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Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Monovalent Pandemic H5N1 Vaccine in Adults

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ClinicalTrials.gov Identifier: NCT01416571
Recruitment Status : Completed
First Posted : August 15, 2011
Results First Posted : April 16, 2014
Last Update Posted : September 21, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE August 12, 2011
First Posted Date  ICMJE August 15, 2011
Results First Submitted Date  ICMJE December 19, 2013
Results First Posted Date  ICMJE April 16, 2014
Last Update Posted Date September 21, 2018
Study Start Date  ICMJE August 12, 2011
Actual Primary Completion Date November 29, 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2014)
  • Number of Seroconverted Subjects Against the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 42 ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination reciprocal HI titer less than (<) 1:10 and a post-vaccination reciprocal HI titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a four-fold increase in post-vaccination reciprocal titer against the vaccine virus.
  • Mean Geometric Increase (MGI) for the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 42 ]
    MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer for the vaccine virus.
  • Number of Seroprotected Subjects Against the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 42 ]
    A seroprotected subject was defined as a vaccinated subject who had H5N1 reciprocal HI titers ≥ 1:40 against the vaccine-homologous virus.
Original Primary Outcome Measures  ICMJE
 (submitted: August 12, 2011)
  • Humoral immune response in terms of H5N1 hemagglutination inhibition (HI) antibody titers [ Time Frame: At Day 0 ]
  • Humoral immune response in terms of H5N1 HI antibody titers [ Time Frame: At Day 42 ]
Change History Complete list of historical versions of study NCT01416571 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2014)
  • Number of Seropositive Subjects Against the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 0 and Day 42 ]
    A seropositive subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:10.
  • Titers for Serum HI Antibodies Against the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 0 and Day 42 ]
    Titers are presented as geometric mean titers (GMTs).
  • Number of Seropositive Subjects Against the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 0 and Day 182 ]
    A seropositive subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:10.
  • Titers for Serum HI Antibodies Against the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 0 and Day 182 ]
    Titers are presented as geometric mean titers (GMTs).
  • Number of Seroprotected Subjects Against the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 0 and Day 182 ]
    A seroprotected subject was defined as a vaccinated subject who had H5N1 reciprocal HI titers ≥ 1:40 against the vaccine-homologous virus.
  • Number of Seroconverted Subjects Against the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 182 ]
    A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination reciprocal HI titer < 1:10 and a post-vaccination reciprocal HI titer (≥) 1:40 or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a four-fold increase in post-vaccination reciprocal titer against the vaccine virus.
  • Mean Geometric Increase (MGI) for the H5N1 Strain of Influenza Disease. [ Time Frame: At Day 182 ]
    MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination (Day 0) reciprocal HI titer for the vaccine virus.
  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 7-day follow-up period (Days 0-6) after any vaccination ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptoms regardless of intensity grade. Grade 3 pain = significant pain at rest; prevented normal activities. Grade 3 Redness/Swelling = Redness/Swelling >100 millimeters (mm).
  • Duration of Solicited Local Symptoms After Vaccination. [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose ]
    Assessed solicited local symptoms were pain, redness and swelling. Duration was defined as the number of days with any grade of local symptoms.
  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 7-day follow-up period (Days 0-6) after any vaccination ]
    Assessed solicited general symptoms were fatigue, gastrointestinal, headache, joint pain at other location (joint pain), muscle aches, shivering, sweating and fever. Any = occurrence of any solicited general symptoms regardless of intensity grade or relationship to vaccination. Any fever was defined as axillary temperature ≥ 38 degrees Celsius (°C). Grade 3 = general symptom that prevented normal activities. Grade 3 fever = fever ≥ 39.0°C. Related = general symptom assessed by the investigator as causally related to the vaccination.
  • Duration of Solicited General Symptoms After Vaccination. [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose ]
    Assessed solicited general symptoms were fatigue, gastrointestinal, headache, joint pain at other location (joint pain), muscle aches, increased sweating and shivering. Duration was defined as the number of days with any grade of general symptoms.
  • Number of Subjects With Any, Grade 3 and Related Medically Attended Adverse Events (MAEs). [ Time Frame: From Day 0 to Day 84 ]
    MAE was defined as any unsolicited symptom that received medical attention such as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any = occurrence of any MAEs regardless of intensity grade or relationship to vaccination. Grade 3 = event which prevented normal activities Related = event assessed by the investigator as causally related to the study vaccination.
  • Number of Subjects With Any, Grade 3 and Related Medically Attended Adverse Events (MAEs). [ Time Frame: From Day 0 to Day 385 ]
    MAE was defined as any unsolicited symptom that received medical attention such as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason. Any = occurrence of any MAEs regardless of intensity grade or relationship to vaccination. Grade 3 = event which prevented normal activities. Related = event assessed by the investigator as causally related to the study vaccination.
  • Number of Subjects With Potential Immune Mediated Disease (s) (pIMDs). [ Time Frame: From Day 0 to Day 84 and from Day 0 to Day 385 ]
    pIMDs are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune aetiology.
  • Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. [ Time Frame: At Day 0 and Day 42 ]
    Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIR), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents BAS, EOS and HCRIT results.
  • Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. [ Time Frame: At Day 0 and Day 42 ]
    Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIR), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents HBIN, LYM and MON results.
  • Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. [ Time Frame: At Day 0 and Day 42 ]
    Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIR), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents NEU, PLA and RBC results.
  • Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. [ Time Frame: At Day 0 and Day 42 ]
    Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIR), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents WBC, ALT and AST results.
  • Number of Subjects With Normal and Abnormal Biochemical and Haematological Parameters. [ Time Frame: At Day 0 and Day 42 ]
    Assessed biochemical and haematological parameters were alanine aminotransferase (ALT), aspartate aminotransferase (AST), basophils (BAS), blood urea nitrogen (BUN), creatinine (CREA), eosinophils (EOS), haematocrit (HCRIT), haemoglobin (HBIN), lymphocytes (LYM), monocytes (MON), neutrophils (NEU), platelets (PLA), red blood cells (RBC), white blood cells (WBC), total bilirubin (Total BIL), bilirubin conjugated/direct (BIL con/dir). Per parameter, it was assessed whether subjects had laboratory values unknown, below, within or above the normal ranges. This outcome presents Total BIL, BIL con/dir, CREA and BUN results.
  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: From Day 0 to Day 20 and from Day 0 to Day 84. ]
    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) 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 = occurrence of an unsolicited AE regardless of intensity grade or relationship to vaccination. Grade 3 = event which prevented normal activities. Related = event assessed by the investigator as causally related to the study vaccination.
  • Number of Subjects With Any and Related Serious Adverse Events (SAEs) [ Time Frame: From Day 0 to Day 84 and from Day 0 to Day 385 ]
    A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or resulted in 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2011)
  • Humoral immune response in terms of H5N1 HI antibody titers [ Time Frame: At Day 0, Day 42 and Day 182 ]
  • Occurrence of solicited local and general symptoms [ Time Frame: During a 7-day follow-up period after each vaccination ]
  • Occurrence of unsolicited adverse events (AE) [ Time Frame: During a 21-day (Day 0 to Day 20) follow-up period after each vaccination and overall up to Day 84 ]
  • Occurrence of AEs with medically attended visits [ Time Frame: During the entire study period (Day 0 to Day 385) ]
  • Occurrence of potential immune-mediated diseases [ Time Frame: During the entire study period (Day 0 to Day 385) ]
  • Occurrence of serious adverse events [ Time Frame: During the entire study period (Day 0 to Day 385) ]
  • Number of subjects with clinical safety laboratory abnormalities [ Time Frame: At Day 0 and Day 42 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Monovalent Pandemic H5N1 Vaccine in Adults
Official Title  ICMJE Immunogenicity and Safety Study of GSK Biologicals' Monovalent Pandemic H5N1 Vaccine 1557484A in Adults Aged 18 - 64 Years
Brief Summary This trial will assess the immunogenicity and safety of GSK Biologicals' vaccine GSK1557484A, prepared from old concentrated monobulk material, in adults aged 18 to 64 years, when administered up to 5 years following production.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Influenza
Intervention  ICMJE Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Intramuscular (IM), two doses
Study Arms  ICMJE Experimental: Influenza A (H5N1) Group
Healthy subjects aged between 18 and 64 years at the time of vaccination received two doses of the Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, at Day 0 and Day 21. The vaccine was administered intramuscularly in the deltoid region of the arm.
Intervention: Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted
Publications * Godeaux O, Izurieta P, Madariaga M, Dramé M, Li P, Vaughn DW. Immunogenicity and safety of AS03A-adjuvanted H5N1 influenza vaccine prepared from bulk antigen after stockpiling for 4 years. Vaccine. 2015 Apr 27;33(18):2189-95. doi: 10.1016/j.vaccine.2014.07.062. Epub 2014 Jul 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 12, 2011)
78
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 28, 2012
Actual Primary Completion Date November 29, 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects who the investigator believes can and will comply with the requirements of the protocol.
  • A male or female 18 to 64 years of age at the time of the first vaccination.
  • Written informed consent obtained from the subject.
  • Stable general health as established by medical history and clinical examination before entering into the study.
  • Subject access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device.
  • Female subjects of non-childbearing potential may be enrolled in the study.
  • 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 completion of the vaccination series.

Exclusion Criteria:

  • Previous vaccination at any time with an H5N1 vaccine.
  • Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Presence of significant acute or chronic, uncontrolled medical or psychiatric illness.
  • Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
  • Presence of a temperature ≥ 38.0ºC, or acute symptoms greater than "mild" severity on the scheduled date of first dose.
  • Diagnosed with cancer, or treatment for cancer, within 3 years.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • Receipt of systemic glucocorticoids within 1 month prior to study enrolment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrolment. Topical, intra-articularly injected, or inhaled glucocorticoids, topical calcineurin inhibitors or imiquimod are allowed.
  • Receipt of any immunoglobulins and/or any blood products within 3 months before first study vaccination or planned administration of any of these products during the study period.
  • Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to dosing, are eligible. Persons receiving prophylactic antiplatelet medications, and without a clinically-apparent bleeding tendency, are eligible.
  • An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine.
  • Administration of an inactivated or a live, attenuated seasonal influenza vaccine within 14 days before the first study vaccine dose, or of any other vaccine(s) not foreseen by the study protocol within 30 days before the first study vaccine dose.
  • Planned administration of any vaccine(s) not foreseen by the study protocol through completion of the Day 42 visit.
  • Any known or suspected allergy to any constituent of influenza vaccines, or history of severe reaction to a previous influenza vaccination.
  • Known pregnancy or a positive urine beta-human chorionic gonadotropin test result prior to the first study vaccine dose.
  • Lactating or nursing women.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01416571
Other Study ID Numbers  ICMJE 112691
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP