Reactogenicity, Safety and Immunogenicity of a LAIV H7N9 Influenza Vaccine

Reactogenicity, Safety and Immunogenicity of a Live Monovalent A/17/Anhui/2013/61 (H7N9) Influenza Vaccine

This is a single centre phase I, double-blind placebo-controlled study to assess reactogenicity, safety and immunogenicity of a live monovalent A/17/Anhui/2013/61 (H7N9) influenza vaccine in healthy male and female adults, 18 through 49 years of age .

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: H7N9 live influenza vaccine; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.
• A signed 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 through day 56.

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 (more than 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 H7 or H5 containing influenza vaccine.
• History of bronchial asthma.
• Hypersensitivity and allergy reactions after previous administration of any vaccine.
• History of wheezing after past receipt of any live influenza vaccine.
• Other AE following immunization (body temperature more than 40°C, collapse, non-febrile seizures, anaphylaxis), at least possibly related to previous receipt of any vaccine (not only influenza).
• 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 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 HBV or 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.
• Allergic, including anaphylactic, reactions to the introduction of any vaccines in the subject's medical history (not only flu vaccine).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: H7N9 LAIV; H7N9 live influenza vaccine	Biological: H7N9 live influenza vaccine; H7N9 live influenza vaccine; Other Names: LAIV H7N9
Placebo Comparator: Placebo; Lyophilized purified allantoic fluid of chicken embryos with stabilizers	Biological: Placebo; Lyophilized purified allantoic fluid of chicken embryos with stabilizers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immediate reactions	Immediate reactions occurring within two hours of administration of any dose, measured as observed by study staff or reported by the subject to study staff	2 hours
Solicited adverse events	Adverse events commonly associated with intranasal vaccination (solicited local and systemic reactions), measured as observed by study staff or reported by the subject to study staff	Greater than two hours after administration of any dose of study vaccine or placebo through 6 days following any dose
Changes from baseline in laboratory findings	Abnormal laboratory findings from blood and urine specimens	Days 3, 6 and 34
Serious adverse events (SAEs)	All SAEs during 56 days, as observed by study staff, reported by the subject to study staff, or noted by the subject on a diary card, including abnormal laboratory findings from blood specimens collected on Days 28 (pre-vaccination) and 56	4 weeks of receipt of any dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune responses	Immune responses was parameterized as the proportion of subjects with at least a four-fold rise after each dose from baseline or as the mean titer after each dose in any of the following: Serum hemagglutination inhibition (HAI) antibodies; Serum neutralizing antibodies; Serum immunoglobulin class A (IgA) or immunoglobulin class G (IgG) antibodies measured by enzyme-linked immunosorbent assay (ELISA); Secretory IgA antibodies from the nasal mucosa detected in nasal wick specimens using ELISA; Secretory IgA antibodies in saliva specimens using ELISA	Days 0, 28 and 56
Virus shedding	Virus shedding with virus detected by real-time reverse transcriptase polymerase chain reaction rRTPCR in nasal swabs at any time point (at day of vaccination and daily during hospitalization).	Days 0-6 after each dose
Virus stability	Virus stability (virus detected and sequenced after inoculation into chicken eggs)	Days 0-6 after each dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cellular immune responses (cytokine and T-cell)	Cellular immune responses (cytokine and T-cell) was measured using isolated peripheral blood mononuclear cells (PBMCs) tested by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT) assay.	Days 0, 28 and 56

Collaborators and Investigators

• Sponsor: Research Institute of Influenza, Russia
• Collaborators: World Health Organization; Institute of Experimental Medicine, Russia
• Investigators: Study Chair: Larisa G Rudenko, MD PhD DSc, Institute of Experimental Medicine

Publications and helpful links

General Publications

• Rudenko L, Isakova-Sivak I, Naykhin A, Kiseleva I, Stukova M, Erofeeva M, Korenkov D, Matyushenko V, Sparrow E, Kieny MP. H7N9 live attenuated influenza vaccine in healthy adults: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Infect Dis. 2016 Mar;16(3):303-10. doi: 10.1016/S1473-3099(15)00378-3. Epub 2015 Dec 8.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: June 19, 2015
• First Posted (Estimate): June 24, 2015

Study Record Updates

• Last Update Posted (Estimate): June 24, 2015
• Last Update Submitted That Met QC Criteria: June 19, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: influenza vaccine pandemic
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: LAIV-H7N9-01