A study to evaluate the safety, reactogenicity nad immunogenicity of the GSK investigational vaccine GSK3003891A in healthy pregnant women and infants born to vaccinated mothers

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2016-002733-30-GB
• Date of registration: 31/01/2017
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: A study to evaluate the safety, reactogenicity nad immunogenicity of the GSK investigational vaccine GSK3003891A in healthy pregnant women and infants born to vaccinated mothers
• Scientific title: A Phase I/II, randomised, observer-blind, controlled multi-country study to assess the safety, reactogenicity and immunogenicity of a single intramuscular dose of GSK Biologicals’ investigational RSV vaccine (GSK3003891A), in healthy pregnant women aged 18 to 40 years and infants born to vaccinated mothers - RSV F-004
• Date of first enrolment: 08/03/2017
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002733-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Observer blind; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Finland, Honduras, New Zealand, Panama, South Africa, Spain, United Kingdom, United States

Contacts

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 500
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 complian

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Healthy pregnant women (Respiratory Syncytial Virus)
MedDRA version: 19.1 Level: PT Classification code 10061603 Term: Respiratory syncytial virus infection System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: 30µg PreF
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: -
Other descriptive name: Pre F protein
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Product Name: 60µg PreF
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: -
Other descriptive name: Pre F protein
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Product Name: 120 µg PreF
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: -
Other descriptive name: Pre F protein
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

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

Main Objective: To evaluate the safety and reactogenicity of the investigational vaccines

Secondary Objective: To evaluate the safety and humoral immunogenicity of the investigational vaccines

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

Secondary Outcome(s)

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

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

Secondary ID(s)

204810

Source(s) of Monetary Support

GlaxoSmithKline Biologicals