Assess Consistency of Immunogenicity of GlaxoSmithKline Biologicals' Pandemic Influenza Vaccine (GSK1562902A) in Adults

Phase 3

Completed

• Conditions: Influenza; Influenza Vaccines
• Interventions: Biological: H5N1 adjuvanted split virus vaccine (A/Vietnam/1194/2004 strain); Biological: H5N1 non-adjuvanted split virus vaccine (A/Vietnam/1194/2004 strain); Biological: H5N1 adjuvanted split virus vaccine (A/Indonesia/05/2005 strain)

• Registration Number: NCT00449670
• Lead Sponsor: GlaxoSmithKline

Brief Summary

The present study is designed to assess the lot-to-lot consistency of the immunogenicity of a GlaxoSmithKline Biologicals' pandemic influenza candidate vaccine (GSK1562902A) in adults aged between 18 and 60 years.

Detailed Description

The protocol posting has been updated to reflect changes due to an amendment to the protocol (addition of an exclusion criterion). The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Timeline

• Study First Submitted: 2007-03-19
• Study First Submitted QC: 2007-03-19
• Study First Posted: 2007-03-20
• Study Start: 2007-03-24
• Primary Completion: 2007-07-12
• Study Completion: 2008-06-10
• Results First Submitted: 2017-09-29
• Status Verified: 2020-03
• Results First Submitted QC: 2020-03-24
• Last Update Submitted: 2020-03-24
• Results First Posted: 2020-04-09
• Last Update Posted: 2020-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1206

Inclusion Criteria

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol
• A male or female between, and including, 18 and 60 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria

• Administration of any licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study.
• Planned administration of a vaccine not foreseen by the study protocol during the following periods: from Day 0 up to Day 51, 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Month 6; from Month 6 up to Month 6 + 30 days (or Month 6 + 51 days for the control groups).
• Previous vaccination with a pandemic candidate vaccine or a vaccine containing the same adjuvant as the study vaccine.
• Previous proven contact with H5N1 wild type virus (i.e. contact with an individual with laboratory-confirmed H5N1 infection, or contact with an animal (e.g. poultry) which died as a result of H5N1 infection).
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first administration of the candidate vaccines.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, or autoimmune diseases such as Guillain Barre Syndrome, based on medical history and physical examination (no laboratory testing required).
• History of hypersensitivity to vaccines.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• History of chronic alcohol consumption and/or drug abuse.
• Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination.
• Acute disease at the time of enrolment.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the first administration of the candidate vaccine or during the study.
• Lactating women.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days prior to the first vaccination, or planned use during the study period.
• Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
H5N1 Adjuvanted Group	H5N1 adjuvanted split virus vaccine (A/Vietnam/1194/2004 strain)	Subjects received 2 doses of H5N1 adjuvanted split virus vaccine (lot 1, 2, 3 or 4) containing A/Vietnam/1194/2004 strain at Day 0 and Day 21 during Primary Phase. A subset of these subjects (Boosted sub-cohort) received a single dose of heterologous H5N1 adjuvanted vaccine containing A/Indonesia/05/2005 strain at Month 6 during Booster Phase. The remaining subjects (Non-Boosted sub-cohort) received a single booster dose at Month 12 or 36 after initial priming in study 111443 (NCT00652743).
H5N1 Un-adjuvanted Group	H5N1 non-adjuvanted split virus vaccine (A/Vietnam/1194/2004 strain)	Subjects received 2 doses of a H5N1 non-adjuvanted split virus vaccine containing A/Vietnam/1194/2004 strain at Day 0 and Day 21 and two booster doses of heterologous H5N1 adjuvanted vaccine containing A/Indonesia/05/2005 strain at Month 6 and Month 6 + 21 days.
H5N1 Un-adjuvanted Group	H5N1 adjuvanted split virus vaccine (A/Indonesia/05/2005 strain)	Subjects received 2 doses of a H5N1 non-adjuvanted split virus vaccine containing A/Vietnam/1194/2004 strain at Day 0 and Day 21 and two booster doses of heterologous H5N1 adjuvanted vaccine containing A/Indonesia/05/2005 strain at Month 6 and Month 6 + 21 days.
H5N1 Adjuvanted Group	H5N1 adjuvanted split virus vaccine (A/Indonesia/05/2005 strain)	Subjects received 2 doses of H5N1 adjuvanted split virus vaccine (lot 1, 2, 3 or 4) containing A/Vietnam/1194/2004 strain at Day 0 and Day 21 during Primary Phase. A subset of these subjects (Boosted sub-cohort) received a single dose of heterologous H5N1 adjuvanted vaccine containing A/Indonesia/05/2005 strain at Month 6 during Booster Phase. The remaining subjects (Non-Boosted sub-cohort) received a single booster dose at Month 12 or 36 after initial priming in study 111443 (NCT00652743).

Primary Outcome Measures

Name	Time	Method
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease	Within 21 days following 2-dose primary vaccination (at Day 42)	Titers are presented as geometric mean titers (GMTs). The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). The reference seropositivity cut-off value was ≥ 1:10.

Secondary Outcome Measures

Name	Time	Method
Number of Seroconverted Subjects for HI Antibodies Against 2 Strains of Influenza Disease	Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)	Seroconversion was defined as: for initially seronegative subjects, antibody titer greater than or equal to ≥ 1:40 after vaccination; and for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Number of Seroconverted Subjects for Neutralizing Antibodies Against 2 Strains of Influenza Disease - Booster Phase	Following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)	Seroconversion was defined as: for initially seronegative subjects, antibody titer ≥ 1:56 after vaccination; and for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer.
Number of Seroprotected Subjects Against 2 Strains of Influenza Disease	Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D), at Month 6+42 days (M6+42D) and at Month 12 (M12)	A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms - Booster Phase	During the 7-days (Days 0-6) post-booster vaccination period	Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], headache, myalgia, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever higher than (\>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Number of Subjects With Any Unsolicited Adverse Events (AEs)	During the booster phase (from Month 6 to Month 12)	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Number of Subjects With Serious Adverse Events (SAEs) for Subjects Not Boosted at Month 6	From Month 6 to Month 12	This group consists of the remaining subjects from the GSK1562902A Pooled Group who received a single dose of H5N1 vaccine at Month 12 or 36.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease in Adults Who Had Not Received the Booster Dose at Month 6	At Day 0, at Day 21, at Day 42, at Month 6 and at Month 12	Titers are presented as geometric mean titers (GMTs). The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). The reference seropositivity cut-off value was ≥ 1:10.
Titers for Serum Neutralization (SN) Antibodies Against 2 Strains of Influenza Disease in Adults Who Had Not Received the Booster Dose at Month 6	At Month 12	Titers are presented as geometric mean titers (GMTs). The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). The reference seropositivity cut-off value was ≥ 1:10.
Number of Seroconverted Subjects for HI Antibodies Against 2 Strains of Influenza Disease for Adults Who Received the Booster Dose at Month 6 - Booster Phase	At Month 12	Seroconversion was defined as: for initially seronegative subjects, antibody titer greater than or equal to ≥ 1:40 after vaccination; and for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Titers for Serum Neutralization (SN) Antibodies Against 2 Strains of Influenza Disease	Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)	Titers are presented as geometric mean titers (GMTs). The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). The reference seropositivity cut-off value was ≥ 1:10.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease	Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D) and at Month 12 (M12)	Titers are presented as geometric mean titers (GMTs). The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). The reference seropositivity cut-off value was ≥ 1:10.
Titers for Serum Neutralizing (SN) Antibodies Against 2 Strains of Influenza Disease	Before vaccination at Day 0 (D0) and within 21 days following 2-dose primary vaccination at Day 42 (D42)	Titers are presented as geometric mean titers (GMTs). The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1). The reference seropositivity cut-off value was ≥ 1:28.
Number of Seroconverted Subjects for Neutralizing Antibodies Against 2 Strains of Influenza Disease	Within 21 days following 2-dose primary vaccination at Day 42	Seroconversion was defined as: antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Number of Seroconverted Subjects for HI Antibodies Against 2 Strains of Influenza Disease for Adults Who Have Not Received Booster at Month 6	At Day 21, Day 42, Month 6 and Month 12 following primary vaccination	Seroconversion defined as: for initially seronegative subjects, antibody titer ≥ 1:40 after vaccination; and for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-booster antibody titer.
Number of Seroconverted Subjects for Neutralizing Antibodies Against 2 Strains of Influenza Disease for Subjects Not Boosted at Month 6	At Month 12	Seroconversion was defined as: for initially seronegative subjects, antibody titer ≥ 1:56 after vaccination; and for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer.
Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease	Before booster vaccination at Month 6 (M6) and within 21 days following each booster dose: At Month 6 + 21 days (M6+21D) and, for H5N1 Un-adjuvanted Group only, at Month 6 + 42 days (M6+42D)	The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Booster Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease	At Month 12	The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease for Subjects Not Boosted at Month 6	At Day 21, at Day 42, at Month 6 and at Month 12	The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Number of Subjects Seroprotected Against 2 Strains of Influenza Disease	Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D) and at Month 6+42 days (M6+42D)	A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Frequency of Influenza-specific Cluster of Differentiation 8+ (CD8+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation	Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D), at Month 6+42 days (M6+42D) and at Month 12 (M12)	The analyzed cytokines were CD40 Ligand (CD40L), Interleukin 2 (IL-2), Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN-γ). The stimulating antigen used was A/Vietnam/1194/2004.
Frequency of Influenza-specific Cluster of Differentiation 4+ (CD4+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation for Subjects Not Boosted at Month 6	At Month 6 and Month 12	The analyzed cytokines were CD 40 Ligand (CD40L), Interleukin 2 (IL-2), Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN-γ). The stimulating antigen used was A/Vietnam/1194/2004.
Number of Subjects Seroprotected Against 2 Strains of Influenza Disease for Subjects Not Boosted at Month 6	At Day 0, Day 21, Day 42, Month 6 and Month 12	A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. The 2 flu strains assessed were A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1).
Frequency of Influenza-specific Cluster of Differentiation 4+ (CD4+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation	Before booster vaccination at Month 6 (M6) and following booster vaccination at Month 6+21 days (M6+21D), at Month 6+42 days (M6+42D) and at Month 12 (M12)	The analyzed cytokines were CD 40 Ligand (CD40L), Interleukin 2 (IL-2), Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN-γ). The stimulating antigen used was A/Vietnam/1194/2004.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	During the 7-days (Days 0-6) post-primary vaccination period following each dose and overall	Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 ecchymosis/induration/redness/swelling = ecchymosis/induration/redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Frequency of Influenza-specific Cluster of Differentiation 8+ (CD8+) T Cells Expressing at Least 2 Markers Among the Analyzed Cytokines Upon in Vitro Stimulation for Subjects Not Boosted at Month 6	At Month 6 and at Month 12	The analyzed cytokines were CD 40 Ligand (CD40L), Interleukin 2 (IL-2), Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN-γ). The stimulating antigen used was A/Vietnam/1194/2004.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	During the 7-days (Days 0-6) post-primary vaccination period following each dose and overall	Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], headache, myalgia, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever higher than (\>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Booster Phase	During the 7-days (Days 0-6) post-booster vaccination period	Assessed solicited local symptoms were ecchymosis, induration, pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 ecchymosis/induration/redness/swelling = ecchymosis/induration/redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Number of Subjects With Serious Adverse Events (SAEs).	During the booster phase (from Month 6 to Month 12)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Trial Locations

Locations (1)

GSK Investigational Site; 🇹🇭 Bangkok, Thailand