A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Infants

NCT00322049 | Completed Phase 1 Results DMC

• 4 other identifiers: WRAIR 824HSRRB Log A-10064GSK CPMS7663310/001DEN-001
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

The main target populations for the tetravalent live attenuated dengue virus vaccine are indigenous populations, especially infants less than 2 years old, residing in areas of the world endemic for dengue and at risk of developing dengue hemorrhagic fever (DHF). The presence of maternal dengue antibody during the first year of life makes it unlikely that a vaccine given during that time will have long-term efficacy, as the vaccine virus would likely be neutralized prior to necessary replication. Children older than 18 months may have preexisting flavivirus antibody. Therefore, vaccination of infants living in Thailand early in the second year of life (between the ages of 12 and 18 months) seems most beneficial. The aim of this trial is to evaluate the safety and immunogenicity of a two-dose schedule of a tetravalent live attenuated dengue vaccine in flavivirus antibody naïve infants beginning at 12-15 months of age.

• To assess the kinetics of dengue neutralizing antibodies to each dengue virus serotype one and four years following dose 2 of dengue/control vaccination in the setting of potential wild-type dengue virus exposure.
• To assess the immunogenicity, the safety and reactogenicity of a booster dose of dengue vaccine administered at Year 3 following primary vaccination.

Conditions

Dengue

Keywords

Dengue, Vaccine, Thailand

Outcome Measures

Primary Outcomes (5)

• Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.

  Local and general solicited reactogenicity using diary cards for 21 days (days 0-20) after the first dose of dengue/control vaccine

  21-day follow-up period after Dose 1

• Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine

  Assess the immunogenicity of the dengue vaccine in terms of GMTs 30 days post-Dose 2 of dengue vaccine for all four serotypes (DEN-1, 2, 3, 4 and JE (Japanese encephalitis)). Analysis of immunogenicity was performed on the ATP cohort.

  30 days post Dose 2

• Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2

  Seronegative for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2. Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.

  month 7 after dose 2

• Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE

  Seropositivity for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2 (and 2 doses of JE). Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.

  month 8.5

• JE Vaccine Response

  Seropositivity rates and GMTs for N lg to JEV antibodies. Pre= Pre vaccination, blood sampling prior to the first vaccine dose; PI(M1)= Post 1, month 1, blood sampling one month after dose 1 at study month 1; PI(M6)= Post 1, month 6, blood sampling 6 months after dose 1 at study month 6; PII(M7)= Post II, month 7, blood sampling one month after dose 2 at study month 7; PIV(M8.5)= Post IV, month 8.5, blood sampling after 2 doses of dengue/control and 2 doses of JE vaccines at study month 8.5

  Pre-vaccination, 1, 6, 7 and 8.5 months after two doses of dengue vaccine

Secondary Outcomes (2)

• Incidence of Dengue Specific Symptoms

  30-day follow-up period after dose 1 and 2

• Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose

  10 days after post dose 1 and 2

Study Arms (3)

Cohort A: Dengue Vaccine- Full Dose (T-DEN F17 )

EXPERIMENTAL

Dengue vaccine at Months 0 and 6 and booster follow-up at 3 years; DEN candidate vaccine: One dose of the tetravalent, live attenuated DEN vaccine candidate, F17, contains dengue serotype 1, 2, 3 and 4 vaccines. This formulation contains 50 mcg/mL neomycin base, 5.5% lactose, and 1.9 g/dL human serum albumin; for subcutaneous injection. All infants subsequently received an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. The licensed JE vaccine in liquid form, was dosed at 0.25 ml for subcutaneous injection.

Biological: Tetravalent live attenuated dengue vaccine

Cohort B: Control vaccines

ACTIVE COMPARATOR

Control vaccines: Hemophilus influenza type b (Hib) vaccine and varicella vaccine

Biological: Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine

Cohort C: Dengue Vaccine - 1/10 Dose (T-DEN F17 )

EXPERIMENTAL

Dengue vaccine at Months 0 and 6 and booster follow-up at 3 years

Biological: Tetravalent live attenuated dengue vaccine

Interventions

Tetravalent live attenuated dengue vaccine BIOLOGICAL

DEN candidate vaccine: One dose of the tetravalent, live attenuated DEN vaccine candidate, F17, contains dengue serotype 1, 2, 3 and 4 vaccines. This formulation contains 50 mcg/mL neomycin base, 5.5% lactose, and 1.9 g/dL human serum albumin; for subcutaneous injection. Infants received dengue vaccine at study months 0 and 6 or control vaccine (varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both control vaccines are licensed for use in Thailand. All infants subsequently received an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. The licensed JE vaccine in liquid form, was dosed at 0.25 ml for subcutaneous injection. A booster dose of DEN vaccine was given to all subjects previously vaccinated with DEN vaccine in Dengue -001. The booster dose was administered approximately 42 months after dose 2 (at the Year 3 visit).

Cohort A: Dengue Vaccine- Full Dose (T-DEN F17 ); Cohort C: Dengue Vaccine - 1/10 Dose (T-DEN F17 )

Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine BIOLOGICAL

Infants received dengue vaccine at study months 0 and 6 or control vaccine (varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both control vaccines are licensed for use in Thailand.

Cohort B: Control vaccines

Eligibility Criteria

• Age: 12 Months - 15 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Male and female infants between 12 and 15 months (12 and \<16 months) of age at the time of the first dengue vaccination
• Free of obvious health problems as established by medical history and clinical examination before entering into the study. As a marker of nutritional status, an infant's weight to height ratio will be above the 5th percentile compared to the standards for same sex and age children cared for at Phramongkutklao Hospital, Bangkok, Thailand
• Written informed consent obtained from the parent of the subject.
• Completed the Dengue-001 study having previously received 2 doses of experimental dengue vaccine according to protocol.
• Written informed consent obtained from the parent or guardian of the subject. (obtained in amendment 5)
• Written informed consent obtained from the parent or guardian of the subject who agrees to their child's participation to receive a dengue booster dose and booster follow-up.

You may not qualify if:

• Use of any investigational or non-registered drug or vaccine other than the protocol-specified vaccines within 30 days preceding the administration of the first dose of dengue/control vaccine or planned use during the study period
• Administration of a registered vaccine within 30 days preceding the first study vaccination or planned administration within 30 days prior to, or 30 days after any protocol-specified vaccine administration
• MMR vaccination given within 60 days prior to the first dose of dengue/control vaccine (added bullet point, or planned administration within 60 days prior to, or 30 days after any protocol-specified vaccine administration
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the study period. (For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.
• Any confirmed or suspected immunosuppressive or immunodeficient condition
• Any clinically significant history, including any seizures or other serious medical condition as determined by the investigator
• A first order family member (parent or sibling) with a history of chronic headaches
• A first order family member (parent or sibling) with a history of a congenital or hereditary immunodeficiency
• Abnormal clinical laboratory screening test results (based on normal values set by the laboratory) that are deemed clinically significant by study investigators and/or the Medical Monitor
• The presence of HBsAg or antibodies against HIV or HCV at screening
• Pre-existing antibody to dengue 1-4 virus serotypes or Japanese encephalitis virus (JEV) by HAI or PRNT50 at screening
• Previous vaccination against yellow fever virus, JEV, tick-borne encephalitis virus (TBE), varicella virus or booster dose of Hib in the second year of life
• History of varicella disease or invasive Haemophilus Influenzae B disease
• Acute disease at time of enrollment (Acute illness is defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness such as diarrhea or mild upper respiratory infection with or without low-grade febrile illness, i.e., axillary temperature \<37.5°C (\<99.5°F).
• Administration of immunoglobulins and/or blood products since birth or planned administration during the study period

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

USAMC-AFRIMS/Department of Pediatrics, Pharamongkutklao Hospital

Bangkok, 10400, Thailand

Location

Related Publications (1)

• Watanaveeradej V, Simasathien S, Nisalak A, Endy TP, Jarman RG, Innis BL, Thomas SJ, Gibbons RV, Hengprasert S, Samakoses R, Kerdpanich A, Vaughn DW, Putnak JR, Eckels KH, Barrera Rde L, Mammen MP Jr. Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus-naive infants. Am J Trop Med Hyg. 2011 Aug;85(2):341-51. doi: 10.4269/ajtmh.2011.10-0501.

  PMID: 21813857 DERIVED

MeSH Terms

Conditions

Dengue

Interventions

Chickenpox Vaccine

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Herpesvirus Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Wipa Chawachalasai
• Organization: U.S. Army Medical Component Armed Forces Research Institute of Medical Services

wipac@afrims.org

662-696-2700

Study Officials

• Robert V. Gibbons, MD

  U.S. Army Medical Component Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS)

  PRINCIPAL INVESTIGATOR

• Veerachai Watanaveeradej, MD

  Infectious Disease Department of Pediatrics Phramongkutklao Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2006
• First Posted: May 4, 2006
• Study Start: February 1, 2004
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: January 19, 2018
• Results First Posted: July 19, 2017

Record last verified: 2017-12

Locations

TH (1)