Clinical trial NCT05875961: Study to Evaluate Immunogenicity, Safety and Tolerability of Adjuvanted and Non-Adjuvanted H2N3 Influenza Vaccines in Adults
Official title: A Phase 1, Randomized, Observer-Blind, Multi-Center, Dose Ranging Study to Evaluate the Immunogenicity, Safety and Tolerability of Different Formulations of an Adjuvanted or Non-Adjuvanted Cell Culture-derived A/H2N3 Subunit Influenza Virus Vaccine in Healthy Subjects 18 Years and Above
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza, Human
Infections
Respiratory Tract Infections
Virus Diseases
Infection Viral
Keywords: Influenza
Vaccine
MF59
Adjuvant
H2N3
Lead sponsor: Seqirus
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2023-05-25
Enrollment: 600
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 an equal ratio to one of the 6 different treatment groups (formulations) and will receive two doses of the allocated H2N3c vaccine (adjuvanted or non-adjuvanted) at 3 weeks apart, ie, at Day 1 and Day 22.
Primary purpose: PREVENTION

Brief summary: This Phase 1, randomized, observer-blind, dose-ranging clinical study is evaluating 6 different formulations of MF59-adjuvanted and non-adjuvanted H2N3 influenza vaccine. Approximately 600 healthy adult subjects are to be randomized into 1 of 6 possible treatment groups with 100 subjects per group, stratified by age group (born after or before 1968). Each subject will receive an influenza vaccine injection on Day 1 and Day 22. Subjects will be followed up for approximately 12 months after the second vaccine injection.

The primary immunogenicity analysis is based on the Day 1, Day 8, Day 22, Day 29, and Day 43 serology data. The primary safety analysis is based on solicited local and systemic adverse events (AEs) reported within 10 days after each vaccination, unsolicited AEs reported within 3 weeks after each vaccination, and serious AEs (SAEs), medically attended AEs (MAAEs), AEs leading to withdrawal from the study, and AEs of special interest (AESIs) reported throughout the study.


Eligibility criteria: Inclusion Criteria:

* Individuals of 18 years of age and older on the day of informed consent who were not born in 1968.
* Individuals who have voluntarily given written informed 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, at least 30 days prior to informed consent, which they intend to use for at least 2 months after the last study 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.
* A body mass index (BMI) ≥35 kg/m2.
* Progressive, unstable, or uncontrolled clinical conditions as per investigator's assessment. Subjects must be stable and unchanged for a minimum of 3 months.
* 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 of ≥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 adverse event of special interest (AESI).
* Received immunoglobulins with immunomodulating effects or any blood products within 180 days prior to informed consent.
* Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
* 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 subject 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 the study vaccines.
* 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 14 days from study vaccination.
* 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 homologous H2N3 strain - Day 1
timeFrame: Day 1
measure: GMT of HI antibodies against homologous H2N3 strain - Day 8
timeFrame: Day 8
measure: GMT of HI antibodies against homologous H2N3 strain Day 22
timeFrame: Day 22
measure: GMT of HI antibodies against homologous H2N3 strain - Day 29
timeFrame: Day 29
measure: GMT of HI antibodies against homologous H2N3 strain - Day 43
timeFrame: Day 43
measure: GMT of microneutralization (MN) antibodies against homologous H2N3 strain - Day 1
timeFrame: Day 1
measure: GMT of MN antibodies against homologous H2N3 strain - Day 8
timeFrame: Day 8
measure: GMT of MN antibodies against homologous H2N3 strain - Day 22
timeFrame: Day 22
measure: GMT of MN antibodies against homologous H2N3 strain - Day 29
timeFrame: Day 29
measure: GMT of MN antibodies against homologous H2N3 strain - Day 43
timeFrame: Day 43
measure: Geometric mean fold increase (GMFI) of HI antibodies against homologous H2N3 strain - Day 8
timeFrame: Day 8
measure: GMFI of HI antibodies against homologous H2N3 strain - Day 22
timeFrame: Day 22
measure: GMFI of HI antibodies against homologous H2N3 strain - Day 29
timeFrame: Day 29
measure: GMFI of HI antibodies against homologous H2N3 strain - Day 43
timeFrame: Day 43
measure: GMFI of MN antibodies against homologous H2N3 strain - Day 8
timeFrame: Day 8
measure: GMFI of MN antibodies against homologous H2N3 strain - Day 22
timeFrame: Day 22
measure: GMFI of MN antibodies against homologous H2N3 strain - Day 29
timeFrame: Day 29
measure: GMFI of MN antibodies against homologous H2N3 strain - Day 43
timeFrame: Day 43
measure: Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 1
timeFrame: Day 1
measure: Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 8
timeFrame: Day 8
measure: Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 22
timeFrame: Day 22
measure: Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 29
timeFrame: Day 29
measure: Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 43
timeFrame: Day 43
measure: Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 1
timeFrame: Day 1
measure: Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 8
timeFrame: Day 8
measure: Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 22
timeFrame: Day 22
measure: Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 29
timeFrame: Day 29
measure: Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 43
timeFrame: Day 43
measure: Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 8
timeFrame: Day 8
measure: Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 22
timeFrame: Day 22
measure: Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 29
timeFrame: Day 29
measure: Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 43
timeFrame: Day 43
measure: Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 8
timeFrame: Day 8
measure: Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 22
timeFrame: Day 22
measure: Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 29
timeFrame: Day 29
measure: Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 43
timeFrame: Day 43
measure: Number and percentages of subjects reporting solicited local and systemic adverse events (AEs) - Day 1 through Day 10
timeFrame: Day 1 through Day 10
measure: Number and percentages of subjects reporting solicited local and systemic AEs - Day 22 through Day 31
timeFrame: Day 22 through Day 31
measure: Number and percentage of subjects reporting any unsolicited AEs
timeFrame: Day 1 through Day 43
measure: Number and percentage of subjects reporting serious AEs (SAEs), AEs leading to withdrawal, AEs of special interest (AESI) and medically attended AEs (MAAEs)
timeFrame: Day 1 through Day 387
Secondary outcomes:
measure: GMT of ELLA titers as a measure of anti-neuraminidase (NA) immunogenicity
timeFrame: Day 1, Day 8, Day 22, Day 29, Day 43
measure: GMFI of ELLA titers as a measure of anti-NA immunogenicity
timeFrame: Day 8, Day 22, Day 29, Day 43
measure: Percentage of subjects with ≥4-fold increase in ELLA titer as a measure of anti-NA immunogenicity
timeFrame: Day 8, Day 22, Day 29, Day 43
measure: GMT of HI antibodies against homologous H2N3 strain - Persistence
timeFrame: Day 202, Day 387
measure: GMT of MN antibodies against homologous H2N3 strain - Persistence
timeFrame: Day 202, Day 387
measure: GMT of ELLA titer as a measure of anti-NA immunogenicity- Persistence
timeFrame: Day 202, Day 387
measure: GMFI of HI antibodies against homologous H2N3 strain - Persistence
timeFrame: Day 202, Day 387
measure: GMFI of MN antibodies against homologous H2N3 strain - Persistence
timeFrame: Day 202, Day 387
measure: GMFI of ELLA titer as a measure of anti-NA immunogenicity- Persistence
timeFrame: Day 202, Day 387
measure: Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Persistence
timeFrame: Day 202, Day 387
measure: Percentages of subjects with MN titers ≥1:40, ≥1:80 and ≥1:160 against homologous H2N3 strain - Persistence
timeFrame: Day 202, Day 387
measure: Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Persistence
timeFrame: Day 202, Day 387
measure: Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Persistence
timeFrame: Day 202, Day 387
measure: Percentage of subjects with ≥4-fold increase in ELLA titer as a measure of anti-NA immunogenicity - Persistence
timeFrame: Day 202, Day 387
Other outcomes:
Locations:
city: Rockville
country: United States
facility: Meridian Clinical Research
state: Maryland
city: Lincoln
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Iloilo City
country: Philippines
facility: West Visayas State University Medical Center
city: Manila
country: Philippines
facility: Manila Doctors Hospital
city: Quezon City
country: Philippines
facility: Quirino Memorial Medical Center
city: Silang
country: Philippines
facility: Silang Specialists Medical Center
Study officials:
affiliation: Seqirus
name: Clinical Science and Strategy
role: STUDY_CHAIR
References: