H5N1 Priming and Boosting Strategies

NCT00703053 | Completed Phase 2 Results

• 2 other identifiers: 07-0019N01AI80003C
• Study Type: interventional
• Target: 505
• Locations: 1 country
• Sites: 5

Brief Summary

Severe disease in humans due to bird influenza viruses (H5N1) has led to concern that this virus may result in a widespread outbreak of bird flu. The purpose of this study is to evaluate the dose and dosing schedule for 2 different types of H5N1 vaccine. Participants will be randomly assigned to 1 of 9 possible vaccine groups. All participants will receive 2 doses of Clade 1, Clade 2, or combination Clade 1 and 2 on Day 0. All participants will receive a second dose of the same vaccine or a different vaccine type on study day 7, 14, 28 or 180. Study participants will include about 500 healthy adult subjects, ages 18-49 years old, who have no history of prior H5 flu exposure or vaccination. Study procedures may include medical history, physical exam, and blood sampling. Subject participation may last up to 372 days. Several DMID studies have recently evaluated H5N1 vaccines in healthy adults, 04-063, 05-0090, 05-0015, and 05-0043.

Conditions

Influenza

Keywords

influenza, H5N1, vaccine, avian influenza, parent protocol

Outcome Measures

Primary Outcomes (6)

• Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen

  The GMTs are as assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.

  28 days post last vaccination.

• Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen

  The GMTs are as assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.

  28 days post last vaccination.

• Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen

  The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise.

  28 days post last vaccination.

• Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen

  The number of subjects who achieve a 4-fold or greater rise in titer, relative to the baseline (Day 0) titer, assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. Subjects whose baseline titer is \<10 must have a post vaccination titer of at least 1:40 to be considered a 4-fold rise.

  28 days post last vaccination.

• Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen

  The number of subjects who achieve a HAI antibody titer of 1:40 or greater as assessed by the HAI assay against the A/Vietnam/04 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.

  28 days post last vaccination.

• Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen

  The number of subjects who achieve a HAI antibody titer of 1:40 or greater as assessed by the HAI assay against the A/Indonesia/05 antigen at 28 days following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.

  28 days post last vaccination.

Secondary Outcomes (14)

• Number of Serious Adverse Events

  Duration of study

• Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination

  7 days after first vaccination

• Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination

  7 days after second vaccination

• Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen

  28 days post last vaccination.

• Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen

  28 days post last vaccination.

Study Arms (9)

Group 1

EXPERIMENTAL

25 subjects: Day 0, A/Vietnam/04 90 mcg; Day 7, A/Vietnam/04 90 mcg.

Biological: A/Vietnam/1203/04

Group 9

EXPERIMENTAL

100 subjects: Day 0, A/Vietnam/04 90 mcg; Day 28, A/Vietnam/04 90 mcg.

Biological: A/Vietnam/1203/04

Group 8

EXPERIMENTAL

100 subjects: Day 0, A/Vietnam/04 90 mcg.

Biological: A/Vietnam/1203/04

Group 7

EXPERIMENTAL

50 subjects: Day 0, A/Indonesia/05 90 mcg; Day 180, A/Indonesia/05 90 mcg.

Biological: A/Indonesia/05/05

Group 6

EXPERIMENTAL

50 subjects: Day 0, A/Vietnam/04 90 mcg; Day 180, A/Indonesia/05 90 mcg.

Biological: A/Vietnam/1203/04; Biological: A/Indonesia/05/05

Group 5

EXPERIMENTAL

50 subjects: Day 0, A/Vietnam/04 45 mcg + A/Indonesia/05 45 mcg; Day 28, A/Vietnam/04 45 mcg + A/Indonesia/05 45 mcg.

Biological: A/Vietnam/1203/04; Biological: A/Indonesia/05/05

Group 4

EXPERIMENTAL

50 subjects: Day 0, A/Vietnam/04 90 mcg; Day 28, A/Indonesia/05 90 mcg.

Biological: A/Vietnam/1203/04; Biological: A/Indonesia/05/05

Group 3

EXPERIMENTAL

50 subjects: Day 0, A/Indonesia/05 90 mcg; Day 28, A/Indonesia/05 90 mcg.

Biological: A/Indonesia/05/05

Group 2

EXPERIMENTAL

25 subjects: Day 0, A/Vietnam/04 90 mcg; Day 14, A/Vietnam/04 90 mcg.

Biological: A/Vietnam/1203/04

Interventions

A/Vietnam/1203/04 BIOLOGICAL

Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.

Group 1; Group 2; Group 4; Group 5; Group 6; Group 8; Group 9

A/Indonesia/05/05 BIOLOGICAL

Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.

Group 3; Group 4; Group 5; Group 6; Group 7

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 years old, 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 agree to practice 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) 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.
• Has a known allergy to eggs, egg products or other components of the vaccine (including gelatin, formaldehyde, octoxinol, thimerosal and egg or chicken protein).
• 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. 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 (5)

The Hope Clinic of the Emory Vaccine Center

Decatur, Georgia, 30030, United States

Location

Mayo Clinic, Rochester - Vaccine Research Group

Rochester, Minnesota, 55905, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Group Health Cooperative

Seattle, Washington, 98101, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• Belshe RB, Frey SE, Graham I, Mulligan MJ, Edupuganti S, Jackson LA, Wald A, Poland G, Jacobson R, Keyserling HL, Spearman P, Hill H, Wolff M; National Institute of Allergy and Infectious Diseases-Funded Vaccine and Treatment Evaluation Units. Safety and immunogenicity of influenza A H5 subunit vaccines: effect of vaccine schedule and antigenic variant. J Infect Dis. 2011 Mar 1;203(5):666-73. doi: 10.1093/infdis/jiq093. Epub 2011 Jan 31.

  PMID: 21282194 RESULT

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

Results Point of Contact

• Title: Robert Belshe, MD
• Organization: Saint Louis University

belsherb@slu.edu

314-977-9030

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2008
• First Posted: June 23, 2008
• Study Start: September 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: November 1, 2009
• Last Updated: August 23, 2013
• Results First Posted: July 16, 2010

Record last verified: 2009-09

Locations

US (5)