RSVPreF3 Vaccine Safety in Subsequent Pregnancies

No longer recruiting at 172 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: < 65

Sex: Female

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Disqualifiers: Nonchildbearing potential, Child in care

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand the safety of the RSVPreF3 vaccine in women who become pregnant again after receiving it in a previous study. It focuses on ensuring that the vaccine does not cause any issues in future pregnancies. Participants include women from earlier RSV vaccine studies who have since conceived. The trial does not involve administering new treatments or vaccines; instead, it monitors these participants to ensure their safety. Women who have had a pregnancy after participating in one of the past studies and are willing to comply with study requirements may be a good fit for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to important safety data.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to consult with the study team for guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the RSVPreF3 vaccine is safe for pregnant women and their babies. In earlier studies, the vaccine did not cause any major safety issues, and pregnant women who received it did not experience serious side effects. These studies also found that the vaccine helped protect babies from RSV-related illnesses. Thus, the vaccine is generally safe for use during pregnancy. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the RSVPreF3 vaccine because it offers a novel approach to preventing RSV infections, especially in pregnant women. Unlike the standard of care, which typically involves supportive treatments like oxygen therapy and antiviral medications post-infection, the RSVPreF3 vaccine proactively targets the virus by boosting immunity before exposure. This vaccine uses a stabilized prefusion F protein, a key component of the RSV virus, to train the immune system to recognize and fight the virus more effectively. This approach could significantly reduce the incidence and severity of RSV infections, providing better protection for both mothers and their babies.

What evidence suggests that the RSVPreF3 vaccine is safe for subsequent pregnancies?

This trial will compare the RSVPreF3 vaccine with a control group. Research has shown that the RSVPreF3 vaccine helps protect babies from serious RSV-related illnesses. One study found that babies whose mothers received the RSVPreF3 vaccine during pregnancy were less likely to have severe RSV lung infections. Another study showed that the vaccine reduced the chance of babies being hospitalized for RSV by 57%. Additionally, mothers who received the vaccine did not experience an increase in early births. Overall, these findings support the vaccine's ability to protect babies from RSV when administered to pregnant women. ^{3 5 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This study is for adults who previously participated in certain RSV vaccine trials and either became pregnant after receiving the RSVPreF3 vaccine or a control. It includes those currently pregnant or who have given birth, as well as infants born from these pregnancies. Participants must consent to follow-up and be able to comply with study requirements.

Inclusion Criteria

Study participant with any pregnancy conceived post vaccination/control that has reached Day 42 post-delivery prior to/at enrollment

Be willing to comply with all study requirements and be available for the duration of the study

Study participant who has reached 2 years+2 months post vaccine/control prior to/at enrollment or is a Woman of Nonchildbearing Potential (WONCBP) at study enrollment or recipient of bilateral tubal ligation prior to study enrollment

Exclusion Criteria

My child is in the care system and is participating.

I cannot become pregnant, either naturally or through medical procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Follow-up

The purpose of this follow-up study is to describe the safety in subsequent pregnancies in participants who were previously administered the RSVPreF3 maternal vaccine or control during any prior RSV MAT study.

Long-term

Data Analysis

Data collected from follow-up visits are analyzed to assess safety outcomes.

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Control
• RSVPreF3 vaccine

Trial Overview No new interventions are being tested. This follow-up study aims to monitor the safety of participants (and their infants) from previous RSV MAT studies where they received either an experimental RSV vaccine or a control during pregnancy.

How Is the Trial Designed?

Group I: RSVPreF3 Group Experimental Treatment 1 Intervention

Participants received the RSVPreF3 vaccine during the prior RSV MAT studies (RSV MAT-001, RSV MAT-004, RSV MAT-011, RSV MAT-010, RSV MAT-009, RSV MAT-012 and RSV MAT-039) according to the vaccination schedule specific to each study.

Group II: Control Group Experimental Treatment 1 Intervention

Participants received any control (placebo, Tdap or influenza vaccine) during the prior RSV MAT studies (RSV MAT-001, RSV MAT-004, RSV MAT-011, RSV MAT-010, RSV MAT-009, RSV MAT-012 and RSV MAT-039) according to the vaccination schedule specific to each study.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

The RSVPreF3 vaccine candidate was found to be safe for use in 213 healthy pregnant women, with no significant adverse events related to the vaccine or placebo reported during the study.

The vaccine effectively increased RSV-specific neutralizing antibody levels in mothers and successfully transferred these antibodies to newborns, indicating strong immunogenicity and potential protection for infants against RSV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial. Bebia, Z., Reyes, O., Jeanfreau, R., et al.[2023]

The RSV PFP-2 vaccine was found to be safe and well tolerated in 35 pregnant women, with no serious adverse events reported, and only mild injection site pain experienced by some participants.

The vaccine elicited a strong immune response, with 95% of recipients showing a significant increase in IgG antibodies, and their infants had higher antibody levels at birth and during the first six months, indicating effective maternal antibody transfer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women. Munoz, FM., Piedra, PA., Glezen, WP.[2022]

In a phase 2b trial involving 406 pregnant women, the RSVpreF vaccine demonstrated effective neutralizing antibody responses against RSV, with significant transplacental transfer to infants, indicating potential protection for newborns.

The vaccine was generally safe, with most side effects being mild to moderate, and the incidence of adverse events in both mothers and infants was similar to those in the placebo group, suggesting no major safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefusion F Protein-Based Respiratory Syncytial Virus Immunization in Pregnancy. Simões, EAF., Center, KJ., Tita, ATN., et al.[2022]

The RSVPreF3 vaccine candidate from GSK is designed to protect both young children and older adults against respiratory syncytial virus (RSV), with different vaccination strategies for each age group.

In toxicity studies involving rabbits and rats, the RSVPreF3 vaccine was found to be well-tolerated, showing only mild inflammatory reactions and no adverse effects on female fertility or the development of offspring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated Dose Toxicity Study and Developmental and Reproductive Toxicology Studies of a Respiratory Syncytial Virus Candidate Vaccine in Rabbits and Rats. Stokes, AH., Franklin, K., Fisher, DE., et al.[2022]

A study of 43,604 pregnancies in Finland found that vaccination with the AS03 adjuvanted pandemic influenza vaccine did not increase the risk of stillbirth, neonatal death, or adverse birth outcomes, including preterm birth and low birth weight.

Specifically, among 7,839 women vaccinated during the first trimester, there were no indications of negative effects on perinatal survival or health, supporting the safety of influenza vaccination for pregnant women at any stage of pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perinatal survival and health after maternal influenza A(H1N1)pdm09 vaccination: A cohort study of pregnancies stratified by trimester of vaccination. Baum, U., Leino, T., Gissler, M., et al.[2021]

Pregnant women face higher risks of hospitalization and death from influenza, highlighting the critical need for effective vaccination strategies during pregnancy.

Pregnancy exposure registries are essential for monitoring the safety and effects of influenza vaccines and other medications in pregnant women, ensuring that data is collected on both maternal and child health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manufacturers' postmarketing safety surveillance of influenza vaccine exposure in pregnancy. Khromava, A., Cohen, CJ., Mazur, M., et al.[2012]

A study involving 16,606 pregnant women found that receiving the Tdap vaccine after the 27th week of pregnancy did not significantly increase the risk of serious maternal and infant outcomes, supporting its safety during pregnancy.

While there were slight increases in the relative risks for preeclampsia/eclampsia and intrauterine infection, these were consistent with existing trends in the population and did not exceed the pre-specified safety threshold, indicating that Tdap vaccination is a safe option for pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of tetanus, diphtheria, acellular pertussis (Tdap) vaccination during pregnancy. Tseng, HF., Sy, LS., Ackerson, BK., et al.[2022]

Influenza vaccination during pregnancy has been shown to be safe, with nearly 40 years of research indicating no association with adverse fetal or neonatal outcomes.

Maternal influenza vaccination provides benefits to both the fetus and neonate, which supports efforts to increase vaccination coverage among pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of influenza immunization during pregnancy for the fetus and the neonate. Bednarczyk, RA., Adjaye-Gbewonyo, D., Omer, SB.[2014]

The study involving 48 young adults and 1005 older adults demonstrated that the RSVPreF3 vaccine significantly boosted immune responses, particularly after the first dose, with higher levels of RSV-specific antibodies and T cells observed in participants receiving the AS01-adjuvanted formulation.

Safety assessments revealed that most side effects were mild to moderate and temporary, with no significant safety concerns identified, leading to the selection of the AS01E-adjuvanted vaccine for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial. Leroux-Roels, I., Davis, MG., Steenackers, K., et al.[2023]

A scoping review identified 48 studies using real-world data to evaluate the safety and effectiveness of vaccines, specifically the influenza and Tdap vaccines, administered to pregnant women and their impact on infant outcomes.

Many studies lacked detailed information on data sources and definitions, which raises concerns about the reliability of their findings, highlighting the need for more rigorous future research as new vaccines, like those for COVID-19, are introduced without prior testing in pregnant populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodologic approaches in studies using real-world data (RWD) to measure pediatric safety and effectiveness of vaccines administered to pregnant women: A scoping review. Lasky, T., McMahon, AW., Hua, W., et al.[2021]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2820867

Perinatal Outcomes After RSV Vaccination During Pregnancy This study showed no increase in the rate of preterm birth among vaccinated pregnant individuals; 5.9% of RSVpreF-vaccinated pregnancies and 6.7% of ...

2. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf033/7989397

Efficacy, Immunogenicity, and Safety of an Investigational ... In conclusion, this trial suggests that infants born to mothers immunized with RSVPreF3-Mat during pregnancy had a reduced risk of medically assessed RSV-LRTD ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10420396/

A Phase 2 Randomized Trial In this phase 2 study, we investigated the safety and immunogenicity of the RSVPreF3 vaccine given to pregnant women. We also evaluated RSV-specific ...

4. cdc.gov cdc.gov/rsv/hcp/vaccine-clinical-guidance/pregnant-people.html

RSV Vaccine Guidance for Pregnant Women In the same trial, the RSV vaccine reduced the risk of the baby being hospitalized for RSV by 57% and risk of having a healthcare visit for RSV ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2216480

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV ... RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36722147/

A Phase 2 Randomized Trial What is the impact?: RSVPreF3 had an acceptable safety risk profile in pregnant women and their babies. This vaccine induced potent immune ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38477988/

RSV Prefusion F Protein-Based Maternal Vaccine We conducted a phase 3 trial involving pregnant women 18 to 49 years of age to assess the efficacy and safety of RSVPreF3-Mat.

8. publications.aap.org publications.aap.org/aapgrandrounds/article/52/1/5/197576/Maternal-RSV-Prefusion-Protein-Vaccine-Benefits-vs

Maternal RSV Prefusion Protein Vaccine: Benefits vs Risk The authors conclude that RSVPreF3-Mat administered to pregnant women was effective in reducing RSV-associated lower respiratory tract disease ...