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Sanofi 2017 H7N9 With/Without AS03 in Adults/Elderly

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03312231
Recruitment Status : Completed
First Posted : October 17, 2017
Results First Posted : October 12, 2020
Last Update Posted : October 12, 2020
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE October 12, 2017
First Posted Date  ICMJE October 17, 2017
Results First Submitted Date  ICMJE September 17, 2020
Results First Posted Date  ICMJE October 12, 2020
Last Update Posted Date October 12, 2020
Actual Study Start Date  ICMJE February 14, 2018
Actual Primary Completion Date September 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2020)
  • Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 43 ]
    Blood was collected for HAI assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 21 days after the second dose of H7N9.
  • Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Antibodies [ Time Frame: Day 43 ]
    Blood was collected for Neutralizing assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 21 days after the second dose of H7N9.
  • Number of Participants With Clinical Safety Laboratory Adverse Events [ Time Frame: Day 8 ]
    Laboratory parameters include alanine aminotransferase (ALT), bilirubin, creatinine, hemoglobin, platelets and white blood cells (WBC). Thresholds for adverse events were considered as ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male); hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10^3/µL or below or 416 x10^3/µL or greater; or WBC or 3.9 x10^3/µL or lower or 10.6 x10^3/µL or higher.
  • Number of Participants With Clinical Safety Laboratory Adverse Events [ Time Frame: Day 29 ]
    Laboratory parameters include alanine aminotransferase (ALT), bilirubin, creatinine, hemoglobin, platelets and white blood cells (WBC). Thresholds for adverse events were considered as ALT 44 IU/L or greater (female) or 61 IU/L or greater (male); bilirubin 1.30 mg/dL or greater; creatinine 1.1 mg/dL or greater (female) or 1.4 mg/dL or greater (male); hemoglobin 11.4 g/dL or lower (female) or 12.4 g/dL or lower (male); platelets 139 x10^3/µL or below or 416 x10^3/µL or greater; or WBC or 3.9 x10^3/µL or lower or 10.6 x10^3/µL or higher.
  • Number of Participants Reporting Solicited Injection Site Events [ Time Frame: Day 1 to Day 8 ]
    Injection site AEs solicited on a memory aid provided to participants included Pain, Tenderness, Itching/Pruritus, Ecchymosis/Bruising (functional grade based on interference with dailyactivities), Ecchymosis/Bruising (any measured value >0mm), Erythema/Redness (functional grade), Erythema/ Redness (any measured value >0mm), Induration/Swelling (functional grade), and Induration/Swelling (any measured value >0mm). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following the first vaccination.
  • Number of Participants Reporting Solicited Injection Site Events [ Time Frame: Day 22 to Day 29 ]
    Injection site AEs solicited on a memory aid provided to participants included Pain, Tenderness, Itching/Pruritus, Ecchymosis/Bruising (functional grade based on interference with dailyactivities), Ecchymosis/Bruising (any measured value >0mm), Erythema/Redness (functional grade), Erythema/ Redness (any measured value >0mm), Induration/Swelling (functional grade), and Induration/Swelling (any measured value >0mm). Participants are considered reporting the injection site AE if they reported mild or greater severity at any time during the 8 days at or following the second vaccination.
  • Number of Participants Reporting Study Vaccine-related Serious Adverse Events (SAEs) [ Time Frame: Day 1 to Day 387 ]
    SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. Events are included if deemed by the investigator to be related to the study product.
  • Number of Participants Reporting Systemic Reactogenicity Events [ Time Frame: Day 1 to Day 8 ]
    Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, and Nausea. Participants are considered reporting the systemic AE if they reported mild or greater severity at any time during the 8 days at or following the first vaccination.
  • Number of Participants Reporting Systemic Reactogenicity Events [ Time Frame: Day 22 to Day 29 ]
    Systemic AEs solicited on a memory aid provided to participants included Elevated Oral Temperature, Feverishness, Fatigue, Malaise, Myalgia, Arthralgia, Headache, and Nausea. Participants are considered reporting the systemic AE if they reported mild or greater severity at any time during the 8 days at or following the second vaccination.
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibodies Titer of 1:40 or Greater [ Time Frame: Day 43 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with HAI titer >= 1:40 was calculated for each study group from the available results at 21 days after second dose of H7N9.
  • Percentage of Participants Achieving Neutralizing (Neut) Antibodies Titer of 1:40 or Greater [ Time Frame: Day 43 ]
    Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with Neut titer >= 1:40 was calculated for each study group from the available results at 21 days after second dose of H7N9.
  • Percentage of Participants Achieving Seroconversion Defined by Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 43 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as HAI pre-vaccination titer <1:10 and post-vaccination titer >=1:40 or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. 21 days after second dose of H7N9 is Day 43.
  • Percentage of Participants Achieving Seroconversion Defined by Neutralizing (Neut) Antibodies [ Time Frame: Day 43 ]
    Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as Neut pre-vaccination titer <1:10 and post-vaccination titer >=1:40 or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. 21 days after second dose of H7N9 is Day 43.
Original Primary Outcome Measures  ICMJE
 (submitted: October 12, 2017)
  • Geometric Mean Titers (GMTs) of serum HAI antibodies [ Time Frame: Day 43 ]
  • Geometric Mean Titers (GMTs) of serum Neut antibodies [ Time Frame: Day 43 ]
  • Occurrence of clinical safety laboratory adverse events [ Time Frame: Day 1 to day 8 ]
  • Occurrence of clinical safety laboratory adverse events [ Time Frame: Day 22 to day 29 ]
  • Occurrence of solicited injection site events [ Time Frame: Day 1 to day 8 ]
  • Occurrence of solicited injection site events [ Time Frame: Day 22 to day 29 ]
  • Occurrence of study vaccine-related serious adverse events (SAEs) [ Time Frame: Day 1 to day 387 ]
  • Occurrence of systemic reactogenicity events [ Time Frame: Day 1 to day 8 ]
  • Occurrence of systemic reactogenicity events [ Time Frame: Day 22 to day 29 ]
  • Percentage of subjects achieving HAI antibodies titer = / > 1:40 [ Time Frame: Day 43 ]
  • Percentage of subjects achieving Neut antibodies titer = / > 1:40 [ Time Frame: Day 43 ]
  • Percentage of subjects achieving seroconversion (defined as either HAI antibodies pre-vaccination titer <1:10 and a post-vaccination titer = / > 1:40 or a pre-vaccination titer = / > 1:10 and min. 4-fold rise in post-vaccination titer) [ Time Frame: Day 43 ]
  • Percentage of subjects achieving seroconversion (defined as either Neut antibodies pre-vaccination titer <1:10 and a post-vaccination titer = / > 1:40 or a pre-vaccination titer = / > 1:10 and min. 4-fold rise in post-vaccination titer) [ Time Frame: Day 43 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2020)
  • Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 1 ]
    Blood was collected for HAI assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at baseline.
  • Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 8 ]
    Blood was collected for HAI assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 7 days post first vaccination.
  • Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 22 ]
    Blood was collected for HAI assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 21 days post first vaccination.
  • Geometric Mean Titers (GMTs) of Serum Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 29 ]
    Blood was collected for HAI assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 7 days post second vaccination.
  • Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Antibodies [ Time Frame: Day 1 ]
    Blood was collected for Neutralizing assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at baseline.
  • Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Antibodies [ Time Frame: Day 8 ]
    Blood was collected for Neutralizing assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 7 days post first vaccination.
  • Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Antibodies [ Time Frame: Day 22 ]
    Blood was collected for Neutralizing assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 21 days post first vaccination.
  • Geometric Mean Titers (GMTs) of Serum Neutralizing (Neut) Antibodies [ Time Frame: Day 29 ]
    Blood was collected for Neutralizing assay which was conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The geometric mean titer was calculated for each study arm from the available results at 7 days post second vaccination.
  • Number of Participants Reporting Serious Adverse Events (SAEs), Regardless of the Assessment of Relatedness [ Time Frame: Day 1 to Day 387 ]
    SAEs included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation or a congenital anomaly/birth defect. All events are included regardless of relationship to the study product.
  • Number of Participants Reporting Unsolicited Adverse Events (AEs), Regardless of the Assessment of Seriousness or Relatedness [ Time Frame: Day 1 to Day 43 ]
    Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through 21 days after each vaccination. Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
  • Number of Participants Reporting Medically-attended Adverse Events (MAAEs), New-onset Chronic Medical Conditions (NOCMCs), and Potentially Immune-mediated Medical Conditions (PIMMCs) [ Time Frame: Day 1 to Day 387 ]
    For each unsolicited AE experienced, the participants were asked if he/she had received medical attention, defined as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason. AEs characterized by such unscheduled medical care were designated as MAAEs. NOCMCs are defined as any new ICD-10 diagnosis that is applied to the participant during the duration of the study, after receipt of the study agent, that is expected to continue for at least 3 months and requires continued health care intervention. PIMMCs constitute a group of AEs that includes diseases which are clearly autoimmune in etiology and other inflammatory and/or neurologic disorders which may or may not have autoimmune etiologies.
  • Number of Participants Reporting Study Vaccine-related Unsolicited Non-serious Adverse Events (AEs) [ Time Frame: Day 1 to Day 43 ]
    Adverse events were defined as any untoward medical occurrence in a participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Non-serious AEs were collected from participants at follow up visits through 21 days after each vaccination. The site investigator determined vaccine related as "a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the AE." Adverse events were MedDRA coded and are summarized by MedDRA System Organ Class (SOC).
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibodies Titers of 1:40 or Greater [ Time Frame: Day 1 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with HAI titer >= 1:40 was calculated for each study group from the available results at baseline.
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibodies Titers of 1:40 or Greater [ Time Frame: Day 8 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with HAI titer >= 1:40 was calculated for each study group from the available results at 7 days post first vaccination.
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibodies Titers of 1:40 or Greater [ Time Frame: Day 22 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with HAI titer >= 1:40 was calculated for each study group from the available results at 21 days post first vaccination.
  • Percentage of Participants Achieving Hemagglutination Inhibition (HAI) Antibodies Titers of 1:40 or Greater [ Time Frame: Day 29 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with HAI titer >= 1:40 was calculated for each study group from the available results at 7 days post second vaccination.
  • Percentage of Participants Achieving Neutralizing (Neut) Antibodies Titers of 1:40 or Greater [ Time Frame: Day 1 ]
    Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with Neut titer >= 1:40 was calculated for each study group from the available results at baseline.
  • Percentage of Participants Achieving Neutralizing (Neut) Antibodies Titers of 1:40 or Greater [ Time Frame: Day 8 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with HAI titer >= 1:40 was calculated for each study group from the available results at 7 days post first vaccination.
  • Percentage of Participants Achieving Neutralizing (Neut) Antibodies Titers of 1:40 or Greater [ Time Frame: Day 22 ]
    Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with Neut titer >= 1:40 was calculated for each study group from the available results at 21 days post first vaccination.
  • Percentage of Participants Achieving Neutralizing (Neut) Antibodies Titers of 1:40 or Greater [ Time Frame: Day 29 ]
    Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. The percentage of participants with Neut titer >= 1:40 was calculated for each study group from the available results at 7 days post second vaccination.
  • Percentage of Participants Achieving Seroconversion Defined by Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 8 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as HAI pre-vaccination titer <1:10 and post-vaccination titer >=1:40 or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. Day 8 is 7 days after the first dose of H7N9.
  • Percentage of Participants Achieving Seroconversion Defined by Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 22 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as HAI pre-vaccination titer <1:10 and post-vaccination titer >=1:40 or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. Day 22 is 21 days after the first dose of H7N9.
  • Percentage of Participants Achieving Seroconversion Defined by Hemagglutination Inhibition (HAI) Antibodies [ Time Frame: Day 29 ]
    Blood was collected for the HAI assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as HAI pre-vaccination titer <1:10 and post-vaccination titer >=1:40 or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. Day 29 is 7 days after the second dose of H7N9.
  • Percentage of Participants Achieving Seroconversion Defined by Neutralizing (Neut) Antibodies [ Time Frame: Day 8 ]
    Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as Neut pre-vaccination titer <1:10 and post-vaccination titer >=1:40 or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. Day 8 is 7 days after the first dose of H7N9.
  • Percentage of Participants Achieving Seroconversion Defined by Neutralizing (Neut) Antibodies [ Time Frame: Day 22 ]
    Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as Neut pre-vaccination titer <1:10 and post-vaccination titer >=1:40 or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. Day 22 is 21 days after the first dose of H7N9.
  • Percentage of Participants Achieving Seroconversion Defined by Neutralizing (Neut) Antibodies [ Time Frame: Day 29 ]
    Blood was collected for the Neutralizing assay conducted with the 2017 H7N9 vaccine virus as the antigen. Each sample was tested at least twice per the laboratory's standard operating procedure, and the geometric mean of the replicate results was calculated as that sample's result. Seroconversion was defined as Neut pre-vaccination titer <1:10 and post-vaccination titer >=1:40 or pre-vaccination titer 1:10 or greater and minimum 4-fold rise in post-vaccination antibody titer. Day 29 is 7 days after the second dose of H7N9.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2017)
  • GMTs of serum HAI antibodies [ Time Frame: Day 1 ]
  • GMTs of serum HAI antibodies [ Time Frame: Day 22 ]
  • GMTs of serum HAI antibodies [ Time Frame: Day 29 ]
  • GMTs of serum HAI antibodies [ Time Frame: Day 8 ]
  • GMTs of serum Neut antibodies [ Time Frame: Day 1 ]
  • GMTs of serum Neut antibodies [ Time Frame: Day 22 ]
  • GMTs of serum Neut antibodies [ Time Frame: Day 29 ]
  • GMTs of serum Neut antibodies [ Time Frame: Day 8 ]
  • Occurrence of all serious adverse events (SAEs), regardless of the assessment of relatedness [ Time Frame: Day 1 to day 387 ]
  • Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness [ Time Frame: Day 1 to day 43 ]
  • Occurrence of medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs), and potentially immune-mediated medical conditions (PIMMCs ) [ Time Frame: Day 1 to day 387 ]
  • Occurrence of study vaccine-related unsolicited non-serious AEs [ Time Frame: Day 1 to day 43 ]
  • Percentage of subjects achieving HAI antibodies titers of 1:40 or greater [ Time Frame: Day 1 ]
  • Percentage of subjects achieving HAI antibodies titers of 1:40 or greater [ Time Frame: Day 22 ]
  • Percentage of subjects achieving HAI antibodies titers of 1:40 or greater [ Time Frame: Day 29 ]
  • Percentage of subjects achieving HAI antibodies titers of 1:40 or greater [ Time Frame: Day 8 ]
  • Percentage of subjects achieving Neut antibodies titers of 1:40 or greater [ Time Frame: Day 1 ]
  • Percentage of subjects achieving Neut antibodies titers of 1:40 or greater [ Time Frame: Day 22 ]
  • Percentage of subjects achieving Neut antibodies titers of 1:40 or greater [ Time Frame: Day 29 ]
  • Percentage of subjects achieving Neut antibodies titers of 1:40 or greater [ Time Frame: Day 8 ]
  • Percentage of subjects achieving seroconversion against the influenza 2017 H7N9 vaccine strain [ Time Frame: Day 22 ]
  • Percentage of subjects achieving seroconversion against the influenza 2017 H7N9 vaccine strain [ Time Frame: Day 29 ]
  • Percentage of subjects achieving seroconversion against the influenza 2017 H7N9 vaccine strain [ Time Frame: Day 8 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sanofi 2017 H7N9 With/Without AS03 in Adults/Elderly
Official Title  ICMJE A Phase II Study in Healthy Adults 19 Years and Older to Assess the Safety, Reactogenicity and Immunogenicity of a Sanofi Pasteur A/H7N9 Inactivated Influenza Vaccine Administered Intramuscularly With or Without AS03 Adjuvant
Brief Summary This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females 19 years and older that is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine (2017 H7N9 IIV) administered at different dosages given with AS03 adjuvant and phosphate buffered saline (PBS) diluent, with AS03 adjuvant only, and without adjuvant. Eligible subjects will be randomized into 5 study groups, stratified by age. The study will enroll up to 420 individuals 19-64 years old and up to 300 individuals who are 65 years old and older. Study duration is approximately 16 months with subject participation duration approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart given with or without AS03 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of recipient.
Detailed Description This is a randomized, double-blinded, Phase II study in healthy males and non-pregnant females 19 years and older. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a pre-pandemic 2017 monovalent inactivated influenza A/H7N9 virus vaccine (2017 H7N9 IIV) administered at different dosages given with or without adjuvant. 3.75 mcg of HA per dose will be administered with phosphate buffered saline (PBS) diluent and AS03 adjuvant, 7.5 mcg and 15 mcg of HA per dose will be administered with AS03 adjuvant only, and 15 mcg and 45 mcg of HA per dose will be administered without adjuvant. Eligible subjects will be randomized into one of 5 study groups, stratified by age. The study will enroll up to 420 individuals 19-64 years old and up to 300 individuals who are 65 years old and older. The study duration is approximately 16 months with subject participation duration approximately 13 months. The primary objectives of this study are: 1) to assess the safety and reactogenicity following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart given with or without AS03 adjuvant; 2) to assess the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses following receipt of two doses of 2017 H7N9 IIV administered intramuscularly at different dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of recipient. The secondary objectives are: 1) to assess unsolicited non-serious adverse events (AEs) following receipt of two doses of a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without AS03 adjuvant; 2) to assess medically-attended adverse events (MAAEs) including new-onset chronic medical conditions (NOCMCs), potentially immune-mediated medical conditions (PIMMCs), and all serious adverse events (SAEs) following receipt of two doses of a 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without AS03 adjuvant; 3) to assess the serum HAI and Neut antibody responses approximately 7 and 21 days following receipt of a single dose, and approximately 7 days following receipt of two doses of 2017 H7N9 IIV administered IM at different dosages approximately 21 days apart with or without AS03 adjuvant, stratified by age of recipient.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Avian Influenza
  • Influenza Immunisation
Intervention  ICMJE
  • Drug: AS03
    Oil-in-water emulsion based adjuvant system.
  • Biological: Inactivated influenza H7N9 vaccine
    Monovalent 2017 H7N9 inactivated influenza vaccine
  • Other: Phosphate Buffered Saline (PBS) diluent
    Diluent for 2017 Monovalent Inactivated Influenza A/H7N9 virus vaccine (2017 H7N9 IIV)
Study Arms  ICMJE
  • Experimental: Group 1
    3.75 mcg of H7N9 vaccine with PBS diluent plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older)
    Interventions:
    • Drug: AS03
    • Biological: Inactivated influenza H7N9 vaccine
    • Other: Phosphate Buffered Saline (PBS) diluent
  • Experimental: Group 2
    7.5 mcg of H7N9 vaccine plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older)
    Interventions:
    • Drug: AS03
    • Biological: Inactivated influenza H7N9 vaccine
  • Experimental: Group 3
    15 mcg of H7N9 vaccine plus AS03 adjuvant on days 1 and 22, n=100 (19-64 years old) and n=60 (65 and older)
    Interventions:
    • Drug: AS03
    • Biological: Inactivated influenza H7N9 vaccine
  • Experimental: Group 4
    15 mcg of unadjuvanted H7N9 vaccine on days 1 and 22, n=50 (19-64 years old) and n=30 (65 and older)
    Intervention: Biological: Inactivated influenza H7N9 vaccine
  • Experimental: Group 5
    45 mcg of unadjuvanted H7N9 vaccine on days 1 and 22, n=50 (19-64 years old) and n=30 (65 and older)
    Intervention: Biological: Inactivated influenza H7N9 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: November 8, 2018)
720
Original Estimated Enrollment  ICMJE
 (submitted: October 12, 2017)
640
Actual Study Completion Date  ICMJE September 26, 2019
Actual Primary Completion Date September 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provide written informed consent prior to initiation of any study procedures.
  2. Are able to understand and comply with planned study procedures and be available for all study visits.
  3. Are males or non-pregnant females, 19 years of age and older, inclusive.
  4. Are in good health*. *As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, which would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, ER, or urgent care for condition and no adverse symptoms that need medical intervention such as medication change/supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria), herbals, vitamins, and supplements are permitted.
  5. Oral temperature is less than 100.0 degrees Fahrenheit.
  6. Pulse is 47 to 100 bpm, inclusive.
  7. Systolic blood pressure is 85 to 150 mmHg, inclusive (subjects <65 years of age), 85 to 160 mmHg, inclusive (subjects = / > 65 years of age).
  8. Diastolic blood pressure is 55 to 95 mmHg, inclusive.
  9. Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour.
  10. Women of childbearing potential* must use an acceptable contraception method** from 30 days before first study vaccination until 60 days after last study vaccination.

    *Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or <1 year of the last menses if menopausal.

    **Acceptable contraception includes non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the first study vaccination, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, or oral contraceptives ("the pill").

  11. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.

Exclusion Criteria:

  1. Have an acute illness*, as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to study vaccination.

    *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.

  2. Have any medical disease or condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation*.

    *Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial.

  3. Have immunosuppression as a result of an underlying illness or treatment, a recent history or current use of immunosuppressive or immunomodulating disease therapy.
  4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
  5. Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma, treated, skin cancers are permitted.
  6. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
  7. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.
  8. Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
  9. Have a personal or family history of narcolepsy.
  10. Have a history of Guillain-Barré syndrome.
  11. Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.
  12. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).
  13. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.
  14. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
  15. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination.
  16. Have taken oral or parenteral (including intra-articular) corticosteroids of any dose within 30 days prior to study vaccination.
  17. Have taken high-dose inhaled corticosteroids* within 30 days prior to each study vaccination.

    *High-dose defined as per age as using inhaled high dose per reference chart https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/quick-reference-html#estimated-comparative-daily-doses

  18. Received a licensed live vaccine within 30 days prior to the first study vaccination, or plan to receive a licensed live vaccine within 30 days before or after each study vaccination.
  19. Received or plan to receive a licensed, inactivated, vaccine (excluding all flu vaccines) within 14 days before or after each study vaccination.
  20. Received or plan to receive an inactivated seasonal flu vaccine within 21 days before or after each study vaccination.
  21. Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to each study vaccination.
  22. Received an experimental agent* within 30 days prior to the first study vaccination, or expect to receive an experimental agent** during the 13-month trial-reporting period.

    *Including vaccine, drug, biologic, device, blood product, or medication.

    **Other than from participation in this trial.

  23. Are participating or plan to participate in another clinical trial with an interventional agent* that will be received during the 13-month trial-reporting period.

    *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication.

  24. Received or plan to receive an influenza A/H7 vaccine* or have a history of influenza A/H7 subtype infection.

    *And assigned to a group receiving influenza A/H7 vaccine, does not apply to documented placebo recipients.

  25. Have traveled to mainland China and had substantial* direct contact with live or freshly slaughtered poultry or pigeons within the past five years.

    *Substantial contact is defined as visited a poultry farm and/or a live poultry market.

  26. Occupational exposure to or substantial direct physical contact* with birds in the past year and through the 21 days after the second study vaccination.

    *Exposure to free range chickens in the yard is exclusionary. Casual contact with birds at petting zoos or county or state fairs or having pet birds does not exclude subjects from study participation.

  27. Female subjects who are breastfeeding or plan to breastfeed at any given time from the first study vaccination until 30 days after the last study vaccination.
  28. Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment through 21 days after the second study vaccination.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years to 99 Years   (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 NCT03312231
Other Study ID Numbers  ICMJE 17-0075
HHSN272201400004I
Has Data Monitoring Committee Not Provided
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 Not Provided
Current Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Original Responsible Party Same as current
Current Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date September 2019

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