Influenza
Conditions
Keywords
influenza, vaccine, H5N1
Brief summary
Approximately 216, and up to 240, healthy males and non-pregnant females, 18 to 49 years old, inclusive, will be enrolled over a 5-month period into this multicenter, randomized, double-blinded, controlled Phase I study. Subjects who meet the entry criteria for the study and provide informed consent will be randomized 2:1 between adjuvanted and unadjuvanted vaccine and placed into one of 6 groups (see table) to receive two doses of an intramuscular subvirion inactivated monovalent influenza A/H5N1 virus vaccine at 3.75, 7.5, or 15 mcg given with the adjuvant AS03 or diluent (N=216, up to 240). All eligible subjects will receive 2 doses separated by approximately 21 days.
Detailed description
This is a randomized, double-blinded, controlled, Phase I study in healthy male and non-pregnant female subjects, 18 to 49 years old, inclusive, designed to assess the safety, reactogenicity, and immunogenicity of an intramuscular subvirion inactivated monovalent influenza A/H5N1 (HA of A/Indonesia/05/2005) virus vaccine manufactured by sanofi pasteur administered at different dosage levels (3.75, 7.5 or 15 mcg) given with the AS03 adjuvant manufactured by GSK or PBS diluent.
Interventions
DRUGAS03 Adjuvant
Adjuvant/diluent manufactured by GlaxoSmithKline (GSK)
Placebo/diluent provided by sanofi pasteur
BIOLOGICALSanofi H5N1 Antigen
Subvirion inactivated monovalent influenza A/H5N1 (Hemagglutinin (HA) of A/Indonesia/05/2005) virus vaccine manufactured by sanofi pasteur, at 2 doses levels 21 days apart, administered at 3.75, 7.5, or 15mcg, with either AS03 adjuvant or PBS.
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
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion Criteria for study entry and Dose 1: * Are males or non-pregnant females between the ages of 18 and 49 years, inclusive. * Women of childbearing potential (not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy or who are not postmenopausal for \>/=1 year) must agree to practice adequate contraception (that may include, but is not limited to, abstinence, monogamous relationship with vasectomized partner, barrier methods such as condoms or diaphragms with spermicide or foam, intrauterine devices, and licensed hormonal methods) during the study for at least 30 days following the last vaccination. Adherence to contraceptive method will be captured on the appropriate case report form (CRF). * Are in good health, as determined by vital signs (oral temp, pulse and blood pressure), medical history and complete physical examination (without genital and rectal exam) to ensure no existing chronic medical diagnoses or conditions are present. * ESR less than 30 mm per hour. * For women of childbearing potential, negative urine or serum pregnancy test within 24 hours prior to the first vaccination. * Are able to understand and comply with planned study procedures. * Provide written informed consent prior to initiation of any study procedures. Inclusion Criteria for Dose 2: * Have received the first dose of study vaccine. * For women of childbearing potential, negative urine or serum pregnancy test within 24 hours prior to the second vaccination. Adherence to contraceptive method will be captured on the appropriate case report form (CRF).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immunogenicity: Geometric mean titer (GMT) of HAI antibody, subjects with HAI antibody titer 1:40 or greater, and frequency of 4-fold or greater HAI antibody increase against A/H5N1 vaccine in each group 21 days following 2nd vaccine dose (approx Day 42) | Day 42 |
| Safety/Tolerability: Occurrence of solicited local and systemic reactogenicity in the 8 days (Day 0-7) after each vaccination. | Day 0 through Day 7 after each vaccination |
| Safety/Tolerability: Occurrence of vaccine-associated serious adverse events (SAEs) and clinical safety laboratory adverse events (AEs) from the time of first vaccination through 13 months after the first vaccination. | From time of 1st vaccination through 13 months |
Secondary
| Measure | Time frame |
|---|---|
| GMT of neutralizing antibody (NA), proportion of subjects with a serum NA titer of 1:40 or greater, and frequency of 4-fold or greater increases of NA against A/H5N1 virus vaccine in each group 21 days following 2nd dose of vaccine (approximately Day 42) | Day 42 |
Countries
United States
Outcome results
None listed