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

NCT05229068 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: 2147532021-004012-25
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Respiratory Syncytial Virus Infections

Keywords

Respiratory Syncytial Virus Maternal vaccine; Safety; Reactogenicity; Immunogenicity; Healthy pregnant women; Subsequent pregnancy

Outcome Measures

Primary Outcomes (14)

• Percentage of maternal participants with solicited administration site events during the 7-day follow-up period after vaccination in the current study

  The following administration site events are solicited for maternal participants: pain, redness and swelling.

  During the 7-day follow-up period after vaccination in the current study (administered at Day 1)

• Percentage of maternal participants with solicited systemic events during the 7-day follow-up period after vaccination 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.

  During the 7-day follow-up period after vaccination in the current study (administered at Day 1)

• Percentage of maternal participants with unsolicited adverse events (AEs) during the 30-day follow-up period after vaccination 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.

  During the 30-day follow-up period after vaccination in the current study (administered at Day 1)

• 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

  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.

  From Day 1 up to 42 days post-delivery in the current study

• Percentage of maternal participants with pregnancy outcomes 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.

  From Day 1 up to 42 days post-delivery in the current study

• 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

  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.

  From Day 1 up to 42 days post-delivery in the current study

• Percentage of infant participants with neonatal / infant AESIs 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.

  From birth up to 42 days post-birth in the current study

• 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

  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.

  From birth up to 42 days post-birth in the current study

• RSV MAT immunoglobulin G (IgG)-specific antibody geometric mean concentrations (GMCs) for maternal participants 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.

  At Day 31 post-vaccination in the current study

• RSV MAT IgG-specific antibody GMCs for maternal participants 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.

  At delivery in the current study

• RSV-A neutralizing antibody geometric mean titers (GMTs) for maternal participants 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.

  At Day 31 post-vaccination in the current study

• RSV-A neutralizing antibody GMTs for maternal participants 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.

  At delivery in the current study

• RSV-B neutralizing antibody GMTs for maternal participants 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.

  At Day 31 post-vaccination in the current study

• RSV-B neutralizing antibody GMTs for maternal participants 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.

  At delivery in the current study

Secondary Outcomes (19)

• 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 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 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)

• 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 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

Study Arms (2)

Prior_RSV MAT Group

EXPERIMENTAL

Maternal participants who received a single 120 µg dose of RSV MAT vaccine at Day 1 in RSV MAT-004 (NCT04126213), RSV MAT-009 (NCT04605159) or RSV MAT-012 (NCT04980391) parent studies, will receive a single dose of RSV MAT vaccine at Day 1 in the current study and are followed-up until the study end (Day 181 post-delivery).

Biological: RSV MAT

Prior_Placebo Group

EXPERIMENTAL

Maternal participants who received a single dose of placebo at Day 1 in RSV MAT-004 (NCT04126213), RSV MAT-009 (NCT04605159) or RSV MAT-012 (NCT04980391) parent studies or who did not participate in the parent studies and did not receive any RSV vaccine in the past\*, will receive a single dose of RSV MAT vaccine at Day 1 in the current study and are followed-up until the study end (Day 181 post-delivery). \*The unvaccinated participants are enrolled if the study cannot enroll sufficient numbers of the maternal participants who received placebo in the parent studies.

Biological: RSV MAT

Interventions

RSV MAT BIOLOGICAL

Single 120 µg dose of the RSV MAT vaccine reconstituted with NaCl solution, administered intramuscularly in the non-dominant arm, at Day 1.

Prior_Placebo Group; Prior_RSV MAT Group

Eligibility Criteria

• Age: 18 Years - 49 Years
• Gender Eligibility Details: Only pregnant women, 18 to 49 YOA are included in the study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Missoula, Montana, 59804, United States

Location

GSK Investigational Site

Norfolk, Nebraska, 68701, United States

Location

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: February 8, 2022
• Study Start: March 11, 2022
• Primary Completion: November 6, 2023
• Study Completion: October 24, 2024
• Last Updated: April 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (2)