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

Influenza Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00711295
• Other study ID #: 810705
• Status: Completed
• Phase: Phase 3
• First received: July 2, 2008
• Last updated: October 7, 2015
• Start date: August 2008
• Est. completion date: October 2010

Study information

• Verified date: November 2010
• Source: Nanotherapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and Women
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3583
• Est. completion date: October 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted
Intramuscular injection of 7.5 µg hemagglutinin antigen (A/Vietnam/1203/2004 strain) in a non-adjuvanted formulation on Days 0 and 21.
• H5N1 Influenza Vaccine Whole virion, Vero cell-derived, Inactivated Influenza Vaccine, non-adjuvanted
Intramuscular injection of 3.75 µg hemagglutinin antigen (A/Vietnam/1203/2004 strain) in a non-adjuvanted formulation on Days 0 and 21.

Locations

Country	Name	City	State
Austria	Allgemeines Krankenhaus Wien, Innere Medizin, Waehringer Guertel 18-20	Vienna
Austria	Institut für spezifische Prophylaxe und Tropenmedizin, Kinderspitalgasse 15	Vienna
Austria	University Clinic for Clinical Pharmacology, Vienna Medical University / Vienna General Hospital, Waehringer Guertel 18-20	Vienna
Belgium	OLV Hospital Aalst, Research Unit, Moorselbaan 164	Aalst
Belgium	Cliniques Universitaires Saint Luc, Avenue Hippocrate 10, Niveau -1 Couloir C11	Brussels
Belgium	Center for Vaccinologie, UZ Gent, De Pintelaan 185	Gent
Belgium	UZ Leuven, Kapucijnenvoer 35, Block D, Box 7001	Leuven
Belgium	UZ Antwerpen, Universiteitsplein 1	Wilrijk
Finland	Espoon rokotetutkimusklinikka, Keskustorni 7. krs., Tapiontori 1	Espoo
Finland	Etelä-Helsingin rokotetutkimusklinikka, Vuorikatu 18, 3 krs	Helsinki
Finland	Tampereen rokotetutkimusklinikka, Pinninkatu 47, 1.krs	Tampere
Finland	Turun rokotetutkimusklinikka, Lemminkäisenkatu 14-18 B, 4.krs	Turku
Finland	Itä-Vantaan rokotetutkimusklinikka, Asematie 11 A 16	Vantaa
Germany	Charité - Universitaetsmedizin Berlin, Medizinische Klinik III, Haematologie, Onkologie & Transfusionsmedizin, Karl Landsteiner-Haus, 1 OG, Hindenburgdamm 30	Berlin
Germany	Klinische Forschung Berlin Buch GmbH, Robert-Rössle-Str. 10 / Haus 85	Berlin
Germany	Klinikum der Universitaet zu Koeln, Klinik I für Innere Medizin, Studienbüro für Infektiologie, Haus 11, Kerpener Str. 62	Cologne
Germany	Carl Gustav Carus Universitaet, Medizinische Klinik und Poliklinik I, Haematologie/Onkologie Fetscherstr. 74	Dresden
Germany	Klinikum der J.W.Goethe Universitaet, Medizinische Klinik II Schwerpunkt HIV Haus 68, Theodor-Stern-Kai 7	Frankfurt/Main
Germany	Klinische Forschung Hamburg GmbH, Hoheluftchaussee 18	Hamburg
Germany	Universitätsklinikum Leipzig, Selbstständige Abteilung für Hämatologie, Internistische Onkologie und Hämostaseologie, Johannisallee 32A	Leipzig
Germany	Johannes Gutenberg Universitaet, I. Medizinische Klinik und Poliklinik, Langenbeckstr. 1	Mainz
Germany	Johannes Gutenberg-Universitaet, III. Medizinische Klinik und Poliklinik, Langenbeckstr. 1	Mainz
Germany	Studienzentrum Mainz-Mitte am GesundheitsCentrum Mainz, Große Langgasse 1A/Eingang Kötherhofstrasse 4	Mainz
Germany	Institut für Tropenmedizin, Wilhelmstraße 27	Tübingen
Latvia	Private practice, Berzpils street 14-16	Balvi
Latvia	Outpatient clinic " Jelgavas centra doktorats ", Kr. Barona str. 17	Jelgava
Latvia	Private practice, Aptiekas maja, Madliena village, Ogres district	Madlienas parish
Latvia	Outpatient clinic "Adoria", Caka street 70-3	Riga
Latvia	Outpatient clinic "Alma", Kr.Valdemara street 20-4	Riga
Latvia	Outpatient clinic "Veselibas centrs-4", Kr.Barona str. 117	Riga
Latvia	Private practice, Slimnicas street 3	Saldus
Lithuania	Kaunas 2nd Clinical Hospital, Clinic of Infectious Diseases, Baltijos ave. 120	Kaunas
Lithuania	Saules Family Medicine Center, Birzelio 23 ios. 4	Kaunas
Lithuania	Silainiai Family Health Center, Baltu ave. 7a	Kaunas
Lithuania	Klaipeda University Hospital, Department of Infectious Diseases, Liepojos str. 41	Klaipeda
Lithuania	Institute of Psychophysiology and Rehabilitation of Kaunas University of Medicine, Vyduno 4	Palanga
Lithuania	Siauliai District Hospital, Infectious Diseases, Kudirkos 99	Siauliai
Lithuania	National Tuberculosis and Infectious Diseases University Hospital, Vilnius University Clinic of Infectious Diseases, Dermatovenereology and Microbiology, Birutes street 1/20	Vilnius
Netherlands	Andromed Breda, Middellaan 5	Breda
Netherlands	Andromed Eindhoven B.V., Bomanshof 6	Eindhoven
Netherlands	Andromed Noord B.V., Damsterdiep 9	Groningen
Netherlands	Andromed Leiden B.V., Doezastraat 1 GZ	Leiden
Netherlands	Andromed, Kamerlingh Onnestraat 16 -18	Nijmegen
Netherlands	Andromed Oost B.V., Reigerstraat 30E	Velp
Netherlands	Andromed Zoetermeer, Parkdreef 142	Zoetermeer

Sponsors (1)

Lead Sponsor	Collaborator
Nanotherapeutics, Inc.

Countries where clinical trial is conducted

Austria,  Belgium,  Finland,  Germany,  Latvia,  Lithuania,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and severity of systemic reactions until 21 days after the first and second vaccinations		42 days	Yes
Primary	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	Yes
Primary	Antibody response 21 days after the second vaccination as measured by MN assay;		42 days	No
Secondary	Frequency and severity of injection site reactions until 21 days after the first and second vaccinations		42 days	Yes
Secondary	Number of subjects with fever, malaise or shivering with onset within 7 days after the first and second vaccinations		7 days	Yes
Secondary	Frequency and severity of adverse events observed during the entire study period		11 months	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	Antibody response 21 days after the first and second vaccinations as measured by HI and SRH assays		42 days	No
Secondary	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		42 days	No
Secondary	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		42 days	No
Secondary	Number of subjects with antibody response associated with protection 201 days after the first vaccination as measured by MN, HI and SRH assays		201 days	Yes
Secondary	Antibody response 201 days after the first vaccination as measured by MN, HI and SRH assays		201 days	No
Secondary	Fold increase of antibody response 201 days after the first vaccination as compared to baseline as measured by MN, HI and SRH assays		201 days	No
Secondary	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		90 days	Yes
Secondary	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		90 days	No
Secondary	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		90 days	No
Secondary	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		90 days	No
Secondary	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		201 days	No
Secondary	Increase in frequency of cytokine producing T-cells induced by influenza virus antigens after each vaccination as compared to baseline		201 days	No
Secondary	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		21 days	Yes
Secondary	Antibody response 21 days after the first vaccination as measured by MN assay		21 days	No