1089/vim.2006.19.10.
citation: Whitehead SS, Falgout B, Hanley KA, Blaney JE Jr, Markoff L, Murphy BR. A live, attenuated dengue virus type 1 vaccine candidate with a 30-nucleotide deletion in the 3' untranslated region is highly attenuated and immunogenic in monkeys. J Virol. 2003 Jan;77(2):1653-7. doi: 10.1128/jvi.77.2.1653-1657.2003.