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

NCT03191383 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 2048102016-002733-30
• Study Type: interventional
• Target: N/A
• Locations: 3 countries
• Sites: 12

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

Conditions

Respiratory Syncytial Virus Infections

Keywords

Maternal immunization; Immunogenicity; Vaccines; Safety; Reactogenicity; Respiratory Syncytial Virus

Outcome Measures

Primary Outcomes (12)

• Number of subjects with solicited local adverse events (AEs)

  Assessed solicited local symptoms are pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevents normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

  During a 7-day follow-up period after vaccination (i.e. the day of vaccination and 6 subsequent days)

• Number of subjects with solicited general AEs

  Assessed solicited general symptoms are fatigue, fever \[defined as oral/axillary/tympanic route temperature equal to or above 37.5 degrees Celsius (°C) or ≥ 38 °C for rectal route\], gastrointestinal symptoms \[nausea, vomiting, diarrhoea and/or abdominal pain\] and headache. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevents normal activity. Grade 3 fever = fever \> 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination

  During the 7-day follow-up period after vaccination (i.e. the day of vaccination and 6 subsequent days)

• Number of subjects with unsolicited AEs

  An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevents normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  During a 30-day follow-up period after vaccination (i.e. the day of vaccination and 29 subsequent days)

• Number of subjects with haematological abnormalities

  Haematological laboratory abnormalities include haemoglobin level, white blood cell count \[WBC\], lymphocyte, neutrophil, eosinophil, platelet count, red blood cell count and mean corpuscular volume.

  At Day 0

• Number of subjects with haematological abnormalities

  Haematological laboratory abnormalities include haemoglobin level, white blood cell count \[WBC\], lymphocyte, neutrophil, eosinophil, platelet count, red blood cell count and mean corpuscular volume.

  At Day 7

• Number of subjects with biochemical abnormalities

  Biochemical laboratory abnormalities include alanine amino-transferase \[ALT\], aspartate amino-transferase \[AST\], creatinine and blood urea nitrogen.

  At Day 0

• Number of subjects with biochemical abnormalities

  Biochemical laboratory abnormalities include alanine amino-transferase \[ALT\], aspartate amino-transferase \[AST\], creatinine and blood urea nitrogen.

  At Day 7

• Number of subjects with any serious adverse events (SAEs)

  SAEs are defined as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From study start (Day 0) up to 6 months after delivery

• Number of infant subjects with any SAEs

  SAEs are defined as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From birth up to 6 months after birth

• Number of subjects with pregnancy outcomes

  Pregnancy outcomes include live birth with no congenital anomalies, live birth with congenital anomalies, foetal death/still birth with no congenital anomalies, foetal death/still birth with congenital anomalies, elective/therapeutic termination with no congenital anomalies and elective/therapeutic termination with congenital anomalies.

  From study start (Day 0) up to delivery

• Number of subjects with pregnancy-related AEs of specific interest

  Pregnancy-related adverse events of specific interest include: gestational diabetes, gestational liver disease (including obstetric cholestasis and acute fatty liver of pregnancy), chorioamnionitis, labour protraction and arrest disorders, maternal sepsis, pregnancy-related hypertension, preterm premature rupture of membranes, premature labour, intrauterine growth restriction/poor foetal growth, pre-eclampsia and eclampsia, vaginal or intrauterine haemorrhage, medical conditions necessitating early delivery (induced labour or urgent C-section) (placenta abruption, uterine infection, oligohydramnios, etc), maternal death.

  From study start (Day 0) up to delivery

• Number of infant subjects with AEs of specific interest

  Infant-related AEs of specific interest include preterm birth, neonatal death, low birth weight and/or small for gestational age, neonatal sepsis, foetal/perinatal distress or asphyxia, failure to thrive/growth deficiency, congenital anomalies and neurodevelopmental delay.

  From birth up to 6 months after birth

Secondary Outcomes (13)

• Number of infant subjects with SAEs

  From birth and up to study end (Year 2)

• Number of infant subjects with AEs potentially related to maternal vaccination

  From birth up to study end (Year 2)

• Number of infant subjects with neuro-developmental delays

  At Year 1 and Year 2

• Number of infant subjects referred for formal neurological evaluation

  At Year 1 and Year 2

• Number of infant subjects with confirmed developmental delay

  At Year 1 and Year 2

Study Arms (8)

GSK3003891A vaccine formulation 1 mother Group

EXPERIMENTAL

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.

Biological: RSV vaccine (GSK3003891A) formulation 1

GSK3003891A vaccine formulation 2 mother Group

EXPERIMENTAL

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.

Biological: RSV vaccine (GSK3003891A) formulation 2

GSK3003891A vaccine formulation 3 mother Group

EXPERIMENTAL

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.

Biological: RSV vaccine (GSK3003891A) formulation 3

Control group

PLACEBO COMPARATOR

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

Drug: Placebo (Formulation buffer S9b)

GSK3003891A vaccine formulation 1 infant Group

NO INTERVENTION

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

GSK3003891A vaccine formulation 2 infant Group

NO INTERVENTION

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

GSK3003891A vaccine formulation 3 infant Group

NO INTERVENTION

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

Control infant Group

NO INTERVENTION

Infants born to mothers who received a single placebo injection

Interventions

RSV vaccine (GSK3003891A) formulation 1 BIOLOGICAL

Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm

GSK3003891A vaccine formulation 1 mother Group

RSV vaccine (GSK3003891A) formulation 2 BIOLOGICAL

Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm

GSK3003891A vaccine formulation 2 mother Group

RSV vaccine (GSK3003891A) formulation 3 BIOLOGICAL

Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm

GSK3003891A vaccine formulation 3 mother Group

Placebo (Formulation buffer S9b) DRUG

Single dose administered intramuscularly at Day 0 in the deltoid region of the non-dominant arm

Control group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• st 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (12)

GSK Investigational Site

Newton, Kansas, 67114, United States

Location

GSK Investigational Site

Syracuse, New York, 13210, United States

Location

GSK Investigational Site

Ellensburg, Washington, 98926, United States

Location

GSK Investigational Site

Oulu, 90220, Finland

Location

GSK Investigational Site

Seinäjoki, 60100, Finland

Location

GSK Investigational Site

Aravaca, 28023, Spain

Location

GSK Investigational Site

Burgos, 09006, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Majadahonda (Madrid), 28222, Spain

Location

GSK Investigational Site

Santiago, 15705, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Seville, 41014, Spain

Location

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

Respiratory Syncytial Virus Vaccines

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 19, 2017
• Study Start: July 11, 2017
• Primary Completion: July 14, 2017
• Study Completion: July 14, 2017
• Last Updated: October 15, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share

Locations

ES (7); US (3); FI (2)