H7N9 Vaccination With and Without AS03 and Unadjuvanted H3N2v Vaccination: Standard and Systems Biology Analyses

NCT02921997 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 14-0015
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, randomized, partially-blinded, Phase II, small, targeted, prospective study in approximately 30 healthy male and non-pregnant female subjects aged 18 to 49 years old, inclusive, designed to evaluate and compare the immunogenicity between an intramuscular monovalent inactivated influenza A/H7N9 virus vaccine given with and without AS03 adjuvant, and an intramuscular unadjuvanted monovalent inactivated influenza A/H3N2v virus vaccine. The primary objectives are (1) assessing the serum anti-HA hemagglutination-inhibition (HAI) response to influenza A/H7N9 antigen (with and without adjuvant) at Day 57 (approximately one month after the second study vaccination with A/H7N9 vaccine with or without AS03) and influenza A/H3N2v antigen at Day 29 (approximately one month after the study vaccination with A/H3N2v), and (2) identifying differentially expressed genes in human immune cells on Days 2, 4, and 29 (following the first study vaccination with A/H7N9 vaccine with or without AS03) and on Days 30, 32, and 36 (following the second study vaccination with A/H7N9 vaccine with or without AS03), compared to baseline assessments performed prior to each study vaccination (Days -7, 1, and 29).

Conditions

Avian Influenza; H1N1 Influenza; Influenza

Keywords

A/H5N1; A/H7N9; ASO3 Adjuvant; influenza; monovalent; pH1N1; vaccines

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Seroconversion Based on HAI Titer (A/H7N9 Vaccine, With and Without Adjuvant)

  Seroconversion is defined as either a pre-vaccination HAI titer \<1:10 and a post-vaccination HAI titer =\>1:40 or a pre-vaccination HAI titer =\>1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer. Venous blood samples for serum were used for this assay. HAI based on the H7N9 strain A/Shanghai/02/2013xPR8 were assessed.

  Day 29 Post-Vaccination 2 (Day 57)

• Percentage of Participants Achieving Seroconversion Based on HAI Titer (A/H3N2v Vaccine)

  Seroconversion is defined as either a pre-vaccination HAI titer \<1:10 and a post-vaccination HAI titer =\>1:40 or a pre-vaccination HAI titer =\>1:10 and a minimum four-fold rise in post-vaccination HAI antibody titer. Venous blood samples for serum were used for this assay. HAI based on the H3N2 strain A/Minnesota/11/2010 were assessed.

  Day 29 Post-Vaccination 1 (Day 29)

• Number of Differentially Expressed Genes Based on RNA Expression in Human Immune Cells (A/H7N9 Vaccine, With and Without Adjuvant)

  RNA expression levels (read counts) for each gene were determined by RNA-Sequencing of RNA extracted from six separated cell types: monocytes , dendritic cells, neutrophils, NK cells, B cells, and T cells. Post-vaccination gene expression levels were compared to pre-vaccination gene expression levels (combined summed read counts for Day -7 and Day 1 samples for post-vaccination 1 timepoints and Day 29 read counts for post-vaccination 2 timepoints) using a negative binomial model to identify differentially expressed (DE) genes (FDR-adjusted p-value \< 0.05 and mean fold change =\> 1.5 in either direction).

  Days 2, 4, and 29 Post-Vaccination 1 (Day 2, 4, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively)

Secondary Outcomes (12)

• Number of Differentially Expressed Genes Based on RNA Expression in Human Immune Cells (A/H3N2v Vaccine)

  Days 2, 4, and 8 Post-Vaccination 1 (Day 2, 4, and 8, respectively)

• Cytokine and Chemokine Concentration by Study Arm and Study Visit Day - Part 1

  Day 1 Pre-Vaccination 1; Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively)

• Cytokine and Chemokine Concentration by Study Arm and Study Visit Day - Part 2

  Day 1 Pre-Vaccination 1; Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively)

• Cytokine and Chemokine Concentration by Study Arm and Study Visit Day - Part 3

  Day 1 Pre-Vaccination 1; Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively)

• Fold Change in Cytokine and Chemokine Concentrations From Pre-vaccination - Part 1

  Days 2, 4, 8, and 29 Post-Vaccination 1 (Day 2, 4, 8, and 29, respectively); Days 2, 4, and 8 Post-Vaccination 2 (Day 30, 32, and 36, respectively)

Study Arms (3)

Arm 1

EXPERIMENTAL

10 Subjects: one dose of 15 µg of A/H3N2v, at Day 1

Biological: Influenza Virus Vaccine, Monovalent A/H3N2v A/Minnesota/11/2010 NYMC X-203

Arm 2

EXPERIMENTAL

10 Subjects: two doses of 3.75 µg of AH7N9 AS03,at Day 1 and at Day 29

Drug: AS03; Biological: Monovalent influenza A/H7N9 virus vaccine

Arm 3

EXPERIMENTAL

10 Subjects: two doses of 3.75 µg of A/H7N9, at Day 1 and Day 29

Biological: Monovalent influenza A/H7N9 virus vaccine

Interventions

AS03 DRUG

AS03 oil-in-water emulsion adjuvant.

Arm 2

Influenza Virus Vaccine, Monovalent A/H3N2v A/Minnesota/11/2010 NYMC X-203 BIOLOGICAL

Inactivated monovalent subvirion H3N2v vaccine containing hemagglutinin (HA) of A/Minnesota/11/2010 NYMC X-203 virus.

Arm 1

Monovalent influenza A/H7N9 virus vaccine BIOLOGICAL

Monovalent influenza A/H7N9 virus vaccine.

Arm 2; Arm 3

Eligibility Criteria

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

You may qualify if:

• Provide written informed consent prior to initiation of any study procedures.
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Are males or non-pregnant females, 18 to 49 years old, inclusive.
• Are in good health\*.

You may not qualify if:

• Oral temperature is less than 100.4 degrees F.
• Pulse is 50 to 115 bpm, inclusive.
• Systolic blood pressure is 85 to 150 mm Hg, inclusive.
• Diastolic blood pressure is 55 to 95 mm Hg, inclusive.
• Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour.
• Women of childbearing potential\* must use an acceptable contraception method\*\* from 30 days before first study vaccination until 60 days after last study vaccination.
• \*Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy or successful Essure (R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \<1 year of the last menses if menopausal.
• \*\*Includes, but is not limited to, non-male sexual relationships abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the first study vaccination, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing (R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
• Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.
• Have an acute illness\*, as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to study vaccination.
• \*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
• Have any medical disease or condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation\*.
• \*Including acute or chronic medical disease or condition, defined as persisting for at least 90 days that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study.
• Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
• Have known active neoplastic disease (excluding non-melanoma skin cancer) or a history of any hematologic malignancy.

Sponsors & Collaborators

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

Study Sites (1)

Vanderbilt University Medical Center - Vanderbilt Institute for Clinical and Translational Research - Clinical Research Center (VICTR-CRC)

Nashville, Tennessee, 37232-0011, United States

Location

MeSH Terms

Conditions

Influenza in Birds; Orthomyxoviridae Infections; Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

RNA Virus Infections; Virus Diseases; Infections; Bird Diseases; Animal Diseases; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: C. Buddy Creech, MD, MPH
• Organization: Vanderbilt Vaccine Research Program

buddy.creech@vanderbilt.edu

615-343-0332

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2016
• First Posted: October 3, 2016
• Study Start: November 7, 2016
• Primary Completion: March 28, 2017
• Study Completion: February 14, 2018
• Last Updated: October 9, 2024
• Results First Posted: January 26, 2022

Record last verified: 2019-08-08

Locations

US (1)