A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the GlaxoSmithKline (GSK) Biologicals' Respiratory Syncytial Virus (RSV) Investigational Vaccine (GSK3003891A) in Healthy Pregnant Women and Infants Born to Vaccinated Mothers

GlaxoSmithKline (GSK)

Status and phase: Withdrawn; Phase 2

Conditions: Respiratory Syncytial Virus Infections

Treatments: Biological: RSV vaccine (GSK3003891A) formulation 2; Biological: RSV vaccine (GSK3003891A) formulation 1; Biological: RSV vaccine (GSK3003891A) formulation 3; Drug: Placebo (Formulation buffer S9b)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03191383

204810

2016-002733-30 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to assess the safety, reactogenicity and immunogenicity of the investigational GSK RSV vaccine in pregnant women aged 18 to 40 years and infants born to the vaccinated women

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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 legally acceptable representative [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.

Inclusion Criteria infants:

• Re-signed 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.

Exclusion criteria

• Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before vaccination , 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 diphtheria, tetanus, pertussis/tetanus, diphtheria, pertussis [dTpa/Tdap] vaccine as part of standard of care which may be administered ≥ 15 days before or after study vaccination.
• Chronic administration 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 during the current pregnancy, unless there is documented sonographic evidence that the placenta has moved up prior to enrolment.
• 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 during the current pregnancy.
• Prior preterm delivery or having ongoing intervention 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 of eclampsia/pre-eclampsia in previous pregnancy.
• 1st degree relatives family history of major congenital anomalies and/ or hereditary immunodeficiency.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Hemodynamically significant cardiac disorders.
• 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. In countries where glucose challenge/tolerance testing is not routinely performed in all pregnant women, should the screening urinalysis test show presence of glucose in urine, a glucose challenge/tolerance test should be performed and results should be available prior to enrolment, in order to exclude gestational diabetes prior to subject receiving the study vaccine.
• History of gestational diabetes in previous pregnancy(ies).
• Hypertension during the current pregnancy as defined below or if any antihypertensive medication is being provided, or history of hypertension requiring antihypertensive medication:

Hypertension during current pregnancy is defined as:

• a blood pressure systolic > 140 and/or diastolic 90 mmHg, documented in at least 2 separate measurements .

  • Current obstetric cholestasis or history of obstetric cholestasis.
  • Asthma and/or chronic obstructive pulmonary disease [COPD] if the subject is receiving treatment with chronic systemic glucocorticoids at any dose or inhaled glucocorticoids > 500 µg/day of beclomethasone or fluticasone, or > 800 µg/day of budesonide.
  • Significant neuro-psychiatric illness deemed likely to interfere with protocol compliance, safety reporting or receipt of pre-natal care, or requiring treatment with psychotropic drugs.
  • Diagnosed with Zika virus infection or suspected to have or 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.
  • Known or suspected Hepatitis B virus [HBV] or Hepatitis C virus [HCV] infection.
  • Known infection during the current pregnancy with Toxoplasma, Parvovirus B19, Syphilis, Rubella, cytomegalovirus [CMV] or primary Herpes Simplex.
  • Known foetal anomalies in the current pregnancy.
  • Any clinically significant haematological and/or biochemical laboratory abnormality.

• Subjects with haematological/ biochemical values out of normal range which are expected to be temporary may be re-screened at a later date within the allowed time interval.

  • Acute disease and/or fever within 3 days prior to 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 for rectal route.

• Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

• For subjects with acute disease and/ or fever at the time of enrolment, Visit 1 may be scheduled at a later date within the allowed time interval and gestational age.

  • 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.

Exclusion Criteria infants:

• Any condition which, in the investigator's opinion, would increase the risks of study participation to the infant.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 8 patient groups, including a placebo group

GSK3003891A vaccine formulation 1 mother Group

Experimental group

Description:

Subjects in this group will receive a single 30µg dose of the GSK3003891A investigational vaccine, by intramuscular injection into the deltoid region of the non-dominant arm.

Treatment:

Biological: RSV vaccine (GSK3003891A) formulation 1

GSK3003891A vaccine formulation 2 mother Group

Experimental group

Description:

Subjects in this group will receive a single 60µg dose of the GSK3003891A investigational vaccine, by intramuscular injection into the deltoid region of the non-dominant arm.

Treatment:

Biological: RSV vaccine (GSK3003891A) formulation 2

GSK3003891A vaccine formulation 3 mother Group

Experimental group

Description:

Subjects in this group will receive a single 120µg dose of the GSK3003891A investigational vaccine, by intramuscular injection into the deltoid region of the non-dominant arm.

Treatment:

Biological: RSV vaccine (GSK3003891A) formulation 3

Control group

Placebo Comparator group

Description:

Subjects in this group will receive a single placebo injection, intramuscularly into the deltoid region of the non-dominant arm.

Treatment:

Drug: Placebo (Formulation buffer S9b)

GSK3003891A vaccine formulation 1 infant Group

No Intervention group

Description:

Infants born to mothers vaccinated with a single 30µg dose of the investigational GSK3003891A vaccine

GSK3003891A vaccine formulation 2 infant Group

No Intervention group

Description:

Infants born to mothers vaccinated with a single 60µg dose of the investigational GSK3003891A vaccine

GSK3003891A vaccine formulation 3 infant Group

No Intervention group

Description:

Infants born to mothers vaccinated with a single 120µg dose of the investigational GSK3003891A vaccine

Control infant Group

No Intervention group

Description:

Infants born to mothers who received a single placebo injection