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

NCT03014310 | Completed Phase 1 FDA Drug

• 1 other identifier: 15-0066
• Study Type: interventional
• Target: 388
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Avian Influenza

Keywords

A/H5N8; Adjuvants; AS03; Inactivated; Influenza; MF59; Monovalent

Outcome Measures

Primary Outcomes (11)

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

  Day 43

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

  Day 43

• Occurrence of clinical safety laboratory AEs

  Day 1-9

• Occurrence of clinical safety laboratory AEs

  Day 22-30

• 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 SAEs

  Day 1-387

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

  Day 43

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

  Day 43

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

  Day 43

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

  Day 43

Secondary Outcomes (12)

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

  Day 1, 8, 22, 29, 43, 202, and 387

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

  Day 1, 8, 22, 29, 43, 202, and 387

• Occurrence of all serious adverse events (SAEs), regardless of the assessment of relatedness

  Day 1-387

• Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness

  Day 1-22

• Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness

  Day 22-43

Study Arms (6)

Arm 1: 3.75 mcg A/H5N8 + AS03

EXPERIMENTAL

3.75 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30

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

Arm 2: 15 mcg A/H5N8 + AS03

EXPERIMENTAL

15 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30

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

Arm 3: 15 mcg A/H5N8 unadjuvanted

ACTIVE COMPARATOR

15 mcg A/H5N8 unadjuvanted given IM on Day 1 and 22, n=15

Biological: Monovalent Influenza A/H5N8 vaccine

Arm 4: 3.75 mcg A/H5N8 + MF59

EXPERIMENTAL

3.75 mcg A/H5N8 + MF59 given IM on Day 1 and 22, n=30

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

Arm 5: 15 mcg A/H5N8 + MF59

EXPERIMENTAL

15 mcg A/H5N8 + MF59 given IM on Day 1 and 22, n=30

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

Arm 6: 15 mcg A/H5N8 unadjuvanted

ACTIVE COMPARATOR

15 mcg A/H5N8 unadjuvanted given IM on Day and 22, n=15

Biological: Monovalent Influenza A/H5N8 vaccine

Interventions

AS03 DRUG

AS03 oil-in-water emulsion adjuvant.

Arm 1: 3.75 mcg A/H5N8 + AS03; Arm 2: 15 mcg A/H5N8 + AS03

MF59 DRUG

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

Arm 4: 3.75 mcg A/H5N8 + MF59; Arm 5: 15 mcg A/H5N8 + MF59

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).

Arm 1: 3.75 mcg A/H5N8 + AS03; Arm 2: 15 mcg A/H5N8 + AS03; Arm 3: 15 mcg A/H5N8 unadjuvanted; Arm 4: 3.75 mcg A/H5N8 + MF59; Arm 5: 15 mcg A/H5N8 + MF59; Arm 6: 15 mcg A/H5N8 unadjuvanted

Eligibility Criteria

• Age: 19 Years - 64 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, 19 to 64 years old, inclusive.
• Are in good health.

You may not qualify if:

• Oral temperature is less than 100.0°F.
• Pulse is 50 to 115 bpm, inclusive.
• Systolic blood pressure is 85 to 150 mmHg, inclusive.
• Diastolic blood pressure is 55 to 95 mmHg, inclusive.
• Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour.
• Alanine aminotransferase (ALT) is less than 44 IU/L for females or is less than 61 IU/L for males.
• Creatinine is less than 1.11 mg/dL for females or is less than 1.38 mg/dL for males.
• White blood cells (WBC) are greater than 3.9 x10\^3/µL and less than 10.6 x10\^3/µL.
• Hemoglobin (Hgb) is greater than 11.4 g/dL for females or is greater than 12.4 g/dL for males.
• Platelets are greater than 139 x10\^3/µL and less than 416 x10\^3/µL.
• Total bilirubin is less than 1.3 mg/dL.
• 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® 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®, 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.

Sponsors & Collaborators

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

Study Sites (7)

Emory University School of Medicine

Atlanta, Georgia, 30322-1014, United States

Location

University of Maryland Baltimore - School of Medicine - Medicine

Baltimore, Maryland, 21201-1509, United States

Location

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Duke Vaccine and Trials Unit

Durham, North Carolina, 27704, United States

Location

Cincinnati Children's Hospital Medical Center Vaccine Research Center

Cincinnati, Ohio, 45229-3039, United States

Location

Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center

Nashville, Tennessee, 37232-2573, United States

Location

The University of Texas Medical Branch - Sealy Center for Vaccine Development (SCVD)

Galveston, Texas, 77555-1121, United States

Location

MeSH Terms

Conditions

Influenza in Birds; Influenza, Human

Interventions

MF59 oil emulsion

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: January 5, 2017
• First Posted: January 9, 2017
• Study Start: January 9, 2017
• Primary Completion: December 19, 2018
• Study Completion: December 19, 2018
• Last Updated: September 23, 2024

Record last verified: 2017-07-19

Locations

US (7)