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

NCT02624219 | Completed Phase 1 FDA Drug

• 2 other identifiers: 15-0064HHSN272201300020I
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 4

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.

Conditions

Avian Influenza; Influenza

Keywords

A/H5N8; AS03; Controlled; Double-Blind; Immunogenicity; Inactivated; Influenza; MF59; Monovalent; Randomized; Reactogenicity; Safety; Trial; Vaccine

Outcome Measures

Primary Outcomes (10)

• Geometric Mean Titers of serum HAI and Neut antibodies against the A/H5N8 antigen contained in the study vaccine

  Approximately 21 days after the second study vaccination

• Occurrence of clinical safety laboratory adverse events

  Day 22-30

• Occurrence of clinical safety laboratory adverse events

  Day 1-9

• Occurrence of solicited injection site and systemic reactogenicity events

  Day 1-9

• Occurrence of solicited injection site and systemic reactogenicity events

  Day 22-30

• Occurrence of study vaccine-related serious adverse events

  Day 1-387

• Percentage of subjects achieving a serum HAI antibody titer of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine

  Approximately 21 days after the second study vaccination

• Percentage of subjects achieving a serum Neut antibody titer of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine

  Approximately 21 days after the second study vaccination

• Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine

  Approximately 21 days after the second study vaccination

• Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine

  Approximately 21 days after the second study vaccination

Secondary Outcomes (7)

• Geometric Mean Titers of serum HAI and Neut antibodies against the A/H5N8 antigen contained in the study vaccine

  At baseline and approximately 8, 21 and 29 days after the first study vaccination

• Occurrence of MAAEs including new-onset chronic medical conditions and immune-mediated or auto-inflammatory AESIs

  Day 1-387

• Occurrence of study vaccine-related unsolicited non-serious adverse events after vaccination 1

  Day 1-22

• Occurrence of study vaccine-related unsolicited non-serious adverse events after vaccination 2

  Day 22-43

• Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine

  At approximately 8, 21 and 29 days after the first study vaccination

Study Arms (5)

Group 1

EXPERIMENTAL

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

Drug: AS03; Biological: Monovalent Influenza A/H5N8 vaccine

Group 2

EXPERIMENTAL

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

Drug: MF59 adjuvant; Biological: Monovalent Influenza A/H5N8 vaccine

Group 3

EXPERIMENTAL

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

Biological: Monovalent Influenza A/H5N8 vaccine

Group 4

EXPERIMENTAL

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

Drug: AS03; Biological: Monovalent Influenza A/H5N8 vaccine

Group 5

EXPERIMENTAL

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

Drug: MF59 adjuvant; Biological: Monovalent Influenza A/H5N8 vaccine

Interventions

AS03 DRUG

AS03 oil-in-water emulsion adjuvant.

Group 1; Group 4

MF59 adjuvant DRUG

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

Group 2; Group 5

Monovalent Influenza A/H5N8 vaccine 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 1; Group 2; Group 3; Group 4; Group 5

Eligibility Criteria

• Age: 19 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• \. 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.

Sponsors & Collaborators

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

Study Sites (4)

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3039, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

MeSH Terms

Conditions

Influenza in Birds; Influenza, Human

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: November 25, 2015
• First Posted: December 8, 2015
• Study Start: August 16, 2016
• Primary Completion: January 30, 2018
• Study Completion: January 30, 2018
• Last Updated: October 23, 2019

Record last verified: 2019-10

Locations

US (4)