Booster Trial to 07-0019 With A/Anhui/05 With and Without MF59

NCT00912496 | Completed Phase 1

• 2 other identifiers: 08-0013N01AI80003C
• Study Type: interventional
• Target: 637
• Locations: 1 country
• Sites: 10

Brief Summary

This research will study safety and the body's immune (defense system) responses, including anti-H5 flu antibodies (the body's protective proteins found in the blood), to an inactivated influenza "H5" bird flu, virus vaccine. Participants will be assigned by chance to receive the vaccine injections with and without an adjuvant, (substance that can improve vaccine effectiveness so less vaccine may be used) MF59, or placebo (inactive substance). Five different vaccine dose strengths will be evaluated. About 735 healthy participants, ages 18-49 will be asked to take part in this study. Study procedures include physical exam, blood sampling, and use of a memory aid. Volunteers will participate for up to 13 months.

Conditions

Influenza

Keywords

Influenza, H5N1, vaccine, avian influenza

Outcome Measures

Primary Outcomes (2)

• Geometric Mean Titer, frequency of 4-fold or greater antibody titer increases, and proportion of subjects achieving a serum HAI antibody titer of 1:40 or greater against the 2 antigens being evaluated, A/Vietnam/1203/04 and A/Anhui/05 H5N1 virus.

  1 month and 6 months after last vaccination.

• Local and systemic adverse event (AE) or serious adverse event (SAE) information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessments).

  Duration of study.

Secondary Outcomes (2)

• Geometric mean titer in primed versus unprimed subjects to A/Vietnam/1203/04 and A/Anhui/05.

  Days 8 and 14 post-vaccination.

• Geometric mean titer (GMT), frequency of 4-fold or greater increases and proportion of subjects achieving a titer of 1:40 or greater in neutralizing antibody titers against the two antigens being evaluated, A/Vietnam/1203/04 and A/Anhui/05 H5N1 virus.

  1 month and 6 months after last vaccination.

Study Arms (3)

Group 9: 2 dose prime

EXPERIMENTAL

Received two doses of A/Vietnam/1203/04 90mcg vaccine as prime (on Days 0, 28 in DMID 07-0019), will receive a booster dose of A/Anhui/05 vaccine (A) with or without MF59 adjuvant in DMID 08-0013 on Day 0.

Biological: MF-59; Biological: A/Anhui/05

Group 8: 1 dose prime

EXPERIMENTAL

Received A/Vietnam/1203/04 90mcg vaccine as prime (Day 0 in DMID 07-0019), will receive a booster dose of A/Anhui/05 vaccine (A) with or without MF59 adjuvant in DMID 08-0013 on Day 0.

Biological: MF-59; Biological: A/Anhui/05

Group 10: unprimed control/dose response group

EXPERIMENTAL

Unprimed control and dose response group of H5 vaccine naive volunteers will be added in DMID 08-0013 to receive two doses of A/Anhui/05 vaccine (A) with or without MF59 adjuvant or placebo on Day 0 and Day 28.

Biological: MF-59; Biological: A/Anhui/05; Drug: Placebo

Interventions

MF-59 BIOLOGICAL

Doses of A/Anhui/05 vaccine (A) will be administered with or without MF59 adjuvant.

Group 10: unprimed control/dose response group; Group 8: 1 dose prime; Group 9: 2 dose prime

A/Anhui/05 BIOLOGICAL

Monovalent inactivated surface antigen influenza A/H5N1 (modified Hemagglutinin and Neuraminidase of A/Anhui/01/2005) vaccine supplied in 5mL multi-dose vials with thimerosal \[0.01%(w/v)\] as a preservative. Each dose level includes both unadjuvanted and MF59C.1 adjuvanted formulations: 7.5, 15, 30, or 60 micrograms (mcg) of H5 Hemagglutinin per milliliter (mL) with MF59C.1, and 7.5, 15, 30, or 60 micrograms (mcg) of H5 Hemagglutinin per milliliter (mL) without MF59C.1 adjuvant.

Group 10: unprimed control/dose response group; Group 8: 1 dose prime; Group 9: 2 dose prime

Placebo DRUG

Sterile normal saline for injection (0.9% Sodium Chloride Injection, USP Preservative-Free).

Group 10: unprimed control/dose response group

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women, 18 through 49 (Subjects previously enrolled in 07-0019 will be eligible for 08-0013 even if they are older than 49 years of age at the time of enrollment into 08-0013.) years old, who either were previously enrolled and received all scheduled vaccinations in Groups 8 and 9 under Division of Microbiology and Infectious Diseases (DMID) 07-0019, or are new subjects who deny exposure to H5 virus or participation in an H5 vaccine study.
• Women of childbearing potential (not surgically sterile or postmenopausal for greater than or equal to 1 year) must not be pregnant as indicated by a negative pregnancy test (urine or serum) within 24 hours prior to vaccine administration.
• Women of childbearing potential who are at risk of becoming pregnant must have a history of practicing adequate contraception (i.e., barrier methods, abstinence, monogamous relationship with vasectomized partner, intrauterine devices, Depo-Provera, Norplant, oral contraceptives, contraceptive patches or other licensed, effective methods) in the 30 days prior to enrollment, and must agree to practice adequate contraception until 30 days following receipt of the last dose of vaccine.
• Able to understand and comply with planned study procedures.
• Able to provide informed consent prior to initiation of any study procedures and be available for all study visits.

You may not qualify if:

• Has occupational exposure to poultry, to include but is not limited to chicken, turkey, or duck farmer, factory worker in poultry processing plant, veterinary staff that handles poultry; has recreational exposure to poultry, e.g. raising poultry in 4-H club, duck hunter that slaughters/handles the "kill" or history of previous H5N1 vaccination or exposure (other than vaccination in Protocol 07-0019).
• Has a known allergy to egg proteins (egg or egg products), or other components of the vaccine (including thimerosal, polymyxin, neomycin, beta propiolactone, or nonylphenol ethoxylate).
• Is female of child-bearing potential who is breastfeeding or intends to become pregnant during the study period up to 30 days following receipt of the last dose of vaccine.
• Has immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months.
• Has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematologic malignancy. An active neoplastic disease is defined as no neoplastic disease or treatment for neoplastic disease within the past 5 years.
• Has long-term use (greater than 2 weeks) of oral or parenteral steroids (glucocorticoids), or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed).
• Has a history of receiving immunoglobulin or other blood products within the 3 months prior to enrollment in this study.
• Has received any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study, or plans to receive any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) following each study vaccine.
• Has an acute or chronic medical condition that would render vaccination unsafe or would interfere with the evaluation of responses. This includes, but is not limited to: solicited reactogenicity symptoms, known chronic liver disease, significant renal disease, unstable or progressive neurological disorders, diabetes mellitus, and transplant recipients.
• Has a history of severe reactions following vaccination with contemporary influenza virus vaccines.
• Has an acute illness or has an oral temperature greater than 99.9 degrees Fahrenheit (37.7 degrees Celsius) within 3 days prior to enrollment.
• Has received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to enrollment in this study, or expects to receive an experimental agent during the study period.
• Has any condition that would, in the opinion of the site principal investigator place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
• Has a diagnosis of schizophrenia, bipolar disease or other severe (disabling) chronic psychiatric diagnosis.
• Has been hospitalized for psychiatric illness, history of suicide attempt or confinement for danger to self or others.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (10)

Emory Children's Center - Pediatric Infectious Diseases

Atlanta, Georgia, 30322-1014, United States

Location

Emory University School of Medicine - Emory Children's Center - Pediatric Infectious Diseases

Atlanta, Georgia, 30322, United States

Location

University of Iowa - Infectious Disease Clinic

Iowa City, Iowa, 52242-1009, United States

Location

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

Baltimore, Maryland, 21201-1509, United States

Location

Mayo Clinic, Rochester - Vaccine Research Group

Rochester, Minnesota, 55905-0001, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Duke Translational Medicine Institute - Clinical Vaccine Unit

Durham, North Carolina, 27704, United States

Location

Vanderbilt University - Pediatric - Infectious Diseases

Nashville, Tennessee, 37232, United States

Location

University of Texas Medical Branch - Pediatrics - Infectious Diseases and Immunology - Galveston

Galveston, Texas, 77555, United States

Location

Group Health Research Institute - Seattle

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

Influenza, Human; Influenza in Birds

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Bird Diseases; Animal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2009
• First Posted: June 3, 2009
• Study Start: June 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 14, 2013

Record last verified: 2011-10

Locations

US (10)