Influenza
Conditions
Keywords
A/H7N9,Adjuvant,Immunogenicity,Influenza,MF59,Monovalent,Vaccine
Brief summary
This is a Phase II randomized, double-blinded, controlled study in up to 700 males and non-pregnant females, 19 to 64 years old, inclusive, designed to assess the safety, reactogenicity, and immunogenicity of a monovalent influenza A/H7N9 virus vaccine administered at different dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with and without MF59 adjuvant and without adjuvant (15 mcg of HA/0.5 mL dose and 45 mcg of HA/0.75 mL dose). Subjects will receive two doses via intramuscular injection, approximately 21 days apart. Safety, reactogenicity, and immunogenicity data will be collected at standard time points with safety follow-up to continue through one year post dose 2. The duration of the study for each subject will be approximately 13 months.
Detailed description
This is a Phase II randomized, double-blinded, controlled study in up to 700 males and non-pregnant females, 19 to 64 years old, inclusive, who are in good health and meet all eligibility criteria. The study is designed to assess the safety, reactogenicity, and immunogenicity of a monovalent influenza A/H7N9 virus vaccine manufactured by Sanofi Pasteur administered to healthy adults at different dosages (3.75, 7.5, or 15 mcg of HA/0.5 mL dose) given with MF59 adjuvant manufactured by Novartis Vaccines and Diagnostics and without adjuvant (15 mcg of HA/0.5 mL dose and 45 mcg of HA/0.75 mL dose). The A/H7N9 vaccine was made with HA antigen derived from the influenza A/Shanghai/2/2013 virus. Subjects will be randomly assigned to 1 of 7 groups (up to 100 subjects per group) to receive two doses of the A/H7N9 vaccine with and without MF59 adjuvant delivered intramuscularly approximately 21 days apart. The same dosage of A/H7N9 vaccine will be given to subjects at both their first and second study vaccinations. The primary objectives are to: 1) assess the safety and reactogenicity of a monovalent influenza A/H7N9 virus vaccine following receipt of two doses administered with and without MF59 adjuvant; and 2) assess new-onset chronic medical conditions following receipt of two doses of a monovalent influenza A/H7N9 virus vaccine administered with and without MF59 adjuvant. The duration of the study for each subject will be approximately 13 months.
Interventions
Monovalent influenza A/H7N9 virus vaccine for intramuscular use is a sterile, clear and slightly opalescent suspension. sanofi A/H7N9 antigen. Group 1 receives 3.75mcg A/H7N9 IM on days 1 and 21, Group 2 receives 7.5 mcg IM on days 1 and 21, Group 3, 4, 5, & 6 receives 15 mcg IM on days 1 and 21, and Group 7 receives 45 mcg IM on days 1 and 21.
DRUGMF59
MF59 adjuvant is an oil-in-water emulsion composed of a small amount of squalene administered with different dosages. Group 1, 2 & 3 receives 0.7 ml of MF59 Intramuscularly (IM) on days 0 and 21. Group 4 receives MF59 on day 0, Group 5 receives MF59 on Day 21.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
-Provide written informed consent prior to initiation of any study procedures. -Are able to understand and comply with planned study procedures and be available for all study visits. -Are males or non-pregnant females, 19 to 64 years old, inclusive. -Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and targeted physical examination based on medical history to ensure any existing medical diagnoses or conditions (except those in the Subject
Exclusion criteria
) are stable. 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. Note: Topical, nasal, and inhaled medications (with the exception of steroids as outlined in the Subject
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of solicited injection site and systemic reactogenicity on the day of each study vaccination through 7 days after each study vaccination. | Day 0 through Day 29 |
| Occurrence of study vaccine-related serious adverse events from the time of the first study vaccination through approximately 13 months after the first study vaccination. | Day 0 through Day 386 |
| 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 21 days after the second study vaccination. | Day 42 (21 days post second study vaccination) |
| Percentage of subjects achieving seroconversion (pre-vaccination HAI titer <1:10 and post-vaccination HAI titer >/=1:40 or pre-vaccination HAI titer >/=1:10,minimum four-fold rise in post-vaccination HAI antibody titer). | Day 42 (21 days post second study vaccination) |
Secondary
| Measure | Time frame |
|---|---|
| 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 at approximately 8 and 21 days after the first study vaccination | Day 0, 8 and 21 |
| 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 at approximately 8 and 21 days after each study vaccination. | Day 0, 8, 21, 29, and 42 |
| Geometric Mean Titers of serum HAI and Neut antibody at baseline and at approximately 8 and 21 days after each study vaccination. | Day 0, 8, 21, 29, and 42 |
| Percentage of subjects achieving seroconversion (pre-vaccination HAI titer <1:10 and post-vaccination HAI titer >/=1:40 or pre-vaccination HAI titer >/=1:10 and minimum four-fold rise post-vaccination HAI antibody titer) | Day 0, 8 and 21 |
| Percentage of subjects achieving seroconversion (pre-vaccination Neut titer <1:10 and post-vaccination Neut titer >/=1:40 or pre-vaccination Neut titer >/=1:10 and minimum four-fold rise post-vaccination Neut antibody titer). | Day 0, 8, 21, 29, and 42 |
| Percentage of subjects achieving seroconversion (pre-vaccination HAI titer <1:10 and post-vaccination HAI titer >/= 1:40 or pre-vaccination HAI titer >/= 1:10 and minimum four-fold rise post-vaccination HAI antibody titer) | Day 29 (8 days after the second study vaccination) |
| Occurrence of new-onset chronic medical conditions through 13 months after the first study vaccination | Through Day 386 (13 months after the first vaccination) |
| Occurrence of unsolicited adverse events from the time of the first study vaccination through approximately 21 days after the last study vaccination. | Day 42 (21 days post last study vaccination) |
| 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 8 days after the second study vaccination. | Day 29 (8 days after the second study vaccination) |
Countries
United States
Outcome results
None listed