Avian InfluenzaPhase 1NCT03014310
H5N8 Mix and Match With or Without AS03 or MF59 in Healthy Adults: Immunology
A Phase 1 study testing AS03, MF59 and Monovalent Influenza A/H5N8 vaccine in people with Avian Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Avian Influenza
- What is being tested?
- AS03, MF59 and Monovalent Influenza A/H5N8 vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 388 participants
- Where
- 7 sitesUnited States
- Study dates
- 9 Jan 2017to 19 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
- -As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, that would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days. This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria (see Section 5.1.2), herbals, vitamins, and supplements are permitted.
- Oral temperature is less than 100.0°F.
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- 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.
Who cannot join
- 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.
- 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.
- 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.
- Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma skin cancers are permitted.
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- Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
- Have known hypersensitivity or allergy to eggs, egg or chicken protein, squalene-based adjuvants, or other components of the study vaccine.
- Have a history of severe reactions following previous immunization with licensed or unlicensed influenza vaccines.
- Have a personal or family history of narcolepsy.
- Have a history of Guillain-Barré syndrome.
- Have a history of convulsions or encephalomyelitis within 90 days prior to study vaccination.
- Have a history of PIMMCs.
- -Refer to Appendix B: List of Potentially Immune-Mediated Medical Conditions.
- Have a history of alcohol or drug abuse within 5 years prior to study vaccination.
- Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
- 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.
- Have taken oral or parenteral (including intraarticular) corticosteroids of any dose within 30 days prior to study vaccination.
- 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.
- 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.
- 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.
- Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to study vaccination.
- Received an experimental agent within 30 days prior to the first study vaccination, or expect to receive an experimental agent during the 13-month trial-reporting period.
- -Including vaccine, drug, biologic, device, blood product, or medication.
- --Other than from participation in this trial.
- 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.
- Received or plan to receive an 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.
- Occupational exposure to or substantial direct physical contact with birds in the past year and through the 21 days after the second study vaccination.
- -Exposure to free range chickens in the yard does warrant exclusion. Casual contact with birds at petting zoos or county or state fairs or having pet birds does not exclude subjects from study participation.
- 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.
- Plan to travel outside the US (continental US, Hawaii, and Alaska) from enrollment through 21 days after the second study vaccination.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Emory University School of Medicine
Atlanta, Georgia, 30322-1014
University of Maryland Baltimore - School of Medicine - Medicine
Baltimore, Maryland, 21201-1509
Cincinnati Children's Hospital Medical Center Vaccine Research Center
Cincinnati, Ohio, 45229-3039
Duke Vaccine and Trials Unit
Durham, North Carolina, 27704
The University of Texas Medical Branch - Sealy Center for Vaccine Development (SCVD)
Galveston, Texas, 77555-1121
Vanderbilt University - Pediatric - Vanderbilt Vaccine Research Center
Nashville, Tennessee, 37232-2573
Saint Louis University Center for Vaccine Development
St Louis, Missouri, 63104-1015
About this study
Official title: 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
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.
Read the 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
- Being tested
- AS03, MF59, Monovalent Influenza A/H5N8 vaccine
- Keywords
- A/H5N8, Adjuvants, AS03, Inactivated, Influenza, MF59, Monovalent
- Medical subject headings
- Influenza in Birds, Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AS03Drug
AS03 oil-in-water emulsion adjuvant.
MF59Drug
Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion.
Monovalent Influenza A/H5N8 vaccineBiological
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).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: 3.75 mcg A/H5N8 + AS03 | Experimental | 3.75 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Biological: Monovalent Influenza A/H5N8 vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine
Measured: Day 43
Geometric Mean Titers of serum HAI antibodies against the A/H5N8 antigen contained in the study vaccine
Measured: Day 43
Occurrence of clinical safety laboratory AEs
Measured: Day 1-9
Occurrence of clinical safety laboratory AEs
Measured: Day 22-30
Occurrence of solicited injection site and systemic reactogenicity events
Measured: Day 1-9
Occurrence of solicited injection site and systemic reactogenicity events
Measured: Day 22-30
Occurrence of study vaccine-related SAEs
Measured: Day 1-387
Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine
Measured: Day 43
Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine
Measured: 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
Measured: 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
Measured: Day 43
Secondary outcomes (12)
Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine
Measured: 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
Measured: Day 1, 8, 22, 29, 43, 202, and 387
Occurrence of all serious adverse events (SAEs), regardless of the assessment of relatedness
Measured: Day 1-387
Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness
Measured: Day 1-22
Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness
Measured: Day 22-43
Occurrence of MAAEs, including NOCMCs, and PIMMCs
Measured: Day 1-387
Occurrence of study vaccine-related unsolicited non-serious AEs
Measured: Day 1-22
Occurrence of study vaccine-related unsolicited non-serious AEs
Measured: Day 22-43
Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine
Measured: Day 8, 22, 29, 43, 202, and 387
Percentage of subjects achieving Neut antibody titers of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine
Measured: Day 1, 8, 22, 29, 43, 202, and 387
Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine
Measured: Day 8, 22, 29, 43, 202, and 387
Percentage of subjects achieving serum HAI antibody titers of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine
Measured: Day 1, 8, 22, 29, 43, 202, and 387
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2017 (estimated)
- Study start9 Jan 2017
- Primary completion19 Dec 2018
- Study completion19 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Avian InfluenzaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 388 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03014310
- Sponsor's protocol ID
- 15-0066
- Status last verified
- 19 Jul 2017
- First submitted
- 5 Jan 2017
- Last updated
- 23 Sep 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03014310
- Acronym / sponsor ID
- 15-0066
- Conditions
- Avian Influenza
- Keywords
- A/H5N8, Adjuvants, AS03, Inactivated, Influenza, MF59, Monovalent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 388 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 9 Jan 2017 (actual)
- Primary completion
- 19 Dec 2018 (actual)
- Study completion
- 19 Dec 2018 (actual)
- First posted
- 9 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm 1: 3.75 mcg A/H5N8 + AS03 | Experimental | Drug: AS03, Biological: Monovalent Influenza A/H5N8 vaccine3.75 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30 |
| Arm 2: 15 mcg A/H5N8 + AS03 | Experimental | Drug: AS03, Biological: Monovalent Influenza A/H5N8 vaccine15 mcg A/H5N8 + AS03 given IM on Day 1 and 22, n=30 |
| Arm 3: 15 mcg A/H5N8 unadjuvanted | Active comparator | Biological: Monovalent Influenza A/H5N8 vaccine15 mcg A/H5N8 unadjuvanted given IM on Day 1 and 22, n=15 |
| Arm 4: 3.75 mcg A/H5N8 + MF59 | Experimental | Drug: MF59, Biological: Monovalent Influenza A/H5N8 vaccine3.75 mcg A/H5N8 + MF59 given IM on Day 1 and 22, n=30 |
| Arm 5: 15 mcg A/H5N8 + MF59 | Experimental | Drug: MF59, Biological: Monovalent Influenza A/H5N8 vaccine15 mcg A/H5N8 + MF59 given IM on Day 1 and 22, n=30 |
| Arm 6: 15 mcg A/H5N8 unadjuvanted | Active comparator | Biological: Monovalent Influenza A/H5N8 vaccine15 mcg A/H5N8 unadjuvanted given IM on Day and 22, n=15 |
Who may qualify
- Ages
- 19 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- 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.
- -As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days, that would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days. This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled medications (with the exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria (see Section 5.1.2), herbals, vitamins, and supplements are permitted.
Key exclusion criteria (33 listed)
- 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.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AS03AS03 oil-in-water emulsion adjuvant. | Drug | Arm 1: 3.75 mcg A/H5N8 + AS03, Arm 2: 15 mcg A/H5N8 + AS03 |
| MF59Microfluoridized adjuvant 59 (MF59) is an oil-in-water emulsion. | Drug | Arm 4: 3.75 mcg A/H5N8 + MF59, Arm 5: 15 mcg A/H5N8 + MF59 |
| Monovalent Influenza A/H5N8 vaccineMonovalent 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). | Biological | 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 |
Primary outcome
Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine
Time frame: Day 43
Geometric Mean Titers of serum HAI antibodies against the A/H5N8 antigen contained in the study vaccine
Time frame: Day 43
Occurrence of clinical safety laboratory AEs
Time frame: Day 1-9
Occurrence of clinical safety laboratory AEs
Time frame: Day 22-30
Occurrence of solicited injection site and systemic reactogenicity events
Time frame: Day 1-9
Occurrence of solicited injection site and systemic reactogenicity events
Time frame: Day 22-30
Occurrence of study vaccine-related SAEs
Time frame: Day 1-387
Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine
Time frame: Day 43
Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine
Time frame: 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
Time frame: 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
Time frame: Day 43
12 secondary outcomes
Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine
Time frame: 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
Time frame: Day 1, 8, 22, 29, 43, 202, and 387
Occurrence of all serious adverse events (SAEs), regardless of the assessment of relatedness
Time frame: Day 1-387
Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness
Time frame: Day 1-22
Occurrence of all unsolicited adverse events, regardless of the assessment of seriousness or relatedness
Time frame: Day 22-43
Occurrence of MAAEs, including NOCMCs, and PIMMCs
Time frame: Day 1-387
Occurrence of study vaccine-related unsolicited non-serious AEs
Time frame: Day 1-22
Occurrence of study vaccine-related unsolicited non-serious AEs
Time frame: Day 22-43
Percentage of subjects achieving HAI seroconversion against the A/H5N8 antigen contained in the study vaccine
Time frame: Day 8, 22, 29, 43, 202, and 387
Percentage of subjects achieving Neut antibody titers of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine
Time frame: Day 1, 8, 22, 29, 43, 202, and 387
Percentage of subjects achieving Neut seroconversion against the A/H5N8 antigen contained in the study vaccine
Time frame: Day 8, 22, 29, 43, 202, and 387
Percentage of subjects achieving serum HAI antibody titers of 1:40 or greater against the A/H5N8 antigen contained in the study vaccine
Time frame: Day 1, 8, 22, 29, 43, 202, and 387
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AS03, MF59 and Monovalent Influenza A/H5N8 vaccine in people with Avian Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Geometric Mean Titers of Neut antibodies against the A/H5N8 antigen contained in the study vaccine (time frame: Day 43). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.