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Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Children

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ClinicalTrials.gov Identifier: NCT01776554
Recruitment Status : Completed
First Posted : January 28, 2013
Results First Posted : April 20, 2015
Last Update Posted : January 16, 2019
Sponsor:
Collaborator:
Department of Health and Human Services
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )

Tracking Information
First Submitted Date  ICMJE January 20, 2013
First Posted Date  ICMJE January 28, 2013
Results First Submitted Date  ICMJE April 2, 2015
Results First Posted Date  ICMJE April 20, 2015
Last Update Posted Date January 16, 2019
Study Start Date  ICMJE January 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2015)
  • The Percentages Of Subjects Aged 6 to <36 Months, Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain [ Time Frame: Three weeks after 2nd vaccination (day 43) ]
    The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 6 to <36 months, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.
  • The Percentages Of Subjects Aged 3 to <9 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain [ Time Frame: Three weeks after 2nd vaccination (day 43) ]
    The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 3 to <9 years, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the CBER criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.
  • The Percentages Of Subjects Aged 9 to <18 Years, Achieving HI Titers ≥40 Against A/H5N1 Strain [ Time Frame: Three weeks after 2nd vaccination (day 43) ]
    The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects aged 9 to <18 years, achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the CBER criterion. As there is no CBER criteria defined for children, immunogenicity was evaluated using CBER criterion applicable for adults (18-64 years). CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%.
  • The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Three weeks after 2nd vaccination (day 43) ]
    Immunogenicity was measured in terms of the percentages of subjects aged 6 to <36 months, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.
  • The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Three weeks after 2nd vaccination (day 43) ]
    Immunogenicity was measured in terms of the percentages of subjects aged 3 to <9 years, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.
  • The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Three weeks after 2nd vaccination (day 43) ]
    Immunogenicity was measured in terms of the percentages of subjects aged 9 to <18 years, achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criteria. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%.
  • Number of Subjects (6 Month - <6 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination [ Time Frame: From day 1 through day 7 after each vaccination. ]
    Safety was assessed using the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine.
  • Number of Subjects (≥6 Years - 17 Years) Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination [ Time Frame: From day 1 through day 7 after any vaccination. ]
    Safety was assessed using the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine.
  • Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination [ Time Frame: Any unsolicited AEs - day 1 through day 22 after any vaccination; SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387 ]
    Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine.
Original Primary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
  • To select a vaccine dose based on the achievement of CBER criteria for further development [ Time Frame: Day 43 (3 weeks after second vaccination) ]
    Seroprotection and Seroconversion rate measured 3 weeks after second dose of vaccine administration
  • Percentage of subjects with solicited local and systemic adverse events [ Time Frame: 7 days post vaccination ]
  • Percentage of subjects with unsolicited adverse events [ Time Frame: 3 weeks post vaccination ]
  • Percentage of subjects with serious adverse events, medically attended adverse events, adverse events leading to withdrawal and adverse events of special interest [ Time Frame: Day 1 through Day 732 ]
Change History Complete list of historical versions of study NCT01776554 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2015)
  • Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 6 to <36 Months. [ Time Frame: Day 1, day 22, day 43 and day 387 ]
    Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 6 to <36 months is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied.
  • Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 3 to <9 Years. [ Time Frame: Day 1, day 22, day 43 and day 387 ]
    Immunogenicity was measured as geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 3 to <9 years is reported. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5.
  • Geometric Mean Ratios Against A/H5N1 Strain Following 2-Dose Vaccination Schedule Of Either Low Dose Or High Dose AH5N1c Vaccine in Subjects Aged 9 to <18 Years. [ Time Frame: Day 1, day 22, day 43 and day 387 ]
    Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination with either low dose or high dose of aH5N1c in subjects aged 9 to <18 years is reported. As no CHMP criteria are established for the pediatric population, criteria given for subjects 18-60 years of age were applied. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criteria if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5.
  • Percentages Of Subjects Aged 6 to <36 Months, With HI Titers ≥40 Against A/H5N1 Strain [ Time Frame: Day 1, day 22, day 43 and day 387. ]
    Immunogenicity was assessed in terms of percentage of subjects aged 6 to <36 months, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.
  • Percentages Of Subjects Aged 3 to <9 Years, With HI Titers ≥40 Against A/H5N1 Strain [ Time Frame: Day 1, day 22, day 43 and day 387. ]
    Immunogenicity was assessed in terms of percentage of subjects aged 3 to <9 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.
  • Percentages Of Subjects Aged 9 to <18 Years, With HI Titers ≥40 Against A/H5N1 Strain [ Time Frame: Day 1, day 22, day 43 and day 387. ]
    Immunogenicity was assessed in terms of percentage of subjects aged 9 to <18 years, achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%.
  • The Percentages Of Subjects Aged 6 to <36 Months, Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Day 22, day 43 and day 387 ]
    Immunogenicity was assessed in terms of percentages of subjects aged 6 to <36 months achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.
  • The Percentages Of Subjects Aged 3 to <9 Years, Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Day 22, day 43 and day 387 ]
    Immunogenicity was assessed in terms of percentages of subjects aged 3 to <9 years achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.
  • The Percentages Of Subjects Aged 9 to <18 Years, Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Day 22, day 43 and day 387 ]
    Immunogenicity was assessed in terms of percentages of subjects aged 9 to <18 years achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as the percentages of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, and a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Children
Official Title  ICMJE A Phase II, Randomized, Observer-Blind, Multi-Center, Study to Evaluate Safety, Tolerability and Immunogenicity of an Adjuvanted Cell Culture-Derived H5N1 Subunit Influenza Virus Vaccine at Two Different Formulations in Healthy Pediatric Subjects.
Brief Summary Evaluate Safety, Tolerability and Immune response of adjuvanted H5N1 cell culture derived influenza vaccine in children.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Prevention
Condition  ICMJE Pandemic H5N1 Influenza
Intervention  ICMJE Biological: Adjuvanted H5N1 pandemic influenza vaccine
Comparison of two doses of aH5N1c vaccine
Study Arms  ICMJE
  • Experimental: aH5N1c-High dose
    Intervention: Biological: Adjuvanted H5N1 pandemic influenza vaccine
  • Experimental: aH5N1c-Low dose
    Intervention: Biological: Adjuvanted H5N1 pandemic influenza vaccine
Publications * Chanthavanich P, Anderson E, Kerdpanich P, Bulitta M, Kanesa-Thasan N, Hohenboken M. Safety, Tolerability and Immunogenicity of an MF59-adjuvanted, Cell Culture-derived, A/H5N1, Subunit Influenza Virus Vaccine: Results From a Dose-finding Clinical Trial in Healthy Pediatric Subjects. Pediatr Infect Dis J. 2019 Jul;38(7):757-764. doi: 10.1097/INF.0000000000002345.

*   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: April 2, 2015)
662
Original Estimated Enrollment  ICMJE
 (submitted: January 23, 2013)
666
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Healthy pediatric subjects 6 months to 17 years of age,
  2. Individuals' parent(s) or legal guardian(s) willing to provide written informed consent,
  3. Individuals in good health,
  4. Individuals/Individuals' parent(s)/legal guardian(s) willing to allow for serum samples to be stored beyond the study period,
  5. Individuals willing to provide informed assent (where applicable).

Exclusion Criteria:

  1. Individuals' parent(s)/legal guardian(s) not able to understand and follow study procedures,
  2. History of any significant illness,
  3. History of any chronic medical condition or progressive disease,
  4. Presence of medically significant cancer,
  5. Known or suspected impairment/alteration of immune function,
  6. Presence of any progressive or severe neurologic disorder,
  7. Presence of any bleeding disorders or conditions that prolongs bleeding time,
  8. History of allergy to vaccine components,
  9. Receipt of any other investigational product within 30 days prior to entry into the study,
  10. History of previous H5N1 vaccination,
  11. Receipt of any other type of seasonal vaccination within 2 months prior to entry into the study,
  12. Receipt of any other vaccine within 2 weeks prior to entry into the study,
  13. Body temperature ≥38°C (≥100.4° F) and/or acute illness within 3 days of intended study vaccination,
  14. Pregnant or breast feeding,
  15. Females of childbearing potential refusing to use acceptable method of birth control,
  16. Body mass index (BMI) ≥ 35 kg/m2,
  17. History of drug or alcohol abuse,
  18. Any planned surgery during study period,
  19. Individuals conducting the study and their immediate family members,
  20. Individuals with behavioral or cognitive impairment or psychiatric diseases,
  21. Individuals diagnosed with any growth disorders.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Thailand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01776554
Other Study ID Numbers  ICMJE V89_11
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Vaccines )
Study Sponsor  ICMJE Novartis Vaccines
Collaborators  ICMJE Department of Health and Human Services
Investigators  ICMJE
Study Chair: Novartis vaccines and Diagnostics Novartis Vaccines
PRS Account Novartis
Verification Date January 2019

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