Clinical trial NCT05874713: Study to Evaluate Safety and Immunogenicity of Different Priming and Booster Regimens With Adjuvanted H5N8 and/or H5N6 Influenza Vaccine in Adults
Official title: A Phase 2, Multi-Center, Randomized, Observer-Blind Study, to Evaluate Safety and Immunogenicity of Homologous or Heterologous Priming and Booster Vaccinations With H5N8 or H5N6 MF59-adjuvanted, Cell Culture-derived Influenza Vaccine in Healthy Subjects ≥18 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza, Human
Infections
Respiratory Tract Infections
Virus Diseases
Infection Viral
Keywords: Influenza
Vaccine
MF59
Adjuvant
H5N8
H5N6
Pandemic
Avian
Lead sponsor: Seqirus
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2023-05-25
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible subjects are randomized in a 2:1:1 ratio to Treatment Arm A, B, or C, respectively, and will receive two priming doses of the allocated aH5N8c/aH5N6c vaccine 3 weeks apart, ie, at Day 1 and Day 22, and a booster dose of aH5N8c vaccine at Day 202.
Primary purpose: PREVENTION

Brief summary: This Phase 2, randomized, observer-blind clinical study is evaluating 3 different priming and booster regimens with MF59-adjuvanted H5N8 and/or H5N6 cell culture-derived influenza vaccine (aH5N8c; aH5N6c). Approximately 480 healthy adult subjects are to be randomized into 1 of 3 possible treatment groups, stratified by age group (18-64 years and ≥65 years) and by poultry worker status (yes/no). Each subject will receive a priming influenza vaccine injection on Day 1 and Day 22 and a booster vaccination on Day 202. Subjects will be followed up for approximately 6 months after the booster injection.

The primary immunogenicity analysis is based on antibody responses against H5N8 and H5N6 as measured by hemagglutination inhibition (HI) assay on Day 1, Day 22, Day 29, Day 43, Day 202, Day 209 (H5N8 only), and Day 223.


Eligibility criteria: Inclusion Criteria:

* Individuals of ≥18 years of age on the day of informed consent.
* Individuals who or whose legally acceptable representative(s) have voluntarily given written consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
* Individuals who can comply with study procedures including follow-up.
* Males, females of non-childbearing potential or females of childbearing potential who are using an effective birth control method which they intend to use for at least 30 days before the first study vaccination and plan to do so until 2 months after the last study vaccination.
* Individuals must provide a baseline blood sample prior to randomization and vaccination.

Exclusion Criteria:

* Females of childbearing potential who are pregnant, lactating, or who have not adhered to a specified set of contraceptive methods from at least 30 days prior to study entry and who do not plan to do so until 2 months after the last study vaccination.
* Progressive, unstable or uncontrolled clinical conditions.
* Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
* Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
* Abnormal function of the immune system resulting from:

  1. Clinical conditions.
  2. Systemic administration of corticosteroids at a dose ≥20 mg/day of prednisone (or equivalent) for more than 14 consecutive days within 90 days prior to informed consent. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted.
  3. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent.
* History of any medical condition considered an AESI.
* Received immunoglobulins with immunomodulating effects or any blood products within 180 days prior to informed consent.
* Individuals who previously received an H5 influenza vaccine or have a known history of H5 influenza infection prior to enrollment.
* Received an investigational or non-registered medicinal product within 30 days prior to informed consent or are unwilling to refuse participation in another clinical study at any time during the conduct of this study.
* Study personnel or immediate family or household member of study personnel.
* Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the individual due to participation in the study.
* Individuals who received any other vaccines (with the exception of COVID-19 vaccines) within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 28 days from any of the 3 scheduled study vaccinations.
* Receipt of any (investigational or licensed) COVID-19 vaccine within 14 days (non-replicating vaccines) or 28 days (replicating vaccines) prior to enrollment or plan to receive any COVID-19 vaccine within 7 days from any of the 3 scheduled study vaccinations.
* A known history of Guillain-Barre Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis.

Primary outcomes:
measure: Geometric mean titer (GMT) of hemagglutination inhibition (HI) antibodies against H5N8 strain - Day 1
timeFrame: Day 1
measure: GMT of HI antibodies against H5N8 strain - Day 22
timeFrame: Day 22
measure: GMT of HI antibodies against H5N8 strain - Day 43
timeFrame: Day 43
measure: GMT of HI antibodies against H5N8 strain - Day 202
timeFrame: Day 202
measure: GMT of HI antibodies against H5N8 strain - Day 209
timeFrame: Day 209
measure: GMT of HI antibodies against H5N8 strain - Day 223
timeFrame: Day 223
measure: GMT of HI antibodies against H5N6 strain - Day 1
timeFrame: Day 1
measure: GMT of HI antibodies against H5N6 strain - Day 22
timeFrame: Day 22
measure: GMT of HI antibodies against H5N6 strain - Day 43
timeFrame: Day 43
measure: GMT of HI antibodies against H5N6 strain - Day 202
timeFrame: Day 202
measure: GMT of HI antibodies against H5N6 strain - Day 223
timeFrame: Day 223
measure: Geometric mean fold increase (GMFI) of HI antibodies against H5N8 strain - Day 22
timeFrame: Day 22
measure: GMFI of HI antibodies against H5N8 strain - Day 43
timeFrame: Day 43
measure: GMFI of HI antibodies against H5N8 strain - Day 209
timeFrame: Day 209
measure: GMFI of HI antibodies against H5N8 strain - Day 223
timeFrame: Day 223
measure: GMFI of HI antibodies against H5N6 strain - Day 22
timeFrame: Day 22
measure: GMFI of HI antibodies against H5N6 strain - Day 43
timeFrame: Day 43
measure: GMFI of HI antibodies against H5N6 strain - Day 223
timeFrame: Day 223
measure: Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 1
timeFrame: Day 1
measure: Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 22
timeFrame: Day 22
measure: Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 43
timeFrame: Day 43
measure: Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 209
timeFrame: Day 209
measure: Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 223
timeFrame: Day 223
measure: Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Day 1
timeFrame: Day 1
measure: Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Day 22
timeFrame: Day 22
measure: Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Day 43
timeFrame: Day 43
measure: Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Day 223
timeFrame: Day 223
measure: Percentages of subjects with seroconversion by HI against H5N8 strain - Day 22
timeFrame: Day 22
measure: Percentages of subjects with seroconversion by HI against H5N8 strain - Day 43
timeFrame: Day 43
measure: Percentages of subjects with seroconversion by HI against H5N8 strain - Day 209
timeFrame: Day 209
measure: Percentages of subjects with seroconversion by HI against H5N8 strain - Day 223
timeFrame: Day 223
measure: Percentages of subjects with seroconversion by HI against H5N6 strain - Day 22
timeFrame: Day 22
measure: Percentages of subjects with seroconversion by HI against H5N6 strain - Day 43
timeFrame: Day 43
measure: Percentages of subjects with seroconversion by HI against H5N6 strain - Day 223
timeFrame: Day 223
Secondary outcomes:
measure: Frequency and severity of solicited local and systemic adverse events (AEs)
timeFrame: Day 1 through Day 7, Day 22 through Day 28, and Day 202 through 208
measure: Frequency and severity of unsolicited AEs
timeFrame: Day 1 through Day 43 and Day 202 through Day 223
measure: Frequency and severity of serious AEs (SAEs), AEs leading to withdrawal, AEs of special interest (AESI), and medically attended AEs (MAAEs)
timeFrame: Day 1 through Day 382
measure: GMT of HI antibodies against H5N8 strain - Persistence
timeFrame: Day 202, Day 382
measure: GMT of HI antibodies against H5N6 strain - Persistence
timeFrame: Day 202
measure: GMFI of HI antibodies against H5N8 strain - Persistence
timeFrame: Day 202, Day 382
measure: GMFI of HI antibodies against H5N6 strain - Persistence
timeFrame: Day 202
measure: Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Persistence
timeFrame: Day 202, Day 382
measure: Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Persistence
timeFrame: Day 202
measure: Percentages of subjects with seroconversion by HI against H5N8 strain - Persistence
timeFrame: Day 202, Day 382
measure: Percentages of subjects with seroconversion by HI against H5N6 strain - Persistence
timeFrame: Day 202
measure: GMT of microneutralization (MN) antibodies against H5N8 strain
timeFrame: Day 1, Day 22, Day 43, Day 202, Day 223
measure: GMT of MN antibodies against H5N6 strain
timeFrame: Day 1, Day 43, Day 202, Day 223
measure: GMFI of MN antibodies against H5N8 strain
timeFrame: Day 22, Day 43, Day 202, Day 223
measure: GMFI of MN antibodies against H5N6 strain
timeFrame: Day 43, Day 202, Day 223
measure: Percentages of subjects with MN titers ≥1:40 against H5N8 strain
timeFrame: Day 1, Day 22, Day 43, Day 202, Day 223
measure: Percentages of subjects with MN titers ≥1:40 against H5N6 strain
timeFrame: Day 1, Day 43, Day 202, Day 223
measure: Percentages of subjects with seroconversion by MN against H5N8 strain
timeFrame: Day 22, Day 43, Day 202, Day 209, Day 223
measure: Percentages of subjects with seroconversion by MN against H5N6 strain
timeFrame: Day 43, Day 202, Day 209, Day 223
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Cullman Clinical Trials
state: Alabama
city: Lilburn
country: United States
facility: Lifeline Primary Care
state: Georgia
city: Norcross
country: United States
facility: Georgia Clinic
state: Georgia
city: Sioux City
country: United States
facility: Velocity Clinical Research
state: Iowa
city: Baton Rouge
country: United States
facility: Velocity Clinical Research
state: Louisiana
city: Grand Island
country: United States
facility: Velocity Clinical Research
state: Nebraska
city: Norfolk
country: United States
facility: Velocity Clinical Research
state: Nebraska
city: Elizabethton
country: United States
facility: Medical Care LLC
state: Tennessee
city: Bountiful
country: United States
facility: Cope Family Medicine
state: Utah
Study officials:
affiliation: Seqirus
name: Therapeutic Area Head
role: STUDY_CHAIR
References: