Clinical trial NCT04126213: Study of Safety, Reactogenicity and Immunogenicity of GlaxoSmithKline's (GSK)Respiratory Syncytial Virus (RSV)Maternal Unadjuvanted Vaccine in Healthy Pregnant Women (Aged 18 to 40 Years) and Their Infants
Official title: A Phase II, Randomised, Observer-blind, Placebo Controlled Multi-country Study to Assess the Safety, Reactogenicity and Immunogenicity of a Single Intramuscular Dose of GSK Biologicals' Investigational RSV Maternal Unadjuvanted Vaccine (GSK3888550A), in Healthy Pregnant Women Aged 18 to 40 Years and Infants Born to Vaccinated Mothers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-10-15
Enrollment: 534
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 was to evaluate the safety and immune response to a single intramuscular (IM) dose of GSK Biologicals' investigational RSV maternal vaccine (RSVPreF3) in healthy pregnant women 18-40 years of age and in infants born to vaccinated mothers.


Eligibility criteria: Inclusion Criteria:

Maternal subjects

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Subjects who give written or witnessed/thumb printed informed consent after the study has been explained according to local regulatory requirements, and before any study specific procedures are performed. The informed consent given at screening should (consistent with local regulations / guidelines) either:

  * include consent for both the maternal subject's participation and participation of the infant after the infant's birth, or
  * include consent for the maternal subject's participation and expressed willingness to consider permitting the infant to take part after the infant's birth.
  * Both mother and father should consent if local regulations/guidelines require it.
* Age 18 to 40 years, inclusive, when informed consent is given.
* Pre-pregnancy BMI 18.5 to 34.9, inclusive
* Healthy as established by medical history and clinical examination before entering into the study.
* At 28\^0/7 to 33\^6/7 weeks of gestation at the time of study vaccination (Visit 1), as established by last menstrual period (LMP) date corroborated by first or second trimester ultrasound examination (U/S).

  \* If LMP and U/S do not correlate, default to U/S gestational age assessment. The level of diagnostic certainty of the gestational age should be established by using the Global Alignment of Immunisation safety Assessment in pregnancy gestation age assessment tool
* Subject satisfying screening requirements
* Singleton pregnancy
* HIV negative, as assessed by local standard of care serologic tests conducted during the current pregnancy and before enrolment (Visit 1).
* No fetal genetic abnormalities.
* No significant congenital malformations, as assessed by level 2 ultrasound (also known as a fetal anomaly ultrasound scan or fetal morphology assessment) conducted after 18 weeks of gestation
* Willing to provide cord blood
* Willing to have the infant followed-up after delivery for a period of 12 months
* Does not plan after delivery to give the infant for adoption or place the infant in care Note that women whose pregnancies resulted from Assisted Reproductive Technologies may be enrolled if they meet all inclusion criteria and none of the exclusion criteria.

Infant subjects

* Live-born from the study pregnancy.
* Re-signed (confirmed) written or witnessed/thumb printed informed consent for study participation of the infant obtained from the infant's mother and/or father and/or legally authorized representative, as applicable by local law, before performing any study specific procedure.

Exclusion Criteria:

Maternal subjects

Medical conditions

* History of allergic disease or reactions likely to be exacerbated by any component of the RSV vaccine
* Hypersensitivity to latex
* Significant complications in the current pregnancy such as:

  * Gestational hypertension at ≥20 weeks of gestation in the absence of proteinuria in a woman with a previously normal blood pressure
  * Gestational diabetes which is not controlled by diet and exercise
  * Pre-eclampsia
  * Eclampsia during current pregnancy
  * Intrauterine growth restriction
  * Placenta previa
  * Placental abruption, placenta accreta/percreta/increta, chorioamnionitis or any abnormalities that in the opinion of Investigator can impair the maternal-fetal circulation
  * Polyhydramnios
  * Oligohydramnios
  * Cervical suture in place
  * Preterm labour or history of preterm labour in the current pregnancy
  * Ongoing medical intervention to prevent preterm delivery or medical treatment for suspected preterm delivery
  * Cholestasis
  * Other pregnancy-related complications that in the Investigator's judgement would preclude participation of the subjects in an investigational vaccine trial or might pose risk to the subject due to participation in the study
* Significant structural abnormalities of the uterus or cervix
* History of prior stillbirth or neonatal death
* History of preterm birth
* History of ≥2 spontaneous abortions
* Known or suspected HBV or HCV infection, based on medical history and clinical presentation
* Known or suspected infection during the current pregnancy with Toxoplasma, Parvovirus B19, Syphilis, Zika, Rubella, Varicella, CMV or primary genital Herpes Simplex, based on medical history and clinical presentation
* Active infection with tuberculosis, based on medical history and clinical presentation
* Known or suspected impairment of the immune system or autoimmune disorder (based on medical history and physical examination; no laboratory testing required)
* Lymphoproliferative disorder or malignancy within 5 years before vaccination (excluding effectively treated non-melanoma skin cancer)
* Any clinically significant grade 1 hematological and/or biochemical laboratory abnormalities identified at screening, which are clinically significant for pregnant women in the second and third trimester
* Grade ≥ 2 hematological and/or biochemical laboratory abnormalities identified at screening being clinically significant for pregnant women in the second and third trimester
* Acute or chronic clinically significant conditions, that might pose additional risk to the subject due to participation in the study
* Any conditions that, may interfere with subject's ability to comply with study procedures or receipt of prenatal care
* Any condition which, would increase the risks of study participation to the unborn infant

Prior/Concomitant therapy

* Prior receipt of a COVID-19 vaccine.
* Prior receipt of an RSV vaccine
* Use of any investigational or non-registered product other than the study vaccine(s)/product(s) during the period beginning 29 days before the dose of study vaccine/product or planned use during the study period
* Planned administration/administration of any vaccine within 29 days before study vaccine administration and through Day 43 post-delivery, except seasonal influenza vaccines and dTpa/Tdap or tetanus, which may be administered according to standard of care ≥ 15 days before or after study vaccination
* Administration of immunoglobulins, blood products or plasma derivatives within 3 months before study vaccination or planned administration through Visit 5
* Administration of immune-modifying therapy within 6 months before the study vaccine/product dose, or planned administration through delivery. This includes but is not limited to:

  * Azathioprine, mycophenolate mofetil, 6-mercaptopurine, cyclosporine, tacrolimus, monoclonal or polyclonal antibodies;
  * Prednisone, ≥ 5 mg/day or equivalent for ≥ 14 days. Topical, steroids are allowed. Inhaled steroids are allowed if ≤ 500µg/day of beclomethasone or fluticasone, or ≤ 800µg/day of budesonide.

Prior/Concomitant clinical study experience

* Previous participation in a clinical trial of an RSV vaccine
* Concurrently participating in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product

Other exclusions

* Alcoholism or substance use disorder within the past 24 months based on the presence of two or more abuse criteria
* A local condition that precludes injection of the study drug or precludes assessment of local reactogenicity
* Consanguinity of maternal subject and her partner (second degree cousins or closer)
* Any study personnel or their immediate dependants, family, or household members

Infant subjects

* Concurrently participating in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product
* Child in care

Primary outcomes:
measure: Percentage of Maternal Subjects With Any Solicited Administration Site Events
timeFrame: During the 7-day follow-up period after vaccination (i.e. day of vaccination and 6 subsequent days)
measure: Percentage of Maternal Subjects With Any Solicited Systemic Events
timeFrame: During the 7-day follow-up period after vaccination (i.e. day of vaccination and 6 subsequent days)
measure: Number of Maternal Subjects With Any Haematological Laboratory Abnormalities at Day 8 by Baseline Ranges
timeFrame: At Day 8
measure: Number of Maternal Subjects With Any Biochemical Laboratory Abnormalities at Day 8 by Baseline Ranges
timeFrame: At Day 8
measure: Percentage of Maternal Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: During 30-day follow-up period after vaccination (i.e. the day of vaccination and 29 subsequent days)
measure: Percentage of Maternal Subjects With Any Serious Adverse Events (SAEs)
timeFrame: From Day 1 to Day 43 post-delivery
measure: Percentage of Maternal Subjects With AEs Leading to Study Withdrawal
timeFrame: From Day 1 to Day 43 post-delivery
measure: Percentage of Maternal Subjects With Any Medically Attended AEs (MAE)
timeFrame: From Day 1 to Day 43 post-delivery
measure: Percentage of Maternal Subjects With Pregnancy Outcomes
timeFrame: From Day 1 to Day 43 post-delivery
measure: Percentage of Maternal Subjects With Pregnancy-related Adverse Events of Special Interest (AESIs)
timeFrame: From Day 1 to Day 43 post-delivery
measure: Percentage of Infant Subjects With Neonatal AESIs
timeFrame: From birth to Day 43 post-birth
measure: Percentage of Infant Subjects With Any SAEs
timeFrame: From birth to Day 43 post-birth
measure: Percentage of Infant Subjects With AEs Leading to Study Withdrawal
timeFrame: From birth to Day 43 post-birth
measure: Percentage of Infant Subjects With Any MAEs
timeFrame: From birth to Day 43 post-birth
measure: RSV MAT Immunoglobulin G (IgG)-Specific Antibody Concentrations in Terms of Geometric Mean Concentrations (GMCs) in Maternal Subjects
timeFrame: At Day 1 (before vaccination), Day 31 and at delivery
measure: RSV-A Neutralizing Antibody Geometric Mean Titers (GMTs) in Maternal Subjects
timeFrame: At Day 1 (before vaccination), Day 31 and at delivery
measure: RSV MAT IgG Antibody GMCs in Infants Born to Maternal Subjects
timeFrame: At delivery or within 3 days after birth
measure: RSV-A Neutralizing Antibody GMTs in Infants Born to Maternal Subjects
timeFrame: At delivery or within 3 days after birth
measure: Geometric Mean Ratio Between Cord Blood and Maternal RSV MAT IgG-specific Antibody Concentrations
timeFrame: At delivery (for maternal subjects) or within 3 days after birth (for infants)
Secondary outcomes:
measure: Percentage of Maternal Subjects With Any SAE From Day 1 to Day 181 Post Delivery
timeFrame: From Day 1 to Day 181 post-delivery
measure: Percentage of Maternal Subjects With Any MAE From Day 1 to Day 181 Post Delivery
timeFrame: From Day 1 to Day 181 post-delivery
measure: Percentage of Maternal Subjects With AE Leading to Study Withdrawal From Day 1 to Day 181 Post Delivery
timeFrame: From Day 1 to Day 181 post-delivery
measure: Percentage of Infant Subjects With Any SAE From Birth to Day 181 Post-birth
timeFrame: From birth to Day 181 post-birth
measure: Percentage of Infant Subjects With AE Leading to Study Withdrawal From Birth to Day 181 Post-birth
timeFrame: From birth to Day 181 post-birth
measure: Percentage of Infant Subjects With Any MAE From Birth to Day 181 Post-birth
timeFrame: From birth to Day 181 post-birth
measure: Percentage of Infant Subjects With Any SAE From Birth to Month 12 Post-birth
timeFrame: From birth to Month 12 post-birth
measure: Percentage of Infant Subjects With Any AE Leading to Study Withdrawal From Birth to Month 12 Post-birth
timeFrame: From birth to Month 12 post-birth
measure: Percentage of Infant Subjects With Any MAE From Birth to Month 12 Post-birth
timeFrame: From birth to Month 12 post-birth
measure: Percentage of Maternal Subjects With RSV-associated Medically Attended Respiratory Tract Illnesses (MA-RTI)
timeFrame: From delivery to Day 181 post-delivery
measure: Percentage of Infant Subjects With RSV-associated Lower Respiratory Tract Illness (LRTI)
timeFrame: From birth to Day 181 post-birth
measure: Percentage of Infant Subjects With RSV-associated Severe LRTI
timeFrame: From birth to Day 181 post-birth
measure: Percentage of Infant Subjects With RSV-associated Very Severe LRTI
timeFrame: From birth to Day 181 post-birth
measure: Percentage of Infant Subjects With RSV-associated Hospitalisation
timeFrame: From birth to Day 181 post-birth
measure: RSV MAT IgG Antibody GMCs in Maternal Subjects, at Day 43 Post-delivery
timeFrame: At Day 43 post-delivery
measure: RSV-A Neutralizing Antibody GMTs in Maternal Subjects, at Day 43 Post-delivery
timeFrame: At Day 43 post-delivery
measure: RSV-B Neutralizing Antibody GMTs in Maternal Subjects
timeFrame: At Day 1 (before vaccination), Day 31, at delivery and Day 43 post-delivery
measure: RSV MAT IgG Antibody GMCs in Infants Born to Maternal Subjects, at Day 43 After Birth
timeFrame: At Day 43 after birth
measure: RSV MAT IgG Antibody GMCs in Infants Born to Maternal Subjects, at Day 121 After Birth
timeFrame: At Day 121 after birth
measure: RSV MAT IgG Antibody GMCs in Infants Born to Maternal Subjects, at Day 181 After Birth
timeFrame: At Day 181 after birth
measure: RSV-A Neutralizing Antibody GMTs in Infants Born to Maternal Subjects, at Day 43 After Birth
timeFrame: At Day 43 after birth
measure: RSV-A Neutralizing Antibody GMTs in Infants Born to Maternal Subjects, at Day 121 After Birth
timeFrame: At Day 121 after birth
measure: RSV-A Neutralizing Antibody GMTs in Infants Born to Maternal Subjects, at Day 181 After Birth
timeFrame: At Day 181 after birth
measure: RSV-B Neutralizing Antibody GMTs in Infants Born to Maternal Subjects, at Birth
timeFrame: At delivery or within 3 days after birth
measure: RSV-B Neutralizing Antibody GMTs in Infants Born to Maternal Subjects, at Day 43 After Birth
timeFrame: At Day 43 after birth
measure: RSV-B Neutralizing Antibody GMTs in Infants Born to Maternal Subjects, at Day 121 After Birth
timeFrame: At Day 121 after birth
measure: RSV-B Neutralizing Antibody GMTs in Infants Born to Maternal Subjects, at Day 181 After Birth
timeFrame: At Day 181 after birth
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Huntington Park
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Nampa
country: United States
facility: GSK Investigational Site
state: Idaho
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Gulfport
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Saint Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Johnson City
country: United States
facility: GSK Investigational Site
state: New York
city: Englewood
country: United States
facility: GSK Investigational Site
state: Ohio
city: Beaumont
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Plano
country: United States
facility: GSK Investigational Site
state: Texas
city: South Brisbane
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Québec
country: Canada
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Clermont Ferrand
country: France
facility: GSK Investigational Site
city: Saint Etienne Cedex 02
country: France
facility: GSK Investigational Site
city: Auckland
country: New Zealand
facility: GSK Investigational Site
city: Wellington
country: New Zealand
facility: GSK Investigational Site
city: Panama City
country: Panama
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Soweto
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Malaga
country: Spain
facility: GSK Investigational Site
state: Andalucia
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Majadahonda (Madrid)
country: Spain
facility: GSK Investigational Site
city: Marbella
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: