Clinical trial NCT05229068: A Study of Safety, Reactogenicity and Immune Response of the Repeat Vaccination Against RSV When Given to Female Participants of 18-49 Years of Age During Their Subsequent Uncomplicated Pregnancy
Official title: A Phase IIIB, Open Label, Non-randomized, Controlled, Multi-country Study to Evaluate Safety, Reactogenicity and Immunogenicity of the Repeat Vaccination With 120 µg Dose of RSV Maternal Vaccine During Subsequent Pregnancy in Healthy Maternal Participants 18-49 Years of Age
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Respiratory Syncytial Virus Infections
Keywords: Respiratory Syncytial Virus Maternal vaccine
Safety
Reactogenicity
Immunogenicity
Healthy pregnant women
Subsequent pregnancy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-02-08
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety, reactogenicity and immunogenicity of a single intramuscular dose of the investigational respiratory syncytial virus (RSV) maternal (RSV MAT) vaccine during subsequent uncomplicated pregnancy in maternal participants, 18 to 49 years of age (YOA), who have previously received the RSV MAT vaccine or placebo in the RSV MAT-004 (NCT04126213), RSV MAT-009 (NCT04605159) and RSV MAT-012 (NCT04980391) primary studies.


Eligibility criteria: Inclusion Criteria:

Maternal participants

* Only those pregnant participants who received a single 120 µg dose of RSV MAT vaccine or placebo in the RSV MAT-004, RSV MAT-009 or RSV MAT-012 studies OR healthy pregnant participants who had at least one prior live birth and have not received any RSV vaccine in the past.
* Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written or witnessed/thumb printed informed consent obtained from the participants prior to performance of any study-specific procedure. The informed consent given at screening should (consistent with local regulations/guidelines) 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.
* In good general maternal health as established by medical history and clinical examination before entering into the study.
* Participants between and including 18 and 49 YOA, inclusive at the time of consent.
* Pre-pregnancy body mass index (based on participant's report) 17 to 39.9 kg/m\^2, inclusive.
* Singleton pregnancy (including instances where the singleton pregnancy derives from a vanishing twin syndrome).
* Pregnant females at 24\^0/7 to 36\^0/7 weeks of gestation at the time of study intervention administration (Visit 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 a U/S performed after 28 weeks of gestation is also acceptable.

NOTE: If pregnancy resulted from assisted reproductive technologies, LMP date may be replaced by IUI (intrauterine insemination) or ET (embryo-transfer) date.

* No fetal genetic abnormalities (based on genetic testing, if performed).
* No significant congenital malformations conducted at or beyond 18 weeks of gestation.
* Participants who are willing to provide cord blood.
* Participants who do not plan to give their offspring for adoption or place the child in care.
* Participants who plan to reside in the study area for at least one year after delivery.
* Willing to have their infant followed-up after delivery for a period of 12 months.

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 study-specific procedure. To comply other protocol required procedures that begin immediately after birth: If written consent cannot be provided by the infant's parent(s)/LAR(s) readily post-birth, verbal consent, if permitted per local regulation, may be sought from the infant's parent(s)/LAR(s) instead. Verbal consent should be documented in the source data by the investigator or delegate. The infant's 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.
* Acute or chronic clinically significant abnormality or poorly controlled pre-existing condition or any other clinical conditions.
* Subjects who have received 2 or more doses of any RSV vaccine in the past.
* 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 medication, diet and/or exercise
  * Pre-eclampsia
  * Eclampsia
  * Intrauterine Growth Restriction/Fetal Growth Restriction
  * Placenta previa
  * Placental abruption, placenta accreta/percreta/increta, chorioamnionitis or any abnormalities
  * Polyhydramnios
  * Oligohydramnios
  * Preterm labor or history of preterm labor in the current pregnancy.
  * Any intervention to prevent preterm delivery or medical treatment for suspected preterm delivery
  * Cholestasis
  * Other pregnancy-related complications
* History of 2 or more prior stillbirths or neonatal deaths, or history of 2 or more preterm births at ≤ 34 weeks gestation, or 3 or more consecutive spontaneous abortions.
* Significant structural abnormalities of the uterus or cervix.
* Known human immunodeficiency virus infection, as assessed by local standard of care serologic tests.
* Known or suspected hepatitis B or C virus infection.
* Known or suspected infection during the current pregnancy with Toxoplasma, Parvovirus B19, Syphilis, Zika, Rubella, Varicella, CMV or primary genital Herpes Simplex.
* Active infection with tuberculosis.
* Any confirmed or suspected immunosuppressive or immunodeficient condition.
* Current autoimmune disorder.
* Lymphoproliferative disorder or malignancy within 5 years before study vaccination.
* Any conditions that, in the investigator's judgement, may interfere with participant's ability to comply with study procedures or receipt of prenatal care.
* Any condition which, in the investigator's opinion, would increase the risks of study participation to the unborn infant.

Prior/Concomitant therapy

* Prior receipt of any RSV vaccine in the current pregnancy or prior receipt of 2 or more doses of any RSV vaccine prior to study vaccination.
* Use of any investigational or non-registered product other than the study vaccine/product, or planned use during the study period).

The exception to this are investigational products administered in the setting of a pandemic.

* Planned administration/administration of any vaccine within 29 days before study vaccine administration (Day -28 to Day 1) or planned administration through delivery, except:

  * Seasonal influenza vaccines, tetanus vaccines, dTpa/Tdap - alone vaccines, dTpa/Tdap vaccines that also contain other antigens and Hepatitis B vaccines, which may be administered ≥ 15 days before or after study vaccination.

    * Note that if public health authorities organize an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) outside the routine immunisation program, then the intervals described above can be reduced if necessary for that mass vaccination vaccine, provided the vaccine is licensed and used according to its Product Information. In that sense, COVID-19 vaccines may be allowed, when administered ≥ 15 days before or after study vaccination.
* Administration of immunoglobulins (except anti-Rh0D IG, which may be administered at any time), blood products or plasma derivatives within 3 months before study vaccination or planned administration through delivery (Visit 3).
* Administration of immune-modifying therapy within 6 months before the study vaccination, or planned administration through delivery.

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.
* Subjects who were lost to follow-up or prematurely withdrawn before Day 43 in the RSV MAT-004, RSV MAT-009 and RSV MAT-012 studies.

Other exclusions

* Alcoholism or substance use disorder within the past 24 months based on the presence of 2 or more abuse criteria.
* A local condition that in the opinion of the Investigator 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 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 vaccine/product.
* Any condition which, in the investigator's opinion, would increase the risks of study participation to the infant.
* Child in care.

Primary outcomes:
measure: Percentage of maternal participants with solicited administration site events during the 7-day follow-up period after vaccination in the current study
timeFrame: During the 7-day follow-up period after vaccination in the current study (administered at Day 1)
measure: Percentage of maternal participants with solicited systemic events during the 7-day follow-up period after vaccination in the current study
timeFrame: During the 7-day follow-up period after vaccination in the current study (administered at Day 1)
measure: Percentage of maternal participants with unsolicited adverse events (AEs) during the 30-day follow-up period after vaccination in the current study
timeFrame: During the 30-day follow-up period after vaccination in the current study (administered at Day 1)
measure: Percentage of maternal participants with serious adverse events (SAEs), AEs leading to study withdrawal and medically attended AEs (MAEs) from Day 1 up to 42 days post-delivery in the current study
timeFrame: From Day 1 up to 42 days post-delivery in the current study
measure: Percentage of maternal participants with pregnancy outcomes from Day 1 up to 42 days post-delivery in the current study
timeFrame: From Day 1 up to 42 days post-delivery in the current study
measure: Percentage of maternal participants with pregnancy-related adverse events of special interest (AESIs) from Day 1 up to 42 days post-delivery in the current study
timeFrame: From Day 1 up to 42 days post-delivery in the current study
measure: Percentage of infant participants with neonatal / infant AESIs from birth up to 42 days post-birth in the current study
timeFrame: From birth up to 42 days post-birth in the current study
measure: Percentage of infant participants with SAEs, (S)AEs leading to study withdrawal and MAEs from birth up to 42 days post-birth in the current study
timeFrame: From birth up to 42 days post-birth in the current study
measure: RSV MAT immunoglobulin G (IgG)-specific antibody geometric mean concentrations (GMCs) for maternal participants at Day 31 post-vaccination in the current study
timeFrame: At Day 31 post-vaccination in the current study
measure: RSV MAT IgG-specific antibody GMCs for maternal participants at delivery in the current study
timeFrame: At delivery in the current study
measure: RSV-A neutralizing antibody geometric mean titers (GMTs) for maternal participants at Day 31 post-vaccination in the current study
timeFrame: At Day 31 post-vaccination in the current study
measure: RSV-A neutralizing antibody GMTs for maternal participants at delivery in the current study
timeFrame: At delivery in the current study
measure: RSV-B neutralizing antibody GMTs for maternal participants at Day 31 post-vaccination in the current study
timeFrame: At Day 31 post-vaccination in the current study
measure: RSV-B neutralizing antibody GMTs for maternal participants at delivery in the current study
timeFrame: At delivery in the current study
Secondary outcomes:
measure: Percentage of maternal participants with SAEs and AEs leading to study withdrawal from Day 1 up to Day 181 post-delivery in the current study
timeFrame: From Day 1 up to Day 181 post-delivery in the current study
measure: Percentage of maternal participants in Prior_RSV MAT group with solicited administration site events during the 7-day follow-up period after administration of the first and repeat vaccination
timeFrame: During the 7-day follow-up period after administration of the first vaccination (administered at Day 1 in NCT04126213, NCT04605159 or NCT04980391 studies) and the repeat vaccination (administered at Day 1 in the current study)
measure: Percentage of maternal participants in Prior_RSV MAT group with solicited systemic events during the 7-day follow-up period after administration of the first and repeat vaccination
timeFrame: During the 7-day follow-up period after administration of the first vaccination (administered at Day 1 in NCT04126213, NCT04605159 or NCT04980391 studies) and repeat vaccination (administered at Day 1 in the current study)
measure: Percentage of maternal participants in Prior_RSV MAT group with unsolicited AEs during the 30-day follow-up period after administration of the first and repeat vaccination
timeFrame: During the 30-day follow-up period after administration of the first vaccination (administered at Day 1 in NCT04126213, NCT04605159 or NCT04980391 studies) and repeat vaccination (administered at Day 1 in the current study)
measure: Percentage of maternal participants in Prior_RSV MAT group with SAEs and AEs leading to study withdrawal from Day 1 up to Day 181 post-delivery after administration of the first and repeat vaccination
timeFrame: From Day 1 up to Day 181 post-delivery after administration of the first vaccination in NCT04126213, NCT04605159 or NCT04980391 studies and repeat vaccination in the current study
measure: Percentage of maternal participants in Prior_RSV MAT group with MAEs from Day 1 up to 42 days post-delivery after administration of the first and the repeat vaccination
timeFrame: From Day 1 up to 42 days post-delivery after administration of the first vaccination in NCT04126213, NCT04605159 or NCT04980391 studies and repeat vaccination in the current study
measure: Percentage of maternal participants in Prior_RSV MAT group with pregnancy outcomes from Day 1 up to 42 days post-delivery after administration of the first and repeat vaccination
timeFrame: From Day 1 up to 42 days post-delivery after administration of the first vaccination in NCT04126213, NCT04605159 or NCT04980391 studies and repeat vaccination in the current study
measure: Percentage of maternal participants in Prior_RSV MAT group with pregnancy-related AESIs from Day 1 up to 42 days post-delivery after administration of the first and repeat vaccination
timeFrame: From Day 1 up to 42 days post-delivery after administration of the first vaccination in NCT04126213, NCT04605159 or NCT04980391 studies and repeat vaccination in the current study
measure: Percentage of infant participants with SAEs, (S)AEs leading to study withdrawal and MAEs from birth up to Day 366 post-birth in the current study
timeFrame: From birth up to Day 366 post-birth in the current study
measure: RSV MAT IgG-specific antibody GMCs for maternal participants in Prior_RSV MAT group at Day 31 post-repeat and first vaccination
timeFrame: At Day 31 post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies
measure: RSV MAT IgG-specific antibody GMCs for maternal participants in Prior_RSV MAT group at delivery post-repeat and first vaccination
timeFrame: At delivery post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies
measure: RSV-A neutralizing antibody GMTs for maternal participants in Prior_RSV MAT group at Day 31 post-repeat and first vaccination
timeFrame: At Day 31 post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies
measure: RSV-A neutralizing antibody GMTs for maternal participants in Prior_RSV MAT group at delivery post-repeat and first vaccination
timeFrame: At delivery post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies
measure: RSV-B neutralizing antibody GMTs for maternal participants in Prior_RSV MAT group at Day 31 post-repeat and first vaccination
timeFrame: At Day 31 post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies
measure: RSV-B neutralizing antibody GMTs for maternal participants in Prior_RSV MAT group at delivery post-repeat and first vaccination
timeFrame: At delivery post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies
measure: Geometric mean ratio between cord blood and maternal RSV MAT IgG-specific antibody concentrations at delivery in the current study
timeFrame: At delivery in the current study
measure: RSV MAT IgG-specific antibody GMCs for infant participants at delivery in the current study
timeFrame: At delivery in the current study
measure: RSV-A neutralizing antibody GMTs for infant participants at delivery in the current study
timeFrame: At delivery in the current study
measure: RSV-B neutralizing antibody GMTs for infant participants at delivery in the current study
timeFrame: At delivery in the current study
Other outcomes:
Locations:
city: Missoula
country: United States
facility: GSK Investigational Site
state: Montana
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Nebraska
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: