Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory Syncytial Virus Maternal vaccine, Safety, Reactogenicity, Immunogenicity, Healthy pregnant women, Subsequent pregnancy
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.
Interventions
BIOLOGICALRSV MAT
Single 120 µg dose of the RSV MAT vaccine reconstituted with NaCl solution, administered intramuscularly in the non-dominant arm, at Day 1.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of maternal participants with solicited administration site events during the 7-day follow-up period after vaccination in the current study | During the 7-day follow-up period after vaccination in the current study (administered at Day 1) | The following administration site events are solicited for maternal participants: pain, redness and swelling. |
| Percentage of maternal participants with solicited systemic events during the 7-day follow-up period after vaccination in the current study | During the 7-day follow-up period after vaccination in the current study (administered at Day 1) | The following systemic events are solicited for maternal participants: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache. Fever is defined as temperature \> 38.0°C/100.4°F regardless of the location of measurement. The preferred location for measuring temperature in this study is the oral cavity. |
| Percentage of maternal participants with unsolicited adverse events (AEs) during the 30-day follow-up period after vaccination in the current study | During the 30-day follow-up period after vaccination in the current study (administered at Day 1) | Any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event. |
| 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 | From Day 1 up to 42 days post-delivery in the current study | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes. An MAE is an unsolicited AE for which the participants receive medical attention and is defined as symptoms or illnesses requiring a hospitalization, or an emergency room visit, or visit to/by a health care provider. AE leading to study withdrawal = any AE that leads to withdrawal of the participant from the study. |
| Percentage of maternal participants with pregnancy outcomes from Day 1 up to 42 days post-delivery in the current study | From Day 1 up to 42 days post-delivery in the current study | Pregnancy outcomes include live birth with no congenital anomalies, live birth with minor congenital anomalies only, live birth with at least 1 major congenital anomaly, fetal death/still birth (antepartum or intrapartum) with no congenital anomalies, fetal death/still birth (antepartum or intrapartum) with only minor congenital anomalies, fetal death/still birth (antepartum or intrapartum) with at least 1 major congenital anomaly, elective/therapeutic termination with no congenital anomalies, elective/therapeutic termination with only minor congenital anomalies and elective/therapeutic termination with at least 1 major congenital anomaly. |
| 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 | From Day 1 up to 42 days post-delivery in the current study | Pregnancy-related AESIs include maternal death, hypertensive disorders of pregnancy (gestational hypertension, pre-eclampsia, pre-eclampsia with severe features including eclampsia), fetal growth restriction, gestational diabetes mellitus, pathways to preterm birth (premature preterm rupture of membranes, preterm labor, provider-initiated preterm birth) and chorioamnionitis. |
| Percentage of infant participants with neonatal / infant AESIs from birth up to 42 days post-birth in the current study | From birth up to 42 days post-birth in the current study | Neonatal / infant AESIs include small for gestational age, low birth weight including very low and extremely low birth weight, congenital anomalies, neonatal death and preterm birth. |
| 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 | From birth up to 42 days post-birth in the current study | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes. An MAE is an unsolicited AE for which the participants receive medical attention and is defined as symptoms or illnesses requiring a hospitalization, or an emergency room visit, or visit to/by a health care provider. (S)AE leading to study withdrawal = any (S)AE that leads to withdrawal of the participant from the study. |
| RSV MAT immunoglobulin G (IgG)-specific antibody geometric mean concentrations (GMCs) for maternal participants at Day 31 post-vaccination in the current study | At Day 31 post-vaccination in the current study | IgG antibody concentrations against RSV MAT are measured by enzyme-linked immunosorbent assay (ELISA). This outcome measure is evaluated between participants enrolled in Prior\_RSV MAT group and Prior\_Placebo group. |
| RSV MAT IgG-specific antibody GMCs for maternal participants at delivery in the current study | At delivery in the current study | IgG antibody concentrations against RSV MAT are measured by ELISA. This outcome measure is evaluated between participants enrolled in Prior\_RSV MAT group and Prior\_Placebo group. |
| RSV-A neutralizing antibody geometric mean titers (GMTs) for maternal participants at Day 31 post-vaccination in the current study | At Day 31 post-vaccination in the current study | Serum antibody titers against RSV-A are measured by neutralization assay. This outcome measure is evaluated between participants enrolled in Prior\_RSV MAT group and Prior\_Placebo group. |
| RSV-A neutralizing antibody GMTs for maternal participants at delivery in the current study | At delivery in the current study | Serum antibody titers against RSV-A are measured by neutralization assay. This outcome measure is evaluated between participants enrolled in Prior\_RSV MAT group and Prior\_Placebo group. |
| RSV-B neutralizing antibody GMTs for maternal participants at Day 31 post-vaccination in the current study | At Day 31 post-vaccination in the current study | Serum antibody titers against RSV-B are measured by neutralization assay. This outcome measure is evaluated between participants enrolled in Prior\_RSV MAT group and Prior\_Placebo group. |
| RSV-B neutralizing antibody GMTs for maternal participants at delivery in the current study | At delivery in the current study | Serum antibody titers against RSV-B are measured by neutralization assay. This outcome measure is evaluated between participants enrolled in Prior\_RSV MAT group and Prior\_Placebo group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RSV-B neutralizing antibody GMTs for maternal participants in Prior_RSV MAT group at Day 31 post-repeat and first vaccination | At Day 31 post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies | This outcome measure is evaluated within the participants enrolled in Prior\_RSV MAT group. |
| RSV-B neutralizing antibody GMTs for maternal participants in Prior_RSV MAT group at delivery post-repeat and first vaccination | At delivery post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies | This outcome measure is evaluated within the participants enrolled in Prior\_RSV MAT group. |
| RSV-A neutralizing antibody GMTs for infant participants at delivery in the current study | At delivery in the current study | Serum antibody titers against RSV-A are measured by neutralization assay. |
| RSV MAT IgG-specific antibody GMCs for infant participants at delivery in the current study | At delivery in the current study | IgG antibody concentrations against RSV MAT are measured by ELISA. |
| RSV-B neutralizing antibody GMTs for infant participants at delivery in the current study | At delivery in the current study | Serum antibody titers against RSV-B are measured by neutralization assay. |
| Geometric mean ratio between cord blood and maternal RSV MAT IgG-specific antibody concentrations at delivery in the current study | At delivery in the current study | Transfer of RSV-specific antibodies from maternal participants vaccinated with the RSV MAT vaccine to their infants is calculated as the ratio between cord blood and maternal RSV MAT IgG-specific antibody concentrations. Cord blood or infant blood sample is collected within 3 days after birth (if no cord blood sample can be obtained). |
| 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 | From Day 1 up to Day 181 post-delivery in the current study | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes. AE leading to study withdrawal = any AE that leads to withdrawal of the participant from the study. |
| 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 | 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) | The following administration site events are solicited for maternal participants: pain, redness and swelling. |
| 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 | 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) | The following systemic events are solicited for maternal participants: fatigue, fever, nausea, vomiting, diarrhea, abdominal pain and headache. Fever is defined as temperature \> 38.0°C/100.4°F regardless of the location of measurement. The preferred location for measuring temperature in this study is the oral cavity. |
| 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 | 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) | Any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event. |
| 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 | 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 | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes. AE leading to study withdrawal = any AE that leads to withdrawal of the participant from the study. |
| 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 | 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 | An MAE is an unsolicited AE for which the participants receive medical attention and is defined as symptoms or illnesses requiring a hospitalization, or an emergency room visit, or visit to/by a health care provider. |
| 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 | 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 | Pregnancy outcomes include live birth with no congenital anomalies, live birth with minor congenital anomalies only, live birth with at least 1 major congenital anomaly, fetal death/still birth (antepartum or intrapartum) with no congenital anomalies, fetal death/still birth (antepartum or intrapartum) with only minor congenital anomalies, fetal death/still birth (antepartum or intrapartum) with at least 1 major congenital anomaly, elective/therapeutic termination with no congenital anomalies, elective/therapeutic termination with only minor congenital anomalies and elective/therapeutic termination with at least 1 major congenital anomaly. |
| 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 | 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 | Pregnancy-related AESIs include maternal death, hypertensive disorders of pregnancy (gestational hypertension, pre-eclampsia, pre-eclampsia with severe features including eclampsia), fetal growth restriction, gestational diabetes mellitus, pathways to preterm birth (premature preterm rupture of membranes, preterm labor, provider-initiated preterm birth) and chorioamnionitis. |
| 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 | From birth up to Day 366 post-birth in the current study | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or results in abnormal pregnancy outcomes. An MAE is an unsolicited AE for which the participants receive medical attention and is defined as symptoms or illnesses requiring a hospitalization, or an emergency room visit, or visit to/by a health care provider. (S)AE leading to study withdrawal = any (S)AE that leads to withdrawal of the participant from the study. |
| RSV MAT IgG-specific antibody GMCs for maternal participants in Prior_RSV MAT group at Day 31 post-repeat and first vaccination | At Day 31 post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies | This outcome measure is evaluated within the participants enrolled in Prior\_RSV MAT group. |
| RSV MAT IgG-specific antibody GMCs for maternal participants in Prior_RSV MAT group at delivery post-repeat and first vaccination | At delivery post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies | This outcome measure is evaluated within the participants enrolled in Prior\_RSV MAT group. |
| RSV-A neutralizing antibody GMTs for maternal participants in Prior_RSV MAT group at Day 31 post-repeat and first vaccination | At Day 31 post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies | This outcome measure is evaluated within the participants enrolled in Prior\_RSV MAT group. |
| RSV-A neutralizing antibody GMTs for maternal participants in Prior_RSV MAT group at delivery post-repeat and first vaccination | At delivery post-repeat vaccination administered in the current study and first vaccination administered in NCT04126213, NCT04605159 or NCT04980391 studies | This outcome measure is evaluated within the participants enrolled in Prior\_RSV MAT group. |
Countries
United States
Outcome results
None listed