Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Boostrix™ Vaccine in Pregnant Women

The protocol was amended to include Spain in the study. The reasons for the Spain-specific amendment are listed below:

• Based on the feedback from the Spanish Ethics Committee, the evaluation related to the acceptance of cocooning was added in the protocol.
• The objectives and endpoints to include cocooning were added in the protocol.
• The eligibility criteria for participation of household contacts were defined in the protocol.
• The study procedures for household contacts were included.

Inclusion criteria

for study subjects:

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject prior to performing any study specific procedure, as per local regulations.
• A healthy pregnant woman between, and including, 18 and 45 years of age at the time of screening.
• Pregnant subjects at 27 0/7-36 6/7 weeks (completed 27 weeks but not 37 weeks) of gestation at the time of vaccination (Visit 1), as established by ultrasound examination.
• Not at high risk for complications, as determined by the obstetrical algorithm for identification of eligible subjects and the Obstetrical Risk Assessment Form.
• No significant foetal abnormalities, as observed by the level II ultrasound testing conducted after 18 weeks of gestation.
• Nuchal translucency scan, serum testing and any other prenatal tests, if conducted, should suggest normal pregnancy.
• Willing to have the infant born immunised with Infanrix hexa and Prevenar 13, as per national recommendations, in the follow-up clinical studies DTPA (BOOSTRIX)-048 PRI and DTPA (BOOSTRIX)-049 BST: 048.
• Subjects who do not plan to give their child for adoption or place the child in care.

Inclusion criteria

for household contacts in Spain:

• Household contacts living in the same house as that of the infant.
• Household contacts or parent(s)/LAR(s) of the household contacts who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. reporting of SAEs).
• Written informed consent obtained from the household contacts or the parent(s)/LAR(s) prior to vaccination, as per local regulations.
• Household contacts who are eligible to receive a booster dose of DTP-containing vaccine according to the Summary of Product Characteristics (SmPC) of Boostrix and according to the local governmental recommendations in Spain.
• Female household contacts 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 household contacts of childbearing potential may be enrolled in the study , if the household contact

• has practiced adequate contraception for 30 days prior to vaccination,
• has a negative pregnancy test on the day of vaccination and
• has agreed to continue adequate contraception for 2 months after receiving the vaccine dose.

Exclusion criteria

for study subjects:

• Subjects diagnosed with multiple pregnancies (twins, triplets etc.).
• Previous vaccination containing diphtheria, tetanus or pertussis antigens or diphtheria and tetanus toxoids at any time during the current pregnancy.
• Women with co-morbid medical or obstetric conditions that in the opinion of the investigator have the potential to complicate the pregnancy course and outcomes.
• Gestational diabetes as determined by glucose tolerance test conducted after 20 weeks of gestation, as per local recommendations of the country.
• History of early onset (<34 weeks of gestation) of eclampsia/pre-eclampsia in previous pregnancy.
• History of major congenital anomalies in previous pregnancies.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine anytime during the current pregnancy or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
• Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine. For corticosteroids, this will mean prednisone ≥20 mg/day, 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 in the period within the period starting 30 days before and 30 days after the dose of vaccine with the exception of seasonal influenza vaccine that can be administered anytime during the study period.
• 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).
• Serious underlying medical condition [e.g., immunosuppressive disease or therapy, human immunodeficiency virus infection, collagen vascular disease, epilepsy, diabetes mellitus, chronic hypertension, moderate to severe asthma, lung/heart disease, liver/kidney disease, infections including TORCHES (toxoplasmosis, rubella, cytomegalovirus, herpes simplex, syphilis) infections].
• History of an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis-containing vaccine.
• History of transient thrombocytopenia or neurological complications (for convulsions or hypotonic-hyporesponsive episodes) following an earlier immunisation against diphtheria and/or tetanus
• Significant mental illness (e.g. schizophrenia, psychosis and major depression).
• Family history (first degree relatives only) of congenital anomalies, recurrent pregnancy losses (two or more consecutive losses) and unexplained neonatal death(s) in the subject.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• History of febrile illness within the past 72 hours.
• History of physician-diagnosed or laboratory-confirmed pertussis within the past five years.
• Anything that would prevent subject from completing the study or put the subject at risk, as determined by the investigator.
• Acute disease and/or fever at the time of enrolment.

• Fever is defined as temperature ≥ 37.5°C /99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C /100.4°F on rectal route.
• Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• 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, with the exception of anti-D (Rh)-immunoglobulin.
• History of chronic excessive alcohol consumption and/or drug abuse.

Exclusion criteria

for household contacts in Spain:

• Child in care.
• Concurrently participating in another clinical study, at any time during the study period, in which the household contact has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• History of an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis-containing vaccine.
• Acute disease and/or fever at the time of enrolment.

• Fever is defined as temperature ≥ 37.5°C /99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C /100.4°F on rectal route. The preferred route of recording temperature will be axillary in household contacts.
• Household contacts with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Anything that would put the household contact at risk, as determined by the investigator.
• Pregnant or lactating household contacts.
• Household contacts planning to become pregnant or planning to discontinue contraceptive precautions prior to 2 months post-vaccination.