NCT01110551

Tetravalent Chimeric Dengue Vaccine Trial

A Double-Blind Randomized, Placebo-Controlled, Phase I Dose Escalation Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Adult Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 72 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to test the safety and immune response to a live attenuated dengue vaccine that could protect people against all 4 types of dengue virus. Live attenuated means that while this vaccine contains 4 live dengue viruses the viruses have been attenuated (weakened) so as not to cause dengue disease in people. Dengue virus is spread to people by mosquitoes and can cause sickness and even death. Seventy-two subjects between the ages of 18-45 years old will be enrolled in this research study at Saint Louis University Center for Vaccine Development. Participants will be randomly assigned to 1 of 4 groups to receive 2 doses of the study vaccine or placebo (inactive substance). Study procedures include: maintaining a diary to record temperature and side effects, physical exam, electrocardiogram (ECG) (measures the activity of the heart), and blood samples. Participants will be involved in study related procedures for about 10 months.

Detailed description

The purpose of this study is to evaluate the safety and immunogenicity of a tetravalent dengue vaccine administered subcutaneously or intradermally. The hypotheses being tested in this study is whether or not a tetravalent dengue vaccine may be safely administered to healthy normal individuals by intradermal (ID) or subcutaneous (SC) injection and provide measurable levels of serum neutralizing antibodies against all four dengue virus serotypes. The study is also designed to compare safety and immunogenicity between routes of administration and dose levels. The primary objective of this study is to evaluate the safety and tolerability of a two-dose regimen tetravalent dengue vaccine administered either SC or ID to healthy adult volunteers. Two dose levels will be tested in a dose-escalation format. Safety and tolerability will be measured by conducting post-vaccination safety assessments including physical examinations, injection site examinations, adverse event monitoring, hematology, blood chemistry, and urine dipstick. The secondary objective of this study is to assess the immunogenicity of the vaccine, in terms of neutralizing antibodies, against all four dengue serotypes when administered at two dose levels by two routes of administration in healthy adults. Titers of serum neutralizing antibodies will be measured at pre-vaccination, after prime and boost vaccinations and assessed by comparing titers at the two dose levels as well as the two routes of administration. In addition, viremia deriving from the attenuated vaccine viruses will be measured on days 0 (baseline), 2, 4, 5/6, 7, 9, 11, and 14 after both prime and boost vaccinations. Levels of neutralizing antibodies will also be measured in samples to be obtained on days 180 and 270 for analysis and submission in a supplement to the study report. This study will enroll 72 healthy flavivirus-negative male and female subjects between the ages of 18 and 45.

Conditions

• Dengue

Interventions

Type	Name	Description
DRUG	Placebo (SC)	Phosphate buffered saline administered subcutaneously.
DRUG	Placebo (ID)	Phosphate buffered saline administered intradermally.
BIOLOGICAL	Modified Live Tetravalent Chimeric Dengue Vaccine (SC)	DENVax is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: DEN-2 PDK-53 (DENVax-2), DEN-2/1 chimera (DENVax-1), DEN-2/3 chimera (DENVax-3) and DEN-2/4 chimera (DENVax-4). The drug product is formulated in buffer and stored frozen. Low dose contains (dose volume 0.1 mL): D1: 8 x 10\^3, D2: 5 x 10\^3, D3: 1 x 10\^4, and D4: 2 x 10\^5, total virus dose \[plaque forming units (PFU)\]: 2.2 x 10\^5. High dose contains (dose volume 0.1 mL): D1: 2 x 10\^4, D2: 5 x 10\^4, D3: 1 x 10\^5, and D4: 3 x 10\^5, total virus dose (PFU): 4.7 x 10\^5. DENVax administered subcutaneously.
BIOLOGICAL	Modified Live Tetravalent Chimeric Dengue Vaccine (ID)	DENVax is a tetravalent dengue vaccine comprised of four recombinant, live attenuated dengue virus strains: DEN-2 PDK-53 (DENVax-2), DEN-2/1 chimera (DENVax-1), DEN-2/3 chimera (DENVax-3) and DEN-2/4 chimera (DENVax-4). The drug product is formulated in buffer and stored frozen. Low dose contains (dose volume 0.1 mL): D1: 8 x 10\^3, D2: 5 x 10\^3, D3: 1 x 10\^4, and D4: 2 x 10\^5, total virus dose \[plaque forming units (PFU)\]: 2.2 x 10\^5. High dose contains (dose volume 0.1 mL): D1: 2 x 10\^4, D2: 5 x 10\^4, D3: 1 x 10\^5, and D4: 3 x 10\^5, total virus dose (PFU): 4.7 x 10\^5. DENVax administered intradermally.

Timeline

• Start date: 2010-05-01
• Primary completion: 2012-04-01
• Completion: 2012-12-01
• First posted: 2010-04-26
• Last updated: 2013-02-04

Locations

1 site across 1 country: United States