Safety and Immunogenicity of a Monovalent Inactivated Influenza H3N2 Variant (H3N2v) Vaccine in Adult and Elderly Populations

NCT ID: NCT01746082

Last Updated: 2014-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

211 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2013-08-31

Brief Summary

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This is a Phase II open-label study in approximately 200, and up to 240, healthy males and non-pregnant females, aged 18 years and older. This study is designed to assess the safety, reactogenicity, and immunogenicity of an unadjuvanted subvirion monovalent inactivated influenza H3N2v vaccine manufactured by Sanofi Pasteur. Subjects will be stratified by age (approximately 100 (up to 120) subjects 18-64 years old and approximately 100 (up to 120) subjects \>/= 65 years old) to receive two doses of vaccine, delivered intramuscularly as 15mcg HA/0.5mL dose, 21 days apart. The duration of the study for each subject will be approximately 7 months.

Detailed Description

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This is a Phase II open-label study in approximately 200 (up to 240) healthy males and non-pregnant females, aged 18 years and older. This study is designed to assess the safety, reactogenicity, and immunogenicity of an unadjuvanted subvirion monovalent inactivated influenza H3N2 variant (H3N2v) vaccine (MIV) manufactured by Sanofi Pasteur. Subjects will be stratified by age (approximately 100 (up to 120) subjects 18-64 years old and approximately 100 (up to 120) subjects \>/= 65 years old) to receive two doses of H3N2v MIV, delivered intramuscularly as 15 micrograms (mcg) of hemagglutinin (HA)/0.5 milliliter (mL) dose, 21 days apart (see Table 1). Subjects may receive licensed seasonal influenza vaccine prior to (2 weeks if given the inactivated vaccine or 4 weeks if given the live, attenuated vaccine) the first H3N2v vaccination. Alternatively, subjects may receive licensed seasonal influenza vaccine at any time after completion of the Day 42 visit or following an early termination visit. Safety will be measured by the occurrence of solicited injection site and systemic reactogenicity on the day of each H3N2v vaccination through 7 days after each H3N2v vaccination, adverse events through 42 days after the first H3N2v vaccination, and serious adverse events (SAEs) and new-onset chronic medical conditions through 7 months after the first H3N2v vaccination. Immunogenicity testing will include performing hemagglutination inhibition (HAI) and neutralizing (Neut) antibody assays on serum obtained on the day of and prior to each H3N2v vaccination (Days 0 and 21), approximately 8 days after each H3N2v vaccination (Days 8 and 29), and approximately 21 days after the second H3N2v vaccination (Day 42).

From a subset of healthy adult subjects (up to 30 volunteers 18-64 years old enrolled at the Emory VTEU site who consent to blood donation for the immunology exploratory assays), an additional volume of venous blood will be drawn on Days 0, 8, 21, 29 and 42 to determine the specificity/cross reactivity of antibodies from H3N2v-reactive B cells with other influenza subtypes (e.g., 2009 H1N1 pandemic HA) and most recent H3 seasonal HA to define the molecular profile of antibody repertoire changes in circulating B cells after H3N2v vaccination, and to characterize the antibody-secreting cell (ASC), monoclonal antibody (mAb), and CD4+ T cell responses to H3N2v vaccination. The duration of the study for each subject will be approximately 7 months. Parent protocol to sub-study 12-0089 and 12-0015.

Conditions

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Influenza

Keywords

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influenza, H3N2, H3N2v, vaccine, unadjuvanted, Parent Protocol

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Subjects 18 - 64 years

100 (up to 120) subjects 18 - 64 years old receive two doses of monovalent inactivated influenza H3N2 variant (MIV), delivered intramuscularly as 15 micrograms (mcg) of hemagglutinin (HA)/0.5 milliliter (mL) dose, 21 days apart.

Group Type EXPERIMENTAL

Influenza A/H3N2 variant Vaccine

Intervention Type BIOLOGICAL

Investigational influenza virus H3N2v vaccine, a monovalent type A inactivated vaccine (H3N2v MIV) for intramuscular use, is a sterile clear and slightly opalescent suspension prepared from influenza virus propagated in embryonated chicken eggs. The H3N2v MIV contains no preservative. Subjects will be stratified by age (approximately 100 (up to 120) subjects 18-64 years old and approximately 100 (up to 120) subjects \>/=65 years old) to receive two doses of H3N2v MIV, delivered intramuscularly as 15 micrograms (mcg) of hemagglutinin (HA)/0.5 milliliter (mL) dose, 21 days apart

Subjects > /= 65 years

100 (up to 120) subjects greater than or equal to 65 years old receive two doses of monovalent inactivated influenza H3N2 variant (MIV), delivered intramuscularly as 15 micrograms (mcg) of hemagglutinin (HA)/0.5 milliliter (mL) dose, 21 days apart.

Group Type EXPERIMENTAL

Influenza A/H3N2 variant Vaccine

Intervention Type BIOLOGICAL

Investigational influenza virus H3N2v vaccine, a monovalent type A inactivated vaccine (H3N2v MIV) for intramuscular use, is a sterile clear and slightly opalescent suspension prepared from influenza virus propagated in embryonated chicken eggs. The H3N2v MIV contains no preservative. Subjects will be stratified by age (approximately 100 (up to 120) subjects 18-64 years old and approximately 100 (up to 120) subjects \>/=65 years old) to receive two doses of H3N2v MIV, delivered intramuscularly as 15 micrograms (mcg) of hemagglutinin (HA)/0.5 milliliter (mL) dose, 21 days apart

Interventions

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Influenza A/H3N2 variant Vaccine

Investigational influenza virus H3N2v vaccine, a monovalent type A inactivated vaccine (H3N2v MIV) for intramuscular use, is a sterile clear and slightly opalescent suspension prepared from influenza virus propagated in embryonated chicken eggs. The H3N2v MIV contains no preservative. Subjects will be stratified by age (approximately 100 (up to 120) subjects 18-64 years old and approximately 100 (up to 120) subjects \>/=65 years old) to receive two doses of H3N2v MIV, delivered intramuscularly as 15 micrograms (mcg) of hemagglutinin (HA)/0.5 milliliter (mL) dose, 21 days apart

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Provide written informed consent prior to initiation of any study procedures.
2. Are able to understand and comply with planned study procedures and be available for all study visits.
3. Are males or non-pregnant females, aged 18 years or older, inclusive.

Exclusion Criteria

5. Oral temperature is less than 100.4°F.
6. Pulse is 50 to 100 bpm.
7. Systolic blood pressure is 90 to 150 mm Hg.
8. Diastolic blood pressure is 60 to 100 mmHg.
9. Women of childbearing potential (not surgically sterile via tubal ligation, bilateral oophorectomy or hysterectomy or who are not postmenopausal for greater than or equal to 1 year) must agree to practice adequate contraception (abstinence from sexual intercourse with men, monogamous relationship with a vasectomized partner who was vasectomized at least 6 months prior to the subject receiving the first H3N2v vaccination, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices NuvaRing®, successful Essure® placement (permanent, non-surgical, non-hormonal sterilization) with documented confirmation test at least 3 months after the procedure), licensed hormonal methods such as implants, injectables or oral contraceptives (the pill), and any other Food and Drug Administration (FDA) approved birth control method) for at least 30 days prior to the first H3N2v vaccination through at least 30 days after the last H3N2v vaccination . Method of contraception will be captured on the appropriate data collection form.
10. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each H3N2v vaccination.


1. Have an acute illness, including an oral temperature greater than or equal to 100.4°F, within 3 days prior to each H3N2v vaccination.
2. Have any condition that, in the opinion of the site principal investigator or appropriate sub-investigator, would place the subject at an unacceptable risk of injury, render them unable to meet the requirements of the protocol or confound the interpretation of results.
3. Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months.
4. Have known active neoplastic disease or a history of any hematologic malignancy.
5. Have known HIV, hepatitis B, or hepatitis C infection.
6. Have a known allergy to eggs, egg or chicken protein, or other components of the H3N2v MIV (including octylphenol ethoxylate (Triton® X-100), gelatin, formaldehyde, and phosphate buffered saline).
7. Have a history of severe reactions following previous immunization with licensed influenza virus vaccines.
8. Have a history of Guillain-Barre Syndrome.
9. Have a history of alcohol or drug abuse in the last 5 years.
10. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other major psychiatric diagnosis.
11. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others, within the past 10 years.
12. Have taken high dose oral or parenteral glucocorticoids for 2 weeks or more in total at any time during the past 2 months. High dose defined as prednisone greater than or equal to 20mg total daily dose, or equivalent dose of other glucocorticoids.
13. Have taken high-dose inhaled steroids within the past 4 weeks. High dose defined as \>800mcg/day of beclomethasone dipropionate or equivalent.
14. Have taken systemic corticosteroids of any dose within the past 4 weeks.
15. Received any licensed live vaccine within 4 weeks or any licensed inactivated vaccine within 2 weeks prior to the first H3N2v vaccination or planned receipt of any vaccine within 42 days after the first H3N2v vaccination. This is inclusive of licensed seasonal influenza vaccines.
16. Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within the 3 months prior to each H3N2v vaccination.
17. Received an experimental agent (vaccine, drug, biologic, device, blood product, or medication) within 1 month prior to the first H3N2v vaccination.
18. Are participating or plan to participate in another clinical trial with an interventional agent (licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication) during the 7-month study period.
19. Are enrolled or plan to enroll in another clinical trial that has a study intervention such as a drug, biologic, device, blood product, or medication that could interfere with the safety assessment of the investigational product at any time during the 7-month study period.
20. Participated in an influenza A/H3N2v vaccine study in the past in a group receiving vaccine (does not apply to documented placebo recipients) or have a history of A/H3N2v infection prior to enrollment.
21. Plan to travel outside the U.S. (continental U.S., Hawaii and Alaska) in the time between the first H3N2v vaccination and 42 days after the first H3N2v vaccination.
22. Women who are breastfeeding or plan to breastfeed at any given time during the 7-month study period.
23. Occupational exposure to or direct physical contact with pigs in the past year.
24. Blood donation within 30 days prior to enrollment (only for a subset of healthy adult subjects - up to 30 volunteers 18-64 years old enrolled at the Emory VTEU site who consent to blood donation for the immunology exploratory assays).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, United States

Site Status

University of Iowa - Infectious Disease Clinic

Iowa City, Iowa, United States

Site Status

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, United States

Site Status

Group Health Research Institute - Seattle

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Keitel WA, Jackson LA, Edupuganti S, Winokur PL, Mulligan MJ, Thornburg NJ, Patel SM, Rouphael NG, Lai L, Bangaru S, McNeal MM, Bellamy AR, Hill HR; VTEU H3N2v Vaccine Study Work Group. Safety and Immunogenicity of a Subvirion Monovalent Unadjuvanted Inactivated Influenza A(H3N2) Variant Vaccine in Healthy Persons >/=18 Years Old. J Infect Dis. 2015 Aug 15;212(4):552-61. doi: 10.1093/infdis/jiv056. Epub 2015 Feb 3.

Reference Type DERIVED
PMID: 25649171 (View on PubMed)

Other Identifiers

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HHSN272200800002C

Identifier Type: -

Identifier Source: secondary_id

12-0011

Identifier Type: -

Identifier Source: org_study_id