InfluenzaPhase 2NCT00703053

H5N1 Priming and Boosting Strategies

A Phase 2 study testing A/Vietnam/1203/04 and A/Indonesia/05/05 in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 49 yearsHealthy volunteers can take part
Conditions the study is for: Influenza
What is being tested?: A/Vietnam/1203/04 and A/Indonesia/05/05
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 505 participants
Where: 5 sitesUnited States
Study dates: Sep 2008to Nov 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 49 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Men and women, 18 through 49 years old, who deny exposure to H5 virus or participation in an H5 vaccine study.
In good health, as determined by vital signs (heart rate less than 100 bpm; blood pressure: systolic less than or equal to 140 mm Hg; diastolic less than or equal to 90 mm Hg; oral temperature less than 100.0 degrees Fahrenheit), medical history to ensure stable medical condition and a targeted physical examination, as indicated, based on medical history. A stable medical condition is defined as no recent change in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months. Any change that is due to change of health care provider, insurance company, etc, or is done for financial reasons, as long as in the same class of medication, will not be considered a violation of the inclusion criterion. Any change to prescription medication due to improvement of a disease outcome will not be considered a violation of the inclusion criterion.
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.

Who cannot join

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).

Show all 21Show fewer

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.
Is receiving psychiatric drugs. Subjects who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study.
Has known human immunodeficiency virus, hepatitis B, or hepatitis C infection.
Has a history of alcohol or drug abuse in the 5 years prior to enrollment.
Has a history of Guillain-Barré syndrome.
Has any condition that the investigator believes may interfere with successful completion of the study.
Plans to enroll in another clinical trial (that has a study intervention in the form of drug, biologic or device that could interfere with safety assessment of H5N1 vaccine) at any time during the study period.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

The Hope Clinic of the Emory Vaccine Center
Decatur, Georgia, 30030
Mayo Clinic, Rochester - Vaccine Research Group
Rochester, Minnesota, 55905
Group Health Cooperative
Seattle, Washington, 98101
University of Washington
Seattle, Washington, 98104
Saint Louis University
St Louis, Missouri, 63104

Other trials in United States

About this study

Official title: A Phase II Randomized Study of the Safety and Immunogenicity of Vaccination Strategies Using One or Two Clades and Different Schedules of H5N1 Unadjuvanted, Inactivated Subvirion Influenza Vaccines in H5 Naïve Healthy Adults

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.

Read the detailed description

Severe disease in humans due to avian influenza viruses of the H5N1 subtype has raised concern regarding the potential emergence of these viruses in pandemic form. Results of earlier studies suggest that previous priming can significantly affect the responses to subsequent booster doses, even if these booster doses represent an antigenic variant. Both the length of time between priming and revaccination, as well as the antigenic relatedness of the priming and revaccination antigens, may impact the response. These issues could have an important impact on pre-vaccination strategies prior to the emergence of a pandemic. This study will evaluate immunogenicity with the same or with different H5 variants. In this study, "different" will be defined as clade 1 followed by clade 1, clade 1 followed by clade 2, clade 2 followed by clade 2, or a combination of clades 1 \& 2 followed by a combination of clades 1 \& 2. In addition, the study will evaluate the effect of the interval between doses on the subsequent response, with "ultra-short" intervals defined as 7 or 14 days, a "short" interval defined as 28 days and a "long" interval defined as 180 days. The study will evaluate whether the use of a longer duration between doses or cross-clade priming will result in enhanced immunogenicity. Primary objectives are: evaluate the dose and schedules of unadjuvanted inactivated subvirion H5N1 vaccines belonging to the same or different clades in H5-naïve, healthy adults; determine if boosting of subjects given the inactivated influenza rg A/Vietnam/1203/04 vaccine with a heterologous antigen inactivated influenza rg A/Indonesia/05/05 results in broader or higher immune responses compared with boosting with the homologous antigen; and evaluate the immune response to 2 doses of H5 vaccine given at times < 1 month apart. Secondary objectives are: determine the safety of 2 doses of inactivated H5 vaccines in healthy adults given at different schedules and antigen combinations; obtain additional information regarding the antibody response to a single dose and to ultra-short immunization schedules; and evaluate the effect on antibody levels after receiving an antigenic variant to the priming virus given as a booster or simultaneously. The study will be conducted as a randomized, prospective controlled, multi-center trial. Approximately 500 healthy adult subjects, aged 18-49, who have no history of prior H5 influenza exposure or vaccination will be enrolled. Subjects will be randomized to receive varying schedules, (2 doses separated by 7, 14, 28 or 180 days), and clades of unadjuvanted inactivated subvirion H5N1 vaccine.

Conditions: Influenza
Being tested: A/Vietnam/1203/04, A/Indonesia/05/05
Keywords: influenza, H5N1, vaccine, avian influenza, parent protocol
Medical subject headings: Influenza, Human, Influenza in Birds

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

A/Vietnam/1203/04Biological
Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.
A/Indonesia/05/05Biological
Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.

Study groups in NCT00703053
Study group	Role	What they receive
Group 1	Experimental	25 subjects: Day 0, A/Vietnam/04 90 mcg; Day 7, A/Vietnam/04 90 mcg. Receives: Biological: A/Vietnam/1203/04
Group 9	Experimental	100 subjects: Day 0, A/Vietnam/04 90 mcg; Day 28, A/Vietnam/04 90 mcg. Receives: Biological: A/Vietnam/1203/04
Group 8	Experimental	100 subjects: Day 0, A/Vietnam/04 90 mcg. Receives: Biological: A/Vietnam/1203/04
Group 7	Experimental	50 subjects: Day 0, A/Indonesia/05 90 mcg; Day 180, A/Indonesia/05 90 mcg. Receives: Biological: A/Indonesia/05/05
Group 6	Experimental	50 subjects: Day 0, A/Vietnam/04 90 mcg; Day 180, A/Indonesia/05 90 mcg. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: A/Indonesia/05/05
Group 2	Experimental	25 subjects: Day 0, A/Vietnam/04 90 mcg; Day 14, A/Vietnam/04 90 mcg. Receives: Biological: A/Vietnam/1203/04

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 28 days post last vaccination.

Secondary outcomes (14)

Number of Serious Adverse Events
Serious adverse events were collected at each study visit from the time of first vaccination through the final study visit at 180 days after the last vaccination.
Measured: Duration of study
Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after first vaccination and review the Memory Aid with clinic staff at follow a up visit on Day 8. Subjects are counted if they indicated experiencing the symptom at any severity during the reporting period. The symptoms of redness and swelling were solicited as both functional grading as impact on daily activies as well as collected as a measured value in mm. The number reported for all symptoms is the number reporting greater than none.
Measured: 7 days after first vaccination
Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination
Subjects record the occurrence of solicited symptoms on a Memory Aid for 7 days after the second vaccination and review the Memory Aid with clinic staff at a follow up visit on Day 8. Subjects are counted if they indicated experiencing the symptom at any severity during the reporting period. The symptoms of redness and swelling were solicited as both functional grading as impact on daily activies as well as collected as a measured value in mm. The number reported for all symptoms is the number reporting greater than none.
Measured: 7 days after second vaccination
Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen
The GMTs are as assessed by the microneutralization assay against the A/Vietnam/04 antigen at 1 month following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Measured: 28 days post last vaccination.
Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen
The GMTs are as assessed by the microneutralization assay against the A/Indonesia/05 antigen at 1 month following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Measured: 28 days post last vaccination.
Number of Subjects Achieving a 4-fold or Greater Neutralizing 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 microneutralization 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.
Measured: 28 days post last vaccination.
Number of Subjects Achieving a 4-fold or Greater Neutralizing 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 microneutralization 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.
Measured: 28 days post last vaccination.
Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen
The number of subjects who achieve a titer of 1:40 or greater as assessed by the microneutralization 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.
Measured: 28 days post last vaccination.
Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen
The number of subjects who achieve a titer of 1:40 or greater as assessed by the microneutralization 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.
Measured: 28 days post last vaccination.
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination
The GMTs are as assessed by the HAI assay against the A/Vietnam/04 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Measured: Six months post last vaccination
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination
The GMTs are as assessed by the HAI assay against the A/Indonesia/05 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations. The CI shown as 5.0 to 5.0 reflect that all subjects had a titer of 5.0 for the VN,VN, Day 0,14 and VN, Day 0 groups.
Measured: Six months after last vaccination
Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination
The GMTs are as assessed by the microneutralization assay against the A/Vietnam/04 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Measured: Six months post last vaccination
Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination
The GMTs are as assessed by the microneutralization assay against the A/Indonesia/05 antigen at 6 months following the last vaccination. One group (VN, Day 0) receives only one vaccination, all other groups receive two vaccinations.
Measured: Six months post last vaccination
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses
The kinetics of the antibody response to vaccination with A/Vietnam/04 is evaluated by the HAI GMT against the A/Vietnam/04 antigen at weekly intervals after receipt of 2 doses 7, 14 and 28 days apart
Measured: Weeks 1, 2, 3 and 4 after the second dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2008Nov 2009

First posted23 Jun 2008 (estimated)
Study startSep 2008
Primary completionJul 2009
Study completionNov 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for InfluenzaStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 505 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00703053
Sponsor's protocol ID: 07-0019
Other IDs: N01AI80003C
Status last verified: Sep 2009
First submitted: 19 Jun 2008
Last updated: 23 Aug 2013
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 21282194

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Post Influenza

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Study at a glance

From the registry record, last updated by the sponsor on 23 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Randomized Study of the Safety and Immunogenicity of Vaccination Strategies Using One or Two Clades and Different Schedules of H5N1 Unadjuvanted, Inactivated Subvirion Influenza Vaccines in H5 Naïve Healthy Adults
ClinicalTrials.gov ID: NCT00703053
Acronym / sponsor ID: 07-0019
Conditions: Influenza
Keywords: influenza, H5N1, vaccine, avian influenza, parent protocol
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 505 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: Sep 2008
Primary completion: Jul 2009 (actual)
Study completion: Nov 2009 (actual)
First posted: 23 Jun 2008 (estimated)
Results: Posted 16 Jul 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 9

Arm	Type	Receives
Group 1	Experimental	Biological: A/Vietnam/1203/0425 subjects: Day 0, A/Vietnam/04 90 mcg; Day 7, A/Vietnam/04 90 mcg.
Group 9	Experimental	Biological: A/Vietnam/1203/04100 subjects: Day 0, A/Vietnam/04 90 mcg; Day 28, A/Vietnam/04 90 mcg.
Group 8	Experimental	Biological: A/Vietnam/1203/04100 subjects: Day 0, A/Vietnam/04 90 mcg.
Group 7	Experimental	Biological: A/Indonesia/05/0550 subjects: Day 0, A/Indonesia/05 90 mcg; Day 180, A/Indonesia/05 90 mcg.
Group 6	Experimental	Biological: A/Vietnam/1203/04, Biological: A/Indonesia/05/0550 subjects: Day 0, A/Vietnam/04 90 mcg; Day 180, A/Indonesia/05 90 mcg.
Group 5	Experimental	Biological: A/Vietnam/1203/04, Biological: A/Indonesia/05/0550 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.
Group 4	Experimental	Biological: A/Vietnam/1203/04, Biological: A/Indonesia/05/0550 subjects: Day 0, A/Vietnam/04 90 mcg; Day 28, A/Indonesia/05 90 mcg.
Group 3	Experimental	Biological: A/Indonesia/05/0550 subjects: Day 0, A/Indonesia/05 90 mcg; Day 28, A/Indonesia/05 90 mcg.
Group 2	Experimental	Biological: A/Vietnam/1203/0425 subjects: Day 0, A/Vietnam/04 90 mcg; Day 14, A/Vietnam/04 90 mcg.

Who may qualify

Ages: 18 to 49 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Men and women, 18 through 49 years old, who deny exposure to H5 virus or participation in an H5 vaccine study.
In good health, as determined by vital signs (heart rate less than 100 bpm; blood pressure: systolic less than or equal to 140 mm Hg; diastolic less than or equal to 90 mm Hg; oral temperature less than 100.0 degrees Fahrenheit), medical history to ensure stable medical condition and a targeted physical examination, as indicated, based on medical history. A stable medical condition is defined as no recent change in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months. Any change that is due to change of health care provider, insurance company, etc, or is done for financial reasons, as long as in the same class of medication, will not be considered a violation of the inclusion criterion. Any change to prescription medication due to improvement of a disease outcome will not be considered a violation of the inclusion criterion.
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.

Key exclusion criteria (21 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
A/Vietnam/1203/04Inactivated subvirion influenza rg A/Vietnam/1203/04 (clade 1) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.	Biological	Group 1, Group 2, Group 4, Group 5, Group 6, Group 8, Group 9
A/Indonesia/05/05Inactivated subvirion influenza rg A/Indonesia/05/05 (clade 2) x PR8 A/H5N1 vaccine; dosages 45 mcg and 90 mcg.	Biological	Group 3, Group 4, Group 5, Group 6, Group 7

Primary outcome

Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen
Time frame: 28 days post last vaccination.
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.
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen
Time frame: 28 days post last vaccination.
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.
Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Vietnam/04 Antigen
Time frame: 28 days post last vaccination.
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.
Number of Subjects Achieving a 4-fold or Greater HAI Antibody Titer Increase Against A/Indonesia/05 Antigen
Time frame: 28 days post last vaccination.
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.
Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen
Time frame: 28 days post last vaccination.
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.
Number of Subjects Achieving a HAI Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen
Time frame: 28 days post last vaccination.
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.

14 secondary outcomes

Number of Serious Adverse Events
Time frame: Duration of study
Number of Subjects Reporting Solicited Symptoms Within 7 Days of First Vaccination
Time frame: 7 days after first vaccination
Number of Subjects Reporting Solicited Symptoms Within 7 Days of Second Vaccination
Time frame: 7 days after second vaccination
Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen
Time frame: 28 days post last vaccination.
Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen
Time frame: 28 days post last vaccination.
Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Vietnam/04 Antigen
Time frame: 28 days post last vaccination.
Number of Subjects Achieving a 4-fold or Greater Neutralizing Antibody Titer Increase Against A/Indonesia/05 Antigen
Time frame: 28 days post last vaccination.
Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Vietnam/04 Antigen
Time frame: 28 days post last vaccination.
Number of Subjects Achieving Neutralizing Antibody Titer of 1:40 or Greater Against A/Indonesia/05 Antigen
Time frame: 28 days post last vaccination.
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination
Time frame: Six months post last vaccination
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination
Time frame: Six months after last vaccination
Neutralizing Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 6 Months Post Last Vaccination
Time frame: Six months post last vaccination
Neutralizing Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen at 6 Months Post Last Vaccination
Time frame: Six months post last vaccination
Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen at 1, 2, 3 and 4 Weeks After 2 Doses
Time frame: Weeks 1, 2, 3 and 4 after the second dose

Results and safety

Results posted to the registry on 16 Jul 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
VN/VN, Day 0, 7	27	26
VN/VN, Day 0, 14	26	24
I/I, Day 0, 28	51	48
VN/I, Day 0, 28	49	46
VN+I/VN+I, Day 0, 28	51	50
VN/I, Day 0, 180	49	43
I/I, Day 0, 180	52	45
VN, Day 0	97	91
VN/VN, Day 0, 28	103	102

Primary outcome: Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen

Time frame: 28 days post last vaccination.. Geometric mean (95% Confidence Interval). Unit: Titer

Measure	VN/VN, Day 0, 7 n = 26	VN/VN, Day 0, 14 n = 24	I/I, Day 0, 28 n = 45	VN/I, Day 0, 28 n = 43	VN+I/VN+I, Day 0, 28 n = 48	VN/I, Day 0, 180 n = 43	I/I, Day 0, 180 n = 46	VN, Day 0 n = 94	VN/VN, Day 0, 28 n = 95
Value	14.7 (7.6 to 28.5)	27.9 (11.6 to 67.0)	6.7 (5.2 to 8.7)	13.6 (8.8 to 20.9)	15.1 (9.4 to 24.1)	39.7 (23.7 to 66.4)	10.5 (7.7 to 14.1)	9.1 (7.0 to 11.6)	22.9 (16.3 to 32.2)

Population analysed: Analyses are based on a modified intent to treat population. 1 subject is excluded at all timepoints due to steroid receipt. 21 subjects not receiving vaccination 2 and one misdosed at vaccination 2 were dropped at timepoints post vaccination 2 only, as were 5 due to receipt of prohibited vaccines/steroids.

Primary outcome: Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Indonesia/05 Antigen

Time frame: 28 days post last vaccination.. Geometric mean (95% Confidence Interval). Unit: Titer

Measure	VN/VN, Day 0, 7 n = 26	VN/VN, Day 0, 14 n = 24	I/I, Day 0, 28 n = 45	VN/I, Day 0, 28 n = 43	VN+I/VN+I, Day 0, 28 n = 48	VN/I, Day 0, 180 n = 43	I/I, Day 0, 180 n = 46	VN, Day 0 n = 94	VN/VN, Day 0, 28 n = 95
Value	5.1 (4.9 to 5.2)	5.1 (4.9 to 5.2)	27.6 (16.8 to 45.5)	10.1 (7.1 to 14.4)	24.3 (15.1 to 39.2)	41.3 (22.9 to 74.7)	58.7 (38.0 to 90.7)	5.3 (4.8 to 5.9)	5.7 (5.2 to 6.3)

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

Time frame: 28 days post last vaccination.. Number. Unit: Participants

Measure	VN/VN, Day 0, 7 n = 26	VN/VN, Day 0, 14 n = 24	I/I, Day 0, 28 n = 45	VN/I, Day 0, 28 n = 43	VN+I/VN+I, Day 0, 28 n = 48	VN/I, Day 0, 180 n = 43	I/I, Day 0, 180 n = 46	VN, Day 0 n = 94	VN/VN, Day 0, 28 n = 95
Value	8	10	3	11	14	25	8	14	41

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

Time frame: 28 days post last vaccination.. Number. Unit: Participants

Measure	VN/VN, Day 0, 7 n = 26	VN/VN, Day 0, 14 n = 24	I/I, Day 0, 28 n = 45	VN/I, Day 0, 28 n = 43	VN+I/VN+I, Day 0, 28 n = 48	VN/I, Day 0, 180 n = 43	I/I, Day 0, 180 n = 46	VN, Day 0 n = 94	VN/VN, Day 0, 28 n = 95
Value	0	0	23	9	22	24	32	1	3

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited symptoms were collected for 7 days after each vaccination, unsolicited non-serious adverse events were collected through 28 days after each vaccination. Serious adverse events were collected through 180 days after the last vaccination.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
VN/VN, Day 0, 7	0 of 26 (0%)	23 of 26 (88.5%)	Not reported
VN/VN, Day 0, 14	1 of 25 (4%)	23 of 25 (92%)	Not reported
I/I, Day 0, 28	0 of 51 (0%)	44 of 51 (86.3%)	Not reported
VN/I, Day 0, 28	0 of 48 (0%)	42 of 48 (87.5%)	Not reported
VN+I/VN+I, Day 0, 28	0 of 51 (0%)	42 of 51 (82.4%)	Not reported
VN/I, Day 0, 180	0 of 49 (0%)	46 of 49 (93.9%)	Not reported
I/I, Day 0, 180	1 of 52 (1.9%)	39 of 52 (75%)	Not reported
VN, Day 0	0 of 97 (0%)	85 of 97 (87.6%)	Not reported
VN/VN, Day 0, 28	0 of 103 (0%)	98 of 103 (95.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21282194Belshe 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing A/Vietnam/1203/04 and A/Indonesia/05/05 in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jul 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hemagglutination Inhibition (HAI) Geometric Mean Titer (GMT) Against A/Vietnam/04 Antigen (time frame: 28 days post last vaccination.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00703053, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2013.