A phase II, open, non-randomized study designed to evaluate the reactogenicity and immunogenicity of one or two booster administrations of an influenza pandemic candidate vaccine (GSK1562902A) in adults aged between 19 and 61 years, previously vaccinated with 2 doses of a pandemic candidate vaccine H5N1 A/Vietnam/1194/2004 containing 3.8, 7.5, 15 or 30 µg HA, adjuvanted or not with AS03. - H5N1-015

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2007-000115-28-BE
• Date of registration: 03/07/2007
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: A phase II, open, non-randomized study designed to evaluate the reactogenicity and immunogenicity of one or two booster administrations of an influenza pandemic candidate vaccine (GSK1562902A) in adults aged between 19 and 61 years, previously vaccinated with 2 doses of a pandemic candidate vaccine H5N1 A/Vietnam/1194/2004 containing 3.8, 7.5, 15 or 30 µg HA, adjuvanted or not with AS03. - H5N1-015
• Scientific title: A phase II, open, non-randomized study designed to evaluate the reactogenicity and immunogenicity of one or two booster administrations of an influenza pandemic candidate vaccine (GSK1562902A) in adults aged between 19 and 61 years, previously vaccinated with 2 doses of a pandemic candidate vaccine H5N1 A/Vietnam/1194/2004 containing 3.8, 7.5, 15 or 30 µg HA, adjuvanted or not with AS03. - H5N1-015
• Date of first enrolment: 16/07/2007
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000115-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Belgium

Key inclusion & exclusion criteria

Inclusion criteria:
•Subjects who the investigator believes can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study.
•For previously primed subjects: participation in study H5N1-007
•For unprimed subjects, male or female between, and including, 19 and 61 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, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•For unprimed subjects who did not participate in the H5N1-007 study:Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. (For corticosteroids, this will mean prednisone, or equivalent, >/= 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
•Planned administration/ administration of an influenza vaccine other than the candidate vaccine during the entire study period.
•Planned administration/ administration of a licenced vaccine not foreseen by the study protocol within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) of the first dose of vaccine(s).
•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 product or device).
•Applicable for control group only: previous vaccination with a pandemic candidate vaccine or a vaccine containing the adjuvant AS03.
•History of hypersensitivity to vaccines.
•Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
•History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
•Major congenital defects or serious chronic illness.
•History of any neurologic disorders or seizures.
•Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever (defined as axillary temperature <37.5°C (99.5°F)
•Acute or chronic, 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. (Subjects suffering from seasonal allergies or asthma under inhalative treatment can be included).
•Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.
•Lactating female.
•History of chronic alcohol consumption and/or drug abuse



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Since 1997, avian H5N1 influenza has caused several human infections and high mortality rate in Southeast Asia. Experts warn that the next influenza pandemic is imminent and could be severe. Prevention and control will depend on the rapid production and worldwide distribution of specific pandemic vaccines. Candidate ‘pandemic-like’ vaccines must be developed and tested in clinical trials to determine the best vaccination schedule.

Intervention(s)

Trade Name: Pre-pandemic influenza vaccine
Product Name: Influenza Monovalent Split Virus (H5N1) vaccine adjuvanted with AS03
Pharmaceutical Form: Suspension for injection
Other descriptive name: HA from A/Indonesia/05/2005 (H5N1)/PR8-IBCDC-RG2
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 7.5-

Primary Outcome(s)

Secondary Objective: •persistence of the humoral immune response in terms of anti-haemagglutinin and neutralizing antibody titers ~14 months after priming.
•safety/reactogenicity of the candidate vaccine in terms of solicited local and general symptoms, unsolicited symptoms and serious adverse events.
•humoral immune response in terms of anti-haemagglutinin and neutralizing antibody titers 7, 14 and 21 days after each administration of the candidate vaccine.
•persistence of humoral immune response in terms of anti-haemagglutinin and neutralizing antibody titers ~6, 12, 18 and 24 months after the administration(s) of booster dose 1 of the candidate vaccine.
•in vitro cell-mediated immune response at 0 and 21 days, and 6, 12, 18 and 24 months after the administration(s) of booster dose 1 of the candidate vaccine in terms of CD4/CD8 T cells expressing immune markers for groups 3.8µg HA, 3.8µg HA/AS03 and control.

Main Objective: To assess if the humoral immune response induced 21 days after one booster administration of the pandemic influenza vaccine fulfils the criteria established by the European Committee for Medicinal Products for Human Use (CHMP) in subjects primed approximately 14 months earlier with two administrations (21 days apart) of the candidate vaccine formulated from an heterologous strain and adjuvanted with AS03.

Primary end point(s): For the humoral immune response in the AS03-adjuvanted vaccine groups (3.8, 7.5, 15 and 30µg HA/AS03):
Observed variables at Day 0 and Day 21, serum anti-HA antibody titers against the A/ Indonesia strain:
Derived variables (with 95% confidence intervals):
•Geometric mean titres (GMTs) of anti-HA antibody titres at Day 0 and Day 21
•Seroconversion rates* (SCR) at Day 21.
•Seroconversion factors** (SCF) at Day 21
•Seroprotection rates*** (SPR) at Day 0 and Day 21.
* Seroconversion rate for anti-HA antibody response is defined as the percentage of vaccinees who have either a prevaccination titre < 1:10 and a post-vaccination titre >/= 1:40 or a prevaccination titre >/= 1:10 and at least a 4-fold increase in post-vaccination titre
**Seroconversion factor is defined as the fold increase in serum anti-HA antibody GMTs post-vaccination compared to Day 0.
***Seroprotection rate is defined as the percentage of vaccinees with a serum anti-HA antibody titre >/=1:40 that usually is accepted as indicating protection.
For the safety/reactogenicity evaluation:
•Percentage, intensity and relationship to vaccination of solicited local and general signs and symptoms during a 7 day follow-up period (i.e. day of vaccination and 6 subsequent days) after each dose of vaccine and overall.
•Percentage, intensity and relationship to vaccination of unsolicited local and general signs and symptoms during a 21 days follow-up period after the first vaccination (i.e. day of first vaccination and 20 subsequent days) and 30 days follow up period after the second vaccination for non-adjuvanted vaccine and control groups, and during the 30-day follow-up period after the single vaccination for the adjuvanted vaccine group.
•Occurrence of serious adverse events during the entire study period.

Secondary ID(s)

109817