Clinical trial NCT04980391: A Study on the Safety and Immune Response to an Unadjuvanted RSV Maternal Vaccine, in High Risk Pregnant Women Aged 15 to 49 Years and Infants Born to the Vaccinated Mothers
Official title: A Phase III, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Reactogenicity and Immune Response of a Single Intramuscular Dose of Unadjuvanted RSV Maternal Vaccine, in High Risk Pregnant Women Aged 15 to 49 Years and Infants Born to the Vaccinated Mothers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory Syncytial Virus Maternal vaccine
Safety
Reactogenicity
Immune response
High risk pregnant women
Teenage girls
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-07-28
Enrollment: 384
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 49
Standard ages: CHILD
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, reactogenicity and immune response of a single intramuscular dose of the respiratory syncytial virus (RSV) maternal vaccine compared to placebo, when administered in the second or third trimester of pregnancy in women, 15 to 49 years of age (YOA), with high risk pregnancies and in the infants born to the vaccinated mothers.

Following a recommendation from the Independent Data Monitoring Committee of NCT04605159 (RSV MAT 009), GSK made the decision to stop enrolment and vaccination in the study. Ongoing study participants at that time continued to be monitored as part of the study.


Eligibility criteria: Inclusion Criteria:

Maternal participants

* Participants who can and will comply with the requirements of the protocol.
* Participants and LARs 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 either:

  * include consent for both the maternal participant's participation\* and participation of the infant after the infant's birth, or
  * include consent for the maternal participant's participation\* and expressed willingness to consider permitting the infant to take part after the infant's birth (if local regulations/guidelines require parent(s) to provide an additional informed consent after the infant's birth).
  * both mother and father should consent if local regulations / guidelines require it.
* Pre-pregnancy Body Mass Index (based on participant's report) 18.5 to 39.9 kg/m\^2, inclusive.
* Healthy adolescent pregnant women, 15 to 17 YOA, inclusive, at the time of study intervention administration.

OR

* Pregnant women, 18 to 49 YOA, inclusive, at the time of study intervention administration with:

  * HIV infection AND/OR
  * Obstetric complications or risk factors during the current pregnancy, where the expectant management of the pregnancy is possible and without evidence of non-reassuring fetal status (only cases for which fetal heart rate can be ascertained) as follows:
  * Gestational diabetes, well-controlled on medications (with or without diet or exercise)
  * Gestational hypertension, well-controlled on diet or medications below 160/110 mmHg.
  * Pre-eclampsia without severe features (i.e. eclampsia, severe hypertension \[\>160/110 mmHg\], organ dysfunction, unstable or complicated by \[HELLP\] syndrome).
  * Fetal Growth Restriction in singleton pregnancies, with normal umbilical artery Doppler and estimated fetal weight 3 to 10th percentile for gestational age.
  * History of threatened preterm labor in the current pregnancy, with no cervical dilation greater than 2 cm or effacement exceeding 50%, and/or no progressive change in cervical dilation or effacement detected by serial examinations, when maternal participant is asymptomatic
  * Uncomplicated twin gestation.
* Pregnant females at 24\^0/7 to 36\^0/7 weeks of gestation at the time of study intervention administration (Day 1), as established by:

  * Last menstrual period (LMP) date corroborated by first or second trimester ultrasound examination (U/S) (i.e. at or before 28 weeks of gestation).
  * First or second trimester U/S only, if LMP is unknown/uncertain.
  * Certain LMP, corroborated by an U/S performed after 28 weeks of gestation is also acceptable.

The level of diagnostic certainty of the gestational age should be established by using the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) gestation age assessment tool

* Participants who are willing to provide cord blood.
* Willing to have their offspring followed-up after delivery for a period of 12 months.
* Participants who do not plan to give their offspring for adoption or place the child 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 participants

* Live-born from the study pregnancy.
* If required per local regulations / guidelines, 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 LAR, before performing any infant study specific procedure. To comply with RTI surveillance and other protocol required procedures that begin immediately after birth: if written consent cannot be provided by the parent(s)/LAR(s) readily post-birth, verbal consent - if permitted per local regulation -- may be sought from the parent(s) / LAR(s) instead. Verbal consent should be documented in the source data by the investigator or delegate. The parent(s) / LAR(s) will provide additional, written informed consent by (or before) Visit 2-NB.

Exclusion Criteria:

Maternal participants Medical conditions

* History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention.
* Hypersensitivity to latex.
* Any pre-existing medical conditions or obstetric complications in the current pregnancy that, are poorly controlled and/or with clinical evidence of a non-reassuring fetal status and/or are likely to result in delivery within 7 days after study intervention administration and/or when the timing of planned delivery is within 7 days after study intervention administration and/or acute conditions requiring immediate medical attention for maternal stabilization and/or treatment.
* A multiple pregnancy with 3 or more fetuses.
* Complicated twin gestation.
* Placenta Accreta Spectrum, including placenta increta, percreta, and accreta.
* Fetal structural defects or genetic abnormalities that affect (or are likely to affect) fetal health or survival during the first year of life.
* Known or suspected impairment of the immune system or immunodeficiency syndrome other than HIV.
* Lymphoproliferative disorder or malignancy within 5 years before study dose administration.
* Any illness of the mother or conditions of the fetus that, may substantially interfere with the maternal participant's ability to comply with study procedures, or could increase the risks to the mother or the fetus, or could preclude the evaluation of the participant's data.
* Any other clinical condition that, might pose additional risk to the participant due to participation in the study, as determined by medical history, physical examination or laboratory screening tests.
* Women with any diagnosis, condition, treatment, or other factor that, has the potential to affect or confound assessments of immunogenicity or safety
* Any conditions which, in the investigator's opinion, would increase the risks of study participation to the unborn infant.

Prior/Concomitant therapy

* Prior receipt of an RSV maternal vaccine.
* Use of any investigational or non-registered product other than the study intervention(s) during the period beginning:

  * For a drug, vaccine or medical device: 29 days before the dose of study intervention(s) (Day -28 to Day 1), or their planned use during the study period.
  * For immunoglobulins: 90 days before the dose of study intervention(s), or their planned use during the study period.

The exception to this is investigational products administered in the setting of a pandemic. Administration in this case should respect the same period outlined above prior to study intervention administration, but may be allowed following delivery.

* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 29 days before the study Day 1 and ending at delivery, with the exception of seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap - alone vaccines, dTpa/Tdap vaccines that also contain other antigens and Hepatitis B vaccines, all of which may be administered according to standard of care ≥ 15 days before or after study intervention (Day 1).
* Receipt of blood or plasma products or immunoglobulin, from 90 days before study intervention administration, or planned receipt through delivery, with the exception of Rho(D) immunoglobulin, which can be given at any time. In that sense, COVID-19 vaccines may be allowed, when administered ≥ 15 days before or after study vaccination.
* Administration of immune-modifying therapy within 6 months before study intervention administration, or planned administration through delivery, except if it is part of management of HIV infection.

Prior/Concurrent clinical study experience

• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention.

Other exclusions

* Alcoholism or substance use disorder within the past 24 months based on the presence of 2 or more of the following abuse criteria: hazardous use, social/interpersonal problems related to use, neglect of major roles to use, withdrawal, tolerance, use of larger amounts or longer, repeated attempts to quit or control use, much time spent using, physical or psychological problems related to use, activities given up to use, craving.
* A local condition that precludes injection of the study vaccine/product or precludes assessment of local (administration site) reactogenicity.
* Consanguinity of maternal participant and her partner.
* Any study personnel or their immediate dependents, family, or household members.

Infant participants

* Concurrently participating in another clinical trial, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product.
* Any condition which, would increase the risks of study participation to the infant.
* Child in care.

Primary outcomes:
measure: Percentage of Maternal Participants Reporting Any Solicited Administration Site Events
timeFrame: From Day 1 to Day 7 included
measure: Percentage of Maternal Participants Reporting Any Solicited Systemic Events
timeFrame: From Day 1 to Day 7 included
measure: Percentage of Maternal Participants Reporting Any Unsolicited Adverse Events (AEs)
timeFrame: From Day 1 to Day 30 included
measure: Percentage of Maternal Participants Reporting Any Serious Adverse Events (SAEs) From Day 1 up to 42 Days Post-delivery
timeFrame: From Day 1 up to 42 days post-delivery, an average of 2 months
measure: Number of Maternal Participants Reporting (S)AEs Leading to Study Withdrawal From Day 1 up to 42 Days Post-delivery
timeFrame: From Day 1 up to 42 days post-delivery, an average of 2 months
measure: Percentage of Maternal Participants Reporting Medically Attended Adverse Events (MAEs) From Day 1 up to 42 Days Post-delivery
timeFrame: From Day 1 up to 42 days post-delivery, an average of 2 months
measure: Percentage of Live Births With no Congenital Anomalies, Live Births With Minor Congenital Anomaly(Ies) and Live Births With at Least 1 Major Congenital Anomaly
timeFrame: From Day 1 up to 42 days post-delivery, an average of 2 months
measure: Percentage of Maternal Participants Reporting Pregnancy-related Adverse Events of Special Interest (AESIs) From Day 1 up to 42 Days Post-delivery
timeFrame: From Day 1 up to 42 days post-delivery, an average of 2 months
measure: Percentage of Maternal Participants Reporting Worsening of Pre-existing Medical Conditions and/or Obstetric Complications From Day 1 up to 42 Days Post-delivery
timeFrame: From Day 1 up to 42 days post-delivery, an average of 2 months
measure: Percentage of Infant Participants Reporting Neonatal/Infant AESIs From Birth up to 42 Days Post-birth
timeFrame: From birth up to 42 days post-birth, an average of 2 months
measure: Percentage of Infant Participants Reporting Any SAEs From Birth up to 42 Days Post-birth
timeFrame: From birth up to 42 days post-birth, an average of 2 months
measure: Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal From Birth up to 42 Days Post-birth
timeFrame: From birth up to 42 days post-birth, an average of 2 months
measure: Percentage of Infant Participants Reporting MAEs From Birth up to 42 Days Post-birth
timeFrame: From birth up to 42 days post-birth, an average of 2 months
measure: Percentage of Infant Participants Reporting Any SAEs From Birth up to 180 Days Post-birth
timeFrame: From birth up to 180 days post-birth
measure: Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal From Birth up to 180 Days Post-birth
timeFrame: From birth up to 180 days post-birth
measure: Percentage of Infant Participants Reporting MAEs From Birth up to 180 Days Post-birth
timeFrame: From birth up to 180 days post-birth
measure: Percentage of Infant Participants Reporting Any SAEs From Birth up to 365 Days Post-birth
timeFrame: From birth up to 365 days post-birth
measure: Number of Infant Participants Reporting (S)AEs Leading to Study Withdrawal From Birth up to 365 Days Post-birth
timeFrame: From birth up to 365 days post-birth
measure: Percentage of Infant Participants Reporting MAEs From Birth up to 365 Days Post-birth
timeFrame: From birth up to 365 days post-birth
measure: RSV MAT Immunoglobulin G (IgG)-Specific Antibody Concentrations for Maternal Participants at Pre-dosing (Day 1)
timeFrame: At pre-dosing (Day 1)
measure: RSV MAT IgG-specific Antibody Concentrations for Maternal Participants at Delivery
timeFrame: At delivery
measure: RSV-A Neutralizing Titers for Maternal Participants at Pre-dosing (Day 1)
timeFrame: At pre-dosing (Day 1)
measure: RSV-A Neutralizing Titers for Maternal Participants at Delivery
timeFrame: At delivery
measure: Geometric Mean Ratio (GMR) Between Cord Blood and Maternal RSV MAT IgG-specific Antibody Concentrations
timeFrame: At delivery (for maternal participants) or within 72 hours after birth (for infant participants)
measure: RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Delivery or Within 72 Hours After Birth
timeFrame: At delivery or within 72 hours after birth
measure: RSV-A Neutralizing Titers for Infant Participants at Delivery or Within 72 Hours After Birth
timeFrame: At delivery or within 72 hours after birth
Secondary outcomes:
measure: Percentage of Maternal Participants Reporting Any SAEs From Day 1 up to 180 Days Post-delivery
timeFrame: From Day 1 up to 180 days post-delivery
measure: Number of Maternal Participants Reporting (S)AEs Leading to Study Withdrawal From Day 1 up to 180 Days Post-delivery
timeFrame: From Day 1 up to 180 days post-delivery
measure: Percentage of Maternal Participants Reporting MAEs From Day 1 up to 180 Days Post-delivery
timeFrame: From Day 1 up to 180 days post-delivery
measure: Percentage of Maternal Participants Reporting Worsening of Pre-existing Medical Conditions and/or Obstetric Complications From Day 1 up to 180 Days Post-delivery
timeFrame: From Day 1 up to 180 days post-delivery
measure: Number of Maternal Participants Reporting RSV-associated Medically Attended Respiratory Tract Illnesses (MA-RTIs) From Day 1 up to 180 Days Post-delivery
timeFrame: From Day 1 up to 180 days post-delivery
measure: Percentage of Infant Participants Reporting Medically Assessed, RSV-associated Lower Respiratory Tract Illness (LRTIs) of Any Severity and RSV-associated Severe LRTIs From Birth up to 365 Days Post-birth
timeFrame: From birth up to 365 days post-birth
measure: Percentage of Infant Participants Reporting Medically Assessed, RSV-associated Hospitalizations From Birth up to 365 Days Post-birth
timeFrame: From birth up to 365 days post-birth
measure: RSV MAT IgG-specific Antibody Concentrations for Maternal Participants at Day 31 Post-dosing
timeFrame: At Day 31 post-dosing
measure: RSV-A Neutralizing Titers for Maternal Participants at Day 31 Post-dosing
timeFrame: At Day 31 post-dosing
measure: RSV-B Neutralizing Titers for Maternal Participants at Pre-dosing (Day 1), Day 31 Post-dosing and Delivery
timeFrame: At pre-dosing (Day 1), Day 31 post-dosing and delivery
measure: RSV-B Neutralizing Titers for Infant Participants at Delivery or Within 72 Hours After Birth
timeFrame: At delivery or within 72 hours after birth
measure: RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Day 43 Post-birth
timeFrame: At Day 43 post-birth
measure: RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Day 121 Post-birth
timeFrame: At Day 121 post-birth
measure: RSV MAT IgG-specific Antibody Concentrations for Infant Participants at Day 181 Post-birth
timeFrame: At Day 181 post-birth
measure: RSV-A Neutralizing Titers for Infant Participants at Day 43 Post-birth
timeFrame: At Day 43 post-birth
measure: RSV-A Neutralizing Titers for Infant Participants at Day 121 Post-birth
timeFrame: At Day 121 post-birth
measure: RSV-A Neutralizing Titers for Infant Participants at Day 181 Post-birth
timeFrame: At Day 181 post-birth
measure: RSV-B Neutralizing Titers for Infant Participants at Day 43 Post-birth
timeFrame: At Day 43 post-birth
measure: RSV-B Neutralizing Titers for Infant Participants at Day 121 Post-birth
timeFrame: At Day 121 post-birth
measure: RSV-B Neutralizing Titers for Infant Participants at Day 181 Post-birth
timeFrame: At Day 181 post-birth
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Dothan
country: United States
facility: GSK Investigational Site
state: Alabama
city: Mobile
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Covington
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Lafayette
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Slidell
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Missoula
country: United States
facility: GSK Investigational Site
state: Montana
city: Arlington
country: United States
facility: GSK Investigational Site
state: Texas
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Grapevine
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: League City
country: United States
facility: GSK Investigational Site
state: Texas
city: Plano
country: United States
facility: GSK Investigational Site
state: Texas
city: Weatherford
country: United States
facility: GSK Investigational Site
state: Texas
city: Caxias do Sul
country: Brazil
facility: GSK Investigational Site
city: RibeirAo PretoSP
country: Brazil
facility: GSK Investigational Site
city: Santa Maria
country: Brazil
facility: GSK Investigational Site
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Bhubaneswar
country: India
facility: GSK Investigational Site
city: Mysuru
country: India
facility: GSK Investigational Site
city: Messina
country: Italy
facility: GSK Investigational Site
city: Perugia
country: Italy
facility: GSK Investigational Site
city: Prato
country: Italy
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Soweto Gauteng
country: South Africa
facility: GSK Investigational Site
city: Boadilla Del Monte Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: TorrejOn Ardoz Madrid
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: