Evaluating the Safety and Immunogenicity of a Live Attenuated Virus Vaccine to Prevent Influenza H3N2v Disease

Evaluation of the Safety and Immunogenicity of Live Influenza A Vaccine H3N2v (6-2) AA ca Recombinant (A/Minnesota/11/2010 (H3N2v) x A/Ann Arbor/6/60 ca), a Live Attenuated Virus Vaccine Candidate for Prevention of Influenza H3N2v Disease

This study will evaluate the safety and immunogenicity of the H3N2v MN 2010/AA ca live attenuated influenza vaccine (H3N2v LAIV) in healthy children and adults, 6 to 26 years old.

Study Overview

• Status: Terminated
• Conditions: Influenza
• Intervention / Treatment: Biological: H3N2v MN 2010/AA ca live attenuated influenza vaccine (LAIV); Biological: H3N2v inactivated subvirion influenza vaccine; Biological: Placebo

Detailed Description

The potential for widespread human disease due to the H3N2v influenza viruses is considerable. Infection with these viruses would most likely impact young children. This study will evaluate the safety and immunogenicity of the H3N2v MN 2010/AA ca live attenuated influenza vaccine (H3N2v LAIV) in healthy children and adults, 6 to 26 years old.

The study will enroll participants sequentially in four groups: Group 1 will include H3N2v seronegative adults ages 18-26 years; Group 2 will include H3N2v seropositive adolescents ages 13-17 years; Group 3 will include H3N2v seronegative adolescents ages 13-17 years; and Group 4 will include children ages 6 to 12 years, who will not be screened for H3N2v serostatus.

At study entry (Day 0), participants in Group 1 will receive one dose of H3N2v LAIV. Participants in Groups 2, 3, and 4 will be randomly assigned to receive two doses of either H3N2v LAIV or placebo, receiving the first dose on Day 0 and the second dose on Day 28. On Day 84, all participants will receive one dose of H3N2v IIV (an inactivated booster vaccine).

Participants will attend several additional study visits through Day 180. These visits may include a physical examination; respiratory examination; and collection of blood, urine, or nasal fluids.

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

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center (URMC), Vaccine Research Unit (Outpatient)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and non-pregnant females between 6 and 26 years of age inclusive.
• For children, presence of an adult caregiver who is in good health and able to understand and carry out the requirements
• General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator.
• Agree to storage of blood specimens for future research.
• Available for the duration of the trial.
• Willingness to participate in the study as evidenced by signing the informed consent document. Verbal assent will be obtained from minors 6 to 12 years of age and signed assent will be obtained from minors 13 and older.
• Female subjects of childbearing potential must agree to use effective birth control methods for the duration of the study (e.g., pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; intrauterine device; abstinence from heterosexual intercourse, surgical sterilization).

Exclusion Criteria:

• Anticipated direct routine [e.g. weekly or more frequent] contact with individuals younger than the designated age groups being studied as a result of household contact, occupation, or participation in day care with such individuals.
• Pregnancy as determined by a positive urine or serum human choriogonadotropin (β-HCG) test.
• Currently breast-feeding.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history or physical examination.
• Behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, affects the ability of the subject to understand and cooperate with the study protocol.
• Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol.
• History of anaphylaxis.
• Allergy to oseltamivir as determined by subject report.
• Current diagnosis of asthma or reactive airway disease (within the past 2 years).
• Use of aspirin or salicylate-containing medications within 28 days prior to randomization or expected receipt through 28 days after final vaccination.
• History of Guillain-Barré Syndrome.
• Known history of HIV, hepatitis C, or active hepatitis B infection.
• Known immunodeficiency syndrome.
• Use of corticosteroids (excluding topical preparations) or immunosuppressive drugs within 30 days prior to vaccination.
• Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to study vaccination.
• Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination.
• Travel to the Southern Hemisphere within 14 days prior to study vaccination.
• Travel on a cruise ship within 14 days prior to study vaccination.
• Receipt of another investigational vaccine or drug within 30 days prior to study vaccination.
• Allergy to eggs or egg products, gentamicin, or gelatin.
• Chronic use of intranasal medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: H3N2v Seronegative Adults: H3N2v LAIV; Participants will receive one dose of H3N2v LAIV on Day 0 (study entry). They will then receive one dose of H3N2v IIV on Day 84.	Biological: H3N2v MN 2010/AA ca live attenuated influenza vaccine (LAIV); Approximately 10^7.0 Fluorescent Focus Units (FFU) per 0.2 mL dose; administered intranasally; Other Names: H3N2v LAIV; Biological: H3N2v inactivated subvirion influenza vaccine; 15 μg; administered intramuscularly; Other Names: H3N2v IIV
Experimental: Group 2: H3N2v Seropositive Adolescents: H3N2v LAIV; Participants will receive two doses of H3N2v LAIV, the first dose on Day 0 (study entry) and the second dose on Day 28. They will then receive one dose of H3N2v IIV on Day 84.	Biological: H3N2v MN 2010/AA ca live attenuated influenza vaccine (LAIV); Approximately 10^7.0 Fluorescent Focus Units (FFU) per 0.2 mL dose; administered intranasally; Other Names: H3N2v LAIV; Biological: H3N2v inactivated subvirion influenza vaccine; 15 μg; administered intramuscularly; Other Names: H3N2v IIV
Placebo Comparator: Group 2: H3N2v Seropositive Adolescents: Placebo; Participants will receive two doses of placebo, the first dose on Day 0 (study entry) and the second dose on Day 28. They will then receive one dose of H3N2v IIV on Day 84.	Biological: H3N2v inactivated subvirion influenza vaccine; 15 μg; administered intramuscularly; Other Names: H3N2v IIV; Biological: Placebo; Administered by nasal spray
Experimental: Group 3: H3N2v Seronegative Adolescents: H3N2v LAIV; Participants will receive two doses of H3N2v LAIV, the first dose on Day 0 (study entry) and the second dose on Day 28. They will then receive one dose of H3N2v IIV on Day 84.	Biological: H3N2v MN 2010/AA ca live attenuated influenza vaccine (LAIV); Approximately 10^7.0 Fluorescent Focus Units (FFU) per 0.2 mL dose; administered intranasally; Other Names: H3N2v LAIV; Biological: H3N2v inactivated subvirion influenza vaccine; 15 μg; administered intramuscularly; Other Names: H3N2v IIV
Placebo Comparator: Group 3: H3N2v Seronegative Adolescents: Placebo; Participants will receive two doses of placebo, the first dose on Day 0 (study entry) and the second dose on Day 28. They will then receive one dose of H3N2v IIV on Day 84.	Biological: H3N2v inactivated subvirion influenza vaccine; 15 μg; administered intramuscularly; Other Names: H3N2v IIV; Biological: Placebo; Administered by nasal spray
Experimental: Group 4: Children: H3N2v LAIV; Participants will receive two doses of H3N2v LAIV, the first dose on Day 0 (study entry) and the second dose on Day 28. They will then receive one dose of H3N2v IIV on Day 84.	Biological: H3N2v MN 2010/AA ca live attenuated influenza vaccine (LAIV); Approximately 10^7.0 Fluorescent Focus Units (FFU) per 0.2 mL dose; administered intranasally; Other Names: H3N2v LAIV; Biological: H3N2v inactivated subvirion influenza vaccine; 15 μg; administered intramuscularly; Other Names: H3N2v IIV
Placebo Comparator: Group 4: Children: Placebo; Participants will receive two doses of placebo, the first dose on Day 0 (study entry) and the second dose on Day 28. They will then receive one dose of H3N2v IIV on Day 84.	Biological: H3N2v inactivated subvirion influenza vaccine; 15 μg; administered intramuscularly; Other Names: H3N2v IIV; Biological: Placebo; Administered by nasal spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of vaccine-related reactogenicity events (REs) that occur during the acute monitoring phase of the study		Measured through Day 180
Area under the curve of nasal virus shedding after each dose of vaccine	As assessed by liquid titration of nasal secretions on Madin Darby canine kidney (MDCK) cells at 33°C	Measured through Day 180
Development of serum antibody	Assessed by either hemagglutination inhibition (HAI) or microneutralization (MN) assays	Measured through Day 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of a significant increase in nasal secretion hemagglutinin (HA)-specific antibody	Assessed by enzyme-linked immunosorbent assay (ELISA), luminex or microneutralization assay	Measured through Day 180

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): January 5, 2017

Study Registration Dates

• First Submitted: August 25, 2016
• First Submitted That Met QC Criteria: August 25, 2016
• First Posted (Estimate): August 30, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2018
• Last Update Submitted That Met QC Criteria: May 1, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: H3N2v Influenza Viruses
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: URMC 16-001