Clinical trial NCT00617344: Immunogenicity and Safety of Three Formulations of Dengue Vaccines in Healthy Adults Aged 18 to 45 Years in the US
Official title: Immunogenicity and Safety of Three Tetravalent Formulations of Dengue Vaccine Candidates in Healthy Adults Aged 18 to 45 Years in the US
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue Fever
Dengue Hemorrhagic Fever
Dengue Virus
Keywords: Dengue fever
Dengue hemorrhagic fever
Dengue virus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-02-18
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study used 3 different formulations of tetravalent CYD dengue vaccine.

The primary objective of the study was to evaluate the neutralizing antibody response after 2 doses of two different formulations of tetravalent dengue vaccine administered at Month 0 and Month 6.

The secondary objectives were:

* To evaluate the safety of the 3 formulations of tetravalent CYD dengue vaccine.
* To describe the neutralizing antibody responses to each of the 3 vaccine formulations.
* To describe vaccine viremia after the first and second dose of each of the 3 vaccine formulations in a subset of participants.

Detailed description: All participants provided blood samples for immunogenicity assessments, while vaccine viremia was assessed in a subset of participants in each group.

Safety was assessed in all participants as follows: solicited adverse event (AE) prelisted in the diary card were collected for 7 days after vaccination for solicited injection site reactions and 14 days for solicited systemic reactions , unsolicited AEs were collected for 28 days after vaccination, and serious adverse event (SAE) information collected throughout the study up to 6 months after vaccination.

Eligibility criteria: Inclusion Criteria:

* Healthy, as determined by medical history, clinical examination, and biological safety parameters.
* Aged 18 to 45 years on the day of inclusion.
* Provision of informed consent signed by the participant or another legally acceptable representative.
* For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination, and until at least 4 weeks after the last study vaccination.
* Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

* Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
* For a woman of child-bearing potential, known or suspected pregnancy or positive serum/urine pregnancy test.
* Breast-feeding woman.
* Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
* Planned participation in another clinical trial during the present trial period.
* Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 10 mg). Topical steroids were allowed.
* Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine or to a vaccine containing any of the same substances.
* Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the investigator.
* Current or past alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.
* Receipt of blood or blood-derived products in the past 3 months, that might interfere with the assessment of immune response.
* Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
* Planned receipt of any vaccine in the 4 weeks following each of the trial vaccinations.
* Human Immunodeficiency Virus (HIV), hepatitis B surface antigen, or hepatitis C virus seropositivity in blood sample taken at Screening.
* Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
* Clinically significant laboratory test abnormalities (as determined by the investigator) in blood sample taken at Screening.
* Previous residence in, travel or planned travel of more than 2 weeks during the study period to areas with high dengue infection endemicity.
* Reported history of flavivirus infection as reported by the participant.
* Previous vaccination against flavivirus diseases (including Japanese encephalitis, tick-borne encephalitis, and yellow fever).
* Flavivirus vaccination planned during the trial period.

Primary outcomes:
measure: Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation
timeFrame: Pre-injection 1 (Day 0), 30 days post-injection 2 (Month 7)
Secondary outcomes:
measure: Percentage of Participants With Antibody Titers of >=10 1/Dil Against Each Dengue Virus Serotype Strain
timeFrame: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
measure: Percentage of Participants With Antibody Titers >=10 1/Dil Against At Least Any 1, 2, 3 or All 4 Dengue Virus Serotypes
timeFrame: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
measure: Geometric Means of Titers of Antibodies Against Each Dengue Virus Serotype Strain
timeFrame: Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
measure: Number of Participants With Solicited Injection Site Reactions After Any Vaccination
timeFrame: 7 days after any injection 1, 2 or 3
measure: Number of Participants With Solicited Systemic Reactions After Any Vaccination
timeFrame: 14 days after any injection 1, 2 or 3
measure: Number of Participants With Vaccine Viremia
timeFrame: 7 days post-injection 1 and 2, 14 days post-injection 1 and 2
Other outcomes:
Locations:
city: Hoover
country: United States
facility: Investigational Site 004
state: Alabama
city: San Diego
country: United States
facility: Investigational Site 002
state: California
city: Vallejo
country: United States
facility: Investigational Site 005
state: California
city: New Orleans
country: United States
facility: Investigational Site 001
state: Louisiana
city: Springfield
country: United States
facility: Investigational Site 003
state: Missouri
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Dayan GH, Thakur M, Boaz M, Johnson C. Safety and immunogenicity of three tetravalent dengue vaccine formulations in healthy adults in the USA. Vaccine. 2013 Oct 17;31(44):5047-54. doi: 10.1016/j.vaccine.2013.08.088. Epub 2013 Sep 7.