A Trial to Test the Response to Different Vaccination Regimens With an H5N1 Vaccine With AS03 in Adults Aged 18-64

Study Overview
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Brief Summary
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The purpose of the study is to characterize the immunogenicity & safety of 2 doses of GSK's avian flu vaccine GSK 1557484A given according to different regimens to adults aged 18 to 64 years

Detailed Description
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A Phase 2, open-label, randomized, parallel group, multi-centered study designed to evaluate the immunogenicity and safety of a 2-dose series of avian influenza vaccine plus AS03 adjuvant according to different regimens, in adults aged 18-64 years. All subjects will receive active study vaccine; no subjects are to receive placebo. A total of 312 subjects will be enrolled in this study at approximately 3 study centers in Canada. All subjects will attend formal study center visits for safety and immunogenicity assessments on Days 0, 21, 42, and 182. Additional formal study center visits will be scheduled at additional timepoints for subjects in particular dose groups. In addition, a telephone call will be conducted for all subjects on Day 51

Official Title
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A Trial to Evaluate the Immunogenicity of Accelerated Primary Vaccination With Monovalent A/Indonesia/5/05 (H5N1) Vaccine Antigen in Association With AS03 Adjuvant in Adults Aged 18-64

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza A (H5N1) Virus Monovalent Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female 18-64 years old at the time of the first vaccination. Written informed consent obtained from the subject. Good general health as established by medical history and clinical examination before entering into the study. Access to a consistent means of telephone contact. Comprehension of the study requirements, ability to comprehend and comply with procedures for collection of short- and long-term safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits. Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study Exclusion Criteria: Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if clinically stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Diagnosed with cancer, or treatment for cancer, within 3 years. Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Persons with a history of histologically-confirmed basal cell carcinoma of the skin successfully treated with local excision only are excepted and may be enrolled, but other histological types of skin cancer are exclusionary. Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen are excepted and may be enrolled. Presence of an oral temperature ≥37.8ºC, or acute symptoms greater than mild severity on the scheduled date of first vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Receipt of systemic glucocorticoids within 1 month of study enrollment, or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. Any significant disorder of coagulation or treatment with Coumadin derivatives or heparin. Administration of any vaccines within 30 days before study enrollment or during the 30 days following the last test article dose. Subjects who receive such immunizations on an emergent basis after enrollment will be followed per protocol and included in the Total Vaccinated Cohort (TVC), but excluded from the According to Protocol (ATP) Cohort for both safety and immunogenicity. Previous administration of any H5N1 vaccine. Use of any investigational or non-registered product (drug or vaccine) or planned participation in another investigational study within 30 days prior to study enrollment, or during the 182 days following the first test article dose. Use of any investigational or non-registered product with immunosuppressive properties is exclusionary at any time during the trial. Receipt of any immunoglobulins and/or any blood products within 6 months of study enrollment or planned administration of any of these products during the study period. Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins or mercurial preservatives); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine. Known pregnancy or a positive urine beta-human chorionic gonadotropin (β-hCG) test result prior to either vaccination. Lactating or nursing. Women of child bearing potential who lack a history of reliable contraceptive practices. The provision of this history does NOT replace the requirement to perform, and obtain negative results in pregnancy urine tests prior to treatments. Note: all women will have urine pregnancy tests regardless of their status. Known receipt of analgesic or antipyretic medication on the day of treatment with specific intent of prophylaxis of vaccine reactogenicity on the day of first or any treatment. Subjects on stable chronic regimens of potentially analgesic or anti-pyretic medications for pre-existing diagnoses are not required to discontinue them

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Influenza A (H5N1) 1 Group<br>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. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Influenza A (H5N1) 2 Group<br>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 14. The vaccine was administered intramuscularly in the deltoid region of the arm. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Influenza A (H5N1) 3 Group<br>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 7. The vaccine was administered intramuscularly in the deltoid region of the arm. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|
| Experimental: Influenza A (H5N1) 4 Group<br>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. The vaccine was administered intramuscularly in the deltoid region of the arm. | Biological: Influenza A (H5N1) Virus Monovalent Vaccine<br>* Two doses administered intramuscularly (IM), the first in the deltoid region of the non-dominant arm and the second in the deltoid region of the dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal hemagglutination inhibition (HI) titer less than (<) 1:10 and a post-vaccination (at Day 14 post Dose 2) reciprocal 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 (at Day 14 post Dose 2) titer. | At Day 14 post Dose 2 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). The Confidence Interval for this outcome was 98.75%. | At Day 0 and at Day 14 post Dose 2 | 
| Number of Seroprotected Subjects Against 3 Strains the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | A seroprotected subject was defined as a vaccinated subject who had a serum HI titer ≥ 1:40. | At Day 0 and at Day 14 post Dose 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 1 Group. | At Days 0, 21, 28, 35, 42 and 182. | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 2 Group. | At Days 0, 14, 21, 28, 35, 42 and 182. | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 3 Group. | At Days 0, 7, 14, 21, 28, 42 and 182. | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the A/Indonesia/5/2005 (H5N1) Strain of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 4 Group. | At Days 0, 7, 14, 21, 42 and 182. | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 1 Group. | At Days 0, 21, 28, 35, 42 and 182. | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 2 Group. | At Days 0, 14, 21, 28, 35, 42 and 182. | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 3 Group. | At Days 0, 7, 14, 21, 28, 42 and 182. | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 4 Group. | At Days 0, 7, 14, 21, 42 and 182. | 
| Number of Seroconverted Subjects Against the A/Indonesia/5/2005 (H5N1), Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal HI titer < 1:10 and a post-vaccination (at Day 14 post Dose 2) reciprocal titer ≥ 1:40 or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a four-fold increase in post-vaccination (at Day 14 post Dose 2) titer. | At Day 42 | 
| Number of Seroconverted Subjects Against the A/Indonesia/5/2005 (H5N1) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination (Day 0) reciprocal hemagglutination inhibition (HI) titer < 1:10 and a post-vaccination (at Day 14 post Dose 2) reciprocal titer ≥ 1:40 or a pre-vaccination reciprocal HI titer ≥ 1:10 and at least a four-fold increase in post-vaccination (at Day 14 post Dose 2) titer. | At Day 182 | 
| Geometric Mean Fold-rise (GMFR) for the A/Indonesia/5/2005 (H5N1), Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | The GMFR is presented as the GMT ratio between GMTs at Day 42/182 and at Day 0. | At Days 0, 42 and 182. | 
| Micro-neutralization (MN) Titers for Antibodies Against the Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 1 Group. | At Days 0, 21, 28, 35, 42 and 182. | 
| Micro-neutralization (MN) Titers for Antibodies Against the Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 2 Group. | At Days 0, 14, 21, 28, 35, 42 and 182. | 
| Micro-neutralization (MN) Titers for Antibodies Against the Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 3 Group. | At Days 0, 7, 14, 21, 28, 42 and 182. | 
| Micro-neutralization (MN) Titers for Antibodies Against the Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Titers are presented as geometric mean titers (GMTs). This outcome only covers results for the Pumarix 4 Group. | At Days 0, 7, 14, 21, 42 and 182. | 
| Number of Subjects With a Vaccine Response of MN Assessed Antibodies for Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Subjects with a vaccine response were defined as vaccinated subjects who had either a pre-vaccination titer < 1:28 and a post vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:28 and at least a four-fold increase in post-vaccination titer. | At 7, 14 and 21 days after the second dose | 
| Number of Subjects With a Vaccine Response of MN Assessed Antibodies for Flu A/Vietnam/1194/2004 (VIET) and Flu A/Turkey/Turkey/1/2005 (TURK) Strains of Influenza Disease. | Subjects with a vaccine response were defined as vaccinated subjects who had either a pre-vaccination titer < 1:28 and a post vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:28 and at least a four-fold increase in post-vaccination titer. | At Day 42 | 
| Number of Subjects With a Vaccine Response of MN Assessed Antibodies for the Flu A/Turkey/Turkey/1/2005 (TURK) Strain of Influenza Disease. | Subjects with vaccine response were defined as vaccinated subjects who had either a pre-vaccination titer < 1:28 and a post vaccination titer ≥ 1:56 or a pre-vaccination titer ≥ 1:28 and at least a four-fold increase in post-vaccination titer. | At Day 182 | 
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptoms regardless of their intensity grade. | Within the 7-day follow-up period (Days 0-6) after any vaccination | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were fatigue, headache, joint pain at other location (joint pain), muscle aches, shivering, sweating and fever. Fever was defined as oral temperature ≥ 38 degrees Celsius (°C). Any = occurrence of any solicited general symptoms regardless of intensity grade or relationship to vaccination. | Within the 7-day follow-up period (Days 0-6) after any vaccination | 
| Number of Subjects With Medically Attended Adverse Events (MAEs). | A 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. | From Day 0 to 182 | 
| Number of Subjects With 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. | Within the 51-day follow-up period (Days 0-50) after first vaccination. | 
| Number of Subjects With Any Serious Adverse Events (SAEs) | 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. | From Day 0 to 182 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H5N1, immunogenicity, influenza, Avian, pandemic, vaccines, human, safety