A Randomized, Double-Blinded, Controlled, Phase I Study in Healthy Adults to Assess the Safety, Reactogenicity, and Immunogenicity of Intramuscular Subvirion Inactivated Monovalent Influenza A/H5N1 Virus Vaccine Administered at Different Dose Levels Given With and Without MF59 Adjuvant
Overview
- Phase
- Phase 1
- Intervention
- Phosphate Buffered Saline (PBS) diluent
- Conditions
- Influenza
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 270
- Locations
- 5
- Primary Endpoint
- Safety/Tolerability: Occurrence of solicited local and systemic reactogenicity in the 8 days (Day 0-7) after each vaccination.
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
Approximately 216, and up to 270, 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 MF59 or diluent (N=216, up to 270). 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 MF59 adjuvant manufactured by Novartis or PBS diluent.
Investigators
Eligibility Criteria
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.
Exclusion Criteria
- •Exclusion Criteria for study entry and Dose 1:
- •Have a known allergy to eggs or other components of the vaccine (including gelatin, formaldehyde, octoxinol-9, thimerosal and chicken protein), or allergy to squalene-based adjuvants.
- •Women who are breastfeeding or plan to breastfeed at any given time from the first vaccination until 30 days after the last vaccination.
- •Have long term use (defined as taken for 2 weeks or more in total at any time during the past 2 months) of high dose oral or parenteral glucocorticoids (high dose defined as prednisone \>/= 20 mg total daily dose, or equivalent dose of other glucocorticoids); or high-dose inhaled steroids (high dose defined as \>800 mcg/day of beclomethasone dipropionate or equivalent); or systemic corticosteroids of any dose within the past 4 weeks.
- •Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months.
- •Have an active neoplastic disease or a history of any hematologic malignancy.
- •Have a diagnosis of schizophrenia, bipolar disease, or other major psychiatric diagnosis.
- •Hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others, within the past 10 years.
- •Receiving systemic, prescription medications for the treatment of chronic medical conditions, unless such use is on a PRN (as needed) basis only. Non-PRN use of systemic, over-the-counter medications and PRN systemic, prescription medication may be allowed if, in the opinion of the investigator, they pose no additional risk to subject safety or assessment of immunogenicity/reactogenicity. Note: Topical, nasal, and inhaled medications; vitamins; and contraceptives are also permitted.
- •Received pre-medication with analgesic or antipyretic agents in the 6 hours prior to first vaccination, or planned medication with analgesic or antipyretic in the week following first vaccination. This criterion should not preclude subjects receiving such medication if the need arises. However, pre-medication is to be discouraged.
Arms & Interventions
Group 5
Two doses of sanofi H5N1 antigen 7.5 mcg plus PBS diluent
Intervention: Phosphate Buffered Saline (PBS) diluent
Group 5
Two doses of sanofi H5N1 antigen 7.5 mcg plus PBS diluent
Intervention: H5N1 Antigen
Group 4
Two doses of sanofi H5N1 antigen 3.75 mcg plus Phosphate Buffered Saline (PBS) diluent
Intervention: Phosphate Buffered Saline (PBS) diluent
Group 4
Two doses of sanofi H5N1 antigen 3.75 mcg plus Phosphate Buffered Saline (PBS) diluent
Intervention: H5N1 Antigen
Group 3
Two doses of sanofi H5N1 antigen 15 mcg plus Novartis MF59 adjuvant
Intervention: MF59 Adjuvant
Group 3
Two doses of sanofi H5N1 antigen 15 mcg plus Novartis MF59 adjuvant
Intervention: H5N1 Antigen
Group 2
Two doses of sanofi H5N1 antigen 7.5 mcg plus Novartis MF59 adjuvant
Intervention: MF59 Adjuvant
Group 2
Two doses of sanofi H5N1 antigen 7.5 mcg plus Novartis MF59 adjuvant
Intervention: H5N1 Antigen
Group 1
Two doses of sanofi H5N1 antigen 3.75 mcg plus Novartis MF59 adjuvant
Intervention: MF59 Adjuvant
Group 1
Two doses of sanofi H5N1 antigen 3.75 mcg plus Novartis MF59 adjuvant
Intervention: H5N1 Antigen
Group 6
Two doses of sanofi H5N1 antigen 15 mcg plus PBS diluent
Intervention: Phosphate Buffered Saline (PBS) diluent
Group 6
Two doses of sanofi H5N1 antigen 15 mcg plus PBS diluent
Intervention: H5N1 Antigen
Outcomes
Primary Outcomes
Safety/Tolerability: Occurrence of solicited local and systemic reactogenicity in the 8 days (Day 0-7) after each vaccination.
Time Frame: Day 0 through Day 7 after each vaccination
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)
Time Frame: Day 42
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.
Time Frame: From time of 1st vaccination through 13 months
Secondary Outcomes
- 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)