Clinical trial NCT04556526: A Study of a 2-dose Ebola Vaccine Regimen of Ad26.ZEBOV Followed by MVA-BN-Filo in Healthy Pregnant Women
Official title: A Phase 3 Open-label Randomized Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity of a 2-dose Ebola Vaccine Regimen of Ad26.ZEBOV Followed by MVA-BN-Filo in Healthy Pregnant Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
Collaborators: name: Center for Family Health Research (CFHR)
name: Coalition for Epidemic Preparedness Innovations
name: Emory University
First posted: 2020-09-21
Enrollment: 4031
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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 \[Group B\]).


Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants with Maternal Deaths
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Participants with Spontaneous Abortion
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Participants with Stillbirth
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Participants on the Pathways to Preterm Birth
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Participants with Pre-eclampsia/ eclampsia
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Participants with Antenatal Bleeding
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Participants with Postpartum Hemorrhage
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Newborns with Major Congenital Malformations born to Participants
timeFrame: At birth
measure: Percentage of Newborns Small for Gestational age (SGA) born to Participants
timeFrame: At birth
measure: Percentage of Newborns with Low Birth Weight born to Participants
timeFrame: At birth
measure: Percentage of Newborns with Preterm Birth born to Participants
timeFrame: At birth
measure: Percentage of Neonatal Deaths in Neonates Born to Participants
timeFrame: Up to 28 days
measure: Percentage of Infants (of Participants) who Fail to Thrive
timeFrame: From birth up to 14 weeks of age
Secondary outcomes:
measure: Percentage of Participants (Pregnant Women) with Serious Adverse Events (SAEs) for Group A and B
timeFrame: Up to 6 weeks post-partum or post-pregnancy termination, whichever occurs earlier
measure: Percentage of Participants (Pregnant Women) with SAEs for Subset of Group A and B
timeFrame: Up to 365 days or 1 year post dose
measure: Percentage of Newborns (Born to Participants) with SAEs
timeFrame: From birth up to 14 weeks of age
measure: Percentage of Participants with Solicited Local and Systemic Adverse Events (AEs)
timeFrame: 7 Days after each vaccination (up to Day 64)
measure: Percentage of Participants with Unsolicited AEs
timeFrame: 28 Days after each vaccination (up to Day 85)
measure: Percentage of Participants with Normal Delivery
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Participants with Caesarian Section
timeFrame: Up to 6 weeks post-completion/termination of pregnancy
measure: Percentage of Participants with Anti-Ebola virus (EBOV) Glycoprotein (GP) Binding Antibodies
timeFrame: Day 1 (pre-dose 1), Day 78 (21 days post-dose 2), at delivery (Group A subset only), and 1 year post-dose 1 (Day 365)
measure: Percentage of Infants (Born to Participants) with Anti-Ebola virus (EBOV) Glycoprotein (GP) Binding Antibodies
timeFrame: From birth up to 14 weeks of age
Other outcomes:
Locations:
city: Cuangugu
country: Rwanda
facility: Gihundwe District Hospital
city: Gysenyi
country: Rwanda
facility: Gisenyi Hospital
city: Kigali
country: Rwanda
facility: Center for Family Health Research/Project San Francisco
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.