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

NCT ID: NCT03275389

Last Updated: 2021-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 470 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-08
• Study Completion Date: 2020-03-26

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.

Conditions

Influenza, Human

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

D-SUIV Adjuvanted Group 1

Subjects received one dose of D-SUIV cH8/1N1+AS03 vaccine at Day 1, one dose of Placebo at Day 57 and one booster dose of D-SUIV cH5/1N1+AS03 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1+AS03

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 with Adjuvant System 03 (AS03) was administered intramuscularly (IM) in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1+AS03

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 with Adjuvant System 03 (AS03) was administered IM in the deltoid region of non-dominant arm.

Placebo

Intervention Type: BIOLOGICAL

1 dose of Phosphate Buffered Saline (PBS) was administered IM in the deltoid region of non-dominant arm.

D-SUIV Adjuvanted Group 2

Subjects received one dose of D-SUIV cH5/1N1+AS03 vaccine at Day 1, one dose of Placebo at Day 57 and one booster dose of D-SUIV cH8/1N1+AS03 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1+AS03

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 with Adjuvant System 03 (AS03) was administered intramuscularly (IM) in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1+AS03

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 with Adjuvant System 03 (AS03) was administered IM in the deltoid region of non-dominant arm.

Placebo

Intervention Type: BIOLOGICAL

1 dose of Phosphate Buffered Saline (PBS) was administered IM in the deltoid region of non-dominant arm.

D-SUIV Adjuvanted Group 3

Subjects received one dose of D-SUIV cH8/1N1+AS03 vaccine at Day 1, one dose D-SUIV cH5/1N1+AS03 vaccine at Day 57 and one booster dose of D-SUIV cH11/1N1+AS03 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1+AS03

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 with Adjuvant System 03 (AS03) was administered intramuscularly (IM) in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1+AS03

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 with Adjuvant System 03 (AS03) was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH11/1N1+AS03

Intervention Type: BIOLOGICAL

1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH11/1N1 with Adjuvant System 03 (AS03) was administered IM in the deltoid region of non-dominant arm.

D-SUIV Adjuvanted Group 4

Subjects received one dose of D-SUIV cH8/1N1+AS01 vaccine at Day 1, one dose of Placebo at Day 57 and one booster dose of D-SUIV cH5/1N1+AS01 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1+AS01

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1+AS01

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

Placebo

Intervention Type: BIOLOGICAL

1 dose of Phosphate Buffered Saline (PBS) was administered IM in the deltoid region of non-dominant arm.

D-SUIV Adjuvanted Group 5

Subjects received one dose of D-SUIV cH5/1N1+AS01 vaccine at Day 1, one dose of Placebo at Day 57 and one booster dose of D-SUIV cH8/1N1+AS01 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1+AS01

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1+AS01

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

Placebo

Intervention Type: BIOLOGICAL

1 dose of Phosphate Buffered Saline (PBS) was administered IM in the deltoid region of non-dominant arm.

D-SUIV Adjuvanted Group 6

Subjects received one dose of D-SUIV cH8/1N1+AS01 vaccine at Day 1, one dose of D-SUIV cH5/1N1+AS01 vaccine at Day 57 and one booster dose of D-SUIV cH11/1N1+AS01 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1+AS01

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1+AS01

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH11/1N1+AS01

Intervention Type: BIOLOGICAL

1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH11/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

D-SUIV Unadjuvanted Group 1

Subjects received one dose of D-SUIV cH8/1N1 vaccine at Day 1, one dose of Placebo at Day 57 and one booster dose of D-SUIV cH5/1N1 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

Placebo

Intervention Type: BIOLOGICAL

1 dose of Phosphate Buffered Saline (PBS) was administered IM in the deltoid region of non-dominant arm.

D-SUIV Unadjuvanted Group 2

Subjects received one dose of D-SUIV cH5/1N1 vaccine at Day 1, one dose of Placebo at Day 57 and one booster dose of D-SUIV cH8/1N1 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

Placebo

Intervention Type: BIOLOGICAL

1 dose of Phosphate Buffered Saline (PBS) was administered IM in the deltoid region of non-dominant arm.

D-SUIV Unadjuvanted Group 3

Subjects received one dose of D-SUIV cH8/1N1 vaccine at Day 1, one dose of D-SUIV cH5/1N1 vaccine at Day 57 and one booster dose of D-SUIV cH11/1N1 vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: EXPERIMENTAL

D-SUIV cH8/1N1

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH5/1N1

Intervention Type: BIOLOGICAL

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

D-SUIV cH11/1N1

Intervention Type: BIOLOGICAL

1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH11/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

IIV4 Group

Subjects received one dose of Fluarix Quadrivalent (IIV4) vaccine at Day 1, one dose of Placebo at Day 57 and one dose of Fluarix Quadrivalent vaccine at Month 14. All doses were administered intramuscularly in the non-dominant arm.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

1 dose of Phosphate Buffered Saline (PBS) was administered IM in the deltoid region of non-dominant arm.

Fluarix Quadrivalent

Intervention Type: BIOLOGICAL

1 Primary dose and 1 Booster dose was administered IM in the deltoid region of non-dominant arm.

Interventions

D-SUIV cH8/1N1+AS03

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 with Adjuvant System 03 (AS03) was administered intramuscularly (IM) in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

D-SUIV cH5/1N1+AS03

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 with Adjuvant System 03 (AS03) was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

D-SUIV cH11/1N1+AS03

1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH11/1N1 with Adjuvant System 03 (AS03) was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

D-SUIV cH8/1N1+AS01

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

D-SUIV cH5/1N1+AS01

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

D-SUIV cH11/1N1+AS01

1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH11/1N1 with Adjuvant System 01 (AS01) was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

D-SUIV cH8/1N1

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH8/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

D-SUIV cH5/1N1

1 Primary dose or 1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH5/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

D-SUIV cH11/1N1

1 Booster dose of Supraseasonal Universal Influenza Vaccine (Flu D-SUIV), chimeric strain cH11/1N1 without adjuvant was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

Placebo

1 dose of Phosphate Buffered Saline (PBS) was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

Fluarix Quadrivalent

1 Primary dose and 1 Booster dose was administered IM in the deltoid region of non-dominant arm.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

South Miami, Florida, United States

GSK Investigational Site

Wichita, Kansas, United States

GSK Investigational Site

Rochester, New York, United States

GSK Investigational Site

Austin, Texas, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Wilrijk, , Belgium

Countries

United States; Belgium

References

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.

Reference Type: DERIVED

PMID: 35461522 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001584-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

207543

Identifier Type: -

Identifier Source: org_study_id