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

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ClinicalTrials.gov Identifier: NCT01943825
Recruitment Status : Completed
First Posted : September 17, 2013
Results First Posted : February 5, 2020
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE September 12, 2013
First Posted Date  ICMJE September 17, 2013
Results First Submitted Date  ICMJE December 19, 2019
Results First Posted Date  ICMJE February 5, 2020
Last Update Posted Date February 5, 2020
Actual Study Start Date  ICMJE November 5, 2013
Actual Primary Completion Date November 25, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • Geometric Means Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype Strains [ Time Frame: Pre-injection 1, 2 and 3; 28 days post-injection 1, 2 and 3; and 6 months post-injection 3 ]
    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).
  • Number of Participants With Antibody Titers Greater Than or Equal to (>=)10 (1/Dilution) Against Each Dengue Virus Serotype Strains [ Time Frame: Pre-injection 1, 2 and 3; 28 days post-injection 1, 2 and 3; and 6 months post-injection 3 ]
    Antibody titers against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT.
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2013)
  • Neutralizing antibody levels by microneutralization assay and/or plaque reduction neutralization test (PRNT) against each of the 4 parental dengue virus serotypes at baseline and 28 days after each CYD dengue vaccine dose in all four groups [ Time Frame: 28 days post CYD dengue vaccination ]
  • Neutralizing antibody levels by microneutralization assay and/or PRNT against each of the 4 parental dengue virus serotypes 6 and/or 12 months after CYD dengue vaccine Dose 3 in all four groups [ Time Frame: 6 and 12 months post CYD dengue vaccination ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2020)
  • Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains in Participants Who Received Japanese Encephalitis Vaccine - Groups 3 and 4 [ Time Frame: Pre-injection 1, 2 and 3, and 28 days post-injection 1, 2 and 3 ]
    GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT. The LLOQ of the assay was a titer of 10 (1/dilution).
  • Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains [ Time Frame: 6 months and 12 months post-injection 3 ]
    GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT.
  • Number of Participants With Detectable Non Serotype-Specific Vaccine Viremia [ Time Frame: 3, 5, 7 and 14 days post-injection 1, 2 and 3 ]
    Viremia was determined by reverse transcriptase (RT) polymerase chain reaction (PCR) using primer/probes specific to a non serotype-specific part of the dengue vaccine.
  • Number of Participants With Detectable Serotype-Specific Vaccine Viremia [ Time Frame: 3, 5, 7 and 14 days post-injection 1; 3 and 14 days post-injection 2 and 7 days post-injection 3 ]
    Viremia was determined by RT PCR using primer/probes specific to each dengue vaccine serotypes.
  • Geometric Means Titers of Antibodies Against Japanese Encephalitis - Groups 3 and 4 [ Time Frame: Pre-injection 1, and 28 days post-injection 1, 2 and 3 ]
    GMTs of antibodies against JE were measured by JE micro neutralization assay. The LLOQ of the assay was a titer of 10 (1/dilution).
  • Number of Participants With Solicited Injection Site Reactions [ Time Frame: Within 7 days after any CYD dengue vaccine and/or JE vaccine ]
    A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the electronic case report form (eCRF) and considered as related to vaccination. Solicited injection site reactions: pain, erythema, and swelling.
  • Number of Participants With Solicited Systemic Reactions [ Time Frame: Within 14 days after any CYD dengue vaccine and/or JE vaccine ]
    A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions: fever, headache, malaise, myalgia, and asthenia.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2013)
  • Description of the Safety profile in terms of solicited injection site and systemic reaction, unsolicited adverse events and serious adverse events after each vaccination with CYD dengue and/or JE vaccines [ Time Frame: Day 0 up to 6 months post last vaccination ]
  • Neutralizing antibody levels, measured by microneutralization assay and/or PRNT, against each of the four parental dengue virus serotypes at baseline and 28 days after each CYD dengue vaccine dose in Groups 3 and 4. [ Time Frame: 28 days post CYD dengue vaccination ]
  • Neutralizing antibody levels, measured by microneutralization assay and/or PRNT, against each of the four parental dengue virus serotypes at 6 months post Dose 3 in all subjects and at 12 months post Dose 3 in Groups 1 and 3 [ Time Frame: 6 and 12 months post dose 3 CYD dengue vaccination ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immunologic Mechanisms of Immune Interference and/or Cross-Neutralizing Immunity After CYD Tetravalent Dengue Vaccine
Official Title  ICMJE Exploration of Immunologic Mechanisms of Immune Interference and/or Cross-Neutralizing Immunity Following Various Administration Schedules With CYD Tetravalent Dengue Vaccine
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.
Detailed Description Study participants were randomly assigned to one of the four groups to receive assigned study vaccine and were evaluated for neutralizing antibody titers; markers of cell-mediated immunity.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Dengue
  • Dengue Fever
  • Dengue Hemorrhagic Fever
Intervention  ICMJE
  • Biological: CYD Dengue Vaccine
    0.5 mL, Subcutaneous
  • Biological: Japanese Encephalitis Vaccine
    0.5 mL, Intramuscular
    Other Name: IXIARO Japanese Encephalitis Vaccine
Study Arms  ICMJE
  • Experimental: CYD Dengue Vaccine: Group 1
    Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, respectively.
    Intervention: Biological: CYD Dengue Vaccine
  • Experimental: CYD Dengue Vaccine: Group 2
    Participants received 3 doses of CYD dengue vaccine, one each at 0, 6 and 12 months, respectively.
    Intervention: Biological: CYD Dengue Vaccine
  • Experimental: CYD Dengue and JE Vaccine: Group 3
    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.
    Interventions:
    • Biological: CYD Dengue Vaccine
    • Biological: Japanese Encephalitis Vaccine
  • Experimental: CYD Dengue and JE Vaccine: Group 4
    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.
    Interventions:
    • Biological: CYD Dengue Vaccine
    • Biological: Japanese Encephalitis Vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 12, 2013)
90
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 25, 2015
Actual Primary Completion Date November 25, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged greater than or equal to (>=)18 to less than or equal to (<=) 45 years on the day of inclusion.
  • 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.

Exclusion Criteria:

  • 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.
  • Receipt or planned receipt of any vaccine, outside the study protocol in the 4 weeks preceded or followed trial vaccinations. (If influenza activity warranted vaccination of healthy young adults, influenza vaccination was encouraged and did not lead to study exclusion).
  • 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.
  • Temporary Exclusion Criteria: Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature >= 38.0 degree Celsius [>= 100.4 degree fahrenheit]). A prospective participant was not included in the study until the condition had resolved or the febrile event had subsided. If the delay for the febrile illness exceeded the window between screening and vaccination, or if deemed necessary by the Investigator, a prospective participant might be re-screened once the fever had resolved.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01943825
Other Study ID Numbers  ICMJE CYD56
U1111-1143-8391 ( Other Identifier: WHO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to participant level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Participant level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi ( Sanofi Pasteur, a Sanofi Company )
Study Sponsor  ICMJE Sanofi Pasteur, a Sanofi Company
Collaborators  ICMJE United States Department of Defense
Investigators  ICMJE
Study Director: Medical Director Sanofi Pasteur SA
PRS Account Sanofi
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP