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
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Respiratory Syncytial Virus Infections
- Sponsor
- GlaxoSmithKline
- Locations
- 1
- Primary Endpoint
- Percentage of maternal participants with unsolicited adverse events (AEs) during the 30-day follow-up period after vaccination in the current study
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
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.
Investigators
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.
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
Outcomes
Primary Outcomes
Percentage of maternal participants with unsolicited adverse events (AEs) during the 30-day follow-up period after vaccination in the current study
Time Frame: 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
Time Frame: 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 solicited systemic events during the 7-day follow-up period after vaccination in the current study
Time Frame: 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 pregnancy outcomes from Day 1 up to 42 days post-delivery in the current study
Time Frame: 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 infant participants with neonatal / infant AESIs from birth up to 42 days post-birth in the current study
Time Frame: 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 maternal participants with pregnancy-related adverse events of special interest (AESIs) from Day 1 up to 42 days post-delivery in the current study
Time Frame: 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.
RSV MAT immunoglobulin G (IgG)-specific antibody geometric mean concentrations (GMCs) for maternal participants at Day 31 post-vaccination in the current study
Time Frame: 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-A neutralizing antibody geometric mean titers (GMTs) for maternal participants at Day 31 post-vaccination in the current study
Time Frame: 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.
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
Time Frame: 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 IgG-specific antibody GMCs for maternal participants at delivery in the current study
Time Frame: 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 GMTs for maternal participants at delivery in the current study
Time Frame: 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
Time Frame: 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
Time Frame: 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.
Percentage of maternal participants with solicited administration site events during the 7-day follow-up period after vaccination in the current study
Time Frame: 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.
Secondary Outcomes
- 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))
- 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))
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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))
- 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)
- 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)
- 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)
- RSV-B neutralizing antibody GMTs for infant participants at delivery in the current study(At delivery in the current study)
- 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)
- 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)
- 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)
- RSV MAT IgG-specific antibody GMCs for infant participants at delivery in the current study(At delivery in the current study)
- RSV-A neutralizing antibody GMTs for infant participants at delivery in the current study(At delivery in the current study)
- 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)