InfluenzaPhase 3NCT02207413
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
A Phase 3 study testing Influsplit Tetra™ vaccine produced by investigational process (IP) and Influsplit Tetra™ vaccine produced by licensed process (LP) in people with Influenza, run by GlaxoSmithKline at 53 sites in 7 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 months to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Influsplit Tetra™ vaccine produced by investigational process (IP) and Influsplit Tetra™ vaccine produced by licensed process (LP)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,886 participants
- Where
- 53 sitesin 7 countries
- Study dates
- 18 Aug 2014to 18 Apr 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 49 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
53 sites in 7 countries.
53 sites in 7 countries
Germany18 sites
GSK Investigational Site
Berlin, 13055
GSK Investigational Site
Detmold, North Rhine-Westphalia, 32756
GSK Investigational Site
Essen, North Rhine-Westphalia, 45355
GSK Investigational Site
Essen, North Rhine-Westphalia, 45359
GSK Investigational Site
Flensburg, Schleswig-Holstein, 24937
GSK Investigational Site
Goch, North Rhine-Westphalia, 47574
GSK Investigational Site
Kehl, Baden-Wurttemberg, 77694
GSK Investigational Site
Kirchheim, Bavaria, 85551
GSK Investigational Site
Kleve-Materborn, North Rhine-Westphalia, 47533
GSK Investigational Site
Leipzig, Saxony, 04178
GSK Investigational Site
Löhne, North Rhine-Westphalia, 32584
GSK Investigational Site
Neumünster, 24534
GSK Investigational Site
Radebeul, Saxony, 01445
GSK Investigational Site
Schönau am Königssee, Bavaria, 83471
GSK Investigational Site
Stuttgart, Baden-Wurttemberg, 70469
GSK Investigational Site
Trier, Rhineland-Palatinate, 54290
GSK Investigational Site
Würzburg, Bavaria, 97070
GSK Investigational Site
Wurzen, Saxony, 04808
Czechia11 sites
GSK Investigational Site
Brno, 613 00
GSK Investigational Site
Chlumec nad Cidlinou, 50351
GSK Investigational Site
Děčín, 405 01
GSK Investigational Site
Jindřichův Hradec, 37701
GSK Investigational Site
Liberec
GSK Investigational Site
Lipník nad Bečvou, 75131
GSK Investigational Site
Náchod, 547 01
GSK Investigational Site
Odolena Voda, 25070
GSK Investigational Site
Ostrava - Poruba, 70800
GSK Investigational Site
Pardubice, 532 03
GSK Investigational Site
Prague, 1600
France7 sites
GSK Investigational Site
Aix-en-Provence, 13100
GSK Investigational Site
Dax, 40100
GSK Investigational Site
Draguignan, 83300
GSK Investigational Site
Essey-lès-Nancy, 54270
GSK Investigational Site
Le Havre, 76620
GSK Investigational Site
Nantes, 44277
GSK Investigational Site
Nice, 06300
Poland6 sites
GSK Investigational Site
Bydgoszcz, 85-168
GSK Investigational Site
Dębica, 39-200
GSK Investigational Site
Katowice, 40-018
GSK Investigational Site
Poznan, 62-064
GSK Investigational Site
Siemianowice Śląskie, 41-103
GSK Investigational Site
Wroclaw, 54-019
Spain6 sites
GSK Investigational Site
Antequera/Málaga, 29200
GSK Investigational Site
Badalona, 08916
GSK Investigational Site
Burgos, 09006
GSK Investigational Site
Madrid, 28050
GSK Investigational Site
Santiago de Compostela, 15706
GSK Investigational Site
Seville, 41014
United States4 sites
GSK Investigational Site
Nashville, Tennessee, 37203
GSK Investigational Site
Rochester, New York, 14609
GSK Investigational Site
Warwick, Rhode Island, 02886
GSK Investigational Site
Wichita, Kansas, 67207
About this study
Official title: Safety and Immunogenicity Study of GSK Biologicals' Quadrivalent Influenza Candidate Vaccine (GSK23211381A) Manufactured With a New Process in Adults and Children
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]).
Read the 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
- Being tested
- Influsplit Tetra™ vaccine produced by investigational process (IP), Influsplit Tetra™ vaccine produced by licensed process (LP)
- Keywords
- Quadrivalent influenza vaccine, Safety, Children, Adults, Immunogenicity
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Influsplit Tetra™ vaccine produced by investigational process (IP)Biological
Also called Fluarix Tetra™, Fluarix Quadrivalent® (GSK2321138A)
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™ vaccine produced by licensed process (LP)Biological
Also called Fluarix Tetra™, Fluarix Quadrivalent® (GSK2321138A)
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.
| Study group | Role | What they receive |
|---|---|---|
| Influsplit Tetra_IP Adult Group | Experimental | 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. Receives: Biological: Influsplit Tetra™ vaccine produced by investigational process (IP) |
| Influsplit Tetra_LP Adult Group | Active comparator | 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. Receives: Biological: Influsplit Tetra™ vaccine produced by licensed process (LP) |
| Influsplit Tetra_IP 3-17y Group | Experimental | 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). Receives: Biological: Influsplit Tetra™ vaccine produced by investigational process (IP) |
| Influsplit Tetra_LP 3-17y Group | Active comparator | 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). Receives: Biological: Influsplit Tetra™ vaccine produced by licensed process (LP) |
| Influsplit Tetra_IP 6-35m Group | Experimental | 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). Receives: Biological: Influsplit Tetra™ vaccine produced by investigational process (IP) |
| Influsplit Tetra_LP 6-35m Group | Active comparator | 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). Receives: Biological: Influsplit Tetra™ vaccine produced by licensed process (LP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Aged 18-49 Years Reporting Solicited Local Adverse Events (AEs).
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = significant pain at rest and pain that prevented normal everyday activities. Grade 3 redness and swelling = greater than 100 millimeters (mm) i.e. >100mm.
Measured: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 18-49 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were fatigue,gastrointestinal symptoms, headache, Joint Pain, myalgia, shivering and fever. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 was defined as symptoms that prevented normal activities. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (< )38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever was defined as temperature ≥39.0°C.
Measured: During the 7-day (Days 0-6) post-vaccination period
Duration of Solicited Local and General AEs in Subjects Aged 18-49 Years.
Duration was defined as number of days with any grade of local and general symptoms.
Measured: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 18-49 Years Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
Oculorespiratory syndrome (ORS) was defined as the occurrence within 24 hours after vaccination of one or more of the following newly onset symptoms: bilateral red eyes, cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness, sore throat, facial swelling. Any was defined as any ORS symptom regardless of intensity grade or relationship to vaccination. Grade 3 ORS was defined as ORS symptoms that prevented normal activities. Related ORS was defined as ORS symptom(s) assessed by the investigator as causally related to the vaccination.
Measured: During the 3-day (Days 0-2) post-vaccination period
Number of Subjects Aged 18-49 Years Reporting the Occurrence of Medically Attended Events (MAEs).
MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). Grade 3 was defined as MAE that prevented normal activities. Related was defined as MAE assessed by the investigator to be causally related to the study vaccination.
Measured: During the entire study period (approximately 21 days following vaccination)
Number of Subjects Aged 3-17 Years Reporting Solicited Local Adverse Events (AEs).
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = Cried when limb was moved/spontaneously painful. Grade 3 redness and swelling = greater than 50 millimeters (mm) i.e. >50mm.
Measured: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 3-4 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were drowsiness, irritability/fussiness, loss of appetite and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (< )38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>) 39.0°C.
Measured: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 5-17 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, joint pain, myalgia, shivering and fever (Fever = temperature above 38.0 degrees Celsius (°C)). Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Any fever = all subjects with a documented temperature of ≥ 38°C/100.4°F by any route and all subjects reporting temperature < 38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever = temperature above 39.0°C.
Measured: During the 7-day (Days 0-6) post-vaccination period
Duration of Solicited Local AEs in Subjects Aged 3-17 Years.
Duration was defined as number of days with any grade of local symptoms.
Measured: During the 7-day (Days 0-6) post-vaccination period
Duration of Solicited General AEs in Subjects Aged 3-4 Years.
Duration was defined as number of days with any grade of general symptoms.
Measured: During the 7-day (Days 0-6) post-vaccination period
Duration of Solicited General AEs in Subjects Aged 5-17 Years.
Duration was defined as number of days with any grade of general symptoms.
Measured: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 3-17 Years Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
Oculorespiratory syndrome (ORS) was defined as the occurrence within 24 hours after vaccination of one or more of the following newly onset symptoms: bilateral red eyes, cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness, sore throat, facial swelling.
Any = occurrence of any ORS symptom regardless of intensity grade or relationship to vaccination. Grade 3 = ORS symptoms that prevented normal activities. Related = ORS symptom assessed by the investigator as causally related to the vaccination.
Measured: During the 3-day (Days 0-2) post-vaccination period
Number of Subjects Aged 3-17 Years Reporting the Occurrence of All Medically Attended Events (MAEs) .
MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). Grade 3 was a MAE that prevented normal activities. Related was defined as a MAE assessed by the investigator to be causally related to the study vaccination.
Measured: During the entire study period (approximately 28 days (primed subjects) and 56 days (unprimed subjects) following vaccination
Number of Subjects Aged 18-49 Years Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Measured: During the 21-day (Days 0-20) follow-up period after vaccination
Number of Subjects Aged 3-17 Years Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Measured: During the 28-day (Days 0-27) follow-up period after vaccination
Number of Subjects Aged 6-35 Months Reporting Fever ≥38ºC Across Doses.
Any fever = all subjects with a documented temperature of ≥ 38°C/100.4°F by any route and all subjects reporting temperature < 38°C but with missing values (MC) for at least one day during the solicited period.
Measured: During 7 days (Days 0-6) post-vaccination
Number of Subjects Aged 18-49 Years, Reporting Any and Related Serious Adverse Events (SAEs)
A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Measured: During the entire study period (approximately 21 days)
Number of Subjects Aged 3-17 Years, Reporting Any and Related Serious Adverse Events (SAEs)
A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Measured: During the entire study period [approximately 28 days (primed subjects) and 56 days (unprimed subjects)]
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.
HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), FluA/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 28 post last vaccination
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.
HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), FluA/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 28 post last vaccination
Secondary outcomes (23)
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
HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 0 and Day 21
Number of Seroconverted Subjects Aged 18-49 Years for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer.
The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 21
Number of Subjects Aged 18-49 Years, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults.
The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 0 and Day 21
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 18-49 Years.
MGI was defined as the fold increase in serum haemagglutination inhibition (HI) GMTs post-vaccination compared to pre-vaccination (Day 0).
The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 21
Number of Subjects Aged 5-17 Years Reporting Myalgia Across Doses.
Any = occurrence of any myalgia symptom regardless of intensity grade or relationship to vaccination.
Measured: During the 7-day (Days 0-6) post-vaccination period
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
HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 0 and Day 28 post last vaccination
Number of Seroconverted Subjects Aged 3-17 Years for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 28 post last vaccination
Number of Subjects Aged 3-17 Years, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 0 and Day 28 post last vaccination
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 3-17 Years.
MGI was defined as the fold increase in serum haemagglutination inhibition (HI) GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 28 post last vaccination
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
HI antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 0 and Day 28 post last vaccination
Number of Seroconverted Subjects Aged 6-35 Months for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 28 post last vaccination
Number of Subjects Aged 6-35 Months, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 0 and Day 28 post last vaccination
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 6-35 Months.
MGI was defined as the fold increase in serum haemagglutination inhibition (HI) GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
Measured: At Day 28 post last vaccination
Number of Subjects Aged 6-35 Months Reporting Fever ≥38ºC After Dose 1 and After Dose 2.
Any fever = all subjects with a documented temperature of ≥ 38°C/100.4°F by any route and all subjects reporting temperature < 38°C but with missing values (MC) for at least one day during the solicited period.
Fever = temperature of ≥ 38°C/100.4°F by any route
Measured: During 7 days (Days 0-6) post-vaccination
Number of Subjects Aged 6-35 Months Reporting Solicited Local Adverse Events (AEs).
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = significant pain at rest and pain that prevented normal everyday activities. Grade 3 redness and swelling = greater than 50 millimeters (mm) i.e. > 50mm.
Measured: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 6 Months to <5 Years, Reporting Fever ≥38ºC (100.4°F) and >39.0°C (102.2ºF) Across Doses.
Any fever = all subjects with a documented temperature of ≥ 38°C/100.4°F by any route and all subjects reporting temperature < 38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever = temperature above 39.0°C/102.2ºF.
Data of 2 independent groups were pooled.
Measured: During the 2 days (Day 0-Day 1) post-vaccination period
Number of Subjects Aged 6-35 Months Reporting Any, Grade 3 and Related Solicited General Symptoms.
Solicited general symptoms assessed were drowsiness, irritability/fussiness, loss of appetite and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (< )38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>)39.0°C.
Measured: During the 7-day (Days 0-6) post-vaccination period
Duration of Solicited Local AEs in Subjects Aged 6-35 Months.
Duration was defined as number of days with any grade of local symptoms.
Measured: During the 7-day (Days 0-6) post-vaccination period
Duration of Solicited General AEs in Subjects Aged 6-35 Months.
Duration was defined as number of days with any grade of general symptoms.
Measured: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 6-35 Months Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
Oculorespiratory syndrome (ORS) was defined as the occurrence within 24 hours after vaccination of one or more of the following newly onset symptoms: bilateral red eyes, cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness, sore throat, facial swelling. Any = occurrence of any ORS symptom regardless of intensity grade or relationship to vaccination. Grade 3 = ORS symptoms that prevented normal activities. Related = ORS symptom assessed by the investigator as causally related to the vaccination.
Measured: During a 3 day (Days 0-2) follow-up period after vaccination
Number of Subjects Aged 6-35 Months Reporting the Occurrence of All Medically Attended Events (MAEs)
MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). Grade 3 was a MAE that prevented normal activities. Related was defined as a MAE assessed by the investigator to be causally related to the study vaccination.
Measured: During the entire study period (approximately 28 days (primed subjects) and 56 days (unprimed subjects) following vaccination
Number of Subjects Aged 6-35 Months Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 unsolicited AE was defined as an event that prevented normal activity. Related unsolicited AE was defined as an event assessed by the investigator to be causally related to the study vaccination.
Measured: During the 28-day (Days 0-27) follow-up period after vaccination
Number of Subjects Aged 6-35 Months, Reporting Any and Related Serious Adverse Events (SAEs)
A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Measured: During the entire study period [approximately 28 days (primed subjects) and 56 days (unprimed subjects)]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2014 (estimated)
- Study start18 Aug 2014
- Primary completion18 Apr 2015
- Study completion18 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,886 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02207413
- Sponsor's protocol ID
- 201251
- Status last verified
- May 2018
- First submitted
- 24 Jul 2014
- Last updated
- 6 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 29669531
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Immunogenicity Study of GSK Biologicals' Quadrivalent Influenza Candidate Vaccine (GSK23211381A) Manufactured With a New Process in Adults and Children
- ClinicalTrials.gov ID
- NCT02207413
- Acronym / sponsor ID
- 201251
- Conditions
- Influenza
- Keywords
- Quadrivalent influenza vaccine, Safety, Children, Adults, Immunogenicity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,886 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 18 Aug 2014
- Primary completion
- 18 Apr 2015 (actual)
- Study completion
- 18 Apr 2015 (actual)
- First posted
- 4 Aug 2014 (estimated)
- Results
- Posted 20 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Influsplit Tetra_IP Adult Group | Experimental | Biological: Influsplit Tetra™ vaccine produced by investigational process (IP)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. |
| Influsplit Tetra_LP Adult Group | Active comparator | Biological: Influsplit Tetra™ vaccine produced by licensed process (LP)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. |
| Influsplit Tetra_IP 3-17y Group | Experimental | Biological: Influsplit Tetra™ vaccine produced by investigational process (IP)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). |
| Influsplit Tetra_LP 3-17y Group | Active comparator | Biological: Influsplit Tetra™ vaccine produced by licensed process (LP)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). |
| Influsplit Tetra_IP 6-35m Group | Experimental | Biological: Influsplit Tetra™ vaccine produced by investigational process (IP)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). |
| Influsplit Tetra_LP 6-35m Group | Active comparator | Biological: Influsplit Tetra™ vaccine produced by licensed process (LP)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). |
Who may qualify
- Ages
- 6 months to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (38 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Influsplit Tetra™ vaccine produced by investigational process (IP)Also: Fluarix Tetra™, Fluarix Quadrivalent® (GSK2321138A)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. | Biological | Influsplit Tetra_IP 3-17y Group, Influsplit Tetra_IP 6-35m Group, Influsplit Tetra_IP Adult Group |
| Influsplit Tetra™ vaccine produced by licensed process (LP)Also: Fluarix Tetra™, Fluarix Quadrivalent® (GSK2321138A)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. | Biological | Influsplit Tetra_LP 3-17y Group, Influsplit Tetra_LP 6-35m Group, Influsplit Tetra_LP Adult Group |
Primary outcome
Number of Subjects Aged 18-49 Years Reporting Solicited Local Adverse Events (AEs).
Time frame: During the 7-day (Days 0-6) post-vaccination period
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = significant pain at rest and pain that prevented normal everyday activities. Grade 3 redness and swelling = greater than 100 millimeters (mm) i.e. >100mm.
Number of Subjects Aged 18-49 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Solicited general symptoms assessed were fatigue,gastrointestinal symptoms, headache, Joint Pain, myalgia, shivering and fever. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 was defined as symptoms that prevented normal activities. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (< )38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever was defined as temperature ≥39.0°C.
Duration of Solicited Local and General AEs in Subjects Aged 18-49 Years.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Duration was defined as number of days with any grade of local and general symptoms.
Number of Subjects Aged 18-49 Years Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
Time frame: During the 3-day (Days 0-2) post-vaccination period
Oculorespiratory syndrome (ORS) was defined as the occurrence within 24 hours after vaccination of one or more of the following newly onset symptoms: bilateral red eyes, cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness, sore throat, facial swelling. Any was defined as any ORS symptom regardless of intensity grade or relationship to vaccination. Grade 3 ORS was defined as ORS symptoms that prevented normal activities. Related ORS was defined as ORS symptom(s) assessed by the investigator as causally related to the vaccination.
Number of Subjects Aged 18-49 Years Reporting the Occurrence of Medically Attended Events (MAEs).
Time frame: During the entire study period (approximately 21 days following vaccination)
MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). Grade 3 was defined as MAE that prevented normal activities. Related was defined as MAE assessed by the investigator to be causally related to the study vaccination.
Number of Subjects Aged 3-17 Years Reporting Solicited Local Adverse Events (AEs).
Time frame: During the 7-day (Days 0-6) post-vaccination period
Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = Cried when limb was moved/spontaneously painful. Grade 3 redness and swelling = greater than 50 millimeters (mm) i.e. >50mm.
Number of Subjects Aged 3-4 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Solicited general symptoms assessed were drowsiness, irritability/fussiness, loss of appetite and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (< )38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (>) 39.0°C.
Number of Subjects Aged 5-17 Years Reporting Any, Grade 3 and Related Solicited General Symptoms.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, joint pain, myalgia, shivering and fever (Fever = temperature above 38.0 degrees Celsius (°C)). Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Any fever = all subjects with a documented temperature of ≥ 38°C/100.4°F by any route and all subjects reporting temperature < 38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever = temperature above 39.0°C.
Duration of Solicited Local AEs in Subjects Aged 3-17 Years.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Duration was defined as number of days with any grade of local symptoms.
Duration of Solicited General AEs in Subjects Aged 3-4 Years.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Duration was defined as number of days with any grade of general symptoms.
Duration of Solicited General AEs in Subjects Aged 5-17 Years.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Duration was defined as number of days with any grade of general symptoms.
Number of Subjects Aged 3-17 Years Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
Time frame: During the 3-day (Days 0-2) post-vaccination period
Oculorespiratory syndrome (ORS) was defined as the occurrence within 24 hours after vaccination of one or more of the following newly onset symptoms: bilateral red eyes, cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness, sore throat, facial swelling. Any = occurrence of any ORS symptom regardless of intensity grade or relationship to vaccination. Grade 3 = ORS symptoms that prevented normal activities. Related = ORS symptom assessed by the investigator as causally related to the vaccination.
Number of Subjects Aged 3-17 Years Reporting the Occurrence of All Medically Attended Events (MAEs) .
Time frame: During the entire study period (approximately 28 days (primed subjects) and 56 days (unprimed subjects) following vaccination
MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). Grade 3 was a MAE that prevented normal activities. Related was defined as a MAE assessed by the investigator to be causally related to the study vaccination.
Number of Subjects Aged 18-49 Years Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
Time frame: During the 21-day (Days 0-20) follow-up period after vaccination
An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Aged 3-17 Years Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
Time frame: During the 28-day (Days 0-27) follow-up period after vaccination
An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.
Number of Subjects Aged 6-35 Months Reporting Fever ≥38ºC Across Doses.
Time frame: During 7 days (Days 0-6) post-vaccination
Any fever = all subjects with a documented temperature of ≥ 38°C/100.4°F by any route and all subjects reporting temperature < 38°C but with missing values (MC) for at least one day during the solicited period.
Number of Subjects Aged 18-49 Years, Reporting Any and Related Serious Adverse Events (SAEs)
Time frame: During the entire study period (approximately 21 days)
A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
Number of Subjects Aged 3-17 Years, Reporting Any and Related Serious Adverse Events (SAEs)
Time frame: During the entire study period [approximately 28 days (primed subjects) and 56 days (unprimed subjects)]
A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
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.
Time frame: At Day 28 post last vaccination
HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), FluA/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
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.
Time frame: At Day 28 post last vaccination
HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), FluA/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
23 secondary outcomes
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
Time frame: At Day 0 and Day 21
Number of Seroconverted Subjects Aged 18-49 Years for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
Time frame: At Day 21
Number of Subjects Aged 18-49 Years, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
Time frame: At Day 0 and Day 21
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 18-49 Years.
Time frame: At Day 21
Number of Subjects Aged 5-17 Years Reporting Myalgia Across Doses.
Time frame: During the 7-day (Days 0-6) post-vaccination period
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
Time frame: At Day 0 and Day 28 post last vaccination
Number of Seroconverted Subjects Aged 3-17 Years for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
Time frame: At Day 28 post last vaccination
Number of Subjects Aged 3-17 Years, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
Time frame: At Day 0 and Day 28 post last vaccination
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 3-17 Years.
Time frame: At Day 28 post last vaccination
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
Time frame: At Day 0 and Day 28 post last vaccination
Number of Seroconverted Subjects Aged 6-35 Months for Anti- Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
Time frame: At Day 28 post last vaccination
Number of Subjects Aged 6-35 Months, Who Were Seroprotected for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains.
Time frame: At Day 0 and Day 28 post last vaccination
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Four Vaccine Influenza Strains in Subjects Aged 6-35 Months.
Time frame: At Day 28 post last vaccination
Number of Subjects Aged 6-35 Months Reporting Fever ≥38ºC After Dose 1 and After Dose 2.
Time frame: During 7 days (Days 0-6) post-vaccination
Number of Subjects Aged 6-35 Months Reporting Solicited Local Adverse Events (AEs).
Time frame: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 6 Months to <5 Years, Reporting Fever ≥38ºC (100.4°F) and >39.0°C (102.2ºF) Across Doses.
Time frame: During the 2 days (Day 0-Day 1) post-vaccination period
Number of Subjects Aged 6-35 Months Reporting Any, Grade 3 and Related Solicited General Symptoms.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Duration of Solicited Local AEs in Subjects Aged 6-35 Months.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Duration of Solicited General AEs in Subjects Aged 6-35 Months.
Time frame: During the 7-day (Days 0-6) post-vaccination period
Number of Subjects Aged 6-35 Months Reporting Solicited Oculorespiratory Syndrome (ORS) Like Symptoms.
Time frame: During a 3 day (Days 0-2) follow-up period after vaccination
Number of Subjects Aged 6-35 Months Reporting the Occurrence of All Medically Attended Events (MAEs)
Time frame: During the entire study period (approximately 28 days (primed subjects) and 56 days (unprimed subjects) following vaccination
Number of Subjects Aged 6-35 Months Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
Time frame: During the 28-day (Days 0-27) follow-up period after vaccination
Number of Subjects Aged 6-35 Months, Reporting Any and Related Serious Adverse Events (SAEs)
Time frame: During the entire study period [approximately 28 days (primed subjects) and 56 days (unprimed subjects)]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29669531Claeys 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
53 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Influsplit Tetra™ vaccine produced by investigational process (IP) and Influsplit Tetra™ vaccine produced by licensed process (LP) in people with Influenza, run by GlaxoSmithKline at 53 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in Germany, Czechia, France, Poland, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects Aged 18-49 Years Reporting Solicited Local Adverse Events (AEs). (time frame: During the 7-day (Days 0-6) post-vaccination period). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02207413, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2018.