A Study of 2-dose Vaccination Regimen of Ad26.ZEBOV and MVA-BN-Filo in Infants

A Phase 2 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of a Heterologous 2-dose Vaccination Regimen Using Ad26.ZEBOV and MVA-BN®-Filo in Infants Aged 4-11 Months in Guinea and Sierra Leone

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03929757

Enrollment

108

Registered

2019-04-29

Start date

2019-08-19

Completion date

2022-09-28

Last updated

2025-05-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ebola Virus Disease

Brief summary

The purpose of this study is to assess the safety and reactogenicity of a heterologous 2-dose regimen utilizing Ad26.ZEBOV (first vaccination; Dose 1) and MVA-BN-Filo (second vaccination; Dose 2) administered intramuscularly (IM) on Days 1 and 57, respectively (Main Study) and also to provide the heterologous 2-dose vaccination regimen (Ad26.ZEBOV on Day 1 and MVABN-Filo on Day 57) to participants in the control arm of the main study (Extension Phase).

Interventions

BIOLOGICALAd26.ZEBOV

Participants will receive 0.5 mL IM injection of Ad26.ZEBOV as first vaccination.

BIOLOGICALMVA-BN-Filo

Participants will receive 0.5 mL IM injection of MVA-BN-Filo as second vaccination.

BIOLOGICALMenACWY

Participants will receive 0.5 mL IM injection of MenACWY.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

4 Months to 11 Months

Healthy volunteers

Yes

Inclusion criteria

* Parent(s) (preferably both if available or as per local requirements)/guardian must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the study, and potential risks and benefits of the study, and are willing to allow their child to participate in the study * Parent(s)/guardian are willing/able to ensure that their child adheres to the prohibitions and restrictions * The parent(s)/guardian must be at or above the age of legal consent in the jurisdiction in which the study is taking place * Infant must be healthy in the investigator's clinical judgment (and the parent(s)/guardian) on the basis of medical history, physical examination, vital signs and clinical laboratory tests performed at screening * Infant has received all routine immunizations appropriate for his or her age at the time of enrollment as documented in the vaccination cards presented by the parent(s)/guardian. Participants are allowed to catch up on routine immunizations if needed (support for beneficial vaccines may be offered to participants) * Extension Phase: Prior enrollment in the control arm of the main study and did not withdraw consent, and receipt of at least the first vaccination (Dose 1) in the main study

Exclusion criteria

* Having received any candidate or other Ebola vaccine * History of Ebola virus disease (EVD), or prior exposure to Ebola virus, including travel to an area with a current Ebola outbreak less than 1 month prior to screening * Having received any experimental candidate Ad26- or modified vaccinia ankara (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 \[for example, polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-histidine for Ad26.ZEBOV vaccine; tris (hydroxymethyl)-amino methane (THAM) for MVA-BN-Filo vaccine and Neisseria meningitidis polysaccharide or tetanus toxoid for MenACWY\]), including known allergy to chicken or egg proteins and aminoglycosides (gentamicin) * Presence of acute illness (this does not include minor illnesses such as mild diarrhea or mild upper respiratory tract infection) or axillary temperature greater than or equal to (\>=) 37.5 degree celsius on Day 1. Participants with such symptoms will be excluded from enrollment at that time but may be rescheduled for enrollment at a later date * Extension Phase: Having received any candidate or other Ebola vaccine

Design outcomes

Primary

Measure	Time frame	Description
Main Study: Percentage of Participants With Solicited Local and Systemic AEs up to 7 Days Post-dose 2	From dose 2 (Day 57) up to 7 days post-dose 2 (Day 64)	An AE is any untoward medical occurrence in a participants participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site, were pre-defined local (at the injection site) AEs for which participant were specifically questioned and which were noted by participant in their diary for 7 days post vaccination. Solicited systemic events included fever, headache, fatigue/malaise, myalgia, nausea/vomiting, arthralgia and chills.
Main Study: Percentage of Participants With Solicited Local and Systemic Adverse Events (AEs) up to 7 Days Post-dose 1	From dose 1 (Day 1) up to 7 days post-dose 1 (Day 8)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site, were pre-defined local (at the injection site) AEs for which participant were specifically questioned and which were noted by participant in their diary for 7 days post vaccination. Solicited systemic events included fever, headache, fatigue/malaise, myalgia, nausea/vomiting, arthralgia and chills.
Main Study: Percentage of Participants With Unsolicited AEs up to 28 Days Post-dose 2	From dose 2 (Day 57) up to 28 days post-dose 2 (Day 85)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were events which were reported by the participant voluntarily or obtained by means of interviewing the participant in a nondirected manner.
Main Study: Percentage of Participants With SAEs Related to Study Intervention	Up to Day 365	Percentage of participants with SAEs related to study intervention were reported. A SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Main Study: Percentage of Participants With Unsolicited AEs up to 28 Days Post-dose 1	From dose 1 (Day 1) up to 28 days post-dose 1 (Day 29)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were events which were reported by the participant voluntarily or obtained by means of interviewing the participants in a nondirected manner.
Main Study: Percentage of Participants With Serious Adverse Events (SAEs) up to 6 Months Post Dose-2 on Day 57	Up to 6 months post dose-2 on Day 57 (Up to 8 months)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Secondary

Measure	Time frame	Description
Main Study: Geometric Mean of Binding Antibody Levels Against the Ebola Virus Glycoprotein (EBOV GP)	21 days post-dose 2 (Day 78)	Geometric mean of binding antibody levels against the EBOV GP were reported.

Countries

Guinea, Sierra Leone

Participant flow

Participants by arm

Arm	Count
Main Study: Ad26.ZEBOV + MVA-BN-Filo + MenACWY Healthy participants (infants) aged 4-11 months, were administered with 0.5 milliliter (mL) of adenovirus serotype 26 encoding the Ebola virus Mayinga glycoprotein (Ad26.ZEBOV) vaccine (5\10\^10 viral particles \[vp\]) on Day 1 by intramuscular (IM) injection followed by 0.5 mL of Modified Vaccinia Ankara Bavarian Nordic vector encoding multiple filovirus proteins (MVA-BN-Filo; 1\10\^8 infectious units \[Inf U\]) vaccine by IM injection on Day 57. Participants also received a dose of World Health Organisation (WHO)-prequalified 0.5 mL of Meningococcal Group A, C, W135, and Y conjugate (MenACWY) vaccine by IM injection at the 6-months post-dose 2 visit, that is, Day 237.	75
Main Study: MenACWY (Control Arm) Healthy participants were administered with 0.5 mL of MenACWY vaccine by IM injection on Day 1 and Day 57. Participants also received a dose of MenACWY vaccine by IM injection at the 6-months post-dose 2 visit, that is, Day 237.	33
Total	108

Withdrawals & dropouts

Period	Reason	FG000	FG002
Extension Study: Up to Extension Day 85	Adverse Event	0	1
Main Study: Up to Day 365	Other	1	0
Main Study: Up to Day 365	Withdrawal by parent/guardian	2	0

Baseline characteristics

Characteristic	Main Study: Ad26.ZEBOV + MVA-BN-Filo + MenACWY	Main Study: MenACWY (Control Arm)	Total
Age, Continuous	7.7 months STANDARD_DEVIATION 2.51	7.5 months STANDARD_DEVIATION 2.66	7.6 months STANDARD_DEVIATION 2.55
Age, Customized 4 to <= 8 months	43 Participants	19 Participants	62 Participants
Age, Customized >8 to 11 months	32 Participants	14 Participants	46 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants	19 Participants	55 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	39 Participants	14 Participants	53 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	36 Participants	19 Participants	55 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	39 Participants	14 Participants	53 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants
Region of Enrollment Guinea	39 Participants	14 Participants	53 Participants
Region of Enrollment Sierra Leone	36 Participants	19 Participants	55 Participants
Sex: Female, Male Female	37 Participants	13 Participants	50 Participants
Sex: Female, Male Male	38 Participants	20 Participants	58 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 75	0 / 33	0 / 26
other Total, other adverse events	58 / 75	26 / 33	9 / 26
serious Total, serious adverse events	10 / 75	4 / 33	0 / 26

Outcome results

Primary

Main Study: Percentage of Participants With SAEs Related to Study Intervention

Percentage of participants with SAEs related to study intervention were reported. A SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Time frame: Up to Day 365