| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Booster immunisation against diphtheria, tetanus and pertussis diseases. The study population for this study will include pregnant women. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Booster immunisation against diphtheria, lockjaw and whopping cough diseases. The study population for this study will include pregnant women. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10047976 |
| E.1.2 | Term | Whooping cough due to bordetella pertussis (B. pertussis) |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10009663 |
| E.1.2 | Term | Clostridium tetani infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054237 |
| E.1.2 | Term | Corynebacterium diphtheriae infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To demonstrate that the maternally transferred antibodies against pertussis in the dTpa Group is superior to that in the Control Group in terms of geometric mean concentrations (GMCs) for the pertussis antibodies, in the cord blood sample.
Criterion:
The lower limit (LL) of the 95% confidence interval (CI) of the GMC ratio [dTpa Group divided by Control Group] for anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibodies is ≥ 1.5.
|
|
| E.2.2 | Secondary objectives of the trial |
| •Safety of Boostrix, given during pregnancy (outcomes of pregnancy, pregnancy-related AEs of interest/neonate-related events) up to study end (Month 2) •Immunogenicity of Boostrix given during pregnancy (seropositivity status for anti-pertussis antibodies, in cord blood sample) •Immunogenicity of Boostrix given during pregnancy (seroprotection/seropositivity status, vaccine response, GMCs for anti-diphtheria, -tetanus and –pertussis antibodies), 1 month post-vaccination •Reactogenicity of Boostrix given during pregnancy and post-delivery (solicited symptoms during 8-days after vaccination) •Safety of Boostrix given during pregnancy and post-delivery (unsolicited symptoms during the 31-days after vaccination and SAEs during entire study period) •Acceptance rate of Boostrix in eligible household contacts as part of an assessment of cocooning •Safety of Boostrix (SAEs) in vaccinated household contacts as part of an assessment of cocooning, from vaccination to 1 month post vaccination. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria for study subjects:
• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
• 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 270/7-366/7 weeks (completed 27 weeks but not 37 weeks) of gestation at the time of vac-cination (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 preg-nancy.
• 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 premenarche, 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. |
|
| E.4 | Principal exclusion criteria |
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 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 (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the 1st 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 •Serious underlying medical condition •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 following an earlier immunisation against diphtheria and/or tetanus •Significant mental illness •Family history (1st degree relatives only) of congenital anomalies, recurrent pregnancy losses (2 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 •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 5 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 •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 •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 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 •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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Immunogenicity with respect to components of the study vaccine (in cord blood sample):
Anti-PT, anti-FHA and anti-PRN antibody concentrations |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At delivery (28 weeks to 40 weeks of gestation) |
|
| E.5.2 | Secondary end point(s) |
Pregnancy outcomes will include live birth with no congenital anomalies, live birth with congenital anomalies, still birth with no congenital anomalies, still birth with congenital anomalies, elective termination with no congenital anomalies and elective termination with congenital anomalies.
Pregnancy-related adverse events of interest/ neonate-related events will include gestational diabetes, pregnancy-related hypertension, premature rupture of membranes, preterm premature rupture of membranes, premature labour, premature uterine contractions, intrauterine growth restriction/poor foetal growth, pre-eclampsia, eclampsia, vaginal or intrauterine haemorrhage, maternal death, preterm birth, neonatal death, small for gestational age, neonatal hypoxic ischaemic encephalopathy and failure to thrive/growth deficiency.
Anti-D, anti-T, anti-PT, anti-FHA and anti-PRN seroprotection/seropositivity status and antibody concentrations.
Vaccine response to PT, FHA and PRN
Vaccine response to anti-D and anti-T
Anti-PT, anti-FHA and anti-PRN seropositivity status.
Occurrence of each solicited local/general symptoms (at Visit 1 and Visit 3)
Occurrence of unsolicited AEs, according to the Medical Dictionary for Regulatory Activities (MedDRA) classification (at Visit 1 and Visit 3).
Occurrence of serious adverse events.
Percentage of household contacts of the infants born to pregnant women vaccinated in Spain who accepted Boostrix vaccine as part of an assessment of
cocooning among the eligible household contacts.
Occurrence of SAEs among the vaccinated household contacts of the infants born to pregnant women in Spain, as part of an assessment of cocooning, from the day of vaccination till 30 days after vaccination. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
outcome of pregnancy in terms of pregnancy outcomes and pregnancy-related adverse events of interest/ neonate-related events: Up to two months post-delivery.
Seroprotection/seropositivity and vaccine response: One month post vaccination
Anti-PT, anti-FHA and anti-PRN seropositivity: At delivery (28 weeks to 40 weeks of gestation)
Solicited local and general symptoms: During the 8-day (Day 0-Day 7) follow-up period after the vac-cination.
unsolicited AEs: Within 31 days (Day 0 – Day 30) after vaccination
SAEs: From Day 0 up to two months post-delivery.
Percentage of household contacts who accepted Boostrix-
Occurrence of SAEs among the vaccinated household contacts-From the day of vaccination until 30 days after vaccination. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Czech Republic |
| Finland |
| Italy |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
Print
