Clinical Trial: H7N9 Mix and Match With MF59 in Healthy Elderly Persons

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Randomized, Partially-Blinded, Controlled Trial in Healthy Adults Aged 65 Years and Older to Assess the Safety, Reactogenicity, and Immunogenicity of an MF59-Adjuvanted, Monovalent Inactiva

Brief Summary: This is a Phase II randomized, partially-blinded, controlled trial in 360 (up to 600) males and females, 65 years of age and older, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H7N9 virus vaccine manufactured by Sanofi Pasteur administered intramuscularly at different intervals and dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with MF59 adjuvant manufactured by Novartis Vaccines and Diagnostics. Subjects will receive three doses of the vaccine. Safety, reactogenicity, and immunogenicity data will be collected at standard time points with safety follow-up to continue through one year post dose 2. Study Duration is approximately 30 months and Subject Participation is approximately 18 months. The primary objectives are to (1) assess the safety and reactogenicity of different dosages (3.75, 7.5, and 15 mcg of HA/0.5 mL dose) of an MF59-adjuv

Detailed Summary:

This is a Phase II randomized, partially-blinded, controlled trial in males and females, 65 years of age and older, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H7N9 virus vaccine, derived from the influenza A/Shanghai/2/2013 virus, manufactured by Sanofi Pasteur administered intramuscularly at different intervals and dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with MF59 adjuvant manufactured by Novartis Vaccines and Diagnostics. Subjects will be assigned randomly to 1 of 6 groups (60 to 100 subjects per group) to receive three doses intramuscularly of the inactivated A/H7N9 vaccine at dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with MF59 adjuvant using two different study vaccination schedules. The first and third study vaccinations will be administered to all subjects on Day 1 and approximately Day 169. The second study vaccination will be administered either on approximately Day 29 for Groups 1, 3, and 5 or approximately Day 57 for Groups 2, 4, and 6. Reactogenicity will be measured from the time of each study vaccination through 8 days after each study vaccination by the occurrence of solicited injection site and systemic reactions. Unsolicited non-serious adverse events (AEs) will be collected from the time of each study vaccination through approximately 28 days after each study vaccination. Serious adverse events (SAEs) and new-onset chronic medical conditions will be collected from the time of the first study vaccination through approximately 12 months after the last study vaccination.

Immunogenicity testing will include performing hemagglutination inhibition (HAI) and neutralizing (Neut) antibody assays on serum obtained immediately prior to the first study vaccination (Day 1), approximately 28 days aft
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine [ Time Frame: 28 days after the second study vaccination ]
  • Percent of subjects achieving HAI seroconversion against the A/H7N9 antigen contained in the study vaccine (either a pre-vaccine HAI titer < 1:10 and a post-vaccine HAI titer > /= 1:40 or a pre-vaccine HAI titer > /=1:10 and a min 4-fold rise in post-vac [ Time Frame: 28 days after the second study vaccination ]
  • Occurrence of study vaccine-related serious adverse events [ Time Frame: Through Day 1 to 12 months after the last study vaccination ]
  • Occurrence of solicited injection site and systemic reactogenicity events [ Time Frame: Through 8 days after each study vaccination ]


Original Primary Outcome:

  • Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at approximately 28 days after the second study vaccination [ Time Frame: 28 days after the second study vaccination ]
  • Occurrence of study vaccine-related serious adverse events from the time of the first study vaccination through approximately 12 months after the last study vaccination [ Time Frame: Through Day 1 to 12 months after the last study vaccination ]
  • Occurrence of solicited injection site and systemic reactogenicity events from the time of each study vaccination through 8 days after each study vaccination [ Time Frame: Through 8 days after each study vaccination ]
  • Percentage of subjects achieving HAI seroconversion (defined as either a pre-vaccination HAI titer <1:10 and a post-vaccination HAI titer >/=1:40 or a pre-vaccination HAI titer >/= 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer) [ Time Frame: 28 days after the second study vaccination ]


Current Secondary Outcome:

  • Occurrence of study vaccine-related unsolicited non-serious adverse events [ Time Frame: 28 days after each study vaccination ]
  • Occurrence of new-onset chronic medical conditions [ Time Frame: Through Day 1 to 12 months after the last study vaccination ]
  • Percentage of subjects achieving Neut seroconversion against A/H7N9 antigen (either prevaccination Neut titer < 1:10 and postvaccination Neut titer > /=1:40 or prevaccination Neut titer > /=1:10 and minimum fourfold rise in post-vaccination Neut [ Time Frame: 28 days after the second and third study vaccinations ]
  • Geometric Mean Titers of serum HAI and Neut antibodies against the A/H7N9 antigen [ Time Frame: Baseline and 28 days after the second and third study vaccinations ]
  • Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine [ Time Frame: Baseline and 28 days after the third study vaccination ]
  • Percentage of subjects achieving a serum Neut antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine [ Time Frame: Baseline and 28 days after the second and third study vaccinations ]
  • Percentage of subjects achieving HAI seroconversion against the A/H7N9 antigen [ Time Frame: 28 days after the third study vaccination ]


Original Secondary Outcome:

  • Percentage of subjects achieving a serum Neut antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at baseline and approximately 28 days after the second and third study vaccinations [ Time Frame: Baseline and 28 days after the second and third study vaccinations ]
  • Percentage of subjects achieving Neut seroconversion (either a pre-vaccination Neut titer <1:10 and a post-vaccination Neut titer >/=1:40 or a pre-vaccination Neut titer >/=1:10 and a minimum four-fold rise in post-vaccination Neut antibody titer) [ Time Frame: 28 days after the second and third study vaccinations ]
  • Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H7N9 antigen contained in the study vaccine at baseline and approximately 28 days after the third study vaccination [ Time Frame: Baseline and 28 days after the third study vaccination ]
  • Geometric Mean Titers of serum HAI and Neut antibody at baseline and approximately 28 days after the second and third study vaccinations [ Time Frame: Baseline and 28 days after the second and third study vaccinations ]
  • Occurrence of unsolicited adverse events from the time of each study vaccination through approximately 28 days after each study vaccination [ Time Frame: Through 28 days after each study vaccination ]
  • Occurrence of new-onset chronic medical conditions from the time of the first study vaccination through approximately 12 months after the last study vaccination [ Time Frame: Through Day 1 to 12 months after the last study vaccination ]
  • Percentage of subjects achieving HAI seroconversion at approximately 28 days after the third study vaccination [ Time Frame: 28 days after the third study vaccination ]


Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: August 7, 2014
Date Started: October 2014
Date Completion:
Last Updated: August 11, 2016
Last Verified: April 2016