Hemorrhagic Fever, Ebola
Conditions
Keywords
Healthy, Ebola viruses, Ebola virus disease (EVD), Filoviruses, Safety, Human adenovirus serotype 26 (Ad26) expressing the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV), Modified Vaccinia Virus Ankara - Bavarian Nordic Filo-vector (MVA-BN Filo), Hemorrhagic fever
Brief summary
The purpose of the study is to assess the long-term safety profile of Ad26.ZEBOV and MVA-BN-Filo in participants previously exposed to these vaccines in Phase 1, 2, or 3 clinical studies.
Detailed description
This is a multi-country, prospective, long-term clinical safety study for collection of serious adverse events and pregnancy outcomes following administration of Ad26.ZEBOV and/or MVA-BN-Filo vaccines among participants who were enrolled in Phase 1, 2 or 3 clinical studies. The safety data will be collected in 3 cohorts; Cohort 1- adult and pediatric participants that received Ad26.ZEBOV and/or MVA-BN-Filo in Phase 1, 2 or 3 clinical studies (adults, adolescents and children), Cohort 2- Female participants who became pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV will be followed to the end of their pregnancy for pregnancy outcomes (Cohort 2). After the end of pregnancy, female participants will continue to be followed in Cohort 1. Cohort 3 - children born to female participants exposed to Ad26.ZEBOV and/or MVA-BN-Filo who became pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV. Safety data will be collected on all consenting participants.
Interventions
BIOLOGICALAd26.ZEBOV
No vaccine will be administered in the current study. Safety data will be collected from participants who were previously exposed to Ad26.ZEBOV vaccine in Phase 1, 2, or 3 clinical studies up to 60 months and also safety data will be collected from live born children to female participants up to 60 months after birth.
BIOLOGICALMVA-BN-Filo
No vaccine will be administered in the current study. Safety data will be collected from participants who were previously exposed to MVA-BN-Filo vaccine in Phase 1, 2, or 3 clinical studies up to 60 months and also safety data will be collected from live born children to female participants up to 60 months after birth.
Sponsors
Bavarian Nordic
Janssen Vaccines & Prevention B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 71 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female who participated in a Phase 1, 2 or 3 clinical study with Human adenovirus serotype 26 (Ad26) expressing the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV) and/or Modified Vaccinia Virus Ankara - Bavarian Nordic Filo-vector (MVA-BN-Filo) and has been exposed to Ad26.ZEBOV and/or MVA-BN-Filo (Cohort 1) * Female who participated in a Phase 1, 2 or 3 clinical study with Ad26.ZEBOV and/or MVA-BN-Filo and became pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV (Cohort 2) * Child born to female participants exposed to Ad26.ZEBOV and/or MVA-BN-Filo in a Phase 1, 2, or 3 clinical study who became pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV (Cohort 3) * Must sign an informed consent form for the current study (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study (or let their child participate); Assent is also required of children capable of understanding the nature of the study (typically 7 years of age and older)
Exclusion criteria
* No exclusions beyond those that are not meeting the inclusion criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1 and 3: Number of Participants With Serious Adverse Events (SAEs) | Up to 60 months | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. |
Countries
Burkina Faso, France, Kenya, Tanzania, Uganda, United Kingdom, United States
Participant flow
Pre-assignment details
As none of the participants met Cohort 2 eligibility criteria pre-specified in the protocol, therefore no participants were enrolled in Cohort 2. So the results were only presented for Cohorts 1 and 3.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Ad26.ZEBOV + MVA-BN-Filo Male or female participants who received adenovirus serotype 26 encoding the Ebola virus Mayinga glycoprotein (Ad26.ZEBOV) vaccine and/or Modified Vaccinia Ankara Bavarian Nordic vector encoding multiple filovirus proteins (MVA-BN-Filo) in a Phase 1, 2 or 3 (NCT02313077, NCT02325050, NCT02376426, NCT02376400, NCT02416453, NCT02564523, NCT02543567, NCT02543268) clinical study of Ad26.ZEBOV and/or MVA-BN-Filo were enrolled in this study. Participants did not receive any vaccination in the current study. Participants were followed up for safety up to 60 months after Day 1 of vaccination (including participant's original study duration). | 614 |
| Cohort 1: Placebo Male or female participants who received placebo matching to Ad26.ZEBOV and/or MVA-BN-Filo in a Phase 1, 2 or 3 (NCT02313077, NCT02325050, NCT02376426, NCT02376400, NCT02416453, NCT02564523, NCT02543567, NCT02543268) clinical study of Ad26.ZEBOV and/or MVA-BN-Filo were enrolled in this study. Participants did not receive any vaccination in the current study. Participants were followed up for safety up to 60 months after Day 1 of vaccination (including participant's original study duration). | 53 |
| Cohort 3: Ad26.ZEBOV + MVA-BN-Filo Children born to female participants who received Ad26.ZEBOV and/or MVA-BN-Filo in a Phase 1, 2, or 3 (NCT02313077, NCT02325050, NCT02376426, NCT02376400, NCT02416453, NCT02564523, NCT02543567, NCT02543268) clinical study of Ad26.ZEBOV and/or MVA-BN-Filo and became pregnant with estimated conception within 28 days after vaccination with MVA-BN-Filo or within 3 months after vaccination with Ad26.ZEBOV in a Phase 1, 2, or 3 clinical study were enrolled in this study. Participants did not receive any vaccination in the current study. Participants were followed up for safety up to 60 months after birth. | 2 |
| Cohort 3: Placebo Children born to female participants who received placebo matching to Ad26.ZEBOV and/or MVA-BN-Filo in a Phase 1, 2, or 3 (NCT02313077, NCT02325050, NCT02376426, NCT02376400, NCT02416453, NCT02564523, NCT02543567, NCT02543268) clinical study of Ad26.ZEBOV and/or MVA-BN-Filo and became pregnant with estimated conception within 28 days after vaccination with placebo matching to MVA-BN-Filo or within 3 months after vaccination with placebo matching to Ad26.ZEBOV in a Phase 1, 2, or 3 clinical study were enrolled in this study. Participants did not receive any vaccination in the current study. Participants were followed up for safety up to 60 months after birth. | 1 |
| Total | 670 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 28 | 0 | 0 | 0 |
| Overall Study | Participants terminated prematurely | 288 | 52 | 1 | 1 |
| Overall Study | Participants who had no post-baseline visits. | 3 | 4 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Ad26.ZEBOV + MVA-BN-Filo | Total | Cohort 3: Placebo | Cohort 3: Ad26.ZEBOV + MVA-BN-Filo | Cohort 1: Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 35.6 years STANDARD_DEVIATION 13 | 35.6 years STANDARD_DEVIATION 13.2 | 1.3 years | 1.2 years STANDARD_DEVIATION 0.41 | 37 years STANDARD_DEVIATION 13.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 39 Participants | 0 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 569 Participants | 618 Participants | 1 Participants | 2 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 13 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 11 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 249 Participants | 272 Participants | 1 Participants | 2 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 9 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 345 Participants | 373 Participants | 0 Participants | 0 Participants | 28 Participants |
| Region of Enrollment BURKINA FASO | 68 Participants | 79 Participants | 0 Participants | 0 Participants | 11 Participants |
| Region of Enrollment FRANCE | 139 Participants | 157 Participants | 0 Participants | 0 Participants | 18 Participants |
| Region of Enrollment KENYA | 56 Participants | 56 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment TANZANIA, UNITED REPUBLIC OF | 16 Participants | 16 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment UGANDA | 25 Participants | 28 Participants | 1 Participants | 2 Participants | 0 Participants |
| Region of Enrollment UNITED KINGDOM | 170 Participants | 180 Participants | 0 Participants | 0 Participants | 10 Participants |
| Region of Enrollment UNITED STATES OF AMERICA | 140 Participants | 154 Participants | 0 Participants | 0 Participants | 14 Participants |
| Sex: Female, Male Female | 254 Participants | 279 Participants | 0 Participants | 1 Participants | 24 Participants |
| Sex: Female, Male Male | 360 Participants | 391 Participants | 1 Participants | 1 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 614 | 0 / 53 | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 49 / 614 | 1 / 53 | 2 / 2 | 1 / 1 |
Outcome results
Primary
Cohorts 1 and 3: Number of Participants With Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.
Time frame: Up to 60 months
Population: Full analysis set (FAS) included all participants who were enrolled in this study and had at least one post-baseline visit, regardless of the occurrence of protocol deviations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Ad26.ZEBOV + MVA-BN-Filo | Cohorts 1 and 3: Number of Participants With Serious Adverse Events (SAEs) | 49 Participants |
| Cohort 1: Placebo | Cohorts 1 and 3: Number of Participants With Serious Adverse Events (SAEs) | 1 Participants |
| Cohort 3: Ad26.ZEBOV + MVA-BN-Filo | Cohorts 1 and 3: Number of Participants With Serious Adverse Events (SAEs) | 2 Participants |
| Cohort 3: Placebo | Cohorts 1 and 3: Number of Participants With Serious Adverse Events (SAEs) | 1 Participants |