Immune Responses to H5N1 Vaccine With and Without AS03 Adjuvant

NCT01578317 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 12010312-I-0103
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Adjuvants are substances included in vaccines that stimulate the immune system and increase the body's response to the vaccine. The AS03 adjuvant is used in seasonal flu vaccines in Europe. However, it has not been fully tested in the United States. Researchers want to test the immune responses of people who receive a bird flu vaccine with or without AS03 to better understand how the adjuvant works. This information may help develop better flu vaccines. Objectives: \- To compare the healthy immune system responses to bird flu vaccine with or without the AS03 adjuvant. Eligibility: \- Healthy volunteers between 18 and 45 years of age. Design:

• Participants will be screened with a physical exam and medical history.
• Participants will be assigned to one of two groups. Each group will have an initial vaccine, followed by a booster vaccine 21 days later. Both vaccinations will use the same type of vaccine. One group will have the vaccine with AS03; the other group will have the vaccine without it.
• All participants will have two 36-hour inpatient stays to receive the vaccine. Each stay will involve the vaccination, followed by regular and frequent blood draws. Participants will be monitored for any signs or symptoms that may be caused by the vaccine.
• Additional blood samples will be collected 7, 28, 42, and 100 days after the initial vaccination.

Conditions

Influenza

Keywords

H5N1 Vaccine; H5N1 Immunization; AS03 Adjuvant; Biologic Sample Collection; Laboratory Research Specimens; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Flu Antibody Titers

  Flu Antibody titers at days 0, 21, 42, 100. Antibody-neutralization titers by microneutralization were measured against five different H5N1 virus strains (i.e., A/Vietnam/1194/2004 (clade 1), A/Indonesia/5/2005 (clade 2.1), A/Turkey/15/2006 (clade 2.2), A/Egypt/3072/2010 (clade 2.2), and A/Anhui/1/2005 (clade 2.3.4)) at day 0 (prevaccination), day 21 (post first vaccination), day 42 (post second vaccination) and day 100 postvaccination for AS03-adjuvanted group and unadjuvanted group. Sera were tested at an initial dilution of 1:20, and those that were negative (\<1:20) were assigned a titer of 10.

  Days 0, 21, 42, and 100

Study Arms (2)

AS03 adjuvanted

EXPERIMENTAL

Adminsitered day 1, booster at Day 21

Biological: H5N1 vaccine plus AS03 adjuvant

unadjuvanted

EXPERIMENTAL

Administer day 1 and booster at Day 21

Biological: H5N1 vaccine without adjuvant

Interventions

H5N1 vaccine plus AS03 adjuvant BIOLOGICAL

H5N1 influenza vaccine with AS03 at the 3.75 mcg dose level given 21 days apart.

AS03 adjuvanted

H5N1 vaccine without adjuvant BIOLOGICAL

H5N1 influenza vaccine non- adjuvanted form at the 3.75 mcg dose level given 21 days apart.

unadjuvanted

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy status confirmed by History, Physical Exam and blood work through the CHI Screening Protocol.
• Age 21 years to 45 years
• Able to comprehend the investigational nature of the protocol and provide informed consent
• Must be willing to use effective birth control for one month before, during and for two months after the last vaccination.

You may not qualify if:

• Severe allergies to eggs or their products, chicken proteins or to any component of the influenza antigen preparation.
• Recipient of AS03 vaccine at any time in the past
• Recipient of the seasonal influenza vaccine within the past 3 months.
• Prior severe reactions to vaccines, including influenza vaccines (e.g. anaphylaxis, angioedema or urticaria)
• Participation on any blood collection or blood donation procedure during study that will bring the total blood draw \>550ml over 8 weeks
• Current pregnancy (women of child bearing potential must have a negative serum pregnancy test done on screening within 1 week of protocol accrual)
• Currently breast-feeding
• History of Guillain Barre syndrome
• Acute illness with patient reported temperature of 38 (Infinite)C or greater within 3 days prior to the proposed time of administration.
• Any history or presence of serious illness, bleeding disorders or autoimmune disorders, or planned surgeries.
• Weight less than 50 kg (110 pounds)
• History of hepatitis or liver disease.
• Subjects receiving immunosuppressive therapy.
• Presence of HLA DQB1\*06:02, the narcolepsy risk associated allele.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Atmar RL, Keitel WA, Patel SM, Katz JM, She D, El Sahly H, Pompey J, Cate TR, Couch RB. Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2 vaccine preparations. Clin Infect Dis. 2006 Nov 1;43(9):1135-42. doi: 10.1086/508174. Epub 2006 Sep 25.

  PMID: 17029131 BACKGROUND

• Banzhoff A, Gasparini R, Laghi-Pasini F, Staniscia T, Durando P, Montomoli E, Capecchi PL, di Giovanni P, Sticchi L, Gentile C, Hilbert A, Brauer V, Tilman S, Podda A. MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS One. 2009;4(2):e4384. doi: 10.1371/journal.pone.0004384. Epub 2009 Feb 6.

  PMID: 19197383 BACKGROUND

• Podda A. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. Vaccine. 2001 Mar 21;19(17-19):2673-80. doi: 10.1016/s0264-410x(00)00499-0.

  PMID: 11257408 BACKGROUND

• Khurana S, Coyle EM, Manischewitz J, King LR, Gao J, Germain RN, Schwartzberg PL, Tsang JS, Golding H; and the CHI Consortium. AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization. NPJ Vaccines. 2018 Oct 1;3:40. doi: 10.1038/s41541-018-0076-2. eCollection 2018.

  PMID: 30302282 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Influenza, Human

Interventions

AS03 adjuvant; Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Results Point of Contact

• Title: John Tsang
• Organization: NIH

tsangjs@mail.nih.gov

301-496-0304

Study Officials

• John S Tsang, Ph.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: April 16, 2012
• Study Start: March 20, 2012
• Primary Completion: January 31, 2016
• Study Completion: January 31, 2016
• Last Updated: February 26, 2019
• Results First Posted: February 26, 2019

Record last verified: 2018-09

Locations

US (1)