Clinical trial NCT03275389: A Study to Evaluate the Reactogenicity, Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Investigational Supra-seasonal Universal Influenza Vaccines - Inactivated (SUIVs) (GSK3816302A) in Healthy Adults Aged 18 to 39 Years
Official title: Reactogenicity, Safety and Immunogenicity Study of GlaxoSmithKline (GSK) Biologicals' Investigational Supra-seasonal Universal Influenza Vaccines - Inactivated (SUIVs) (GSK3816302A) in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Influenza, Human
Keywords: Safety
Healthy adults
Immunogenicity
Supra-seasonal universal influenza vaccines - inactivated (SUIVs)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-09-07
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the reactogenicity, safety and immunogenicity of different formulations of GlaxoSmithKline (GSK) Biologicals' investigational supra-seasonal universal influenza vaccines (SUIVs) (unadjuvanted or adjuvanted) in 18 to 39 year-old healthy subjects. Subjects will be enrolled and vaccinated with one or 2 primary dose(s) followed by a booster dose one year later.

Detailed description: Current seasonal influenza vaccines show good efficacy when they are well-matched with the circulating virus strains.

However, influenza viruses constantly change their surface glycoproteins that are the targets of most immune responses, allowing them to escape pre-existing immunity, a process called antigenic drift. Therefore, seasonal influenza vaccines have to be reformulated and re-administered on an annual basis. In addition, novel viruses can appear at irregular intervals and cause influenza virus pandemics that can claim millions of lives.

GSK Biologicals is now developing a new influenza vaccine that contains modified inactivated influenza viruses. The purpose of this approach is to elicit an immune response that would protect against all current and future circulating influenza strains without having to administer the vaccine each year.

Eligibility criteria: Inclusion Criteria:

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written informed consent obtained from the subject prior to performance of any study specific procedure.
* A male or female between, and including, 18 and 39 years of age at the time of the first vaccination.
* Healthy subjects without acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as established by medical history and clinical examination before first vaccination and laboratory screening tests (the latter being only applicable for subjects enrolled in Phase I).
* Subjects with no history of influenza vaccination within 6 months prior to first study vaccination and who are willing to forego any influenza vaccination during the entire study period.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * Has practiced adequate contraception for 30 days prior to first vaccination, and
  * Has a negative pregnancy test on the day of vaccination, and
  * Has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series (last vaccination at Month 14).

Exclusion Criteria:

* Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines, or planned use during the study period.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
* Administration of long-acting immune-modifying drugs within 6 months before first vaccination, or planned administration any time during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose up to the blood sampling at Day 85 and in the period starting 30 days before booster vaccination at Month 14 up to the blood sample at Month 14 + 28 days.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
* Previous vaccination against influenza within the 6 months preceding the first vaccination at Visit 1 or planned use of such vaccines during the study period.
* History of vaccination with a (pre)pandemic influenza vaccine other than an H1N1pdm09 vaccine or history of laboratory-confirmed influenza infection other than seasonal or H1N1pdm09 influenza.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* History of or current autoimmune disease.
* Subjects diagnosed with excessive daytime sleepiness or narcolepsy; or history of narcolepsy in a subject's parent or sibling.
* History of Guillain-Barré syndrome.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
* Hypersensitivity to latex.
* Acute disease and/or fever at the time of enrolment.

  * Fever is defined as temperature ≥ 38.0°C / 100.4°F. The preferred location for measuring temperature in this study will be the oral cavity.
  * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
  * For subjects with acute disease and/or fever at the time of enrolment, Visit 1 may be re-scheduled within the allowed time-window.
* Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period.
* Blood donation within 30 days before the first study blood sampling or planned blood donation within 30 days before and up to 30 days after any study blood sampling.
* Pregnant or lactating female.
* History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.

Additional criterion applicable for Phase I subjects:

* Hematological and/or biochemical parameters outside the laboratory normal ranges, unless the laboratory abnormalities are considered not clinically significant by the investigator.
* Liver enzymes (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\]) outside of the normal laboratory ranges.

Primary outcomes:
measure: Number of Subjects With Solicited Local Adverse Events (AEs) After First Dose Administration
timeFrame: During the 7-day (Days 1-7) follow-up period after first vaccine dose
measure: Number of Subjects With Solicited Local AEs After Second Dose Administration
timeFrame: During the 7-day (Days 1-7) follow-up period after second vaccine dose
measure: Number of Subjects With Solicited Local AEs After Booster Dose Administration
timeFrame: During the 7-day (Days 1-7) follow-up period after booster vaccine dose
measure: Number of Subjects With Solicited General AEs After First Dose Administration
timeFrame: During the 7-day (Days 1-7) follow-up period after first vaccine dose
measure: Number of Subjects With Solicited General AEs After Second Dose Administration
timeFrame: During the 7-day (Days 1-7) follow-up period after second vaccine dose
measure: Number of Subjects With Solicited General AEs After Booster Dose Administration
timeFrame: During the 7-day (Days 1-7) follow-up period after booster vaccine dose
measure: Number of Subjects With Any Unsolicited AEs Post-vaccination Period
timeFrame: During the 28-day (Days 1-28) follow-up period accross doses
measure: Number of Subjects With Change From Baseline in Hematological and Biochemical Laboratory Results at Day 8 by Toxicity Grading
timeFrame: At Day 8
measure: Number of Subjects With Change in Hematological and Biochemical Laboratory Results From Day 8 to Day 29 Versus Baseline by Toxicity Grading
timeFrame: From Day 8 to Day 29
measure: Number of Subjects With Change in Hematological and Biochemical Laboratory Results From Day 8 to Day 85 Versus Baseline by Toxicity Grading
timeFrame: From Day 8 to Day 85
measure: Number of Subjects With Change in Hematological and Biochemical Laboratory Results From Day 8 to Month 14+28 Days Versus Baseline by Toxicity Grading
timeFrame: From Day 8 to Month 14 + 28 days
measure: Number of Subjects With Change in Hematological and Biochemical Laboratory Results From Day 8 to Month 26 Versus Baseline by Toxicity Grading
timeFrame: From Day 8 to Month 26
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs)
timeFrame: During the entire study period (from Day 1 up to Month 26)
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: During the entire study period (from Day 1 up to Month 26)
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: During the entire study period (from Day 1 up to Month 26)
measure: Number of Seropositive Subjects for Anti-H1 Stalk Antibodies Measured by Enzyme-linked Immunosorbent Assay (ELISA)- Day 1
timeFrame: At Day 1
measure: Number of Seropositive Subjects for Anti-H1 Stalk Antibodies Measured by ELISA- Day 29
timeFrame: At Day 29
measure: Number of Seropositive Subjects for Anti-H1 Stalk Antibodies Measured by ELISA- Day 85
timeFrame: At Day 85
measure: Concentrations of Serum H1 Stalk Antibodies Measured by ELISA- Day 1
timeFrame: At Day 1
measure: Concentrations of Serum H1 Stalk Antibodies Measured by ELISA- Day 29
timeFrame: At Day 29
measure: Concentrations of Serum H1 Stalk Antibodies Measured by ELISA- Day 85
timeFrame: At Day 85
measure: Number of Seropositive Subjects for Anti-H1 Stalk Antibodies Measured by Microneutralization (MN) Assay - Day 1
timeFrame: At Day 1
measure: Number of Seropositive Subjects for Anti-H1 Stalk Antibodies Measured by MN Assay - Day 29
timeFrame: At Day 29
measure: Number of Seropositive Subjects for Anti-H1 Stalk Antibodies Measured by MN Assay - Day 85
timeFrame: At Day 85
measure: Titers for Serum H1 Stalk Antibodies Measured by MN Assay - Day 1
timeFrame: At Day 1
measure: Titers for Serum H1 Stalk Antibodies Measured by MN Assay - Day 29
timeFrame: At Day 29
measure: Titers for Serum H1 Stalk Antibodies Measured by MN Assay - Day 85
timeFrame: At Day 85
measure: Percentage of Subjects With a ≥ 4-fold Increase of Anti-H1 Stalk Antibody Concentration Measured by ELISA - Day 29
timeFrame: At Day 29, compared to pre-vaccination at Day 1
measure: Percentage of Subjects With a ≥ 4-fold Increase of Anti-H1 Stalk Antibody Concentration Measured by ELISA - Day 85
timeFrame: At Day 85, compared to pre-vaccination at Day 1
measure: Percentage of Subjects With a ≥ 4-fold Increase of Anti-H1 Stalk Titer Measured by MN Assay - Day 29
timeFrame: At Day 29, compared to pre-vaccination at Day 1
measure: Percentage of Subjects With a ≥ 4-fold Increase of Anti-H1 Stalk Titer Measured by MN Assay - Day 85
timeFrame: At Day 85, compared to pre-vaccination at Day 1
measure: Percentage of Subjects With a ≥ 10-fold Increase of Anti-H1 Stalk Antibody Concentration Measured by ELISA - Day 29
timeFrame: At Day 29, compared to pre-vaccination at Day 1
measure: Percentage of Subjects With a ≥ 10-fold Increase of Anti-H1 Stalk Antibody Concentration Measured by ELISA - Day 85
timeFrame: At Day 85, compared to pre-vaccination at Day 1
measure: Percentage of Subjects With a ≥ 10-fold Increase of Anti-H1 Stalk Titer Measured by MN Assay - Day 29
timeFrame: At Day 29, compared to pre-vaccination at Day 1
measure: Percentage of Subjects With a ≥ 10-fold Increase of Anti-H1 Stalk Titer Measured by MN Assay - Day 85
timeFrame: At Day 85, compared to pre-vaccination at Day 1
measure: Mean Geometric Increase (MGI) for Anti-H1 Stalk Antibody Concentration Measured by ELISA - Day 29
timeFrame: At Day 29, compared to pre-vaccination at Day 1
measure: MGI for Anti-H1 Stalk Antibody Concentration Measured by ELISA - Day 85
timeFrame: At Day 85, compared to pre-vaccination at Day 1
measure: MGI for Anti-H1 Stalk Antibody Titer Measured by MN Assay - Day 29
timeFrame: At Day 29, compared to pre-vaccination at Day 1
measure: MGI for Anti-H1 Stalk Antibody Titer Measured by MN Assay - Day 85
timeFrame: At Day 85, compared to pre-vaccination at Day 1
Secondary outcomes:
measure: Adjusted GMCs for Anti-H1 HA Stalk Antibody Measured by ELISA
timeFrame: 28 days post priming dose(s) i.e. at Day 29 for 1 priming dose groups and at Day 85 for 2 priming doses groups
measure: Concentrations of Serum H1 Stalk Antibodies Measured by ELISA- Month 8 to 26
timeFrame: At Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26.
measure: Number of Seropositive Subjects for Anti-H1 Stalk Antibodies Measured by ELISA- Month 8 to 26
timeFrame: At Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26.
measure: Percentage of Subjects With a ≥ 4-fold Increase of Anti-H1 Stalk Antibody Concentration, Measured by ELISA - Month 8 to 26.
timeFrame: At Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26, compared to Day 1
measure: Percentage of Subjects With a ≥ 10-fold Increase of Anti-H1 Stalk Antibody Concentration, Measured by ELISA - Month 8 to 26.
timeFrame: At Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26, compared to Day 1
measure: MGI for Anti-H1 Stalk Antibody Measured by ELISA - Month 8 to 26
timeFrame: At Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26, compared to Day 1
measure: Concentrations of Anti-H2 and Anti-H18 Antibodies Measured by ELISA
timeFrame: At Days 1, 29, 85, Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26
measure: Number of Seropositive Subjects for Anti-H2 and Anti-H18 Antibodies Measured by ELISA
timeFrame: At Days 1, 29, 85, Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26
measure: Percentage of Subjects With a ≥ 4-fold Increase of Anti-H2 and Anti-H18 Antibody Concentration Measured by ELISA
timeFrame: At Day 29, at Day 85, Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26, compared to Day 1
measure: Percentage of Subjects With a ≥ 10-fold Increase of Anti-H2 and Anti-H18 Antibody Concentration Measured by ELISA
timeFrame: At Day 29, at Day 85, Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26, compared to Day 1
measure: MGI for Anti-H2 and Anti-H18 Antibodies Concentrations Measured by ELISA
timeFrame: At Day 29, at Day 85, Month 8, Month 14, Month 14 + 28 days, Month 20 and Month 26, compared to Day 1
measure: Titers for Anti-H1N1 Swine Influenza and Anti-IIV4-H1N1 Anti-bodies Measured by MN Assay
timeFrame: At Days 1, 29 and 85
measure: Number of Seropositive Subjects for Anti-H1N1 Swine Influenza and Anti-IIV4-H1N1 Antibodies Measured by MN Assay
timeFrame: At Days 1, 29 and 85
measure: Percentage of Subjects With a ≥ 4-fold Increase of Anti-H1N1 Swine Influenza and Anti-IIV4-H1N1 Antibody Titers Measured by MN Assay
timeFrame: At Day 29 and Day 85, compared to Day 1
measure: Percentage of Subjects With a ≥ 10-fold Increase of Anti-H1N1 Swine Influenza and Anti-IIV4-H1N1 Antibody Titers Measured by MN Assay
timeFrame: At Day 29 and Day 85, compared to Day 1
measure: MGI for Anti-H1N1 Swine Influenza and Anti-IIV4-H1N1 Antibodies Titers Measured by MN Assay
timeFrame: At Day 29 and at Day 85, compared to Day 1
Other outcomes:
Locations:
city: South Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Wilrijk
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Folschweiller N, Vanden Abeele C, Chu L, Van Damme P, Garcia-Sastre A, Krammer F, Nachbagauer R, Palese P, Solorzano A, Bi D, David MP, Friel D, Innis BL, Koch J, Mallett CP, Rouxel RN, Salaun B, Vantomme V, Verheust C, Struyf F. Reactogenicity, safety, and immunogenicity of chimeric haemagglutinin influenza split-virion vaccines, adjuvanted with AS01 or AS03 or non-adjuvanted: a phase 1-2 randomised controlled trial. Lancet Infect Dis. 2022 Jul;22(7):1062-1075. doi: 10.1016/S1473-3099(22)00024-X. Epub 2022 Apr 21.