Immunologic Mechanisms of Immune Interference and/or Cross-Neutralizing Immunity After CYD Tetravalent Dengue Vaccine

NCT01943825 | Completed Phase 2 Results

• 2 other identifiers: CYD56U1111-1143-8391
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study was to evaluate a compressed dosing schedule and the immunologic effects of co-administration of a CYD dengue vaccine with a licensed flavivirus (FV) with Japanese encephalitis (JE) vaccine. Primary Objectives:

• To describe and compare the humoral immune response to each of the 4 parental dengue virus serotypes at baseline and 28 days after each CYD dengue vaccine dose.
• To describe the persistence of the humoral immune response to each of the 4 parental dengue virus serotypes 6 after CYD dengue vaccine Dose 3, irrespective of whether or not JE vaccine had been previously administered. Secondary Objectives:
• To describe the safety profile after each injection of CYD dengue vaccine.
• To describe the humoral immune response to each of the 4 parental dengue virus serotypes at baseline and 28 days after each CYD dengue vaccine dose when administered with or after JE virus vaccine in Groups 3 and 4.
• To describe the persistence of the humoral immune response to each of the 4 parental dengue virus serotypes at 6 months post-dose 3 in all four groups and at 12 months post-dose 3 in Groups 1 and 3 with the compressed schedule.
• To determine the level of viremia on Day (D)0, D3, D5, D7 and D14 following each CYD vaccine dose administered in Groups 1-4.
• To describe the JE humoral immune response at baseline and 28 days after each injection of CYD dengue vaccine in Groups 3 and 4.

Conditions

Dengue; Dengue Fever; Dengue Hemorrhagic Fever

Keywords

Dengue; Dengue fever; CYD dengue vaccine; IXIARO JE vaccine; Flavivirus

Outcome Measures

Primary Outcomes (2)

• Geometric Means Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype Strains

  GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by plaque reduction neutralization test (PRNT). The lower limit of quantitation (LLOQ) of the assay was a titer of 10 (1/dilution).

  Pre-injection 1, 2 and 3; 28 days post-injection 1, 2 and 3; and 6 months post-injection 3

• Number of Participants With Antibody Titers Greater Than or Equal to (>=)10 (1/Dilution) Against Each Dengue Virus Serotype Strains

  Antibody titers against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT.

  Pre-injection 1, 2 and 3; 28 days post-injection 1, 2 and 3; and 6 months post-injection 3

Secondary Outcomes (7)

• Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains in Participants Who Received Japanese Encephalitis Vaccine - Groups 3 and 4

  Pre-injection 1, 2 and 3, and 28 days post-injection 1, 2 and 3

• Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains

  6 months and 12 months post-injection 3

• Number of Participants With Detectable Non Serotype-Specific Vaccine Viremia

  3, 5, 7 and 14 days post-injection 1, 2 and 3

• Number of Participants With Detectable Serotype-Specific Vaccine Viremia

  3, 5, 7 and 14 days post-injection 1; 3 and 14 days post-injection 2 and 7 days post-injection 3

• Geometric Means Titers of Antibodies Against Japanese Encephalitis - Groups 3 and 4

  Pre-injection 1, and 28 days post-injection 1, 2 and 3

Study Arms (4)

CYD Dengue Vaccine: Group 1

EXPERIMENTAL

Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, respectively.

Biological: CYD Dengue Vaccine

CYD Dengue Vaccine: Group 2

EXPERIMENTAL

Participants received 3 doses of CYD dengue vaccine, one each at 0, 6 and 12 months, respectively.

Biological: CYD Dengue Vaccine

CYD Dengue and JE Vaccine: Group 3

EXPERIMENTAL

Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, and 2 doses of JE (IXIARO) vaccine at 0 and 1 months, respectively.

Biological: CYD Dengue Vaccine; Biological: Japanese Encephalitis Vaccine

CYD Dengue and JE Vaccine: Group 4

EXPERIMENTAL

Participants received 2 doses of JE (IXIARO) vaccine at 0 and 1 months; and 3 doses of CYD dengue vaccine at 7, 9 and 13 months, respectively.

Biological: CYD Dengue Vaccine; Biological: Japanese Encephalitis Vaccine

Interventions

CYD Dengue Vaccine BIOLOGICAL

0.5 mL, Subcutaneous

CYD Dengue Vaccine: Group 1; CYD Dengue and JE Vaccine: Group 3; CYD Dengue and JE Vaccine: Group 4

Japanese Encephalitis Vaccine BIOLOGICAL

0.5 mL, Intramuscular

Also known as: IXIARO Japanese Encephalitis Vaccine

CYD Dengue and JE Vaccine: Group 3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent form had been signed and dated.
• Able to attend all scheduled visits and complied with all trial procedures.
• Participant was in good health, based on medical history and physical examination.

You may not qualify if:

• Participant was pregnant, or lactating, or of childbearing potential (were considered of non-childbearing potential, a female had to be post- menopausal for at least 1 year, surgically sterile, or used an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination).
• Participation in the 4 weeks preceding the first trial vaccination, or planned participation during the present trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
• Any history of FV vaccination, or planned FV vaccination during the trial period.
• Previous residence (greater than \[\>\]12 months) in, or travel in the last 30 days to dengue endemic regions.
• Receipt of immune globulins, blood or blood-derived products in the 3 months prior to first vaccination or planned use during the study period.
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceded 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Known systemic hypersensitivity to any of the vaccine components (including protamine sulfate), or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances, including dry natural latex.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Excessive alcohol consumption or drug addiction.
• Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion.
• Identified as an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employee or the Investigator.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead
• United States Department of Defense: collaborator

Study Sites (1)

Unknown Facility

Syracuse, New York, 13210, United States

Location

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Japanese Encephalitis Vaccines

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)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Study Officials

• Medical Director

  Sanofi Pasteur SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2013
• First Posted: September 17, 2013
• Study Start: November 5, 2013
• Primary Completion: November 25, 2015
• Study Completion: November 25, 2015
• Last Updated: March 24, 2022
• Results First Posted: February 5, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)