Safety and Immunogenicity of a Live Attenuated H7N9 Influenza Virus Vaccine in Healthy Adults

NCT01995695 | Completed Phase 1

• 1 other identifier: URMC 13-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

H7N9 avian influenza (AI) viruses have caused a recent outbreak of severe respiratory disease in humans in China. The purpose of this study is to evaluate the safety and immunogenicity of a live attenuated H7N9 A/Anhui/13 ca influenza virus vaccine in healthy adults. A single dose of inactivated subvirion H7N9 influenza vaccine will be administered 3 months later.

Conditions

Influenza A Virus, H7N9 Subtype

Outcome Measures

Primary Outcomes (5)

• Frequency of vaccine-related reactogenicity events that occur during the acute monitoring (inpatient) phase of the study

  Measured through Day 9 (Group 1) or Day 37 (Group 2)

• Area under the curve (AUC) 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

• Vaccine virus shedding on one or more days on Days 2 through 9 as assessed by culture or real-time reverse transcriptase polymerase chain reaction (rRT-PCR)

  Measured through Day 9

• Evidence of a 4-fold or greater increase in either hemagglutination inhibition (HAI) or microneutralization (MN) antibody comparing pre-vaccination to either Day 29 or Day 56 post-dose two samples

  Measured through Day 56

• Development of serum antibody assessed by either HAI or MN assays

  Measured through Day 180

Secondary Outcomes (3)

• Development of a significant increase in nasal secretion HA-specific antibody assessed by enzyme-linked immunosorbent assay (ELISA)

  Measured through Day 180

• Development of greater than 200 influenza-specific interferon-gamma-secreting cells per million lymphocytes as assessed by enzyme-linked immunosorbent spot (ELISPOT) on Day 28 after immunization

  Measured through Day 28

• Detection of influenza-specific immunoglobulin G (IgG) or IgA secreting B cells on Day 7 following vaccination assessed by antibody secreting cells (ASC) assay

  Measured through Day 7

Study Arms (2)

Group 1: One Vaccine Dose and One Booster Vaccine Dose

EXPERIMENTAL

Participants will receive one dose of live attenuated H7N9 A/Anhui/13 ca influenza virus vaccine at study entry. They will then receive one dose of inactivated subvirion H7N9 influenza vaccine on Day 98.

Biological: Live attenuated H7N9 A/Anhui/13 ca influenza virus vaccine; Biological: Inactivated subvirion H7N9 influenza vaccine

Group 2: Two Vaccine Doses and One Booster Vaccine Dose

EXPERIMENTAL

Participants will receive two doses of live attenuated H7N9 A/Anhui/13 ca influenza virus vaccine: one dose at study entry and one dose on Day 28. They will then receive one dose of inactivated subvirion H7N9 influenza vaccine on Day 98.

Biological: Live attenuated H7N9 A/Anhui/13 ca influenza virus vaccine; Biological: Inactivated subvirion H7N9 influenza vaccine

Interventions

Live attenuated H7N9 A/Anhui/13 ca influenza virus vaccine BIOLOGICAL

Participants will receive approximately 10\^7.0 focus forming units (FFU) of the live attenuated H7N9 A/Anhui/13 ca influenza virus vaccine. The vaccine will be delivered by an Accuspray nasal spray device (0.25 mL per nostril for a total of 0.5 mL of vaccine).

Group 1: One Vaccine Dose and One Booster Vaccine Dose; Group 2: Two Vaccine Doses and One Booster Vaccine Dose

Inactivated subvirion H7N9 influenza vaccine BIOLOGICAL

Participants will receive 30 mcg of the inactivated subvirion H7N9 vaccine by intramuscular injection.

Group 1: One Vaccine Dose and One Booster Vaccine Dose; Group 2: Two Vaccine Doses and One Booster Vaccine Dose

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult males and non-pregnant females between 18 years and 49 years of age, inclusive. Children will not be recruited or enrolled in this study because they are not in the apparent risk group, and for safety considerations and because of the need for isolation.
• 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
• Female participants of child-bearing potential must agree to use effective birth control methods for the duration of the study (for example, pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; intrauterine device; abstinence from heterosexual intercourse; surgical sterilization). All female participants will be considered being of child-bearing potential except those who have undergone hysterectomy and those in whom menopause occurred at least 1 year prior to the study.

You may not qualify if:

• Pregnancy, as determined by a positive human choriogonadotropin (beta-HCG) test
• Currently breastfeeding
• Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol
• Previous enrollment in an H7 influenza vaccine trial or in any study of an avian influenza vaccine
• Seropositive to the H7N9 influenza A virus (serum HAI titer greater than 1:8)
• Positive urine drug toxicology test indicating narcotic use/dependency
• Have medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months
• Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol
• History of anaphylaxis
• Allergy to oseltamivir as determined by participant report
• Current diagnosis of asthma or reactive airway disease (within the past 2 years)
• History of Guillain-Barré Syndrome
• Positive ELISA and confirmatory Western blot tests for human immunodeficiency virus-1 (HIV-1)
• Positive ELISA and confirmatory test (e.g., recombinant immunoblot assay) for hepatitis C virus (HCV)
• Positive hepatitis B virus surface antigen (HBsAg) by ELISA

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• University of Rochester: collaborator

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Sobhanie M, Matsuoka Y, Jegaskanda S, Fitzgerald T, Mallory R, Chen Z, Luke C, Treanor J, Subbarao K. Evaluation of the Safety and Immunogenicity of a Candidate Pandemic Live Attenuated Influenza Vaccine (pLAIV) Against Influenza A(H7N9). J Infect Dis. 2016 Mar 15;213(6):922-9. doi: 10.1093/infdis/jiv526. Epub 2015 Dec 9.

  PMID: 26655841 DERIVED

Study Officials

• John Treanor, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2013
• First Posted: November 26, 2013
• Study Start: October 1, 2013
• Primary Completion: January 1, 2016
• Last Updated: July 27, 2016

Record last verified: 2016-07

Locations

US (1)