H5N8 Mix and Match With or Without AS03 or MF59 in Healthy Adults

NCT ID: NCT02624219

Last Updated: 2019-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 276 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-16
• Study Completion Date: 2018-01-30

Brief Summary

This is a Phase I randomized, double-blind, controlled trial in 275 males and non-pregnant females, 19 to 64 years old, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine manufactured by bioCSL administered at different dosages (7.5 or 15 mcg of HA/0.5 mL dose) given with or without AS03 or MF59 adjuvants manufactured by GlaxoSmithKline Biologicals and Novartis Vaccines and Diagnostics, respectively.

Detailed Description

This is a Phase I randomized, double-blind, controlled trial in 275 males and non-pregnant females, 19 to 64 years old, inclusive, who are in good health and meet all eligibility criteria which include screening hematology, chemistry and erythrocyte sedimentation rate (ESR) laboratory evaluations. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine manufactured by bioCSL administered at different dosages (7.5 or 15 mcg of HA/0.5 mL dose) given with or without AS03 or MF59 adjuvants manufactured by GlaxoSmithKline Biologicals and Novartis Vaccines and Diagnostics, respectively. The primary objectives of this study is to assess 1) the safety and reactogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine and 2) the serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody responses to a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered intramuscularly at different dosages (7.5 or 15 mcg of HA/0.5 mL dose) given with or without AS03 or MF59 approximately 21 days apart. The secondary objectives of this study are to 1) assess study vaccine-related unsolicited non-serious adverse events following receipt of two doses of a monovalent inactivated influenza A/H5N8 virus vaccine, 2) assess medically attended adverse events (MAAEs) including new-onset chronic medical conditions and immune-mediated or auto-inflammatory adverse events of special interest following receipt of two doses of a monovalent inactivated influenza A/H5N8 virus vaccine, and 3) assess the serum HAI and Neut antibody responses to a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of one dose administered intramuscularly at different dosages (7.5 or 15 mcg of HA/0.5 mL dose) given with or without AS03 or MF59. This study will span approximately 24 months. Subject participation duration will span approximately 13 months.

Conditions

Avian Influenza; Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Group 1

N = 55 receive 7.5 mcg A/H5N8 + AS03 on Day 1, 22

Group Type: EXPERIMENTAL

AS03

Intervention Type: DRUG

AS03 oil-in-water emulsion adjuvant.

Monovalent Influenza A/H5N8 vaccine

Intervention Type: BIOLOGICAL

Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).

Group 2

N = 55 receive 7.5 mcg A/H5N8 + MF59 on Day 1, 22

Group Type: EXPERIMENTAL

MF59 adjuvant

Intervention Type: DRUG

Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.

Monovalent Influenza A/H5N8 vaccine

Intervention Type: BIOLOGICAL

Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).

Group 3

N = 55 receive 15 mcg A/H5N8 unadjuvanted on Day 1, 22

Group Type: EXPERIMENTAL

Monovalent Influenza A/H5N8 vaccine

Intervention Type: BIOLOGICAL

Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).

Group 4

N = 55 receive 15 mcg A/H5N8 + AS03 on Day 1, 22

Group Type: EXPERIMENTAL

AS03

Intervention Type: DRUG

AS03 oil-in-water emulsion adjuvant.

Monovalent Influenza A/H5N8 vaccine

Intervention Type: BIOLOGICAL

Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).

Group 5

N = 55 receive 15 mcg A/H5N8 + MF59 on Day 1, 22

Group Type: EXPERIMENTAL

MF59 adjuvant

Intervention Type: DRUG

Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.

Monovalent Influenza A/H5N8 vaccine

Intervention Type: BIOLOGICAL

Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).

Interventions

AS03

AS03 oil-in-water emulsion adjuvant.

Intervention Type: DRUG

MF59 adjuvant

Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.

Intervention Type: DRUG

Monovalent Influenza A/H5N8 vaccine

Monovalent inactivated influenza A/H5N8 virus vaccine for IM injection. prepared from influenza virus propagated in chicken egg fluid using seed virus prepared from the candidate vaccine virus (CVV), influenza virus A/gyrfalcon/Washington/41088-6/2014(H5N8)-PR8-IDCDC-RG43A (abbreviated as IDCDC-RG43A).

Intervention Type: BIOLOGICAL

Eligibility Criteria

Exclusion Criteria

1. 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. 2. 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 trial. 3. 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. 4. Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma skin cancers are permitted. 5. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection. 6. Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine. 7. Have a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines. 8. Have a personal or family history of narcolepsy. 9. Have a history of Guillain-Barré syndrome. 10. Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination. 11. Have a history of autoimmune or auto-inflammatory disease***. ***Including, but not limited to, autoimmune or auto-inflammaory processes resulting in neuralgia, paresthesia, neuritis, neuroinflammatory diseases, vasculitis, clotting disorders, dermatitis, arthritis, thyroiditis, hypothyroidism, hyperthyroidism, or muscle, liver, or kidney disease. Refer as well to the list of AESIs. 12. Have a history of alcohol or drug abuse within 5 years prior to study vaccination. 13. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations. 14. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination. 15. Have taken oral or parenteral (including intraarticular) corticosteroids of any dose within 30 days prior to study vaccination. 16. Have taken high-dose inhaled corticosteroids within 30 days prior to study vaccination. High-dose defined as >840 mcg/day of beclomethasone dipropionate CFC or equivalent. 17. Received a licensed live vaccine within 30 days prior to the first study vaccination, or plan to receive a licensed live vaccine within 30 days before or after each study vaccination. 18. Received a licensed inactivated vaccine within 14 days prior to the first study vaccination, or plan to receive a licensed inactivated vaccine within 14 days before or after each study vaccination. 19. Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to study vaccination. 20. Received an experimental agent7 within 30 days prior to the first study vaccination, or expect to receive an experimental agent8 during the 13-month trial-reporting period. 7Including vaccine, drug, biologic, device, blood product, or medication. 8Other than from participation in this trial. 21. Are participating or plan to participate in another clinical trial with an interventional agent**** that will be received during the 13-month trial-reporting period. ****Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. 22. Prior participation in a clinical trial of influenza A/H5 vaccine***** or have a history of influenza A/H5 virus actual or potential exposure or infection prior to the first study vaccination. *****And assigned to a group receiving influenza A/H5 vaccine, does not apply to documented placebo recipients. 23. Occupational exposure to or substantial direct physical contact (Note) with birds in the past year or during the 21 days after each study vaccination. Note: Casual contact with birds at petting zoos, county or state fairs, or having pet birds does not exclude subjects from study participation. 24. Female subjects who are breastfeeding or plan to breastfeed at any given time from the first study vaccination until 30 days after the last study vaccination. 25. Plan to travel outside the US (continental US, Hawaii, and Alaska) within 21 days after each study vaccination.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, United States

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, United States

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, United States

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, United States

Countries

United States

Other Identifiers

HHSN272201300020I

Identifier Type: -

Identifier Source: secondary_id

15-0064

Identifier Type: -

Identifier Source: org_study_id