Comparison of the Immunogenicity, Safety and Reactogenicity of FluBlok, To a Licensed Vaccine In Elderly Adults

NCT ID: NCT00395174

Last Updated: 2009-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

870 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-10-31

Study Completion Date

2007-05-31

Brief Summary

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The purpose of this study were to obtain additional evidence in support of the safety and immunogenicity of a recombinant hemagglutinin (rHA) vaccine in an elderly population, and to establish non-inferiority of the immunogenicity of the rHA vaccine when compared with a licensed trivalent influenza vaccine (TIV). Another purpose was to provide a preliminary estimate of the relative efficacy of the two vaccines against culture-positive influenza-like illness during the subsequent epidemic.

Detailed Description

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Annual influenza epidemics are associated with serious excess morbidity and mortality, particularly among the elderly. Licensed trivalent inactivated influenza vaccines (TIVs) have been shown to reduce hospitalization and death following influenza in this vulnerable population, but their efficacy is lower than that observed in younger, healthy populations. In addition, recent studies have questioned the level of effectiveness of TIV in the elderly, suggesting that cohort studies have overestimated the benefits of immunization with current TIV formulations in this age group. In view of these considerations, it is widely accepted that improved and alternative vaccines are needed for control of seasonal and pandemic influenza.

Currently available TIVs are prepared from viruses that are grown in embryonated hens' eggs. Alternative substrates for vaccine production are desirable in order to reduce the vulnerability of and to expand influenza vaccine supply. Recombinant DNA techniques allow for expression of the influenza hemagglutinin (rHA) by baculovirus vectors in insect cell cultures. Advantages of this technique include speed of production, absence of egg protein, and a highly purified product. Previous studies among healthy younger and older adults have confirmed that rHA vaccines are safe, well tolerated and immunogenic at dosages up to nine times higher than those contained in TIV. Dose-related increases in serum antibody levels after immunization also were observed.

Conditions

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Influenza

Keywords

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Influenza

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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FluBlok

Recombinant Trivalent Hemagglutinin Influenza Vaccine: 2005-2006 formulation containing 45μg of each hemagglutinin derived from A/New Caledonia (H1N1), A/Wisconsin (H3N2) and B/Ohio

135μg total

Group Type EXPERIMENTAL

Influenza Vaccination

Intervention Type BIOLOGICAL

0.5mL dose for intramuscular injection

TIV (Fluzone)

Licensed trivalent influenza vaccine (TIV): 2005-2006 formulation containing 15μg of each hemagglutinin derived from A/Wisconsin (H3N2), A/New Caledonia (H1N1) and B/Malaysia

45μg total

(Fluzone, sanofi pasteur)

Group Type ACTIVE_COMPARATOR

Influenza Vaccination

Intervention Type BIOLOGICAL

0.5mL dose for intramuscular injection

Interventions

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Influenza Vaccination

0.5mL dose for intramuscular injection

Intervention Type BIOLOGICAL

Other Intervention Names

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FluBlok Fluzone rHA rHA0 recombinant hemagglutinin TIV

Eligibility Criteria

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Inclusion Criteria

* Ambulatory adults aged 65 and older
* Medically stable, as determined by oral temperature \<100.0°F, medical history, and targeted physical examination based on medical history
* Able to understand and comply with planned study procedures
* Provides written informed consent prior to initiation of any study procedure.

Exclusion Criteria

* Known allergy to eggs or other vaccine components.
* Immunosuppression as a result of an underlying illness or treatment, or used anticancer chemotherapy or radiation therapy within the preceding 36 months.
* Any malignancy (excluding nonmelanotic skin cancer or lymphoproliferative disorder), other than localized prostrate cancer, diagnosed or treated actively during the past 5 years. Subjects with any history of lymphoproliferative disorder will be excluded, while subjects with a history of localized nonmelanotic skin cancer may be eligible.
* Long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids within the preceding 6 months (Nasal and topical steroids are allowed).
* Major psychiatric diagnosis including schizophrenia, bipolar disease or other major depression, or any diagnosis of dementia or associated concomitant medications (e.g., Aricept) used for treating dementia
* History of receiving immunoglobulin or other blood product within the 3 months prior to enrollment in this study.
* Receipt of any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.
* History of severe reactions following immunization with influenza virus vaccines.
* Moderate to severe acute illness or febrile illness (oral temperature greater than 100\*F) within 1 week prior to vaccination.
* Receipt of 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 study period.
* Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection.
* History of alcohol or drug abuse in the last 5 years.
* History of Guillain-Barré Syndrome.
* Any acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe, interfere with the evaluation of responses, or render the subject unable to meet the requirements of the protocol. These conditions include, but are not limited to: history of significant renal impairment (dialysis and treatment for kidney disease, including diabetic and hypertensive kidney disease); subjects with diabetes mellitus, well-controlled with oral agents may enroll as long there has been no dosage increase within the past 6 months; insulin-dependent diabetes is excluded; cardiac insufficiency, if heart failure is present (New York Heart Association Functional Class III or IV); an arteriosclerotic event during the 6 months prior to enrollment (e.g., history of myocardial infarction, stroke, recanalization of femoral arteries, or transient ischemic attack).
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Protein Sciences Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Protein Sciences Corporation

Principal Investigators

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Wendy A. Keitel, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Hana M. El-Sahly, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

John J. Treanor, MD

Role: PRINCIPAL_INVESTIGATOR

University of Rochester Medical

Keith S. Reisinger, MD

Role: PRINCIPAL_INVESTIGATOR

Primary Physicians research

Gregory A. Poland, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic College of Medicine

Kenneth D. Lessans, MD

Role: PRINCIPAL_INVESTIGATOR

Passport Health Maryland

John J. Minneti, MD

Role: PRINCIPAL_INVESTIGATOR

Passport Health New Jersey

Kristen Lyke, MD

Role: PRINCIPAL_INVESTIGATOR

Center of Vaccine Development, University of Maryland

Locations

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Center of Vaccine Development, Univ. of Maryland

Baltimore, Maryland, United States

Site Status

Passport Health Maryland

Baltimore, Maryland, United States

Site Status

Mayo Clinic College of Medicine

Rochester, Minnesota, United States

Site Status

Passport Health New Jersey

Shrewsbury, New Jersey, United States

Site Status

Rochester Medical Center

Rochester, New York, United States

Site Status

Primary Physicians Research

Pittsburgh, Pennsylvania, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

References

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Keitel WA, Treanor JJ, El Sahly HM, Gilbert A, Meyer AL, Patriarca PA, Cox MM. Comparative immunogenicity of recombinant influenza hemagglutinin (rHA) and trivalent inactivated vaccine (TIV) among persons > or =65 years old. Vaccine. 2009 Dec 11;28(2):379-85. doi: 10.1016/j.vaccine.2009.10.037. Epub 2009 Oct 29.

Reference Type RESULT
PMID: 19879222 (View on PubMed)

Rajendran M, Nachbagauer R, Ermler ME, Bunduc P, Amanat F, Izikson R, Cox M, Palese P, Eichelberger M, Krammer F. Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin. mBio. 2017 Mar 21;8(2):e02281-16. doi: 10.1128/mBio.02281-16.

Reference Type DERIVED
PMID: 28325769 (View on PubMed)

Nachbagauer R, Choi A, Izikson R, Cox MM, Palese P, Krammer F. Age Dependence and Isotype Specificity of Influenza Virus Hemagglutinin Stalk-Reactive Antibodies in Humans. mBio. 2016 Jan 19;7(1):e01996-15. doi: 10.1128/mBio.01996-15.

Reference Type DERIVED
PMID: 26787832 (View on PubMed)

Related Links

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Other Identifiers

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PSC03

Identifier Type: -

Identifier Source: org_study_id