H5N1 Mix and Match With MF59
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
2 other identifiers
interventional
270
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2011
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 16, 2011
CompletedFirst Posted
Study publicly available on registry
March 17, 2011
CompletedStudy Start
First participant enrolled
May 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2012
CompletedJanuary 25, 2013
August 1, 2012
1.3 years
March 16, 2011
January 24, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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 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
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
Secondary Outcomes (1)
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
Study Arms (6)
Group 5
PLACEBO COMPARATORTwo doses of sanofi H5N1 antigen 7.5 mcg plus PBS diluent
Group 4
PLACEBO COMPARATORTwo doses of sanofi H5N1 antigen 3.75 mcg plus Phosphate Buffered Saline (PBS) diluent
Group 3
EXPERIMENTALTwo doses of sanofi H5N1 antigen 15 mcg plus Novartis MF59 adjuvant
Group 2
EXPERIMENTALTwo doses of sanofi H5N1 antigen 7.5 mcg plus Novartis MF59 adjuvant
Group 1
EXPERIMENTALTwo doses of sanofi H5N1 antigen 3.75 mcg plus Novartis MF59 adjuvant
Group 6
PLACEBO COMPARATORTwo doses of sanofi H5N1 antigen 15 mcg plus PBS diluent
Interventions
Placebo/diluent provided be sanofi pasteur
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 MF59 adjuvant or PBS.
Eligibility Criteria
You may qualify if:
- 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.
- 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).
You may not qualify if:
- 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.
- Received immunoglobulin or other blood products (with exception of Rho D immune globulin) within the 3 months prior to the first vaccination..
- Received any live licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks prior to the first vaccination or plan receipt of such vaccines within 42 days following the first vaccination. This is inclusive of licensed seasonal influenza vaccines.
- Have an acute or chronic medical condition that, in the opinion of the site principal investigator or appropriate sub-investigator, would render vaccination unsafe, would interfere with the evaluation of responses or is not generally seen in "normal, healthy subjects".
- Have a history of severe reactions following previous immunization with contemporary influenza virus vaccines.
- Have an acute illness, including an oral temperature greater than or equal to 100.4 degrees F, within 3 days prior to the first vaccination.
- Pulse is less than 40 bpm or greater than 100 bpm. An ECG documenting only sinus bradycardia is required for pulses less than 50 bpm.
- +31 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Emory Children's Center - Division of Pediatric Infectious Diseases
Atlanta, Georgia, 30322, United States
Emory Vaccine Center - The Hope Clinic
Decatur, Georgia, 30030-2517, United States
University of Iowa - Infectious Disease Clinic
Iowa City, Iowa, 52242-1009, United States
Saint Louis University - Center for Vaccine Development
St Louis, Missouri, 63104-1015, United States
Cincinnati Children's Hospital Medical Center - Infectious Diseases
Cincinnati, Ohio, 45229-3026, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 16, 2011
First Posted
March 17, 2011
Study Start
May 1, 2011
Primary Completion
September 1, 2012
Study Completion
September 1, 2012
Last Updated
January 25, 2013
Record last verified: 2012-08