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Long-Term Study of Hospitalized Dengue & Safety in Thai Children Included in a Tetravalent Dengue Vaccine Efficacy Study

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ClinicalTrials.gov Identifier: NCT01983553
Recruitment Status : Completed
First Posted : November 14, 2013
Results First Posted : July 29, 2019
Last Update Posted : August 27, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information
First Submitted Date November 6, 2013
First Posted Date November 14, 2013
Results First Submitted Date May 23, 2019
Results First Posted Date July 29, 2019
Last Update Posted Date August 27, 2019
Actual Study Start Date September 10, 2013
Actual Primary Completion Date June 15, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 23, 2019)
  • Event Rate Per 100 Participant-years for Hospitalized Virologically-Confirmed Dengue (VCD) Cases Due to Any and Each Serotype Following Vaccination With Either CYD Dengue Vaccine or Placebo in the Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported.
  • Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With Either CYD Dengue Vaccine or a Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Cases were defined as the number of participants with at least one hospitalized VCD episode.
  • Number of Episodes of Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With Either CYD Dengue Vaccine or a Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Episodes were defined as the number of hospitalized VCD episodes.
  • Event Rate Per 100 Participant-years for Hospitalized VCD Cases Due to Any and Each Serotype Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1.
  • Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Cases were defined as the number of participants with at least one hospitalized VCD episode.
  • Number of Episodes of Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Episodes were defined as the number of hospitalized VCD episodes.
  • Event Rate Per 100 Participant-years for Clinically Severe Hospitalized VCD Cases Due to Any and Each Serotype Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Event rate per 100 participant-years for Clinically Severe hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1.
  • Number of Clinically Severe Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Cases were defined as the number of participants with at least one hospitalized VCD episode.
  • Number of Episodes of Clinically Severe Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Episodes were defined as the number of hospitalized VCD episodes.
  • Number of Cases of Non-Serotype Specific Dengue Viremia Among Hospitalized VCD Cases Following Vaccination With CYD Dengue Vaccine or Placebo in Previous Study (CYD23) [ Time Frame: During Year 1 to Year 4 post 3rd vaccination at Month 12 in CYD23 at each of the following time points: Anytime, 0-3 days, 4-7 days, 0-7 days, After 7 days during the sera sample collection time interval of 14 days ]
    Cases were defined as the number of participants with at least one non-serotype specific dengue viremia among hospitalized VCD cases.
  • Non-Serotype Specific Dengue Viremia Among Hospitalized VCD Cases Following Vaccination With CYD Dengue Vaccine or Placebo in Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post-vaccination after 3rd vaccination at Month 12 in CYD23 at each of the following time points: Anytime, 0-3 days, 4-7 days, 0-7 days, After 7 days during the sample collection time interval of 14 days ]
    Quantified viremia was defined as greater than or equal to (>=) lower limit of quantitation (log10 plaque forming unit [pfu]/mL).
  • Event Rate Per 100 Participant-years for Hospitalized VCD Cases Due to Any and Each Serotype and Meeting World Health Organization (WHO) 1997 Criteria Collected Following Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1. The WHO criteria were fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue haemorrhagic fever was graded as Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.
  • Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) and Meeting WHO 1997 Criteria Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Cases were defined as the number of participants with at least one hospitalized VCD episode meeting WHO criteria. The WHO criteria was fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue hemorrhagic fever was graded as - Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation was a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.
  • Number of Episodes of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) and Meeting WHO 1997 Criteria Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [ Time Frame: Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23 ]
    Episodes were defined as the number of hospitalized virologically confirmed dengue episodes meeting WHO criteria. The WHO criteria was fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue haemorrhagic fever was graded as Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.
Original Primary Outcome Measures
 (submitted: November 7, 2013)
Number of hospitalized, virologically confirmed dengue case following participation in Study CYD23 [ Time Frame: Up to 5 years post vaccination in subjects who participated in study CYD23 ]
Case are defined as (1) An acute febrile illness with fever lasting for at least 1 day (temperature 37.5 C measured at least twice with an interval of at least 4 hours) (2) Virologically confirmed by reverse transcriptase polymerase chain reaction (RT PCR) or dengue non structural protein 1 (NS1) enzyme linked immunosorbent assay (ELISA) Antigen (Ag) test with the addition of serotype strain specific analyses where appropriate and (3) In patient hospitalization
Change History Complete list of historical versions of study NCT01983553 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures
 (submitted: November 7, 2013)
  • Classification of dengue cases following participation in Study CYD23 [ Time Frame: Up to 5 years post vaccination in subjects who participated in study CYD23 ]
    Classification will be based on: (1) Detection of dengue viremia, clinical signs and symptoms, duration of clinical syndrome, duration of hospitalization, neutralizing antibody titers and other pertinent criteria (2) A severity assessment using the World Health Organization (WHO) 1997 severity definition and the IDMC severity definition and (3) A dengue serological profile based on immunoglobulin G (IgG) and IgM ELISA results in all acute febrile episodes. Neutralizing antibody titers will be assessed in all virologically confirmed dengue cases
  • Number and nature of reported serious adverse events following vaccination in study CYD23 [ Time Frame: Up to 5 years post vaccination in subjects who participated in Study CYD23 ]
    This include the occurrence, nature (MedDRA preferred term), seriousness criteria, relationship, outcome, and whether the SAE led to early termination from the study of SAEs related to study procedures or to previous injection from study CYD23 and fatal (even if unrelated) SAEs in all subjects
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Long-Term Study of Hospitalized Dengue & Safety in Thai Children Included in a Tetravalent Dengue Vaccine Efficacy Study
Official Title Long-Term Follow-Up of Hospitalized Dengue and Safety in Thai Children Who Were Included in an Efficacy Study of a Tetravalent Dengue Vaccine
Brief Summary

The purpose of this study was to conduct a passive surveillance of hospitalized dengue cases in participants who participated in study CYD23 (NCT00842530).

The Objectives:

  • To describe the incidence of virologically-confirmed hospitalized dengue cases.
  • To characterize hospitalized dengue cases.
  • To evaluate the occurrence of related and fatal serious adverse events (SAEs).
Detailed Description

This study was a passive surveillance of hospitalized dengue cases in participants who participated in study CYD23 (NCT00842530) where participants were initially randomized to receive 3 injections of either CYD dengue vaccine or control at 6 month intervals. Any SAE related to a study procedure or related to a previous injection from study CYD23, or any fatal SAEs (even if unrelated) were reported to the Sponsor.

An Independent Data Monitoring Committee (IDMC) was also involved in the regular review of virologically-confirmed hospitalized dengue cases. Any fatal outcome or related SAE were be promptly reviewed by the IDMC.

No study vaccinations were administered.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Participants in study CYD23 (NCT00842530) who were hospitalized with dengue cases.
Condition
  • Dengue
  • Dengue Fever
  • Dengue Hemorrhagic Fever
Intervention Not Provided
Study Groups/Cohorts
  • CYD Dengue Vaccine Group
    Participants who received 3 injections of 0.5 milliliter (mL) CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
  • Control Group
    Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively in the study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: September 27, 2016)
3203
Original Estimated Enrollment
 (submitted: November 7, 2013)
3997
Actual Study Completion Date August 2016
Actual Primary Completion Date June 15, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Ongoing participation in study CYD23 at the time of enrolment.
  • Assent form was signed and dated by the participant (for participants >= 7 years old), and informed consent form was signed and dated by the parent(s) or another legally accepted representative and by 2 independent witnesses.
  • Participant and parent/legally accepted representative were able to attend all scheduled visits to comply with all study procedures.

Exclusion Criteria:

  • Planned participation in another dengue clinical trial during the present study
  • Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
Sex/Gender
Sexes Eligible for Study: All
Ages 7 Years to 16 Years   (Child)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Thailand
Removed Location Countries  
 
Administrative Information
NCT Number NCT01983553
Other Study ID Numbers CYD57
U1111-1127-7380 ( Other Identifier: WHO )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
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 Sanofi Pasteur, a Sanofi Company
Collaborators Not Provided
Investigators
Study Director: Medical Director Sanofi Pasteur SA
PRS Account Sanofi
Verification Date August 2019