Immunogenicity and Safety of Three Formulations of Dengue Vaccines in Healthy Adults Aged 18 to 45 Years in the US

Phase 2

Completed

• Conditions: Dengue Virus; Dengue Fever; Dengue Hemorrhagic Fever
• Interventions: Biological: Tetravalent CYD Dengue Vaccine, 4444 formulation; Biological: Tetravalent CYD Dengue Vaccine , 5553 formulation; Biological: Tetravalent CYD Dengue Vaccine , 5555 formulation

• Registration Number: NCT00617344
• Lead Sponsor: Sanofi

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.

Study Timeline

• Study First Submitted: 2008-02-06
• Study First Submitted QC: 2008-02-06
• Study First Posted: 2008-02-18
• Study Start: 2008-04-17
• Primary Completion: 2009-12
• Study Completion: 2010-02
• Disposition First Submitted: 2011-02-15
• Disposition First Submitted QC: 2011-02-15
• Disposition First Posted: 2011-02-18
• Status Verified: 2019-05
• Results First Submitted: 2019-05-21
• Results First Submitted QC: 2019-05-21
• Last Update Submitted: 2019-05-21
• Results First Posted: 2019-06-11
• Last Update Posted: 2019-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 260

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CYD Dengue Vaccine 4444 Formulation	Tetravalent CYD Dengue Vaccine, 4444 formulation	Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.
CYD Dengue Vaccine 5553 Formulation	Tetravalent CYD Dengue Vaccine , 5553 formulation	Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.
CYD Dengue Vaccine 5555 Formulation	Tetravalent CYD Dengue Vaccine , 5555 formulation	Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation	Pre-injection 1 (Day 0), 30 days post-injection 2 (Month 7)	Percentage of participants with antibody titers \>= 10 (1/dil) against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by dengue plaque reduction neutralization test (PRNT).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Injection Site Reactions After Any Vaccination	7 days after any injection 1, 2 or 3	Solicited injection site reactions: Pain, Erythema, and Swelling. Pain: Grade 1: Easily tolerated, Grade 2: Sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema:- Grade 1: \<2.5 cm, Grade 2: \>=2.5 to \<5 cm, Grade 3: \>=5 cm. Swelling:- Grade 1: \<2.5 cm, Grade 2: \>=2.5 to \<5 cm, Grade 3: \>=5 cm.
Geometric Means of Titers of Antibodies Against Each Dengue Virus Serotype Strain	Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)	Geometric mean titers against each dengue virus serotype (1, 2, 3 and 4) strain was measured by PRNT.
Number of Participants With Solicited Systemic Reactions After Any Vaccination	14 days after any injection 1, 2 or 3	Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever: - Grade1: \>=37.5°C to \<=38.0°C (\>=99.5°F to \<=100.4°F), Grade 2: \>38.0°C to \<=39.0°C (\>100.4°F to \<= 102.2°F), Grade 3: \>39.0°C (\>102.2°F). Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.
Percentage of Participants With Antibody Titers of >=10 1/Dil Against Each Dengue Virus Serotype Strain	Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)	Percentage of participants with antibody titers \>= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT.
Number of Participants With Vaccine Viremia	7 days post-injection 1 and 2, 14 days post-injection 1 and 2	Vaccine viremia (level of vaccine virus in blood samples taken from participants) was measured by an assay yellow fever reverse transcriptase polymerase chain reaction which allowed the detection of vaccine viremia of any serotype (1, 2, 3 and 4).
Percentage of Participants With Antibody Titers >=10 1/Dil Against At Least Any 1, 2, 3 or All 4 Dengue Virus Serotypes	Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)	Percentage of participants with antibody titers \>= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT. In this outcome measure, participants with antibody titers \>= 10 1/dil against any 1 of the 4 serotypes or any 2 of the 4 serotypes or any 3 of the 4 serotypes or with all 4 serotypes were reported.

Trial Locations

Locations (5)

Investigational Site 001; 🇺🇸 New Orleans, Louisiana, United States

Investigational Site 003; 🇺🇸 Springfield, Missouri, United States

Investigational Site 004; 🇺🇸 Hoover, Alabama, United States

Investigational Site 002; 🇺🇸 San Diego, California, United States

Investigational Site 005; 🇺🇸 Vallejo, California, United States