Clinical trial NCT02207413: 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
Official title: Safety and Immunogenicity Study of GSK Biologicals' Quadrivalent Influenza Candidate Vaccine (GSK23211381A) Manufactured With a New Process in Adults and Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Quadrivalent influenza vaccine
Safety
Children
Adults
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-08-04
Enrollment: 1886
Sex: ALL
Minimum age (years): 6
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Number of Subjects Aged 18-49 Years Reporting Solicited Local Adverse Events (AEs).
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Aged 18-49 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Duration of Solicited Local and General AEs in Subjects Aged 18-49 Years.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Aged 18-49 Years Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
timeFrame: During the 3-day (Days 0-2) post-vaccination period
measure: Number of Subjects Aged 18-49 Years Reporting the Occurrence of Medically Attended Events (MAEs).
timeFrame: During the entire study period (approximately 21 days following vaccination)
measure: Number of Subjects Aged 3-17 Years Reporting Solicited Local Adverse Events (AEs).
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Aged 3-4 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Aged 5-17 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Duration of Solicited Local AEs in Subjects Aged 3-17 Years.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Duration of Solicited General AEs in Subjects Aged 3-4 Years.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Duration of Solicited General AEs in Subjects Aged 5-17 Years.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Aged 3-17 Years Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
timeFrame: During the 3-day (Days 0-2) post-vaccination period
measure: Number of Subjects Aged 3-17 Years Reporting the Occurrence of All Medically Attended Events (MAEs) .
timeFrame: During the entire study period (approximately 28 days (primed subjects) and 56 days (unprimed subjects) following vaccination
measure: Number of Subjects Aged 18-49 Years Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 21-day (Days 0-20) follow-up period after vaccination
measure: Number of Subjects Aged 3-17 Years Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
timeFrame: During the 28-day (Days 0-27) follow-up period after vaccination
measure: Number of Subjects Aged 6-35 Months Reporting Fever ≥38ºC Across Doses.
timeFrame: During 7 days (Days 0-6) post-vaccination
measure: Number of Subjects Aged 18-49 Years, Reporting Any and Related Serious Adverse Events (SAEs)
timeFrame: During the entire study period (approximately 21 days)
measure: Number of Subjects Aged 3-17 Years, Reporting Any and Related Serious Adverse Events (SAEs)
timeFrame: During the entire study period [approximately 28 days (primed subjects) and 56 days (unprimed subjects)]
measure: Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects Aged 3-17 Years by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Vaccine Strains.
timeFrame: At Day 28 post last vaccination
measure: Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects Aged 6-35 Months by Calculating Serum Antihaemagglutination (HA) Antibody Titers Against the 4 Vaccine Strains.
timeFrame: At Day 28 post last vaccination
Secondary outcomes:
measure: Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects Aged 18-49 Years by Calculating Serum Anti-haemagglutination (HA) Antibody Titers Against the 4 Vaccine Strains
timeFrame: At Day 0 and Day 21
measure: Number of Seroconverted Subjects Aged 18-49 Years for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 21
measure: Number of Subjects Aged 18-49 Years, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 0 and Day 21
measure: Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 18-49 Years.
timeFrame: At Day 21
measure: Number of Subjects Aged 5-17 Years Reporting Myalgia Across Doses.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects Aged 3-17 Years by Calculating Serum Anti-haemagglutination (HA) Antibody Titers Against the 4 Vaccine Strains
timeFrame: At Day 0 and Day 28 post last vaccination
measure: Number of Seroconverted Subjects Aged 3-17 Years for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 28 post last vaccination
measure: Number of Subjects Aged 3-17 Years, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 0 and Day 28 post last vaccination
measure: Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 3-17 Years.
timeFrame: At Day 28 post last vaccination
measure: Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibodies in Subjects Aged 6-35 Months by Calculating Serum Anti-haemagglutination (HA) Antibody Titers Against the 4 Vaccine Strains
timeFrame: At Day 0 and Day 28 post last vaccination
measure: Number of Seroconverted Subjects Aged 6-35 Months for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 28 post last vaccination
measure: Number of Subjects Aged 6-35 Months, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
timeFrame: At Day 0 and Day 28 post last vaccination
measure: Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 6-35 Months.
timeFrame: At Day 28 post last vaccination
measure: Number of Subjects Aged 6-35 Months Reporting Fever ≥38ºC After Dose 1 and After Dose 2.
timeFrame: During 7 days (Days 0-6) post-vaccination
measure: Number of Subjects Aged 6-35 Months Reporting Solicited Local Adverse Events (AEs).
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Aged 6 Months to <5 Years, Reporting Fever ≥38ºC (100.4°F) and >39.0°C (102.2ºF) Across Doses.
timeFrame: During the 2 days (Day 0-Day 1) post-vaccination period
measure: Number of Subjects Aged 6-35 Months Reporting Any, Grade 3 and Related Solicited General Symptoms.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Duration of Solicited Local AEs in Subjects Aged 6-35 Months.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Duration of Solicited General AEs in Subjects Aged 6-35 Months.
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Aged 6-35 Months Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
timeFrame: During a 3 day (Days 0-2) follow-up period after vaccination
measure: Number of Subjects Aged 6-35 Months Reporting the Occurrence of All Medically Attended Events (MAEs)
timeFrame: During the entire study period (approximately 28 days (primed subjects) and 56 days (unprimed subjects) following vaccination
measure: Number of Subjects Aged 6-35 Months Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
timeFrame: During the 28-day (Days 0-27) follow-up period after vaccination
measure: Number of Subjects Aged 6-35 Months, Reporting Any and Related Serious Adverse Events (SAEs)
timeFrame: During the entire study period [approximately 28 days (primed subjects) and 56 days (unprimed subjects)]
Other outcomes:
Locations:
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Warwick
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Dhaka
country: Bangladesh
facility: GSK Investigational Site
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Chlumec nad Cidlinou
country: Czechia
facility: GSK Investigational Site
city: Decin
country: Czechia
facility: GSK Investigational Site
city: Jindrichuv Hradec
country: Czechia
facility: GSK Investigational Site
city: Liberec
country: Czechia
facility: GSK Investigational Site
city: Lipnik nad Becvou
country: Czechia
facility: GSK Investigational Site
city: Nachod
country: Czechia
facility: GSK Investigational Site
city: Odolena voda
country: Czechia
facility: GSK Investigational Site
city: Ostrava - Poruba
country: Czechia
facility: GSK Investigational Site
city: Pardubice
country: Czechia
facility: GSK Investigational Site
city: Praha 6
country: Czechia
facility: GSK Investigational Site
city: Aix en Provence
country: France
facility: GSK Investigational Site
city: Dax
country: France
facility: GSK Investigational Site
city: Draguignan
country: France
facility: GSK Investigational Site
city: Essey les Nancy
country: France
facility: GSK Investigational Site
city: Le Havre
country: France
facility: GSK Investigational Site
city: Nantes cedex 2
country: France
facility: GSK Investigational Site
city: Nice
country: France
facility: GSK Investigational Site
city: Kehl
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Kirchheim
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Schoenau Am Koenigssee
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Detmold
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Goch
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Kleve-Materborn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Loehne
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Trier
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Radebeul
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Wurzen
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Flensburg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Neumuenster
country: Germany
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Debica
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Siemianowice Slaskie
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Antequera/Málaga
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.