Safety and Immunogenicity of A/H1N1-SOIV (Swine Flu) Vaccine With and Without Adjuvant in Children (3 to < 9 Years)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT00972816
First received: September 2, 2009
Last updated: March 14, 2016
Last verified: March 2016
  Purpose
This study will evaluate the safety and immunogenicity of different combinations of A/H1N1 S-OIV (swine flu) vaccine in healthy young children.

Condition Intervention Phase
Influenza
Biological: MF59-eH1N1
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: A Pivotal Randomized, Single-Blind, Dose-Finding Study to Evaluate Immunogenicity, Safety and Tolerability of Different Formulations of an Adjuvanted and Non-Adjuvanted Egg-Derived, Inactivated Novel Swine Origin A/H1N1 Monovalent Subunit Influenza Virus Vaccine in Healthy Pediatric Subjects 3 to < 9 Years of Age

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Antibody Responses According to the Hemagglutinin Inhibition (HI) Assay After the First and Second Vaccinations [ Time Frame: Day 22, Day 29, Day 43, Day 202 and Day 387 ] [ Designated as safety issue: No ]

    HI antibody assay (used to assess immune responses in subjects following vaccination) according to the Center for Biologics Evaluation and Research (CBER) guidance for <65 years of age: The lower bound of the two-sided 95% Confidence Interval (CI) for the percentages of subjects achieving seroconversion for HI antibody should be ≥ 40% and the lower bound of the two-sided 95% CI for the percentages of subjects achieving an HI antibody titer ≥ 1:40 should be ≥ 70%. Both criteria (seroconversion and HI antibody titer ≥ 40) had to be fulfilled to establish immunogenicity.

    PPS Day 1-29 analysis set: N= 143, 149, 149, 146, 147, 147, 144, and 144 for Groups A, B, C, D, E, F,G,and H respectively.

    PPS Day 1-202 analysis set: N= 82, 85, 84, 84, 86, 87, 82, and 79 for Groups A, B, C, D, E, F, G, and H respectively.

    PPS Day 1-387 analysis set: N= 55, 63, 61, 58, 61, 65, 59, and 63 for Groups A, B, C, D, E, F, G, and H respectively.



Secondary Outcome Measures:
  • Geometric Mean Titer (GMT) After Each Vaccination by Vaccine Group [ Time Frame: Day 22, Day 29, Day 43, Day 202 and Day 387 ] [ Designated as safety issue: No ]

    Immunogenicity was measured in terms of GMTs After each vaccination by vaccine Group.

    PPS Day1-29 analysis set: N=143, 149, 149, 146, 147, 147, 144, and 144 for Groups A, B, C, D, E, F, G, and H respectively.

    PPS Day 1-202 analysis set. N= 82, 85, 84, 84, 86, 87, 82, and 79 for Groups A, B, C, D, E, F, G, and H respectively.


  • Antibody Responses With and Without Seasonal Influenza Vaccination for Year 2009 to 2010. [ Time Frame: Day 22, Day 29, Day 43 ] [ Designated as safety issue: No ]
    HI antibody assay (used to assess immune responses in subjects following vaccination) according to the Committee for Medicinal Products for Human Use (CHMP) guidance: in adults ages 18 to 60 years are:The percentage of subjects with seroconversion or significant increase in HI antibody is > 40%.The percentage of subjects achieving an HI titer ≥ 40 is > 70% and The GMR is > 2.5. All 3 criteria (seroconversion/significant increase, HI antibody titer ≥ 40, and GMR) had to be fulfilled to establish immunogenicity.Subgroup analysis based on receipt of recent seasonal vaccination. Comparison between subjects previously vaccinated versus not vaccinated with seasonal influenza vaccines.Subgroups without recent seasonal flu vaccine:PPS Day1, Day 1-22 and Day1-43 analysis set. N= 141, 147, 150, 148, 146, 146, 150, and 146 for Groups A, B, C, D, E, F, G, and H respectively. PPS Day 1-29 analysis set. N= 132, 140, 143, 139, 138, 136, 139, and 138 for Groups A, B, C, D, E, F, G,and H respectively.

  • Geometric Mean Titers (GMTs) With and Without Seasonal Influenza Vaccination for Year 2009 to 2010 [ Time Frame: Day 1, Day 22, Day 29, Day 43 ] [ Designated as safety issue: No ]

    Immunogenicity was measured in terms of GMTs of Subgroups with receipt of recent seasonal vaccination. Comparison between subjects previously vaccinated versus not vaccinated with seasonal influenza vaccines

    Subgroups without recent seasonal flu vaccine:

    PPS Day 1, Day 1-22 and Day 1-43 analysis set. N= 141, 147, 150, 148, 146, 146, 150, and 146 for Groups A, B, C, D, E, F, G, and H respectively.

    PPS Day 1-29 analysis set. N= 132, 140, 143, 139, 138, 136, 139, and 138 for Groups A, B, C, D, E, F,G, and H respectively.

    Subgroups with recent seasonal flu vaccine:PPS Day 1-22 and Day 1-43 analysis set. N= 11, 9, 6, 8, 9, 11, 6, and 7 for Groups A, B, C, D, E, F, G,and H respectively.

    PPS Day 1-29 analysis set. N= 11, 9, 6, 7, 9, 11, 5, and 6 for Groups A, B, C, D, E, F, G, and H respectively


  • Antibody Response Based on Baseline Seropositivity [ Time Frame: Day 22, Day 29 and Day 43 ] [ Designated as safety issue: No ]

    Subgroup analysis based on Subjects with seropositivity (pre-vaccination HI antibody titer < 1:10 and prevaccination HI antibody titer ≥ 1:10) at baseline.

    Subgroups with baseline HI titer < 1:10: PPS Day 1-29 analysis set. N= 104, 116, 111, 107, 109, 113,120, and 103 for Groups A, B, C, D, E, F, G, and H respectively.

    Subgroups with baseline HI titer ≥ 1:10: PPS Day 1-29 analysis set. N= 39, 33, 38, 39, 38, 34, 24, and 41 for Groups A, B, C, D, E, F, G, and H respectively.


  • Geometric Mean Titers (GMTs) Based on Baseline Seropositivity [ Time Frame: Day 1, Day 22, Day 29, Day 43 ] [ Designated as safety issue: No ]

    Subgroup analysis based on Subjects with seropositivity (pre-vaccination HI antibody titer < 1:10 and prevaccination HI antibody titer ≥ 1:10) at baseline.

    Immunogenicity responses in subjects who are seropositive (A/H1N1 2009 HI titer ≥ 1:10) at Baseline [Day 1 (pre-vaccination)] as compared to those who are seronegative (HI titer < 1:10).


  • Number of Subjects Reporting Solicited Local and Systemic Symptoms After the First Vaccination [ Time Frame: 7 days after first vaccination ] [ Designated as safety issue: Yes ]
    Solicited local and systemic reactions were assessed after the first vaccination by vaccine group. Source Vocabulary Name: MedDRA (13.1).

  • Number of Subjects Reporting Solicited Local and Systemic Symptoms After the Second Vaccination [ Time Frame: 7 days after second vaccination ] [ Designated as safety issue: Yes ]
    Solicited local and systemic reactions were assessed after the second vaccination by vaccine group.Source Vocabulary Name: MedDRA (13.1)

  • Number of Participants Reporting Unsolicited Adverse Events (AEs) [ Time Frame: Safety monitoring periods were the Primary Period: Day 1 (1st vaccination) through ≤21 days post second vaccination, and the Follow-up Period: >21 Days post second vaccination to 12 months after second vaccination ] [ Designated as safety issue: Yes ]
    Safety was measured in terms of the Number of Participants Reporting Unsolicited AEs. Source Vocabulary Name: MedDRA (13.1)


Enrollment: 1357
Study Start Date: September 2009
Study Completion Date: October 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 3.75_(50)MF59
3.75 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22
Biological: MF59-eH1N1
MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).
Experimental: 7.5_(0) MF59
7.5 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22
Biological: MF59-eH1N1
MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).
Experimental: 7.5_(50) MF59
7.5 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22
Biological: MF59-eH1N1
MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).
Experimental: 7.5_(100) MF59
7.5 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22
Biological: MF59-eH1N1
MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).
Experimental: 15_(0) MF59
15 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22
Biological: MF59-eH1N1
MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).
Experimental: 15_(50)MF59
15 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22
Biological: MF59-eH1N1
MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).
Experimental: 15_(100) MF59
15 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22
Biological: MF59-eH1N1
MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).
Experimental: 30_(0) MF59
30 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22
Biological: MF59-eH1N1
MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).

  Eligibility

Ages Eligible for Study:   3 Years to 8 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Children 3 to < 9 years of age in good health as determined by medical history, physical assessment and clinical judgement of the investigator and without influenza within the past 6 months.

Exclusion Criteria:

  • History of serious disease.
  • History of serious reaction following administration of vaccine or hypersensitivity to vaccine components.
  • Known or suspected impairment/alteration of immune function.
  • Receipt or planned receipt of seasonal trivalent influenza vaccine within 1 week before or after each study vaccination.

For additional entry criteria, please refer to protocol.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00972816

  Show 35 Study Locations
Sponsors and Collaborators
Novartis Vaccines
Investigators
Study Director: Novartis Vaccines and Diagnostics Novartis
  More Information

Responsible Party: Novartis Vaccines
ClinicalTrials.gov Identifier: NCT00972816     History of Changes
Other Study ID Numbers: V112_02 
Study First Received: September 2, 2009
Results First Received: December 6, 2010
Last Updated: March 14, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Swine Flu
Flu
Vaccine
Children
Adjuvant

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
MF59 oil emulsion
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on July 28, 2016