NCT03014310

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

A Phase I Cohort-Randomized, Double-Blind, Controlled Trial in Healthy Adults to Assess the Safety, Reactogenicity, and Immunogenicity of a Monovalent Inactivated Influenza A/H5N8 Virus Vaccine Administered Intramuscularly at Different Dosages Given With or Without AS03 or MF59 Adjuvants: Assessment of Immunological Responses and Lymphocyte Interplay

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 388 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 19 Years – 64 Years
• Healthy volunteers: Accepted

Summary

This is a Phase I cohort-randomized, double-blind, controlled trial designed to assess the safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine administered at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants. This study will be conducted at 6 sites and enroll 150 (up to 380) males and non-pregnant females, 19 to 64 years old, inclusive who are in good health and meet all eligibility criteria. The entire study duration is approximately 24 months and each subject participation duration is approximately 13 months. The primary objectives are: 1) To assess the safety and reactogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart. 2) To assess the serum HAI and Neut antibody responses to a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart.

Detailed description

This is a Phase I cohort-randomized, double-blind, controlled trial designed to assess the safety, reactogenicity, and immunogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine manufactured by bioCSL administered at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants manufactured by GlaxoSmithKline Biologicals (GSK) and Novartis Vaccines and Diagnostics (NVD), respectively. This study will be conducted at 6 VTEU sites and enroll 150 (up to 380) males and non-pregnant females, 19 to 64 years old, inclusive who are in good health and meet all eligibility criteria. The entire study duration is approximately 24 months and subject participation duration is approximately 13 months. Subjects will be enrolled in one of two cohorts, and within each cohort subjects will be randomized in a 2:2:1 ratio. Subjects in Cohort 1 will be randomly assigned to 1 of 3 treatment arms to receive two doses of the A/H5N8 vaccine at varying antigen dosages (3.75 or 15 mcg HA) with AS03 (30-76 subjects per treatment arm), or to a comparator arm receiving two doses of the A/H5N8 vaccine (15 mcg HA) without adjuvant (15-38 subjects). Subjects in Cohort 2 will be randomly assigned to 1 of 3 treatment arms to receive two doses of the A/H5N8 vaccine at varying antigen dosages (3.75 or 15 mcg HA) with MF59 (30-76 subjects per treatment arm), or to a comparator arm receiving two doses of the A/H5N8 vaccine (15 mcg HA) without adjuvant (15-38 subjects). All subjects will receive the same dosage of vaccine with or without the same adjuvant at both of their first and second study vaccinations, with the exception that subjects in Cohort 1 who do not receive Vaccination 2 prior to February 28, 2017 will receive a second unadjuvanted vaccination with the same antigen dosage as their randomized assignment. All doses will be administered intramuscularly approximately 21 days apart. Primary objectives are: 1) To assess the safety and reactogenicity of a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart. 2) To assess the serum HAI and Neut antibody responses to a monovalent inactivated influenza A/H5N8 virus vaccine following receipt of two doses administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart. Secondary objectives are: 1) To assess study unsolicited non-serious AEs following receipt of two doses of a monovalent inactivated influenza A/H5N8 virus vaccine administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart. 2) To assess medically-attended adverse events (MAAEs), including new-onset chronic medical conditions (NOCMCs), potentially immune-mediated medical conditions (PIMMCs), and all serious adverse events (SAEs) following receipt of two doses of a monovalent inactivated influenza A/H5N8 virus vaccine administered intramuscularly at different dosages (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants approximately 21 days apart. 3) To 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 (3.75 and 15 mcg of HA per dose) given with or without AS03 or MF59 adjuvants.

Conditions

• Avian Influenza

Interventions

Type	Name	Description
DRUG	AS03	AS03 oil-in-water emulsion adjuvant.
DRUG	MF59	Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.
BIOLOGICAL	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).

Timeline

• Start date: 2017-01-09
• Primary completion: 2018-12-19
• Completion: 2018-12-19
• First posted: 2017-01-09
• Last updated: 2024-09-23

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study