A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Candidate Vaccine (GSK2321138A) Manufactured Using a New Process in Adults and Children

NCT ID: NCT02207413

Last Updated: 2018-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1886 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-18
• Study Completion Date: 2015-04-18

Brief Summary

The purpose of this trial is to demonstrate the acceptable safety profile and the immunological non-inferiority of the FLU D-QIV vaccine manufactured with this investigational process (FLU D-QIV Investigational Process [IP]) compared to FLU D-QIV manufactured with the current licensed process (FLU D-QIV Licensed Process [LP]).

Detailed Description

This study will enroll 3 age cohorts:

Adults: 18-49 years, Children: 3-17 years and 6-35 months of age.

Conditions

Influenza

Study Design

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

Study Groups

Influsplit Tetra_IP Adult Group

Subjects in the Influsplit Tetra\_IP group aged between 18 to 49 years received 1 dose of Influsplit Tetra™ vaccine produced by investigational process (IP) at Day 0. Influsplit Tetra™ vaccine produced by IP was administered intramuscularly in the deltoid region of left or non-dominant arm.

Group Type: EXPERIMENTAL

Influsplit Tetra™ vaccine produced by investigational process (IP)

Intervention Type: BIOLOGICAL

Influsplit Tetra™ vaccine using a new manufacturing process administered intramuscularly (IM) in the deltoid region of non-dominant arm (Dose 1) in Adults Group and in non-dominant deltoid or left anterolateral thigh (Dose 1) and dominant deltoid or right anterolateral (Dose 2 - unprimed subjects) in 6-35m and 3-17y Groups.

Influsplit Tetra_LP Adult Group

Subjects in the Influsplit Tetra\_LP aged between 18 to 49 years received 1 dose of Influsplit Tetra™ vaccine produced by currently licensed process (LP) at Day 0. Influsplit Tetra™ vaccine produced by currently LP was administered intramuscularly in the deltoid region of left or non-dominant arm.

Group Type: ACTIVE_COMPARATOR

Influsplit Tetra™ vaccine produced by licensed process (LP)

Intervention Type: BIOLOGICAL

Influsplit Tetra™ vaccine using a licensed manufacturing process administered IM in the deltoid region of non-dominant arm (Dose 1) in Adults Group and in non-dominant deltoid or left anterolateral thigh (Dose 1) and dominant deltoid or right anterolateral (Dose 2 - unprimed subjects) in 6-35m and 3-17y Groups.

Influsplit Tetra_IP 3-17y Group

Subjects in the Influsplit Tetra\_IP group aged between 3 years to \<9 years received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Influsplit Tetra™ vaccine produced by investigational process (IP). Subjects aged 9-17 years received only 1 dose of Influsplit Tetra™ vaccine produced by IP at Day 0. Influsplit Tetra™ vaccine produced by IP was administered intramuscularly in the deltoid region of left or non-dominant arm (Day 0) and in the deltoid region of right or dominant arm (Day 28).

Group Type: EXPERIMENTAL

Influsplit Tetra™ vaccine produced by investigational process (IP)

Intervention Type: BIOLOGICAL

Influsplit Tetra™ vaccine using a new manufacturing process administered intramuscularly (IM) in the deltoid region of non-dominant arm (Dose 1) in Adults Group and in non-dominant deltoid or left anterolateral thigh (Dose 1) and dominant deltoid or right anterolateral (Dose 2 - unprimed subjects) in 6-35m and 3-17y Groups.

Influsplit Tetra_LP 3-17y Group

Subjects in the Influsplit Tetra\_LP group aged between 3 years to \<9 years received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Influsplit Tetra™ vaccine produced by licensed process (LP). Subjects aged 9-17 years received only 1 dose of Influsplit Tetra™ vaccine produced by LP at Day 0. Influsplit Tetra™ vaccine produced by LP was administered intramuscularly in the deltoid region of left or non-dominant arm (Day 0) and in the deltoid region of right or dominant arm (Day 28).

Group Type: ACTIVE_COMPARATOR

Influsplit Tetra™ vaccine produced by licensed process (LP)

Intervention Type: BIOLOGICAL

Influsplit Tetra™ vaccine using a licensed manufacturing process administered IM in the deltoid region of non-dominant arm (Dose 1) in Adults Group and in non-dominant deltoid or left anterolateral thigh (Dose 1) and dominant deltoid or right anterolateral (Dose 2 - unprimed subjects) in 6-35m and 3-17y Groups.

Influsplit Tetra_IP 6-35m Group

Subjects in the Influsplit Tetra\_IP group aged between 6 months to 35 months received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Influsplit Tetra™ vaccine produced by investigational process (IP). Influsplit Tetra™ vaccine produced by IP was administered intramuscularly the anterolateral region of left thigh for subjects below 12 months of age and in the deltoid region of left or non-dominant arm in subjects ≥ 12 months of age (Day 0) and in the anterolateral region of right thigh for subjects below 12 months of age and in the deltoid region of right or dominant arm in subjects ≥ 12 months of age (Day 28).

Group Type: EXPERIMENTAL

Influsplit Tetra™ vaccine produced by investigational process (IP)

Intervention Type: BIOLOGICAL

Influsplit Tetra™ vaccine using a new manufacturing process administered intramuscularly (IM) in the deltoid region of non-dominant arm (Dose 1) in Adults Group and in non-dominant deltoid or left anterolateral thigh (Dose 1) and dominant deltoid or right anterolateral (Dose 2 - unprimed subjects) in 6-35m and 3-17y Groups.

Influsplit Tetra_LP 6-35m Group

Subjects in the Influsplit Tetra\_LP group aged between 6 months to 35 months received 1 dose (primed subjects) at Day 0 and 2 doses (unprimed subjects) at Days 0 and 28 of Influsplit Tetra™ vaccine produced by licensed process (LP). Influsplit Tetra™ vaccine produced by LP was administered intramuscularly the anterolateral region of left thigh for subjects below 12 months of age and in the deltoid region of left or non-dominant arm in subjects ≥ 12 months of age (Day 0) and in the anterolateral region of right thigh for subjects below 12 months of age and in the deltoid region of right or dominant arm in subjects ≥ 12 months of age (Day 28).

Group Type: ACTIVE_COMPARATOR

Influsplit Tetra™ vaccine produced by licensed process (LP)

Intervention Type: BIOLOGICAL

Influsplit Tetra™ vaccine using a licensed manufacturing process administered IM in the deltoid region of non-dominant arm (Dose 1) in Adults Group and in non-dominant deltoid or left anterolateral thigh (Dose 1) and dominant deltoid or right anterolateral (Dose 2 - unprimed subjects) in 6-35m and 3-17y Groups.

Interventions

Influsplit Tetra™ vaccine produced by investigational process (IP)

Influsplit Tetra™ vaccine using a new manufacturing process administered intramuscularly (IM) in the deltoid region of non-dominant arm (Dose 1) in Adults Group and in non-dominant deltoid or left anterolateral thigh (Dose 1) and dominant deltoid or right anterolateral (Dose 2 - unprimed subjects) in 6-35m and 3-17y Groups.

Intervention Type: BIOLOGICAL

Influsplit Tetra™ vaccine produced by licensed process (LP)

Influsplit Tetra™ vaccine using a licensed manufacturing process administered IM in the deltoid region of non-dominant arm (Dose 1) in Adults Group and in non-dominant deltoid or left anterolateral thigh (Dose 1) and dominant deltoid or right anterolateral (Dose 2 - unprimed subjects) in 6-35m and 3-17y Groups.

Intervention Type: BIOLOGICAL

Other Intervention Names

Fluarix Tetra™; Fluarix Quadrivalent® (GSK2321138A); Fluarix Tetra™; Fluarix Quadrivalent® (GSK2321138A)

Eligibility Criteria

Inclusion Criteria

Adults 18-49 years cohort:

• A male or female between, and including, 18 and 49 years of age at the time of vaccination.
• Subjects who the investigator believes that they/their parent(s)/Legally Acceptable Representatives (LAR(s)) can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject/parent(s)/LAR(s) of the subject.
• Written informed assent obtained from the subject if/as required by local regulations.
• Healthy subjects or those with chronic well-controlled disease as established by medical history and clinical examination before entering into the study.
• Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy.
• Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception for 2 months after vaccination.

Pediatric cohort:

United States:

• A male or female subject between, and including, the ages of 3 and 17 years in the United States.

Rest of the World:

• A male or female subject between, and including, the ages of 6 months to 17 years all countries with the exception of the United States.

All participating countries:

• Subjects who the investigator believes that they/their parent(s)/Legally Acceptable Representatives (LAR(s)) can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject/parent(s)/LAR(s) of the subject.
• Written informed assent obtained from the subject if/as required by local regulations.
• Healthy subjects or those with chronic well-controlled disease as established by medical history and clinical examination before entering into the study.
• Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy.
• Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to 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.

Exclusion Criteria

Adults aged 18-49 years cohort:

• Child in care.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• 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 product (pharmaceutical or device).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose. Inhaled and topical steroids are allowed.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
• Any administration of a long-acting immune-modifying drug within 6 months before study start, or planned administration during the study period.
• Administration of an influenza vaccine during the 6 months preceding entry into the study.
• Administration of a vaccine not foreseen by the study protocol within 30 days before vaccination or planned administration during the study period.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
• Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
• Acute or un-controlled, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests.
• Any history of Guillain-Barré Syndrome.
• Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 38.0ºC/100.4ºF.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• History of chronic alcohol consumption and/or drug abuse.
• Any contra-indication to intramuscular administration of influenza vaccines.
• Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.

Pediatric cohort

• Child in care.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• 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 product (pharmaceutical or device).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccination dose. Inhaled and topical steroids are allowed.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
• Any administration of a long-acting immune-modifying drug within 6 months before study start, or planned administration during the study period.
• Administration of an influenza vaccine during the 6 months preceding entry into the study.
• Administration of a vaccine not foreseen by the study protocol within 30 days before vaccination or planned administration during the study period.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
• Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
• Acute or un-controlled, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests.
• Any history of Guillain-Barré Syndrome.
• Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 38.0ºC/100.4ºF.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• History of chronic alcohol consumption and/or drug abuse.
• Any contra-indication to intramuscular administration of influenza vaccines.
• Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 49 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

Wichita, Kansas, United States

GSK Investigational Site

Rochester, New York, United States

GSK Investigational Site

Warwick, Rhode Island, United States

GSK Investigational Site

Nashville, Tennessee, United States

GSK Investigational Site

Dhaka, , Bangladesh

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Chlumec nad Cidlinou, , Czechia

GSK Investigational Site

Děčín, , Czechia

GSK Investigational Site

Jindřichův Hradec, , Czechia

GSK Investigational Site

Liberec, , Czechia

GSK Investigational Site

Lipník nad Bečvou, , Czechia

GSK Investigational Site

Náchod, , Czechia

GSK Investigational Site

Odolena Voda, , Czechia

GSK Investigational Site

Ostrava - Poruba, , Czechia

GSK Investigational Site

Pardubice, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Aix-en-Provence, , France

GSK Investigational Site

Dax, , France

GSK Investigational Site

Draguignan, , France

GSK Investigational Site

Essey-lès-Nancy, , France

GSK Investigational Site

Le Havre, , France

GSK Investigational Site

Nantes, , France

GSK Investigational Site

Nice, , France

GSK Investigational Site

Kehl, Baden-Wurttemberg, Germany

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, Germany

GSK Investigational Site

Kirchheim, Bavaria, Germany

GSK Investigational Site

Schönau am Königssee, Bavaria, Germany

GSK Investigational Site

Würzburg, Bavaria, Germany

GSK Investigational Site

Detmold, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Goch, North Rhine-Westphalia, Germany

GSK Investigational Site

Kleve-Materborn, North Rhine-Westphalia, Germany

GSK Investigational Site

Löhne, North Rhine-Westphalia, Germany

GSK Investigational Site

Trier, Rhineland-Palatinate, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Radebeul, Saxony, Germany

GSK Investigational Site

Wurzen, Saxony, Germany

GSK Investigational Site

Flensburg, Schleswig-Holstein, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Neumünster, , Germany

GSK Investigational Site

Bydgoszcz, , Poland

GSK Investigational Site

Dębica, , Poland

GSK Investigational Site

Katowice, , Poland

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Siemianowice Śląskie, , Poland

GSK Investigational Site

Wroclaw, , Poland

GSK Investigational Site

Antequera/Málaga, , Spain

GSK Investigational Site

Badalona, , Spain

GSK Investigational Site

Burgos, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Seville, , Spain

Countries

United States; Bangladesh; Czechia; France; Germany; Poland; Spain

References

Claeys C, Drame M, Garcia-Sicilia J, Zaman K, Carmona A, Tran PM, Miranda M, Martinon-Torres F, Thollot F, Horn M, Schwarz TF, Behre U, Merino JM, Sadowska-Krawczenko I, Szymanski H, Schu P, Neumeier E, Li P, Jain VK, Innis BL. Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults. BMC Infect Dis. 2018 Apr 18;18(1):186. doi: 10.1186/s12879-018-3079-8.

Reference Type: DERIVED

PMID: 29669531 (View on PubMed)

Other Identifiers

201251

Identifier Type: -

Identifier Source: org_study_id