Immunogenicity & Safety of GSK's Avian Flu Vaccine 1557484A Given to Adults Aged ≥18 Years

NCT00719043 | Completed Phase 2 Results

• 1 other identifier: 110624
• Study Type: interventional
• Target: 841
• Locations: 2 countries
• Sites: 13

Brief Summary

The purpose of this study is to determine whether GSK's avian flu vaccine GSK 1557484A is immunogenic and safe when given to adults aged \>=18 years. This Protocol Posting has been updated following Amendments 1-3 of the Protocol, Dec 2009. The impacted sections are study design and outcome measures.

Conditions

Influenza

Keywords

Influenza; H5N1; Avian; Vaccines; Safety; Immunogenicity; Pandemic; Human

Outcome Measures

Primary Outcomes (11)

• Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.

  A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. Pre-vaccination for this outcome measure corresponds to Day 549. This outcome concerns solely subjects in the Pumarix Primed-Placebo-A/turkey H5N1-Formulation 3, Pumarix Primed-Placebo-A/turkey H5N1-Formulation 1, Pumarix Primed-Placebo-A/turkey H5N1-Formulation 4 and Pumarix Primed-Placebo-A/turkey H5N1-Formulation 2 groups.

  At Day 559

• Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.

  A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer less than (\<) 1:10 and a post-vaccination reciprocal titer greater than or equal to (≥) 1:40 or a pre-vaccination reciprocal titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. Pre-vaccination for this outcome measure corresponds to Day 182. This outcome concerns solely subjects in the Naïve Placebo-A/turkey H5N1-Formulation 3 Group

  At Day 192

• Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey) Strain.

  HI antibody titers against the A/turkey virus strain were expressed as geometric mean titers (GMTs). This outcome concerns solely subjects in the Pumarix Primed-Placebo-A/turkey H5N1-Formulation 3, Pumarix Primed-Placebo-A/turkey H5N1-Formulation 1, Pumarix Primed-Placebo-A/turkey H5N1-Formulation 4 and Pumarix Primed-Placebo-A/turkey H5N1-Formulation 2 groups.

  At Days 549 and 559

• Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey/Turkey/1/2005 (A/Turkey) Strain.

  HI antibody titers against the A/turkey virus strain were expressed as geometric mean titers (GMTs). This outcome concerns solely subjects in the Naïve Placebo-A/turkey H5N1-Formulation 3 Group.

  At Days 182 and 192

• Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.

  A seroprotected subject was defined as a vaccinated subject with HI antibody titers against the A/turkey virus strain greater than or equal to (≥) 1:40. This outcome concerns solely subjects in the Pumarix Primed-Placebo-A/turkey H5N1-Formulation 3, Pumarix Primed-Placebo-A/turkey H5N1-Formulation 1, Pumarix Primed-Placebo-A/turkey H5N1-Formulation 4 and Pumarix Primed-Placebo-A/turkey H5N1-Formulation 2 groups.

  At Days 549 and 559

• Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.

  A seroprotected subject was defined as a vaccinated subject with HI antibody titers against the A/turkey virus strain greater than or equal to (≥) 1:40. This outcome concerns solely subjects in the Naïve Placebo-A/turkey H5N1-Formulation 3 Group.

  At Days 182 and 192

• Number of Subjects With Solicited Local Symptoms

  Assessed solicited local symptoms were pain, redness and swelling. Any was defined as an occurrence of the specified solicited local symptom regardless of its intensity.

  Within the 7-day (Days 0-6) post vaccination periods

• Number of Subjects With Solicited General Symptoms

  Solicited general symptoms assessed were fatigue, headache, joint pain at other locations (joint pain), muscle aches, shivering, sweating and fever. Any was defined as an occurrence of the specified solicited general symptom, irrespective of its intensity or relationship to vaccination. Any fever was defined as oral temperature higher than or equal to (≥) 38.0 degrees Celsius (°C).

  Within the 7-day (Days 0-6) post vaccination periods

• Number of Subjects With Medically-attended Adverse 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).

  From Day 0 to Day 909

• 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. Any was defined as any occurrence of an unsolicited AE in a subject, regardless of intensity grade or relation to vaccination.

  Within the 43-day (Days 0-42) post-vaccination periods

• Number of Subjects With Serious Adverse Events (SAEs)

  A SAE 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 an occurrence of an SAE, regardless its relationship to vaccination.

  From Day 0 to Day 909

Secondary Outcomes (21)

• Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.

  At Day 192

• Haemagglutination Inhibition (HI) Antibody Titers Against the A/Turkey Virus Strain.

  At Days 182 and 192

• Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.

  At Days 182 and 192

• Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.

  At Day 224

• Number of Seroprotected Subjects for Haemagglutination Inhibition (HI) Antibodies Against the A/Turkey/Turkey/1/2005 (A/Turkey) Virus Strain.

  At Day 591

Study Arms (7)

A/Indonesia primed-A/turkey Influenza (H5N1)-F1-Placebo Group

EXPERIMENTAL

Healthy subjects aged 18 years of age or older at the time of enrolment were primed with one dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) formulation 1 at Day 0 followed by one booster dose of A/turkey H5N1 vaccine formulation 1 at Day 182 and one dose of placebo (phosphate buffered saline, PBS) at Day 549. Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) and Placebo vaccines were administered intramuscularly in the deltoid region of the non-dominant arm while, A/turkey H5N1 vaccine was administered intramuscularly in the deltoid region of the dominant arm.

Biological: A/turkey H5N1 vaccine; Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia); Biological: Placebo

A/Indonesia primed-A/turkey Influenza (H5N1)-F2-Placebo Group

EXPERIMENTAL

Healthy subjects aged 18 years of age or older at the time of enrolment were primed with one dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) formulation 2 at Day 0 followed by one booster dose of A/turkey H5N1 vaccine formulation 2 at Day 182 and one dose of placebo (phosphate buffered saline, PBS) at Day 549. Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) and Placebo vaccines were administered intramuscularly in the deltoid region of the non-dominant arm while, A/turkey H5N1 vaccine was administered intramuscularly in the deltoid region of the dominant arm.

Biological: A/turkey H5N1 vaccine; Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia); Biological: Placebo

A/Indonesia primed-A/turkey Influenza (H5N1)-F3-Placebo Group

EXPERIMENTAL

Healthy subjects aged 18 years of age or older at the time of enrolment were primed with one dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) formulation 3 at Day 0, one dose of placebo (phosphate buffered saline, PBS) at Day 182 followed by one booster dose of A/turkey H5N1 vaccine formulation 3 at Day 549. Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) and A/turkey H5N1 vaccines were administered intramuscularly in the deltoid region of the non-dominant arm while, Placebo vaccine was administered intramuscularly in the deltoid region of the dominant arm.

Biological: A/turkey H5N1 vaccine; Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia); Biological: Placebo

A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F1-Group

EXPERIMENTAL

Healthy subjects aged 18 years of age or older at the time of enrolment were primed with one dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) vaccine formulation 1 at Day 0, one dose of placebo (phosphate buffered saline, PBS) at Day 182 followed by one booster dose of A/turkey H5N1 vaccine formulation 1 at Day 549. Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) and A/turkey H5N1 vaccines were administered intramuscularly in the deltoid region of the non-dominant arm while, Placebo vaccine was administered intramuscularly in the deltoid region of the dominant arm.

Biological: A/turkey H5N1 vaccine; Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia); Biological: Placebo

A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F4-Group

EXPERIMENTAL

Healthy subjects aged 18 years of age or older at the time of enrolment were primed with one dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) formulation 4 at Day 0, one dose of placebo (phosphate buffered saline, PBS) at Day 182 followed by one booster dose of A/turkey H5N1 vaccine formulation 4 at Day 549. Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) and A/turkey H5N1 vaccines were administered intramuscularly in the deltoid region of the non-dominant arm while, Placebo vaccine was administered intramuscularly in the deltoid region of the dominant arm.

Biological: A/turkey H5N1 vaccine; Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia); Biological: Placebo

A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F2-Group

EXPERIMENTAL

Healthy subjects aged 18 years of age or older at the time of enrolment were primed with one dose of Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) formulation 2 at Day 0, one dose of placebo (phosphate buffered saline, PBS) at Day 182 followed by one booster dose of A/turkey H5N1 vaccine formulation 2 at Day 549. Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) and A/turkey H5N1 vaccines were administered intramuscularly in the deltoid region of the non-dominant arm while, Placebo vaccine was administered intramuscularly in the deltoid region of the dominant arm.

Biological: A/turkey H5N1 vaccine; Biological: Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia); Biological: Placebo

Naïve Placebo-A/turkey Influenza (H5N1)-F3-Group

PLACEBO COMPARATOR

Healthy subjects aged 18 years of age or older at the time of vaccination received one dose of placebo (phosphate buffered saline, PBS) at Day 0 followed by two doses of A/turkey H5N1 vaccine formulation 3, one dose administered at Day 182 and the other at Day 549. Placebo vaccine and one dose of A/turkey H5N1 vaccine (Day 549) was administered intramuscularly in the deltoid region of the non-dominant arm while the other dose of A/turkey H5N1 vaccine (Day 182) was administered intramuscularly in the deltoid region of the dominant arm.

Biological: A/turkey H5N1 vaccine; Biological: Placebo

Interventions

A/turkey H5N1 vaccine BIOLOGICAL

Administered as an intramuscular (IM) injection

A/Indonesia primed-A/turkey Influenza (H5N1)-F1-Placebo Group; A/Indonesia primed-A/turkey Influenza (H5N1)-F2-Placebo Group; A/Indonesia primed-A/turkey Influenza (H5N1)-F3-Placebo Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F1-Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F2-Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F4-Group; Naïve Placebo-A/turkey Influenza (H5N1)-F3-Group

Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted (A/Indonesia) BIOLOGICAL

Administered as an intramuscular (IM) injection

A/Indonesia primed-A/turkey Influenza (H5N1)-F1-Placebo Group; A/Indonesia primed-A/turkey Influenza (H5N1)-F2-Placebo Group; A/Indonesia primed-A/turkey Influenza (H5N1)-F3-Placebo Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F1-Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F2-Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F4-Group

Placebo BIOLOGICAL

Administered as an intramuscular (IM) injection

A/Indonesia primed-A/turkey Influenza (H5N1)-F1-Placebo Group; A/Indonesia primed-A/turkey Influenza (H5N1)-F2-Placebo Group; A/Indonesia primed-A/turkey Influenza (H5N1)-F3-Placebo Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F1-Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F2-Group; A/Indonesia primed-Placebo-A/turkey Influenza (H5N1)-F4-Group; Naïve Placebo-A/turkey Influenza (H5N1)-F3-Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A male or female 18 years of age or older at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Stable health status as defined by absence of a health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 1 month prior to enrollment.
• Access to a consistent means of telephone contact, which may be either in the home or at the workplace, land line or mobile, but NOT a pay phone or other multiple-user device.
• Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
• Subjects who the investigator believes can and will comply with the requirements of the protocol

You may not qualify if:

• 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 enroll within 3 years of diagnosis, but other histologic types of skin cancer require a 3 year untreated and disease-free window as above.
• Women who are disease-free 3 years or more after treatment for breast cancer and receiving long-term prophylactic tamoxifen are excepted and may enroll.
• 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 (prednisone \>= 10 mg/day for more than 14 consecutive days) within 1 month prior to 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 the first study vaccine dose.
• Previous administration of any H5N1 vaccine.
• 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 vaccination.
• Lactating or nursing.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (13)

GSK Investigational Site

Denver, Colorado, 80239, United States

Location

GSK Investigational Site

Chicago, Illinois, 60610, United States

Location

GSK Investigational Site

Metairie, Louisiana, 70006, United States

Location

GSK Investigational Site

Milford, Massachusetts, 01757, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64114, United States

Location

GSK Investigational Site

Missoula, Montana, 59801, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

GSK Investigational Site

Bristol, Tennessee, 37620, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76135, United States

Location

GSK Investigational Site

Halifax, Nova Scotia, B3K 6R8, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2K 4L5, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 4J6, Canada

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2008
• First Posted: July 21, 2008
• Study Start: July 11, 2008
• Primary Completion: April 22, 2010
• Study Completion: February 18, 2011
• Last Updated: July 9, 2018
• Results First Posted: February 7, 2014

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); US (10)