Clinical trial NCT00711295: Phase 3 Study of a H5N1 Vaccine in Adults, Elderly and Specified Risk Groups
Official title: An Open-Label Phase 3 Study to Assess the Safety and Immunogenicity of a Vero Cell-Derived Whole Virus H5N1 Influenza Vaccine in an Adult and Elderly Population as Well as in Specified Risk Groups
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Influenza (Pandemic)
Lead sponsor: Resilience Government Services, Inc.
Sponsor class: INDUSTRY
First posted: 2008-07-08
Enrollment: 3583
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety and tolerability of, and the immune response to a non-adjuvanted H5N1 influenza vaccine in an adult and elderly population and in specified risk groups. Furthermore, persistence of H5N1 influenza antibodies after vaccination with this vaccine will be assessed.


Eligibility criteria: Inclusion Criteria:

The following inclusion criteria apply to subjects in all three cohorts:

Male and female subjects will be eligible for participation in this study if they:

* Are 18 years of age or older on the day of screening;
* Have an understanding of the study and its procedures, agree to its provisions, and give written informed consent prior to study entry;
* Are physically and mentally capable of participating in the study and follow its procedures;
* Agree to keep a daily record of symptoms for the duration of the study;
* If female of childbearing potential - have a negative urine pregnancy test result within 24 hours prior to the scheduled first vaccination and agree to employ adequate birth control measures for the duration of the study.

The following inclusion criterion applies to subjects in Cohort 1 only:

- Are generally healthy \[1\], as determined by the investigator's clinical judgment through collection of medical history and performance of a physical examination.

(\[1\]) Subjects with controlled Stage 1 hypertension (blood pressure of 140-159 mmHg systolic and/or 90-99 mmHg diastolic) are eligible for participation in Cohort 1 of this study.

The following inclusion criterion applies to subjects in Cohort 2 only:

- Are immune compromised due to immunosuppressive treatment (e.g. transplant patients \[2\]) or due to acquired immunodeficiency caused by HIV infection with or without treatment with anti-retrovirals.

(\[2\]) Transplant patients should be at least 6 months after transplantation and in stable clinical condition without complications.

The following inclusion criterion applies to subjects in Cohort 3 only:

- Have a chronic cardiovascular (excluding hypertension) \[3\], respiratory, renal, or metabolic (e.g. diabetes mellitus) illness in stable clinical condition without major disease complications such as organ failure, infectious complications, severe asthma or respiratory dysfunction.

(\[3\]) Subjects with cardiovascular disease such as coronary heart disease, angina, heart attack or other heart conditions in stable clinical condition, without major disease complications and who are considered at risk for medical complications from influenza. However, subjects with hypertension (see \[1\] above) not associated with any heart condition will be excluded from participation in Cohort 3 of this study.

Exclusion Criteria:

The following exclusion criteria apply to subjects in all three cohorts:

Subjects will be excluded from participation in this study if they:

* Have a history of exposure to H5N1 virus or a history of vaccination with an H5N1 influenza vaccine;
* Are at high risk of contracting H5N1 influenza infection (e.g. poultry workers);
* Have a history of severe allergic reactions or anaphylaxis;
* Have a rash, dermatological condition or tattoos which may interfere with injection site reaction rating;
* Have donated blood or plasma within 30 days prior to study entry;
* Have received any live vaccine within 4 weeks or inactivated vaccine within 2 weeks prior to vaccination in this study;
* Have a known or suspected problem with alcohol or drug abuse;
* Were administered an investigational drug within 6 weeks prior to study entry or are concurrently participating in a clinical study that includes the administration of an investigational product;
* Are a member of the team conducting this study or are in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study;
* If female: are pregnant or lactating.

The following exclusion criteria apply to subjects in Cohort 1 only:

* Currently have or have a history of a significant neurological, cardiovascular, pulmonary (including asthma), hepatic, metabolic, rheumatic, autoimmune, hematological or renal disorder \[4\];
* Have any inherited or acquired immunodeficiency;
* Have a disease or are currently undergoing a form of treatment or were undergoing a form of treatment within 30 days prior to study entry that can be expected to influence immune response. Such treatment includes, but is not limited to, systemic or high dose inhaled (\>800µg/day of beclomethasone dipropionate or equivalent) corticosteroids, radiation treatment or other immunosuppressive or cytotoxic drugs;
* Have received a blood transfusion or immunoglobulins within 90 days prior to study entry;
* Have a functional or surgical asplenia.

(\[4\]) A significant disorder is defined as a disease or medical condition associated with impaired health status, increased risk for complications, requiring medical treatment and/or follow up.

The following exclusion criteria apply to subjects in Cohort 2 only:

* Are immune compromised due to stem cell or organ-transplantation with significant medical complications such as acute or chronic graft rejection or graft versus host disease requiring intensive immunosuppressive treatment, transplant failure or infectious complications or other conditions that would be considered a contraindication for vaccination with an inactivated vaccine.
* Are immune compromised due to HIV infection with a CD4 count of \< 200x10\^6/L at screening or significant medical complications such as opportunistic infections, malignant complications (e.g. lymphoma, Kaposi sarcoma), other organ manifestations consistent with advanced acquired immunodeficiency syndrome (AIDS) or other conditions that would be considered a contraindication for vaccination with an inactivated vaccine.

The following exclusion criterion applies to subjects in Cohort 3 only:

- Have a chronic cardiovascular, respiratory, renal, or metabolic (e.g. diabetes mellitus) illness with significant complications such as advanced heart failure, liver failure, renal failure, severe asthma or severe respiratory failure, infectious complications or other conditions that would be considered a contraindication for vaccination with an inactivated vaccine.

Primary outcomes:
measure: Frequency and severity of systemic reactions until 21 days after the first and second vaccinations
timeFrame: 42 days
measure: Number of subjects with antibody response to the vaccine strain associated with protection 21 days after the second vaccination defined as titer measured by microneutralization (MN) assay >= 1:20.
timeFrame: 42 days
measure: Antibody response 21 days after the second vaccination as measured by MN assay;
timeFrame: 42 days
Secondary outcomes:
measure: Frequency and severity of injection site reactions until 21 days after the first and second vaccinations
timeFrame: 42 days
measure: Number of subjects with fever, malaise or shivering with onset within 7 days after the first and second vaccinations
timeFrame: 7 days
measure: Frequency and severity of adverse events observed during the entire study period
timeFrame: 11 months
measure: Number of subjects with antibody response associated with protection 21 days after the first and second vaccinations defined as Hemagglutination Inhibition Antibody (HIA) titer >= 1:40 or Single Radial Hemolysis (SRH) area >= 25 mm2
timeFrame: 42 days
measure: Number of subjects with antibody response associated with protection 21 days after the second vaccination defined as titer measured by MN assay >=1:40, >= 1:80, >=1:160
timeFrame: 42 days
measure: Antibody response 21 days after the first and second vaccinations as measured by HI and SRH assays
timeFrame: 42 days
measure: Fold increase of antibody response 21 days after the first and second vaccinations as compared to baseline as measured by MN, HI and SRH assays
timeFrame: 42 days
measure: Number of subjects with seroconversion (MN/HI: min.4-fold titer increase vs baseline;SRH:post-vacc. hemolysis area >=25mm2 or increased by >=50% for pre-vacc. sample <=4mm2 and >4mm2, resp., 21 days after 1st and 2nd vaccinations, measured by MN,HI,SRH
timeFrame: 42 days
measure: Number of subjects with antibody response associated with protection 201 days after the first vaccination as measured by MN, HI and SRH assays
timeFrame: 201 days
measure: Antibody response 201 days after the first vaccination as measured by MN, HI and SRH assays
timeFrame: 201 days
measure: Fold increase of antibody response 201 days after the first vaccination as compared to baseline as measured by MN, HI and SRH assays
timeFrame: 201 days
measure: Number of subjects in the subset included in the assessment of antibody kinetics with antibody response associated with protection 28, 35 and 90 days after the first vaccination as measured by MN, HI and SRH assays
timeFrame: 90 days
measure: Antibody response in the subset of subjects included in the assessment of antibody kinetics 28, 35 and 90 days after the first vaccination as measured by MN, HI and SRH assays
timeFrame: 90 days
measure: Fold increase of antibody response in the subset of subjects included in the assessment of antibody kinetics 28, 35 and 90 days after the first vaccination as compared to baseline as measured by MN, HI and SRH assays
timeFrame: 90 days
measure: Number of subjects in subset for antibody kinetics evaluation with seroconversion (see definitions above) 28, 35, 90 days after 1st vaccination, measured by MN, HI, SRH
timeFrame: 90 days
measure: T-cell response in the subset of subjects included in the evaluation of cellular immunity after each vaccination as determined by the frequency of cytokine producing T-cells induced by influenza virus antigens
timeFrame: 201 days
measure: Increase in frequency of cytokine producing T-cells induced by influenza virus antigens after each vaccination as compared to baseline
timeFrame: 201 days
measure: Number of subjects with antibody response associated with protection 21 days after the first vaccination defined as titer measured by MN assay >=1:20, >=1:40, >=1:80, >=1:160
timeFrame: 21 days
measure: Antibody response 21 days after the first vaccination as measured by MN assay
timeFrame: 21 days
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus Wien, Innere Medizin, Waehringer Guertel 18-20
city: Vienna
country: Austria
facility: Institut für spezifische Prophylaxe und Tropenmedizin, Kinderspitalgasse 15
city: Vienna
country: Austria
facility: University Clinic for Clinical Pharmacology, Vienna Medical University / Vienna General Hospital, Waehringer Guertel 18-20
city: Aalst
country: Belgium
facility: OLV Hospital Aalst, Research Unit, Moorselbaan 164
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc, Avenue Hippocrate 10, Niveau -1 Couloir C11
city: Gent
country: Belgium
facility: Center for Vaccinologie, UZ Gent, De Pintelaan 185
city: Leuven
country: Belgium
facility: UZ Leuven, Kapucijnenvoer 35, Block D, Box 7001
city: Wilrijk
country: Belgium
facility: UZ Antwerpen, Universiteitsplein 1
city: Espoo
country: Finland
facility: Espoon rokotetutkimusklinikka, Keskustorni 7. krs., Tapiontori 1
city: Helsinki
country: Finland
facility: Etelä-Helsingin rokotetutkimusklinikka, Vuorikatu 18, 3 krs
city: Tampere
country: Finland
facility: Tampereen rokotetutkimusklinikka, Pinninkatu 47, 1.krs
city: Turku
country: Finland
facility: Turun rokotetutkimusklinikka, Lemminkäisenkatu 14-18 B, 4.krs
city: Vantaa
country: Finland
facility: Itä-Vantaan rokotetutkimusklinikka, Asematie 11 A 16
city: Berlin
country: Germany
facility: Charité - Universitaetsmedizin Berlin, Medizinische Klinik III, Haematologie, Onkologie & Transfusionsmedizin, Karl Landsteiner-Haus, 1 OG, Hindenburgdamm 30
city: Berlin
country: Germany
facility: Klinische Forschung Berlin Buch GmbH, Robert-Rössle-Str. 10 / Haus 85
city: Cologne
country: Germany
facility: Klinikum der Universitaet zu Koeln, Klinik I für Innere Medizin, Studienbüro für Infektiologie, Haus 11, Kerpener Str. 62
city: Dresden
country: Germany
facility: Carl Gustav Carus Universitaet, Medizinische Klinik und Poliklinik I, Haematologie/Onkologie Fetscherstr. 74
city: Frankfurt/Main
country: Germany
facility: Klinikum der J.W.Goethe Universitaet, Medizinische Klinik II Schwerpunkt HIV Haus 68, Theodor-Stern-Kai 7
city: Hamburg
country: Germany
facility: Klinische Forschung Hamburg GmbH, Hoheluftchaussee 18
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Selbstständige Abteilung für Hämatologie, Internistische Onkologie und Hämostaseologie, Johannisallee 32A
city: Mainz
country: Germany
facility: Johannes Gutenberg Universitaet, I. Medizinische Klinik und Poliklinik, Langenbeckstr. 1
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universitaet, III. Medizinische Klinik und Poliklinik, Langenbeckstr. 1
city: Mainz
country: Germany
facility: Studienzentrum Mainz-Mitte am GesundheitsCentrum Mainz, Große Langgasse 1A/Eingang Kötherhofstrasse 4
city: Tübingen
country: Germany
facility: Institut für Tropenmedizin, Wilhelmstraße 27
city: Balvi
country: Latvia
facility: Private practice, Berzpils street 14-16
city: Jelgava
country: Latvia
facility: Outpatient clinic " Jelgavas centra doktorats ", Kr. Barona str. 17
city: Madlienas parish
country: Latvia
facility: Private practice, Aptiekas maja, Madliena village, Ogres district
city: Riga
country: Latvia
facility: Outpatient clinic "Alma", Kr.Valdemara street 20-4
city: Riga
country: Latvia
facility: Outpatient clinic "Adoria", Caka street 70-3
city: Riga
country: Latvia
facility: Outpatient clinic "Veselibas centrs-4", Kr.Barona str. 117
city: Saldus
country: Latvia
facility: Private practice, Slimnicas street 3
city: Kaunas
country: Lithuania
facility: Kaunas 2nd Clinical Hospital, Clinic of Infectious Diseases, Baltijos ave. 120
city: Kaunas
country: Lithuania
facility: Silainiai Family Health Center, Baltu ave. 7a
city: Kaunas
country: Lithuania
facility: Saules Family Medicine Center, Birzelio 23 ios. 4
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital, Department of Infectious Diseases, Liepojos str. 41
city: Palanga
country: Lithuania
facility: Institute of Psychophysiology and Rehabilitation of Kaunas University of Medicine, Vyduno 4
city: Siauliai
country: Lithuania
facility: Siauliai District Hospital, Infectious Diseases, Kudirkos 99
city: Vilnius
country: Lithuania
facility: National Tuberculosis and Infectious Diseases University Hospital, Vilnius University Clinic of Infectious Diseases, Dermatovenereology and Microbiology, Birutes street 1/20
city: Breda
country: Netherlands
facility: Andromed Breda, Middellaan 5
city: Eindhoven
country: Netherlands
facility: Andromed Eindhoven B.V., Bomanshof 6
city: Groningen
country: Netherlands
facility: Andromed Noord B.V., Damsterdiep 9
city: Leiden
country: Netherlands
facility: Andromed Leiden B.V., Doezastraat 1 GZ
city: Nijmegen
country: Netherlands
facility: Andromed, Kamerlingh Onnestraat 16 -18
city: Velp
country: Netherlands
facility: Andromed Oost B.V., Reigerstraat 30E
city: Zoetermeer
country: Netherlands
facility: Andromed Zoetermeer, Parkdreef 142
Study officials:
affiliation: Baxter Healthcare Corporation
name: Baxter Bio Science Investigator
role: PRINCIPAL_INVESTIGATOR
References:
citation: van der Velden MV, Geisberger A, Dvorak T, Portsmouth D, Fritz R, Crowe BA, Herr W, Distler E, Wagner EM, Zeitlinger M, Sauermann R, Stephan C, Ehrlich HJ, Barrett PN, Aichinger G. Safety and immunogenicity of a vero cell culture-derived whole-virus H5N1 influenza vaccine in chronically ill and immunocompromised patients. Clin Vaccine Immunol. 2014 Jun;21(6):867-76. doi: 10.1128/CVI.00065-14. Epub 2014 Apr 16.