Clinical trial NCT01719783: Reactogenicity, Safety, and Immunogenicity of a Live Monovalent H5N2 Influenza Vaccine
Official title: Reactogenicity, Safety and Immunogenicity of a Live Monovalent A/17/Turkey/Turkey/05/133 (H5N2) Influenza Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza
Keywords: influenza
vaccine
pandemic
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Microgen
name: Institute of Experimental Medicine, Russia
First posted: 2012-11-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To evaluate the safety profile of two intranasal doses of LAIV A/17/turkey/Turkey/05/133 (H5N2) in healthy adults.


Eligibility criteria: Inclusion Criteria:

* Legal male or female adult 18 through 49 years of age at the enrollment visit.
* Literate and willing to provide written informed consent.
* Free of obvious health problems, as established by the medical history and screening evaluations, including physical examination.
* Capable and willing to complete diary cards and willing to return for all follow-up visits
* Willing to comply with the rules of the isolation unit (including willing and able to take oseltamivir influenza antiviral medication, should that be recommended by a study physician).
* For females, willing to take reliable birth control measures throughout the entire period of participation in the study.

Exclusion Criteria:

* Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study.
* Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt of such vaccines until four weeks after study completion.
* Practice of nasal irrigation on a regular basis within the past six months or has engaged in nasal irrigation within two weeks prior to enrollment.
* Recent history of frequent nose bleeds (\>5 within the past year).
* Clinically relevant abnormal paranasal anatomy.
* Recent history (within the past month) of rhino or sinus surgery, or surgery for any traumatic injury of the nose.
* Current or recent (within two weeks of enrollment) acute respiratory illness with or without fever.
* Other acute illness at the time of study enrollment.
* Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products during the period of subject participation in the study.
* Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, 0.5 mg per kg per day; topical steroids are allowed, exclusive of nasal.)
* Participation in any previous trial of any H5 or H7 containing influenza vaccine.
* History of asthma.
* Hypersensitivity after previous administration of any influenza vaccine.
* History of wheezing after past receipt of any live influenza vaccine.
* Other adverse event (AE) following immunization, at least possibly related to previous receipt of any influenza vaccine.
* Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein.
* Seasonal (autumnal) hypersensitivity to the natural environment.
* Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. Subjects with physical examination findings or clinical laboratory screening results which would be graded 2 or higher on the AE severity grading scale (see Attachments) will be excluded from entry into the study and will be excluded from receipt of dose two of study vaccine or placebo.
* History of leukemia or any other blood or solid organ cancer.
* History of thrombocytopenic purpura or known bleeding disorder.
* History of seizures.
* Known or suspected immunosuppressive or immunodeficient condition of any kind, including HIV infection.
* Known chronic hepatitis B (HBV) or hepatitis C (HCV) infection.
* Known tuberculosis infection or evidence of previous tuberculosis exposure.
* History of chronic alcohol abuse and/or illegal drug use.
* Claustrophobia or sociophobia.
* Pregnancy or lactation. (A negative pregnancy test will be required before administration of study vaccine or placebo for all women of childbearing potential.)
* Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives

Primary outcomes:
measure: Adverse Events by Severity
timeFrame: 6 days
Secondary outcomes:
measure: Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI)
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects With Serum Neutralizing Antibodies
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA)
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG)
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects With Seroconversion for Secretory IgA
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects With Seroconversion for IgA in Saliva
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose
timeFrame: 6 days post-vaccination
measure: Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose
timeFrame: 6 days post-vaccination
measure: Geometric Mean Titers for Serum HAI Antibodies
timeFrame: 0 days, 28 days (Dose 1) and 56 days (Dose 2)
measure: Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies
timeFrame: 0 days, 28 days (Dose 1) and 56 days (Dose 2)
Other outcomes:
measure: Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Responses
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Responses
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Effector Memory T Cell Responses
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Central Memory T Cell Responses
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects Exhibiting CD4+ IFNγ+ Effector Memory T Cell Responses
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
measure: Number/Percentage of Subjects Exhibiting CD8+ IFNγ+ Central Memory T Cell Responses
timeFrame: 28 days (Dose 1) and 56 days (Dose 2)
Locations:
city: St. Petersburg
country: Russian Federation
facility: Research Institute of Influenza
Study officials:
References:
citation: Kiseleva I, Dubrovina I, Fedorova E, Larionova N, Isakova-Sivak I, Bazhenova E, Pisareva M, Kuznetsova V, Flores J, Rudenko L. Genetic stability of live attenuated vaccines against potentially pandemic influenza viruses. Vaccine. 2015 Dec 8;33(49):7008-14. doi: 10.1016/j.vaccine.2015.09.050. Epub 2015 Oct 2.
citation: Rudenko L, Kiseleva I, Stukova M, Erofeeva M, Naykhin A, Donina S, Larionova N, Pisareva M, Krivitskaya V, Flores J; Russian LAIV Trial Study Group. Clinical testing of pre-pandemic live attenuated A/H5N2 influenza candidate vaccine in adult volunteers: results from a placebo-controlled, randomized double-blind phase I study. Vaccine. 2015 Sep 22;33(39):5110-7. doi: 10.1016/j.vaccine.2015.08.019. Epub 2015 Aug 19.