A Study of a 2-dose Ebola Vaccine Regimen of Ad26.ZEBOV Followed by MVA-BN-Filo in Healthy Pregnant Women

NCT04556526 | Completed Phase 3 DMC

• 2 other identifiers: CR108739VAC52150EBL3010
• Study Type: interventional
• Target: 4,031
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is: a) to assess adverse maternal/fetal outcomes in pregnant women randomized to receive the 2- dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo \[Group A\]) and in control women (unvaccinated pregnant women \[Group B\]); and b) to assess adverse neonatal/infant outcomes in neonates/infants born to women randomized to receive the 2-dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo \[Group A\]) and in neonates/infants born to control women (unvaccinated during pregnancy \[Group B\]).

Conditions

Healthy

Outcome Measures

Primary Outcomes (13)

• Percentage of Participants with Maternal Deaths

  Percentage of participants with maternal deaths will be reported. Maternal death is the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes.

  Up to 6 weeks post-completion/termination of pregnancy

• Percentage of Participants with Spontaneous Abortion

  Percentage of participants with spontaneous abortion will be reported. Spontaneous abortion is a pregnancy loss that occurs up to 21 weeks 6 days of gestation.

  Up to 6 weeks post-completion/termination of pregnancy

• Percentage of Participants with Stillbirth

  Percentage of participants with stillbirth will be reported. Stillbirth is fetal death at or after 21 weeks 6 days of gestation.

  Up to 6 weeks post-completion/termination of pregnancy

• Percentage of Participants on the Pathways to Preterm Birth

  Percentage of participants on the pathways to preterm birth will be reported. Pathways to preterm birth is a clinical syndrome characterized by any one or some combination of the following four pathways: 1) Premature preterm rupture of membranes, 2) Preterm labor, 3) Insufficient cervix, 4) Provider- initiated preterm birth.

  Up to 6 weeks post-completion/termination of pregnancy

• Percentage of Participants with Pre-eclampsia/ eclampsia

  Percentage of participants with pre-eclampsia/ eclampsia will be reported. Pre-eclampsia is new-onset or worsening of existing hypertension with new-onset proteinuria after 20 weeks gestation.

  Up to 6 weeks post-completion/termination of pregnancy

• Percentage of Participants with Antenatal Bleeding

  Percentage of participants with antenatal bleeding will be reported. Antenatal bleeding is vaginal or suspected intrauterine, intraperitoneal, or retroperitoneal bleeding in the second or third trimester of pregnancy.

  Up to 6 weeks post-completion/termination of pregnancy

• Percentage of Participants with Postpartum Hemorrhage

  Percentage of participants with postpartum hemorrhage will be reported. Postpartum hemorrhage is genital bleeding after delivery estimated at 1000 ml or more, or leading to hypotension or blood transfusion, or leading to severe maternal outcome (maternal death or maternal near miss) as defined by World Health Organization (WHO).

  Up to 6 weeks post-completion/termination of pregnancy

• Percentage of Newborns with Major Congenital Malformations born to Participants

  Percentage of newborns with major congenital malformations born to participants will be reported. Major congenital malformations are abnormalities of body structure or function that are present at birth and are of prenatal origin. Major congenital malformations include structural changes that have significant medical, social or cosmetic consequences for the affected individual, and typically require medical intervention (for example, cleft lip and spina bifida).

  At birth

• Percentage of Newborns Small for Gestational age (SGA) born to Participants

  Percentage of newborns small for gestational age (SGA) born to participants will be reported. Small for gestational age (SGA) means newborns that are smaller in size than normal for the gestational age (weight below the tenth percentile for the gestational age using Rwandan standards).

  At birth

• Percentage of Newborns with Low Birth Weight born to Participants

  Percentage of newborns with low birth weight born to participants will be reported. Low birth weight newborns are babies, weighing less than 2500 grams at birth (regardless of child's sex).

  At birth

• Percentage of Newborns with Preterm Birth born to Participants

  Percentage of newborns with preterm birth born to participants will be reported. Preterm birth means neonates born at less than 37 weeks' gestation.

  At birth

• Percentage of Neonatal Deaths in Neonates Born to Participants

  Percentage of neonatal deaths in neonates born to participants will be reported. Neonatal deaths mean neonate dying in the first 28 days of life.

  Up to 28 days

• Percentage of Infants (of Participants) who Fail to Thrive

  Percentage of infants (of participants) who fail to thrive will be reported. Failure to thrive means weight for age deceleration through at least 2 centile spaces on growth chart of infants or as defined according to Rwandan standards.

  From birth up to 14 weeks of age

Secondary Outcomes (9)

• Percentage of Participants (Pregnant Women) with Serious Adverse Events (SAEs) for Group A and B

  Up to 6 weeks post-partum or post-pregnancy termination, whichever occurs earlier

• Percentage of Participants (Pregnant Women) with SAEs for Subset of Group A and B

  Up to 365 days or 1 year post dose

• Percentage of Newborns (Born to Participants) with SAEs

  From birth up to 14 weeks of age

• Percentage of Participants with Solicited Local and Systemic Adverse Events (AEs)

  7 Days after each vaccination (up to Day 64)

• Percentage of Participants with Unsolicited AEs

  28 Days after each vaccination (up to Day 85)

Study Arms (2)

Group A: Ad26.ZEBOV, MVA-BN-Filo

EXPERIMENTAL

Participants will receive intramuscular (IM) injection (0.5 milliliter \[mL\]) of Adenovirus serotype 26 encoding the ebola virus mayinga glycoprotein (Ad26.ZEBOV) as Dose 1 (5\*10\^10 viral particle(s) \[vp\]) on Day 1, followed by modified vaccinia Ankara Bavarian Nordic vector encoding multiple filovirus proteins (MVA-BN-Filo) as Dose 2 (1\*10\^8 infectious unit(s) \[Inf U\]) on Day 57.

Biological: Ad26.ZEBOV; Biological: MVA-BN-Filo

Group B: No vaccination during pregnancy

OTHER

Participants (pregnant women) in control Group B will not receive any vaccination during pregnancy. However, women in this group will receive the 2-dose vaccination regimen at the earliest 6 weeks after delivery/termination of pregnancy that is Dose 1 of Ad26.ZEBOV vaccine (0.5 mL) (5\*10\^10 vp) on Day 1 by IM injection followed by 0.5 mL of MVA-BN-Filo (1\*10\^8 Inf U) vaccine by IM injection 56 days after Dose 1.

Biological: Ad26.ZEBOV; Biological: MVA-BN-Filo

Interventions

Ad26.ZEBOV BIOLOGICAL

Participants in Group A will receive 0.5 mL IM injection of Ad26.ZEBOV vaccine. Participants in Group B will receive Ad26.ZEBOV 6 weeks after delivery/termination of pregnancy.

Group A: Ad26.ZEBOV, MVA-BN-Filo; Group B: No vaccination during pregnancy

MVA-BN-Filo BIOLOGICAL

Participants in Group A will receive 0.5 mL IM injection of MVA-BN-Filo vaccine. Participants in Group B will receive MVA-BN-Filo 6 weeks after delivery/termination of pregnancy.

Group A: Ad26.ZEBOV, MVA-BN-Filo; Group B: No vaccination during pregnancy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy on the basis of physical examination, medical history, obstetric history, and vital signs performed at screening
• Healthy on the basis of clinical laboratory tests performed at screening
• Confirmed singleton pregnancy by positive urine human chorionic gonadotropin (HCG) and ultrasound at time of screening and informed consent, and reconfirmed pregnancy via ultrasound at Randomization/Day 1
• Residing within catchment area of the study site
• Evidence of normal progress of gestation prior to Randomization (Day 1) based on obstetric evaluation (including obstetric history, obstetric examination and fetal ultrasound)

You may not qualify if:

• History of Ebola Virus Disease (EVD) (self-declared or laboratory confirmed)
• Has received any experimental candidate Ad26- or MVA-based vaccine in the past
• Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines \[for example, polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-histidine for Ad26.ZEBOV vaccine; tris (hydroxymethyl)-amino methane (THAM) for MVA-BN-Filo vaccine\]), including known allergy to egg, egg products, chicken proteins and aminoglycosides
• Participant with acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or body temperature greater than or equal to (\>=)38.0ºC on Day 1 will be excluded from enrollment at that time but may be rescheduled for enrollment at a later date
• During the 6 weeks prior to screening, have had any of (a) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection (clinical features without documented test results), OR (c) close contact with a person with known or suspected SARS-CoV-2 infection
• Obstetric history including: a. \>= 2 consecutive spontaneous abortions, b. history of pre-eclampsia or eclampsia, c. rhesus negative multigravida, d. grand multigravida (greater than \[\>\] 5 previous pregnancies, e. previous late still birth (defined as loss of pregnancy at any time after 28 weeks gestation), f. previous low birth weight baby or premature delivery (defined as a delivery before 37 weeks gestation), g. previous neonatal death (defined as death of an infant within the first 28 days of life), h. previous delivery of an infant with a known or suspected genetic or chromosomal abnormality, i. history of other significant pregnancy-related or neonatal complications judged likely to affect the safety of the mother or infant or to significantly compromise the endpoint data collected

Sponsors & Collaborators

• Janssen Vaccines & Prevention B.V.: lead
• Center for Family Health Research (CFHR): collaborator
• Coalition for Epidemic Preparedness Innovations: collaborator
• Emory University: collaborator

Study Sites (3)

Gihundwe District Hospital

Cuangugu, Rwanda

Location

Gisenyi Hospital

Gysenyi, Rwanda

Location

Center for Family Health Research/Project San Francisco

Kigali, 780, Rwanda

Location

Related Publications (2)

• Nyombayire J, Ingabire R, Mazzei A, Sharkey T, Umuhoza C, Mukamuyango J, Allen S, Tichacek A, Parker R, Wall KM, Katwere M, Keshinro B, Gaddah A, Wang Y, Forcheh CA, McLean C, Oriol-Mathieu V, Luhn K, Robinson C, Karita E. Heterologous two-dose Ebola vaccine regimen in pregnant women in Rwanda: a randomized controlled phase 3 trial. Nat Med. 2025 Nov;31(11):3899-3906. doi: 10.1038/s41591-025-03932-z. Epub 2025 Sep 8.

  PMID: 40921806 DERIVED

• Karita E, Nyombayire J, Ingabire R, Mazzei A, Sharkey T, Mukamuyango J, Allen S, Tichacek A, Parker R, Priddy F, Sayinzoga F, Nsanzimana S, Robinson C, Katwere M, Anumendem D, Leyssen M, Schaefer M, Wall KM. Safety, reactogenicity, and immunogenicity of a 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in healthy adult pregnant women: study protocol for a phase 3 open-label randomized controlled trial. Trials. 2022 Jun 20;23(1):513. doi: 10.1186/s13063-022-06360-3.

  PMID: 35725488 DERIVED

Study Officials

• Janssen Vaccines & Prevention B.V. Clinical Trial

  Janssen Vaccines & Prevention B.V.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: September 21, 2020
• Study Start: October 5, 2020
• Primary Completion: March 2, 2023
• Study Completion: March 2, 2023
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

RW (3)