Evaluation of Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Boostrix Vaccine Administered as a Booster Dose in Healthy Russian Subjects

The study is a phase III, open-label, self-contained, multi-centre, uncontrolled, single-country study with a single group. Treatment will be allocated in a non-randomised process and stratified by age as 4-9 years (children), 10-17 years (adolescents), 18-64 years (adults) and ≥65 years (elderly population). The study will consist of a single primary epoch (001) starting at Visit 1 (Day 1) with the administration of a single dose of Boostrix vaccine and ending at Visit 2 (Day 31). Blood samples will be collected at Visits 1 and 2.

Protocol Amendment 1 was developed to implement the following changes:

• Wording "parents/Legally Acceptable Representative(s) (LAR[s])" was replaced by the wording "parent(s)/adoptive parent(s)". As per Russian legislation, only parents or adoptive parents can give consent for the enrolment of their child in a clinical trial. No other person is allowed to give consent on behalf of a minor to participate in a clinical trial.
• The age groups at inclusion to study were amended according to the approved Boostrix EU label and physiological particularities i.e., from 3-9 to 4-9 years (children), 10-19 to 10-17 years (adolescents), 20-64 to 18-64 years (adults) and ≥65 years (elderly population).
• The inclusion criteria have been amended in order to clarify the following,

• Children from four to seven years of age who have received diphtheria, tetanus and pertussis vaccination prior to study enrolment as per local recommendations will be enrolled
• Subjects eight years of age and older who have received diphtheria, tetanus and pertussis vaccination to the best of their/subjects' parent(s)/subjects' adoptive parent(s) knowledge and did not receive an additional diphtheria, tetanus or pertussis vaccination within five years prior to enrolment in the study will be enrolled.

Protocol amendment 2 was developed after the comments from the Russian regulatory authorities [Ministry of Health (MoH)]. Adjustments to the text were made to clarify the inclusion and exclusion criteria for enrolment of subjects and the conduct of the study. In addition, adjustments for the reporting period and assessment of adverse events in the safety sections were made for consistency. The newly re-developed and re-validated GSK's DTPa ELISA cut-offs were updated as per the most recent CBER recommendation (2017).

Protocol amendment 3 is developed to accommodate older adults (approximately 58 years old and older) who were born before national recommendations in Russia for infant DTP vaccination. Adjustments to the text are made in the inclusion criteria to clarify the enrolment of subjects for age group eight years and above.

Inclusion criteria

• Subjects or subjects' parent(s)/adoptive parent(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• A male or female four years of age and older.
• Written informed consent obtained from the subject/from the parent(s)/adoptive parent(s) of the subject prior to performing any study specific procedure.
• Written informed assent obtained from subjects aged 14 years to <18 years.
• Healthy subjects as established by medical history and physical examination before entering into the study.
• Children 4-7 years of age with documented previous diphtheria, tetanus and pertussis vaccination (primary series and first booster) as per local recommendation prior to study enrolment, but should have not received any further diphtheria-tetanus containing booster planned at 6-7 years of age as per local recommendations or any other diphtheria, tetanus and pertussis containing vaccine.
• Subjects eight years of age and older who can report previous diphtheria, tetanus with or without pertussis vaccination - documented or to the best of their/subjects' parent(s)/subjects' adoptive parent(s) knowledge - and did not receive an additional diphtheria, tetanus with or without pertussis vaccination within five years prior to enrolment in the study will be enrolled.
• Female subjects of non-childbearing potential may be enrolled in the study.

• Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
• Female subjects of childbearing potential may be enrolled in the study, if the subject:

• has practiced adequate contraception within 30 days prior to vaccination, and
• has a negative pregnancy test on the day of vaccination, and
• has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the vaccination.

Exclusion criteria

• Child in care
• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period.
• History of previous or intercurrent diphtheria, tetanus or pertussis diseases since birth in subjects four to seven years of age.
• History of previous or intercurrent diphtheria, tetanus or pertussis diseases within 5 years prior to enrolment in subjects aged eight years and above.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day (for adult subjects, ≥18 years of age) or ≥ 0.5 mg/kg/day (for paediatric subjects, aged 4-17 years), or equivalent. Inhaled and topical steroids are allowed
• Administration of long-acting immune-modifying drugs at any time during the study period.
• Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before and ending 30 days after the dose of vaccine with the exception of inactivated influenza vaccine which can be given at any time during the study conduct as per the Summary of Product Characteristics (SPC) and according to the local governmental recommendations.
• 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 vaccine/product (pharmaceutical product or device).
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Family history of congenital or hereditary immunodeficiency.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• Hypersensitivity to latex.
• History of encephalopathy after administration of a previous dose of pertussis vaccine that could not be attributed to another identifiable cause, progressive neurologic disorder, uncontrolled epilepsy or progressive encephalopathy: pertussis vaccine should not be administered to individuals with these conditions until a treatment regimen has been established and the condition has stabilised.
• Acute disease and/or fever at the time of enrolment.

• Fever is defined as temperature ≥38.0°C. The preferred location for measuring temperature in this study will be the axilla.
• Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
• Acute or chronic, clinically significant uncontrolled pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination and/or laboratory screening tests.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study vaccine or planned administration during the study period.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions during the study conduct.
• Any medical condition that, in the opinion of the investigator, might interfere with the evaluations required by the study.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.