Phase 3 Study of a H5N1 Vaccine in Adults, Elderly and Specified Risk Groups

NCT00711295 | Completed Phase 3 DMC

• 1 other identifier: 810705
• Study Type: interventional
• Target: 3,583
• Locations: 7 countries
• Sites: 45

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.

Conditions

Influenza

Keywords

Influenza (Pandemic)

Outcome Measures

Primary Outcomes (3)

• Frequency and severity of systemic reactions until 21 days after the first and second vaccinations

  42 days

• 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.

  42 days

• Antibody response 21 days after the second vaccination as measured by MN assay;

  42 days

Secondary Outcomes (19)

• Frequency and severity of injection site reactions until 21 days after the first and second vaccinations

  42 days

• Number of subjects with fever, malaise or shivering with onset within 7 days after the first and second vaccinations

  7 days

• Frequency and severity of adverse events observed during the entire study period

  11 months

• 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

  42 days

• 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

  42 days

Study Arms (6)

Cohort 1, Treatment Arm 1

EXPERIMENTAL

Stratum A (18-59 ys)/B(\>=60 ys): 120 healthy volunteers per stratum will receive 2 vaccinations with 7.5 µg A/Vietnam/1203/2004 on Days 0 and 21 and participate in immunogenicity evaluation. Among Stratum A volunteers, 60 will participate in antibody kinetics evaluation and 30 in cellular immunity evaluation. Randomization to Treatment Arms 1 and 2 at 2:1 ratio. Subjects in Treatment Arm 1 will be included in the immunologic determination of lot-to-lot consistency.

Biological: H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted

Cohort 1, Treatment Arm 2

EXPERIMENTAL

Stratum A (18-59 ys)/B(\>=60 ys): 60 healthy volunteers per stratum will receive 2 vaccinations with 3.75 µg A/Vietnam/1203/2004 on Days 0 and 21 and participate in immunogenicity evaluation. Randomization to Treatment Arms 1 and 2 at 2:1 ratio.

Biological: H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted

Cohort 1, Treatment Arm 3

EXPERIMENTAL

Stratum A (18-59 ys): 2060 healthy volunteers will receive 2 vaccinations with 7.5 µg A/Vietnam/1203/2004 on Days 0 and 21 and participate in safety evaluation only. Randomization within Treatment Arms 3 and 4 at 1:1:1 ratio per study site to receive one of three different lots of the H5N1 influenza vaccine.

Biological: H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted

Cohort 2, Treatment Arm 1

EXPERIMENTAL

300 immune compromised individuals 18 years or older will receive 2 vaccinations with 7.5 µg A/Vietnam/1203/2004 on Days 0 and 21. 100 will participate in immunogenicity evaluation and 30 in cellular immunity evaluation.

Biological: H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted

Cohort 3, Treatment Arm 1

EXPERIMENTAL

300 chronically ill patients 18 years or older will receive 2 vaccinations with 7.5 µg A/Vietnam/1203/2004 on Days 0 and 21 and participate in immunogenicity evaluation.

Biological: H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted

Cohort 1, Treatment Arm 4

EXPERIMENTAL

Stratum A (18-59): 540 healthy volunteers will receive 2 vaccinations with 7.5 µg A/Vietnam/1203/2004 on Days 0 and 21 and participate in immunogenicity assessment. Randomization within Treatment Arms 3 and 4 at 1:1:1 ratio per study site to receive one of three different lots of the H5N1 influenza vaccine. Subjects in Treatment Arm 4 will be included in the immunologic determination of lot-to-lot consistency.

Biological: H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted

Interventions

H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted BIOLOGICAL

Intramuscular injection of 7.5 µg hemagglutinin antigen (A/Vietnam/1203/2004 strain) in a non-adjuvanted formulation on Days 0 and 21.

Cohort 1, Treatment Arm 1; Cohort 1, Treatment Arm 3; Cohort 1, Treatment Arm 4; Cohort 2, Treatment Arm 1; Cohort 3, Treatment Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \- 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.
• \- 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.
• \- 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.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• Alachua Government Services, Inc.: lead

Study Sites (45)

Allgemeines Krankenhaus Wien, Innere Medizin, Waehringer Guertel 18-20

Vienna, 1090, Austria

Location

Institut für spezifische Prophylaxe und Tropenmedizin, Kinderspitalgasse 15

Vienna, 1090, Austria

Location

University Clinic for Clinical Pharmacology, Vienna Medical University / Vienna General Hospital, Waehringer Guertel 18-20

Vienna, 1090, Austria

Location

OLV Hospital Aalst, Research Unit, Moorselbaan 164

Aalst, 9300, Belgium

Location

Cliniques Universitaires Saint Luc, Avenue Hippocrate 10, Niveau -1 Couloir C11

Brussels, 1200, Belgium

Location

Center for Vaccinologie, UZ Gent, De Pintelaan 185

Ghent, 9000, Belgium

Location

UZ Leuven, Kapucijnenvoer 35, Block D, Box 7001

Leuven, 3000, Belgium

Location

UZ Antwerpen, Universiteitsplein 1

Wilrijk, 2610, Belgium

Location

Espoon rokotetutkimusklinikka, Keskustorni 7. krs., Tapiontori 1

Espoo, 02100, Finland

Location

Etelä-Helsingin rokotetutkimusklinikka, Vuorikatu 18, 3 krs

Helsinki, 00100, Finland

Location

Tampereen rokotetutkimusklinikka, Pinninkatu 47, 1.krs

Tampere, 33100, Finland

Location

Turun rokotetutkimusklinikka, Lemminkäisenkatu 14-18 B, 4.krs

Turku, 20520, Finland

Location

Itä-Vantaan rokotetutkimusklinikka, Asematie 11 A 16

Vantaa, 01300, Finland

Location

Charité - Universitaetsmedizin Berlin, Medizinische Klinik III, Haematologie, Onkologie & Transfusionsmedizin, Karl Landsteiner-Haus, 1 OG, Hindenburgdamm 30

Berlin, 12200, Germany

Location

Klinische Forschung Berlin Buch GmbH, Robert-Rössle-Str. 10 / Haus 85

Berlin, 13125, Germany

Location

Klinikum der Universitaet zu Koeln, Klinik I für Innere Medizin, Studienbüro für Infektiologie, Haus 11, Kerpener Str. 62

Cologne, 50937, Germany

Location

Carl Gustav Carus Universitaet, Medizinische Klinik und Poliklinik I, Haematologie/Onkologie Fetscherstr. 74

Dresden, 01307, Germany

Location

Klinikum der J.W.Goethe Universitaet, Medizinische Klinik II Schwerpunkt HIV Haus 68, Theodor-Stern-Kai 7

Frankfurt am Main, 60590, Germany

Location

Klinische Forschung Hamburg GmbH, Hoheluftchaussee 18

Hamburg, 20253, Germany

Location

Universitätsklinikum Leipzig, Selbstständige Abteilung für Hämatologie, Internistische Onkologie und Hämostaseologie, Johannisallee 32A

Leipzig, 04103, Germany

Location

Johannes Gutenberg Universitaet, I. Medizinische Klinik und Poliklinik, Langenbeckstr. 1

Mainz, 55101, Germany

Location

Johannes Gutenberg-Universitaet, III. Medizinische Klinik und Poliklinik, Langenbeckstr. 1

Mainz, 55101, Germany

Location

Studienzentrum Mainz-Mitte am GesundheitsCentrum Mainz, Große Langgasse 1A/Eingang Kötherhofstrasse 4

Mainz, 55116, Germany

Location

Institut für Tropenmedizin, Wilhelmstraße 27

Tübingen, 72074, Germany

Location

Private practice, Berzpils street 14-16

Balvi, 4501, Latvia

Location

Outpatient clinic " Jelgavas centra doktorats ", Kr. Barona str. 17

Jelgava, 3001, Latvia

Location

Private practice, Aptiekas maja, Madliena village, Ogres district

Madlienas Parish, 5045, Latvia

Location

Outpatient clinic "Alma", Kr.Valdemara street 20-4

Riga, 1010, Latvia

Location

Outpatient clinic "Adoria", Caka street 70-3

Riga, 1011, Latvia

Location

Outpatient clinic "Veselibas centrs-4", Kr.Barona str. 117

Riga, 1012, Latvia

Location

Private practice, Slimnicas street 3

Saldus, 3801, Latvia

Location

Kaunas 2nd Clinical Hospital, Clinic of Infectious Diseases, Baltijos ave. 120

Kaunas, 47116, Lithuania

Location

Silainiai Family Health Center, Baltu ave. 7a

Kaunas, 48259, Lithuania

Location

Saules Family Medicine Center, Birzelio 23 ios. 4

Kaunas, 50425, Lithuania

Location

Klaipeda University Hospital, Department of Infectious Diseases, Liepojos str. 41

Klaipėda, 92288, Lithuania

Location

Institute of Psychophysiology and Rehabilitation of Kaunas University of Medicine, Vyduno 4

Palanga, 00135, Lithuania

Location

Siauliai District Hospital, Infectious Diseases, Kudirkos 99

Šiauliai, 76231, Lithuania

Location

National Tuberculosis and Infectious Diseases University Hospital, Vilnius University Clinic of Infectious Diseases, Dermatovenereology and Microbiology, Birutes street 1/20

Vilnius, 08117, Lithuania

Location

Andromed Breda, Middellaan 5

Breda, 4811 VL, Netherlands

Location

Andromed Eindhoven B.V., Bomanshof 6

Eindhoven, 5611 NJ, Netherlands

Location

Andromed Noord B.V., Damsterdiep 9

Groningen, 9711 SG, Netherlands

Location

Andromed Leiden B.V., Doezastraat 1 GZ

Leiden, 2311, Netherlands

Location

Andromed, Kamerlingh Onnestraat 16 -18

Nijmegen, 6533 HL, Netherlands

Location

Andromed Oost B.V., Reigerstraat 30E

Velp, 6883 ES, Netherlands

Location

Andromed Zoetermeer, Parkdreef 142

Zoetermeer, 2724 EK, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 24739978 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Study Officials

• Baxter Bio Science Investigator

  Baxter Healthcare Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 2, 2008
• First Posted: July 8, 2008
• Study Start: August 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: October 1, 2010
• Last Updated: October 9, 2015

Record last verified: 2010-11

Locations

BE (5); FI (5); AU (3); DE (11); LA (7); LI (7); NL (7)