| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy pregnant women (Respiratory Syncytial Virus) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Respiratory syncytial virus is a very common virus that leads to mild, cold-like symptoms in adults and older children. RSV can cause more serious disease in infants, such as inflammation of the lungs |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061603 |
| E.1.2 | Term | Respiratory syncytial virus infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 the safety and reactogenicity of the investigational vaccines |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety and humoral immunogenicity of the investigational vaccines |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
MOTHERS:
• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol
• Written informed consent for study participation of the mother obtained from the mother or the mother and father, as applicable by local law, prior to performance of any study specific procedure.
• Written informed consent for study participation of the infant obtained from the infant’s mother and/or father, as applicable by local law, or LAR prior to performance of any study specific procedure.
• Subjects between, and including, 18 and 40 years of age at the time of the first study visit
• Pregnant females > 24 weeks of gestation at the time of screening and at 28 0/7 to 33 6/7 weeks of gestation at the time of vaccination, as established by ultrasound examination and last menstrual period date.
• Healthy pregnant females as established by medical history and clinical examination before entering into the study.
• Pregnant females not at high risk for complications, as determined by the obstetrical risk assessment form.
• No significant foetal findings observed during a second or third trimester ultrasound.
• Subjects who are willing to provide cord blood.
• Subjects who do not plan to give their child for adoption or place the child in care.
INFANTS:
•Re-signed (confirmed) written informed consent for study participation of the infant obtained from the infant’s mother and/or father, as applicable by local law, or LAR. |
|
| E.4 | Principal exclusion criteria |
MOTHERS:
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines during the period starting 30 days before vaccination (Day -29 to Day 0), or planned use during the study period.
•Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before vaccination and ending at delivery with the exception of seasonal influenza vaccine and dTpa/Tdap vac-cine as part of SOC which may be administered ≥ 15 days before or after study vaccination.
•Chronic administration (defined as more than 14 consecutive days) of systemic immunosuppressants or other immune-modifying drugs, as well as administration of long-acting immune-modifying drugs during the period starting 6 months prior to study vaccination, or planned administration up to delivery. Topical steroids are allowed. Inhaled steroids are allowed up to the limit of ≤ 500 µg/day for beclomethasone or fluticasone, or ≤ 800 µg/day for budesonide.
•Administration of immunoglobulins (with the exception of prophylactic anti-Rh0D immune globulin) and/or any blood products during the period starting 3 months before study vaccination or planned administration during the study period.
•Previous experimental vaccination against RSV.
•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.
•Low lying placenta (placenta praevia) during the current pregnancy, unless there is documented sonographic evidence that the placenta has moved up prior to enrolment (Visit 1).
•Any abnormal finding observed in nuchal translucency scan, serum testing and any other prenatal tests, if conducted.
•Incompetent cervix or cerclage during the current pregnancy.
•Having received medical treatment for suspected preterm delivery (e.g. systemic steroids or progesterone) during the current pregnancy.
•Prior preterm delivery (≤ 34 weeks gestation) or having ongoing intervention (medical/surgical) in current pregnancy to prevent preterm delivery.
•Prior stillbirth or neonatal death, or ≥2 spontaneous abortions.
•Personal history of major congenital anomalies or early onset (<34 weeks of gestation) of eclampsia/preeclampsia in previous pregnancy.
•1st degree family history of major congenital anomalies and/ or hereditary immunodeficiency.
•Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical his-tory and physical examination.
•Hemodynamically significant cardiac disorders (previously corrected patent ductus arteriosis is allowed)
•Gestational diabetes as determined by glucose challenge/tolerance test conducted after 20 weeks of gestation or as per local recommendations of the country, requiring intervention other than diet for control.
•History of gestational diabetes in previous pregnancy(ies).
•Hypertension during the current pregnancy or if any antihypertensive medication is being pro-vided.
•Current obstetric cholestasis or history of it during previous pregnancy(ies).
•Current obstetric cholestasis or history of obstetric cholestasis.
•Asthma and/or COPD if the subject is receiving chronic systemic glucocorticoids at any dose or inhaled glucocorticoids > 500 µg/day of beclomethasone or fluticasone, or > 800 µg/day of budesonide.
•Significant neuropsychiatric illness deemed likely to interfere with protocol compliance, safety reporting or receipt of pre-natal care, or requiring treatment with psychotropic drugs.
•Diagnosed or suspected to have/have had Zika virus infection during the current pregnancy.
•Known HIV infection, as assessed by local standard of care serologic tests conducted during the current pregnancy and prior to enrolment (Visit 1).
•Known or suspected HBV or HCV infection.
•Known infection during the current pregnancy with Toxoplasma, Parvovirus B19, Syphilis, Rubella, CMV or primary Herpes Simplex.
•Known foetal anomalies in the current pregnancy.
•Any clinically significant haematological and/or biochemical laboratory abnormality.
•Acute disease and/or fever within 3 days prior to enrolment.
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
•Hypersensitivity to latex.
•Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
•History of drug or alcohol abuse within the past 2 years.
•Any condition which, in the investigator’s opinion, would increase the risks of study participation to the unborn infant.
•Planned move to a location that will prohibit participating in the trial until study end.
INFANTS:
•Any condition which, in the investigator’s opinion, would increase the risks of study participation to the infant. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1) Occurrence of each solicited local and general adverse event (AE), in all pregnant women
2) Occurrence of any unsolicited AE, in all pregnant women
3) Occurrence of any haematological (haemoglobin level, white blood cells [WBC], lymphocyte, neutrophil, eosinophil, platelet count, red blood cell count and mean corpuscular volume) and biochemical (alanine amino-transferase [ALT], aspartate amino-transferase [AST], creatinine and blood urea nitrogen) laboratory abnormality, in all pregnant women
4) Occurrence of any SAE, for all pregnant women
5) Occurrence of any SAE, for all infants born to mothers who were vaccinated
6) Outcome of pregnancy
7) Pregnancy-related adverse events of specific interest for all mothers
8) Infant-related AEs of specific interest for all infants |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) During a 7-day follow-up period after vaccination (i.e. the day of vaccination and 6 subsequent days)
2) During a 30-day follow-up period after vaccination (i.e. the day of vaccination and 29 subsequent days)
3) At Day 0 and Day 7
4) From study start (Day 0) up to 6 months after delivery (Visit 5)
5) From birth up to 6 months after birth (Visit 3-NB)
6) From study start (Day 0) up to delivery
7) From study start (Day 0) up to delivery
8) From birth up to 6 months after birth |
|
| E.5.2 | Secondary end point(s) |
1) Occurrence of any SAE for all infants born to mothers who were vaccinated
2) Any AE occurring in the infant, potentially related to vaccination of the mother during pregnancy, at the discretion of the investigator
3) Neurodevelopment assessment
3.1) proportion of infants with an Ages and Stages questionnaires version 3 (ASQ-3) score in the grey zone (i.e. monitoring zone) or black zone (i.e. referral zone) for any domain
3.2) proportion of infants referred for formal neurological evaluation (using Bayley Scale for Infant Development, version III [BSID-III] or equivalent)
3.3) proportion of infants confirmed with neurodevelopmental delay after detailed evaluation (using BSID-III or equivalent)
4) Humoral immune response to the investigational RSV vaccine for all vaccinated mothers
5) RSV-specific antibodies for all infants born to vaccinated mothers
6)Occurrence of RSV-associated LRTI, severe LRTI and RTI with parental concern (according to the case definitions) for all infants born to vaccinated women
7)Occurrence of medically attended RSV-associated RTI in mothers |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) and 2) From birth and up to study end
3) at Visit 4-NB and Visit 5-NB (age of infants 12 months and 24 months, adjusted for prematurity)
4) at pre-vaccination (Visit 1), 30 days post-vaccination (Visit 3), 60 days post-vaccination (Visit 4) and at Delivery (Visit 5)
5) at birth (Visit 1-NB) (for all infants), at 3 months after birth (for sub-cohort M3), at 6 months after birth (for sub-cohort M6)
6)f rom birth up to 2 years of age (study end)
7) from study start up to 6 months post-delivery |
|
| 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) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| First administration to pregnant women |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| 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 | 4 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 |
| Finland |
| Honduras |
| New Zealand |
| Panama |
| South Africa |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
| Last testing results released for samples collected up to Visit 5-NBNB (i.e. up to the last visit of the last subject -LVLS-), which corresponds to the last testing results released for the assays related to the primary and secondary study endpoints. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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