E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
women in their first trimester of pregnancy |
vrouwen in het eerste trimester van hun zwangerschap |
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E.1.1.1 | Medical condition in easily understood language |
women in their first trimester of pregnancy |
vrouwen in het eerste trimester van hun zwangerschap |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
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 evaluate non-inferiority of anti-Pertussis Toxin (PT) IgG in term infants at 2m of age born of mothers having received a pertussis vaccine between 20-24w Gestational Age (GA) compared to a reference anti-PT IgG at 2m of age in a historical control group of term infants born of mothers who were vaccinated between 30-32w GA.
Likewise, we aim to assess non-inferiority of anti-PT IgG in preterm infants at 2m of age born of mothers having received a pertussis vaccine between 20-24w GA compared to the 20 IU/ml anti-PT IgG cut-off used in many immunogenicity studies.
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het evalueren van non-inferioriteit van anti-PT IgG in op tijd geboren kinderen op leeftijd van 2m, die geboren zijn uit moeders, die tussen 20-24w zwangerschapsduur gevaccineerd zijn tegen kinkhoest t.o.v. een historische controle groep van op tijd geboren kinderen van moeders, die gevaccineerd zijn tussen 30-32w zwangerschapsduur. Daarnaast evalueren we of de anti-PT IgG in te vroeg geboren kinderen op leeftijd van 2m en geboren uit moeders, die gevaccineerd zijn tegen kinkhoest tussen 20-24w zwangerschapsduur non-inferieur is t.o.v. een afkapwaarde van 20IU/ml |
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E.2.2 | Secondary objectives of the trial |
-Compare pertussis specific IgG at 2m of age (i.e. before the first infant vaccination) between preterms and terms.
-Compare the decay between birth and 2 month of age in pertussis specific maternal IgG between terms and preterms at 2m
-Compare pertussis specific IgG at delivery between mothers who delivered preterm and term.
-Compare immunogenicity in mothers who received 2nd trimester pertussis vaccination and a group that received 3rd trimester immunization.
-Determine levels of pertussis specific IgG transferred from mother to neonate relative to the interval from immunization to delivery, depending on the variation in interval.
-Assess tolerability of maternal Tdap vaccination, administered to pregnant women between 20-24wG A.
-Assess possible adverse pregnancy outcomes of this maternal vaccination between 20-24w GA
--Assess social cognitive determinants and underlying beliefs of maternal pertussis immunization between 20-24w GA and their correlation with behavior
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-vergelijken van pertussis specifiek IgG op leeftijd van 2m tussen te vroeg en op tijd geboren kinderen.
-vergelijken van daling tussen geboorte en 2m van kinkhoest specifiek IgG in op tijd en te vroeg geboren kinderen.
-vergelijken van pertussis specifiek IgG tijdens geboorte in moeders van op tijd en te vroeg geboren kinderen.
-vergelijken van immunogeniciteit van 2de en 3de trimester maternale kinkhoestvaccinatie.
- bepalen van hoeveelheid overgedragen pertussis specifiek IgG van moeder naar kind gerelateerd aan tijd tussen vaccinatie en bevalling.
-bepalen van de tolerabiliteit van 2de trimester maternale kinkhoestvaccinatie.
-bepalen van mogelijke negatieve zwangerschapsuitkomsten van 2de trimester maternale kinkhoestvaccinatie
-bepalen van sociaal cognitieve determinanten en overtuigingen t.a.v. kinkhoestvaccinatie tussen 20-24w zwangerschapsduur en hun relatie met gedrag.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 18 years or older
2. Being pregnant
3. Having an antenatal appointment with a midwife or obstetrician in the 1st trimester of pregnancy
4. Signed informed consent
5. Parents who are willing to adhere to the protocol and perform all planned visits and
sample collections for themselves and their newborn child (only relevant for the immunogenicity part
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1. 18 jaar of ouder
2. in eerste trimester van zwangerschap zijn en afspraak met met verloskundig zorgverlener
3. getekend toestemmingsformulier
4. bereidheid mee te werken aan bloedafnames
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E.4 | Principal exclusion criteria |
1. All women with one or more missing inclusion criteria
2. History of having received a pertussis containing vaccination in the past 2 years.
3. History of having had pertussis disease in the past 5 years.
4. Known or suspected serious underlying condition that can interfere with the results
of the study such as but not limited to cancer, autoimmune disease, immunodeficiency, seizure disorder or significant psychiatric illness.
5. Receipt of any high-dose (≥20 mg of prednisone daily or equivalent) daily corticosteroids within 2 weeks of study entry (inhaled or other local steroids are acceptable) with exception of corticosteroids to enhance maturation of fetal lungs in case of imminent early delivery.
6. Receipt of other immune modulating medication, for instance biologicals.
7. Receipt of blood products or immunoglobulins, within three months of study entry
(Rhesus negative women who receive anti-rhesus (D)- immunoglobulin will not be
excluded from the study).
8. Presence of bleeding disorder.
9. Having experienced a previous severe adverse reaction to any vaccine.
10. Receipt of any vaccine(s) within 2 weeks of study vaccine (except influenza
vaccine which may be given concomitantly).
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1. vrouwen met 1 of meer missende inclusiecriteria
2. kinkhoestvaccinatie in afgelopen 2jr
3. kinkhoest in afgelopen 5jr
4. ernstig onderliggend lijden dat kan interfereren met de studie resultaten, zoals maar niet gelimiteerd tot kanker, auto-immuunziekte.
5. toediening van hoge dosis corticosteroïden binnen 2wk voor deelname m.u.v. corticosteoriden i.v.m. longrijping kind bij dreigende vroeggeboorte.
6.toedieing van andere immuun modulerende medicatie
7. toediening van bloedprodukten of immunoglobulinen m.u.v. anti-D binnen 3m voor deelname
8. stollingsstoornis
9. ernstige bijwerking op eerdere vaccinatie
10. toediening van vaccin binnen 2wk voor deelname m.u.v. influenza, dat gelijktijdig gegeven mag worden
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E.5 End points |
E.5.1 | Primary end point(s) |
Serum IgG antibody levels against vaccine antigen PT in preterm and term infants at 2 months of age, before start of infant vaccination. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
blood sampling at birth (mother and infant) and at 2m of age (infant) |
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E.5.2 | Secondary end point(s) |
1. The IgG antibody concentration against pertussis toxin (PT), pertactin (Prn) filamentous hemagglutinin (FHA), tetanus and diphtheria in the mother at delivery.
2. The IgG antibody concentration against PT, Prn, FHA, tetanus and diphtheria in the infant at birth (cord blood).
3. The IgG antibody concentration against Prn, FHA, tetanus and diphtheria in the infant at 2m of age.
4. The decay in IgG antibody concentration against PT, Prn, FHA, tetanus and diphtheria in infants from birth until 2 months of age.
5. The ratio between maternal GMCs and infant GMCs at birth
6. Frequency of local and systemic adverse events occurring within 7 days after vaccination during pregnancy.
7. Frequency of systemic events, occurring in the week before vaccination.
8. Prediction factors of women’s attitude towards maternal pertussis vaccination between 20-24w GA
9. Frequencies of perinatal outcomes, i.e. delivery mode, apgar score, umbilical blood gas, neonatal hospitalization, reason for neonatal hospitalization, duration of neonatal hospitalization, hospitalization in first 2 months of life, reason for this hospitalization, duration of this hospitalization
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
blood sampling at birth (mother and infant) and at 2m of age (infant) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
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 |
effect on anti-PT IgG at 2m of age in infants born of mothers who were vaccinated against pertussis between 20-24w GA |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |