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Safety and Immunogenicity of Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines

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ClinicalTrials.gov Identifier: NCT03308825
Recruitment Status : Completed
First Posted : October 13, 2017
Results First Posted : December 17, 2018
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE September 28, 2017
First Posted Date  ICMJE October 13, 2017
Results First Submitted Date  ICMJE November 22, 2018
Results First Posted Date  ICMJE December 17, 2018
Last Update Posted Date December 17, 2018
Actual Study Start Date  ICMJE September 11, 2017
Actual Primary Completion Date November 22, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2018)
  • Number of Participants Reporting Solicited Injection Site (Tenderness/Pain, Erythema, Swelling) and Systemic Reactions (Fever, Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, Irritability): Group 1 (6 to < 36 Months) [ Time Frame: Within 7 days after any vaccination ]
    Solicited injection site reactions: Pain, Erythema and Swelling (Grade 3: Pain: cries when injected limb moved/ limb movement reduced, erythema and swelling >= 50 mm). Solicited systemic reactions: Fever, vomiting, abnormal crying, drowsiness, appetite lost, Irritability (Grade 3: Fever: >= 39.5 degrees Celsius [103.1 degree Fahrenheit {°F}], vomiting >= six episodes per 24 hours, abnormal crying : > 3 hours, drowsiness: sleeping most of the time or difficult to wake up, appetite lost: refuses >= 3 feeds/meals or refuses most feeds/meals, Irritability: Inconsolable).
  • Number of Participants Reporting Solicited Injection Site (Pain, Erythema, Swelling) and Systemic Reactions(Fever, Headache, Malaise, Myalgia): Group 2 (3 to < 9 Years), Group 3 (18 to < 65 Years) and Group 4(=< 65 Years) [ Time Frame: Within 7 days after any vaccination ]
    Solicited injection site reactions: Pain (Group 2: Grade 3: Incapacitating; Group 3 and 4: Grade 3: significant; prevents daily activity), erythema & swelling (Group 2: Grade 3: >= 50 mm, Group 3 and 4: Grade 3: > 100 mm). Solicited systemic reactions: Fever (Grade 3: >= 39.0 degrees Celsius [102.2°F]), headache, malaise & myalgia (Grade 3: significant interference with daily activities).
  • Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-vaccination) ]
    Anti-influenza antibodies were measured using the hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage.
  • GMTs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) [ Time Frame: Day 0 (pre-vaccination) and Day 21 (post-vaccination) ]
    Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4).
  • GMT Ratios (GMTRs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-final vaccination) ]
    GMTRs are the geometric means of the individual post-final vaccination/pre-vaccination titer ratios for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage, measured using the HAI assay.
  • GMTRs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) [ Time Frame: Day 0 (pre-vaccination) and Day 21 (post-vaccination) ]
    GMTRs are the geometric means of the individual post-final vaccination/pre-vaccination titer ratios for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4), measured using the HAI assay.
  • Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-vaccination) ]
    Anti-influenza antibodies were measured using the HAI assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage. Seroprotection was defined as antibody titer >=40 (1/ dilution) at pre-vaccination or at post-final vaccination.
  • Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) [ Time Frame: Day 0 (pre-vaccination) and Day 21 (post-vaccination) ]
    Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4). Seroprotection was defined as antibody titer >= 40 (1/ dilution) at pre-vaccination or at post-final vaccination.
  • Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-final vaccination) ]
    Anti-influenza antibodies were measured using the HAI assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage. Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-final vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-final vaccination titer.
  • Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) [ Time Frame: Day 0 (pre-vaccination) and Day 21 (post-vaccination) ]
    Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4). Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-final vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-final vaccination titer.
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2017)
  • Percentages of Participants Reporting Solicited Injection-site or Systemic Reactions after Receipt of Either Fluzone Quadrivalent Vaccine (Children and Adults) or Fluzone High-Dose Vaccine (Older Adults) [ Time Frame: From Day 0 through Day 7 post-vaccination ]
    Solicited injection-site reactions: Tenderness (6 to < 36 months)/Pain (3 to 9 years and 18 years and older), Erythema, and Swelling. Solicited systemic reactions: 6 to < 36 months: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, Irritability; 3 to < 9 years and 18 years and older: Fever, Headache, Malaise, Myalgia.
  • Summary of Geometric Mean Titers (GMTs) of Antibodies in Children 6 Months to < 9 Years of Age Receiving Fluzone Quadrivalent Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-final vaccination) ]
    GMTs will be assessed using a hemagglutination inhibition (HAI) assay.
  • Summary of GMTs of Antibodies in Adults Receiving Either Fluzone Quadrivalent Vaccine or Fluzone High-Dose Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 21 (post-vaccination) ]
    GMTs will be assessed using an HAI assay.
  • Geometric Mean Titer Ratios of Antibodies in Children 6 Months to < 9 Years of Age Receiving Fluzone Quadrivalent Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-final vaccination) ]
    GMT ratios will be assessed using an HAI assay
  • Geometric Mean Titer Ratios of Antibodies in Adults Receiving Either Fluzone Quadrivalent Vaccine or Fluzone High-Dose Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 21 (post-vaccination) ]
    GMT ratios will be assessed using an HAI assay
  • Seroprotection Rates in Children 6 Months to < 9 Years of Age Receiving Fluzone Quadrivalent Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-final vaccination) ]
    Seroprotection will be assessed using an HAI assay. Seroprotection is defined as a titer ≥ 40 (1/dil) at pre-vaccination and at post-vaccination
  • Seroprotection Rates in Adults Receiving Either Fluzone Quadrivalent Vaccine or Fluzone High-Dose Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 21 (post-vaccination) ]
    Seroprotection will be assessed using an HAI assay. Seroprotection is defined as a titer ≥ 40 (1/dil) at pre-vaccination and at post-vaccination
  • Seroconversion Rates in Children 6 Months to < 9 Years of Age Receiving Fluzone Quadrivalent Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 28 (post-final vaccination) ]
    Seroconversion will be assessed using an HAI assay. Seroconversion is defined as either a pre-vaccination titer < 10 (1/dil) and a post-vaccination titer ≥ 40 (1/dil) or a pre-vaccination titer ≥ 10 (1/dil) and a ≥ 4-fold increase in post-vaccination titer
  • Seroconversion Rates in Adults Receiving Either Fluzone Quadrivalent Vaccine or Fluzone High-Dose Vaccine [ Time Frame: Day 0 (pre-vaccination) and Day 21 (post-vaccination) ]
    Seroconversion will be assessed using an HAI assay. Seroconversion is defined as either a pre-vaccination titer < 10 (1/dil) and a post-vaccination titer ≥ 40 (1/dil) or a pre-vaccination titer ≥ 10 (1/dil) and a ≥ 4-fold increase in post-vaccination titer
Change History Complete list of historical versions of study NCT03308825 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
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 Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines
Official Title  ICMJE Safety and Immunogenicity of Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines, 2017-2018 Formulations
Brief Summary The aim of the study was to describe the safety and immunogenicity of the 2017-2018 formulation of Fluzone Quadrivalent vaccine in children 6 months to < 9 years of age, and in adults 18 to < 65 years of age, and to describe the safety and immunogenicity of the 2017-2018 formulation of Fluzone High-Dose vaccine in adults ≥ 65 years of age.
Detailed Description

All participants received 1 intramuscular dose of their assigned vaccine during Visit 1. For participants, for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of the same volume as the first dose was administered during Visit 2 (28 days after Visit 1). Solicited adverse reaction (AR) information was collected for 7 days following each vaccination. Unsolicited non-serious adverse event (AE) and serious adverse event (SAE) information was collected from Visit 1 to Visit 2 or from Visit 1 to Visit 3 for those participants receiving 2 doses of study vaccine.

Immunogenicity was evaluated in all participants prior to vaccination on Day 0 (Visit 1) and after the final vaccination (Day 28 post-final vaccination for participants 6 months to < 9 years of age and Day 21 post-vaccination for participants ≥ 18 years of age).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Multicenter, Open-label, Phase IV Study
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Influenza
  • Flu
Intervention  ICMJE
  • Biological: Fluzone Quadrivalent vaccine
    0.25 mL, Intramuscular
  • Biological: Fluzone Quadrivalent vaccine
    0.5 mL, Intramuscular
  • Biological: Fluzone High-Dose vaccine
    0.5 mL, Intramuscular
Study Arms  ICMJE
  • Experimental: Group 1: 6 to < 36 Months
    Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.
    Intervention: Biological: Fluzone Quadrivalent vaccine
  • Experimental: Group 2: 3 to < 9 Years
    Children aged 3 to < 9 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.
    Intervention: Biological: Fluzone Quadrivalent vaccine
  • Experimental: Group 3: 18 to < 65 Years
    Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.
    Intervention: Biological: Fluzone Quadrivalent vaccine
  • Experimental: Group 4: >= 65 Years
    Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.
    Intervention: Biological: Fluzone High-Dose 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: October 6, 2017)
240
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 22, 2017
Actual Primary Completion Date November 22, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged 6 months to < 9 years or ≥ 18 years on the day of first study vaccination (study product administration).
  • For participants 6 to < 12 months of age, born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg (5.5 lbs).
  • Informed consent form has been signed and dated by participants ≥ 18 years of age.
  • Assent form was signed and dated by participants 7 to < 9 years of age, and informed consent form has been signed and dated by parent(s) or guardian(s) for participants 6 months to < 9 years of age.
  • Participant and parent/guardian (of participants 6 months to < 9 years of age) were able to attend all scheduled visits and to comply with all study procedures.

Exclusion Criteria:

  • Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche, or post- menopausal for at least 1 year, or surgically sterile.
  • Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Note: Participants may be considered eligible for enrollment if no intervention for the other study occurred within the 30 days prior to the first study vaccination and none are planned before the participant would complete safety surveillance for the present study.
  • Receipt of any vaccine in the 30 days preceding the first study vaccination, or planned receipt of any vaccine before Visit 2 for participants receiving 1 dose of influenza vaccine or Visit 3 for participants receiving 2 doses of influenza vaccine.
  • Previous vaccination against influenza (in the 2017-2018 influenza season) with either study vaccine or another vaccine.
  • Receipt of immune globulins, blood, or blood-derived products in the 3 months preceding planned inclusion.
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the 6 months preceding planned inclusion; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the 3 months preceding planned inclusion).
  • Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to study vaccine or to a vaccine containing any of the same substances. Note: The list of vaccine components is included in the Prescribing Information for each study vaccine.
  • Thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator.
  • Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
  • Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
  • Current alcohol abuse or drug addiction.
  • Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with study conduct or completion.
  • Moderate or severe acute illness/infection (according to Investigator judgment) on the day of planned vaccination or febrile illness (temperature ≥ 100.4 degree Fahrenheit [°F] [38.0 degrees Celsius {°C}]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
  • Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study (participants ≥ 18 years of age) or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study (all participants).
  • History of serious adverse reaction to any influenza vaccine.
  • Personal history of Guillain-Barré syndrome.
  • Any condition that in the opinion of the Investigator would pose a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine.
  • Personal history of clinically significant developmental delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder.
  • Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months and older   (Child, Adult, Older 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 NCT03308825
Other Study ID Numbers  ICMJE GRC73
U1111-1183-5816 ( Other Identifier: WHO Universal Trial Number (UTN) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available, Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com.
Responsible Party Sanofi ( Sanofi Pasteur, a Sanofi Company )
Study Sponsor  ICMJE Sanofi Pasteur, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Sanofi Pasteur, a Sanofi Company
PRS Account Sanofi
Verification Date November 2018

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