Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3delta30/31‐7164) in Healthy Adults

Tracking Information
First Submitted Date ICMJE	January 27, 2009
First Posted Date ICMJE	January 28, 2009
Last Update Posted Date	November 15, 2013
Study Start Date ICMJE	September 2009
Actual Primary Completion Date	June 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 27, 2009)	Determine the safety of a single dose of the rDEN3Δ30/31‐7164 vaccine, as assessed by the frequency, severity, and seriousness of vaccine related adverse events (AEs). [ Time Frame: Throughout study ]; Determine the immunogenicity of a single dose of the rDEN3delta30/31‐7164 vaccine, as assessed by neutralizing antibody titers to DEN3 at 4 weeks and 6 weeks after vaccination [ Time Frame: Throughout study ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00831012 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 27, 2009)	Assess the frequency, quantity, and duration of viremia after a single dose of vaccine [ Time Frame: Throughout study ]; Determine the number of vaccinees infected with rDEN3delta30/31‐7164. Infection is defined as recovery of vaccine virus from the blood or serum of a volunteer and/or by seroconversion to DEN3 (a ≥4‐fold rise in DEN3 neutralizing antibody titers). [ Time Frame: Throughout study ]; Compare the infectivity rates, safety, and immunogenicity of a single dose of rDEN3delta30/31‐7164 vaccine between the dose level groups. [ Time Frame: Throughout study ]; Determine the durability of antibody response 26 weeks after vaccination [ Time Frame: At 26 weeks ]; Obtain an estimate for the Human Infectious Dose‐50% (HID50) if dose dependent infectivity is observed [ Time Frame: Throughout study ]; Evaluate the phenotype of peripheral blood mononuclear cells at primary infection with the rDEN3delta30/31‐7164 vaccine. [ Time Frame: Throughout study ]; Evaluate the cellular and humoral immune response to primary infection with the rDEN3delta30/31‐7164 vaccine [ Time Frame: Throughout study ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3delta30/31‐7164) in Healthy Adults
Official Title ICMJE	A Phase I Dose Comparison Study of the Safety and Immunogenicity of rDEN3delta30/31‐7164, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3
Brief Summary	Dengue fever, which is caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to test the safety of and immune response to a new dengue virus vaccine in healthy adults.
Detailed Description	More than 2 billion people living in tropical and subtropical regions of the world are at risk of dengue virus infection. Dengue viruses cause dengue fever, as well as the more severe dengue hemorrhagic fever/shock syndrome, and dengue virus infection is the leading cause of hospitalization and death in children in several tropical Asian countries. This study will evaluate the safety and immunogenicity of a live, attenuated dengue virus called rDEN3delta30/31‐7164. This study will consist of two groups, with Group 1 enrolling first. Group 1 participants will be randomly assigned to receive either 10^3 PFU of rDEN3delta30/31-7164 or placebo subcutaneously in their deltoid. Participants will be monitored at the clinic for 30 minutes after receiving the immunization to monitor for adverse effects. After that, participants will be asked to return to the clinic approximately every other day for the next 16 days, and then on Day 21, 28, 42, and 180. At each visit participants will have physical and clinical exams, vital signs, measures, blood drawn, and will be asked about any adverse events they may have experience. Female participants will be given a pregnancy test. In addition, participants will be asked to measure their temperature 3 times a day and record it in a temperature diary for the first 16 days after immunization. If less than 90% of the participants in Group 1 seroconvert to DEN3 then Group 2A will be enrolled. Group 2A will follow the same procedures as Group 1, but will receive a 10^5 PFU dose of rDEN3delta30/31-7164. If more than 90% of the participants in Group 1 seroconvert to DEN3 then Group 2B will be enrolled. Group 2A will follow the same procedures as Group 1, but will receive a 10^1 PFU dose of rDEN3delta30/31-7164.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
Condition ICMJE	Dengue Fever
Intervention ICMJE	Biological: rDEN3delta30/31‐7164; A live attenuated, recombinant DEN3 candidate vaccine virus
Study Arms	Experimental: Group 1 Group 1 will consist of healthy participants receiving an immunization of 10^3 PFU rDEN3delta30/31‐7164 Intervention: Biological: rDEN3delta30/31‐7164; Experimental: Group 2 Group 2A will consist of healthy participants who will receive an immunization of 10^5 PFU of rDEN3delta30/31‐7164 vaccine or placebo. Group 2A participants will be enrolled if less that 90% of Group 1 participants seroconvert to DEN3 by Study Day 42. Group 2B will consist of healthy participants who will receive an immunization of 10^1 PFU of rDEN3delta30/31‐7164 vaccine or placebo. Group 2B participants will be enrolled if more that 90% of Group 1 participants seroconvert to DEN3 by Study Day 42. Intervention: Biological: rDEN3delta30/31‐7164
Publications *	Katzelnick LC, Fonville JM, Gromowski GD, Bustos Arriaga J, Green A, James SL, Lau L, Montoya M, Wang C, VanBlargan LA, Russell CA, Thu HM, Pierson TC, Buchy P, Aaskov JG, Muñoz-Jordán JL, Vasilakis N, Gibbons RV, Tesh RB, Osterhaus AD, Fouchier RA, Durbin A, Simmons CP, Holmes EC, Harris E, Whitehead SS, Smith DJ. Dengue viruses cluster antigenically but not as discrete serotypes. Science. 2015 Sep 18;349(6254):1338-43. doi: 10.1126/science.aac5017.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Estimated Enrollment ICMJE; (submitted: January 27, 2009)	56
Original Estimated Enrollment ICMJE	Same as current
Study Completion Date	Not Provided
Actual Primary Completion Date	June 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Adult male or non-pregnant female between 18 and 50 years of age, inclusive.; Good general health as determined by physical exam, laboratory screening, and review of medical history; Available for the duration of the study, approximately 26 weeks post‐vaccination; Willing to use effective means of contraception for the duration of the trial Exclusion Criteria: Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies; Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer to understand and cooperate with the requirements of the study protocol; Grade 1 or above values for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as protocol defined; Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating n the trial or would render the volunteer unable to comply with the protocol; Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by volunteer history; History of a severe allergic reaction or anaphylaxis; Severe asthma (emergency room visit or hospitalization within the last 6 months); Positive HIV‐1 serology by screening and confirmatory assays; Positive for hepatitis C virus (HCV) by screening and confirmatory assays; Positive for hepatitis B virus (HBV) by hepatitis B surface antigen (HBsAg) screening; Any known immunodeficiency syndrome; Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days prior to Study Day 0; Receipt of a live vaccine within 4 weeks or a killed vaccine within the 2 weeks prior to Study Day 0 or anticipated receipt of any vaccine during the 42 days following Study Day 0; History of a surgical splenectomy; Receipt of 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 Study Day 0; History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus); Previous receipt of yellow fever or dengue vaccine (licensed or experimental); Receipt of any investigational agent in the 30 days prior to Vaccination Day 0 or plan to participate in any investigational drug trials during the next 26 weeks; Definite plans to travel to a dengue endemic area; Pregnancy or breastfeeding
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 50 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00831012
Other Study ID Numbers ICMJE	CIR 257
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor ICMJE	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators ICMJE	Johns Hopkins Bloomberg School of Public Health
Investigators ICMJE	Study Chair: Anna Durbin, MD Center for Immunization Research (CIR), Johns Hopkins School of Public Health
PRS Account	National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date	November 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP