Systems Biology of Influenza A (H5N1) Virus Monovalent Vaccine With and Without Adjuvant System 03 (AS03)

Phase 2

Completed

Conditions: Influenza A Virus, H5N1 Subtype

Interventions: Biological: H5N1 vaccine plus AS03 adjuvant
Biological: H5N1 vaccine without adjuvant

Registration Number: NCT01910519

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary: This study will compare the different immune responses to Influenza A (H5N1) Virus Monovalent Vaccine with and without the AS03 adjuvant. The Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant vaccine is approved for use for adults to protect against flu caused by the A/H5N1 "bird flu" virus in Europe but none of the vaccines to be used in the study are approved for use in the United States. The results of this study will help researchers learn about better ways to vaccinate people against the H5N1 flu.

Detailed Description: The influenza virus (a germ) causes influenza or "flu." The flu is an infection of the breathing tubes and the lungs. In recent years, flu viruses that at first only infected birds have begun to infect humans. One of these strains is called avian influenza (A/H5N1 subtype) or "bird flu". Although no human cases of bird flu have been diagnosed in the United States, this strain has caused severe illness and death in several hundred people since late 2003. .

Vaccination is the most effective way of controlling flu and preventing its illness and complications. Vaccines help prevent illness by causing the body to make antibodies that fight infection. One way to improve the effectiveness of a vaccine is to include a substance that can stimulate the immune system to make more antibodies. This type of substance is called an adjuvant; one type of adjuvant is called AS03 (Adjuvant System 03).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

Inclusion Criteria

Individuals in good health (as determined by vital signs, medical history, physical examination and laboratory tests);
Able to understand and give informed consent;
Women of childbearing potential must agree to practice adequate contraception 1 month prior to study entry and until day 100 of the study.

Exclusion Criteria

Personal or family history of sleeping disorders including any of the following: Narcolepsy with or without cataplexy; Idiopathic Hypersomnia or excessive daytime sleepiness of unknown origin; Sleep paralysis; Sleep related hallucinations (hypnagogic or hypnopompic hallucinations);
Human leukocyte antigen (HLA)-DQB1*06:02 positivity (or DQB1*06 positivity if high resolution HLA testing cannot be performed);
An abnormal erythrocyte sedimentation rate at baseline;
Receipt of blood products 3 months prior to study entry and until day 100 of the study;
Volunteers who donated blood 56 days before screening and have plans to donate on or before day 100 of the study;
Hemoglobin value of less than 12 mg/dL for females and less than 13 mg/dL for males;
A positive result in the Narcolepsy Mini Screen questionnaire;
A score of ≥11 on the Epworth sleepiness scale questionnaire;
Receipt of any experimental agents within 6 weeks prior to first vaccination and until the completion of the study;
Receipt of any licensed live vaccine within 4 weeks or any licensed inactivated vaccine within 2 weeks prior to the first study vaccination or planned receipt of any vaccine within 42 days after study entry;
Receipt of a H5 vaccine or AS03-adjuvanted vaccine at any time in the past prior to current study or have a history of A/H5N1 infection;
Influenza-like illness (ILI) or documented influenza infection during the 2013-2014 influenza season. [Not excluded from the study, volunteers with prior upper respiratory infections other than ILI];
Chronic medical problems including (but not limited to) insulin dependent diabetes, severe heart disease, severe lung disease, severe liver disease, severe kidney disease, autoimmune disease, severe gastrointestinal disease;
Alcohol or drug abuse and psychiatric conditions that in the opinion of the investigator would preclude compliance with the trial or interpretation of safety or endpoint data;
Impaired immune function or chronic infections including (but not limited to) HIV, hepatitis B or C; organ transplant; active cancer or any history of hematologic cancer; receipt of chemotherapy, radiation therapy (past 36 months) or any other potentially immunosuppressive therapy [i.e. Systemic steroids at any dose and intra-articular administration of steroids in the past 3 months; (Nasal and topical steroids are allowed)], congenital immunodeficiency, anatomical or functional asplenia;
Heart rate less than 40 bpm or greater than 100 bpm. Systolic blood pressure is less than 90 mm Hg or equal or greater than 160 mm Hg. Diastolic blood pressure is less than 60 mm Hg or equal or greater than 100 mg Hg;
Pregnancy or postpartum (less than 1 year after delivery) or breast feeding;
Severe reactions to prior vaccination with influenza virus vaccines, including anaphylaxis;
History of Guillain-Barré syndrome;
A previous sudden life-threatening allergic reaction to any ingredient of Influenza A (H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant or to any of the substances that may be present in trace amounts such as thiomersal, egg residues including ovalbumin as well as residual amounts of sodium deoxycholate detergent, formaldehyde and sucrose;
Volunteers with any acute illness, including any fever (> 100.4 F [> 38.0 C], regardless of the route) within 3 days prior to study entry;
Social, occupational, or any other condition that in the opinion of the investigator might interfere with compliance with the study and vaccine evaluation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
H5N1 vaccine plus AS03 adjuvant	H5N1 vaccine plus AS03 adjuvant	H5N1 vaccine plus AS03 adjuvant: Influenza A Vaccine with AS03 adjuvant Participants receive 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine with AS03 adjuvant given 21 days apart (i.e., Administer day 1, booster at Day 21).
H5N1 vaccine without adjuvant	H5N1 vaccine without adjuvant	H5N1 vaccine without adjuvant: Influenza A Vaccine without AS03 adjuvant Participants receive 2 intramuscular doses of Influenza A (H5N1) Virus Monovalent Vaccine without AS03 adjuvant given 21 days apart (i.e., Administer day 1, booster at Day 21).

Primary Outcome Measures

Name	Time	Method
Measurement of Hemagglutination Inhibition Assay (HAI) Titers With Influenza A Vaccine With and Without AS03 Adjuvant	Day 42	To measure selective adaptive immune response; 21 days post second vaccination
Change in Traditional Immune Parameters Measurements Using Luminex Assays and Gene Expression Measurement Using Microarray Experiments From Baseline With Influenza A Vaccine With and Without AS03 Adjuvant	Day 28	To identify innate immune signatures; 7 days post second vaccination
Measurement of Microneutralization (MN) Titers With Influenza A Vaccine With and Without AS03 Adjuvant	Day 42	To measure selective adaptive immune response; 21 days post second vaccination