Clinical trial NCT03191383: 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
Official title: An Observer-blind Study to Assess the Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Investigational RSV Vaccine (GSK3003891A), in Healthy Pregnant Women and Infants Born to Vaccinated Mothers
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Keywords: Maternal immunization
Immunogenicity
Vaccines
Safety
Reactogenicity
Respiratory Syncytial Virus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-06-19
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with solicited local adverse events (AEs)
timeFrame: During a 7-day follow-up period after vaccination (i.e. the day of vaccination and 6 subsequent days)
measure: Number of subjects with solicited general AEs
timeFrame: During the 7-day follow-up period after vaccination (i.e. the day of vaccination and 6 subsequent days)
measure: Number of subjects with unsolicited AEs
timeFrame: During a 30-day follow-up period after vaccination (i.e. the day of vaccination and 29 subsequent days)
measure: Number of subjects with haematological abnormalities
timeFrame: At Day 0
measure: Number of subjects with haematological abnormalities
timeFrame: At Day 7
measure: Number of subjects with biochemical abnormalities
timeFrame: At Day 0
measure: Number of subjects with biochemical abnormalities
timeFrame: At Day 7
measure: Number of subjects with any serious adverse events (SAEs)
timeFrame: From study start (Day 0) up to 6 months after delivery
measure: Number of infant subjects with any SAEs
timeFrame: From birth up to 6 months after birth
measure: Number of subjects with pregnancy outcomes
timeFrame: From study start (Day 0) up to delivery
measure: Number of subjects with pregnancy-related AEs of specific interest
timeFrame: From study start (Day 0) up to delivery
measure: Number of infant subjects with AEs of specific interest
timeFrame: From birth up to 6 months after birth
Secondary outcomes:
measure: Number of infant subjects with SAEs
timeFrame: From birth and up to study end (Year 2)
measure: Number of infant subjects with AEs potentially related to maternal vaccination
timeFrame: From birth up to study end (Year 2)
measure: Number of infant subjects with neuro-developmental delays
timeFrame: At Year 1 and Year 2
measure: Number of infant subjects referred for formal neurological evaluation
timeFrame: At Year 1 and Year 2
measure: Number of infant subjects with confirmed developmental delay
timeFrame: At Year 1 and Year 2
measure: Neutralizing antibody titres against RSV-A, for all vaccinated mothers
timeFrame: At pre-vaccination (Day 0), Day 30 and Day 60 post vaccination and at delivery
measure: Neutralizing antibody titres against RSV-B, for all vaccinated mothers
timeFrame: At pre-vaccination (Day 0), Day 30 and Day 60 post vaccination and at delivery
measure: Palivizumab competing antibody (PCA) concentrations, for all vaccinated mothers.
timeFrame: At pre-vaccination (Day 0), Day 30 and Day 60 post-vaccination and at delivery
measure: Neutralizing antibody titres against RSV-A, for all infants born to vaccinated mothers
timeFrame: At birth, at Month 3 and at Month 6
measure: Neutralizing antibody titres against RSV-B, for all infants born to vaccinated mothers
timeFrame: At birth, at Month 3 and at Month 6
measure: PCA concentrations, for all infants born to vaccinated mothers
timeFrame: At birth, at Month 3 and at Month 6
measure: Number of infant subjects with lower respiratory tract infection (LRTI), severe LRTI and respiratory tract infection (RTI) with parental concern (according to the case definitions) associated with a respiratory syncytial virus (RSV) infection
timeFrame: From birth up to study end (Year 2)
measure: Number of subjects (vaccinated mothers) with medically-attended (MA) RTI associated with an RSV infection
timeFrame: From Day 0 up to Month 6 post delivery
Other outcomes:
Locations:
city: Newton
country: United States
facility: GSK Investigational Site
state: Kansas
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Ellensburg
country: United States
facility: GSK Investigational Site
state: Washington
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Seinajoki
country: Finland
facility: GSK Investigational Site
city: Aravaca
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Majadahonda (Madrid)
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Santiago
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: