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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Ebola Virus Disease

Intervention / Treatment
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* Biological: Ad26.ZEBOV
* Biological: MVA-BN-Filo
* Biological: MenACWY


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 11 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Ad26.ZEBOV, MVA-BN-Filo<br>Participants will be administered 0.5 mL of Ad26.ZEBOV vaccine (5*10^10 viral particles [vp]) on Day 1 by intramuscular (IM) injection followed by 0.5 mL of MVA-BN-Filo (1*10^8 infectious units [Inf U]) vaccine by IM injection on Day 57. Participants will also receive a dose of MenACWY at the 6-months post-dose-2 visit. Upon completion of the main study, participants in the extension phase who were originally randomized to the control arm will receive the same vaccine regimen as the participants in the Ad26.ZEBOV, MVA-BN-Filo arm of the main study. | Biological: Ad26.ZEBOV<br>* Participants will receive 0.5 mL IM injection of Ad26.ZEBOV as first vaccination.<br>Biological: MVA-BN-Filo<br>* Participants will receive 0.5 mL IM injection of MVA-BN-Filo as second vaccination.<br>Biological: MenACWY<br>* Participants will receive 0.5 mL IM injection of MenACWY.<br>|
| Active Comparator: Arm 2: MenACWY<br>Participants will be administered 0.5 mL of MenACWY vaccine by IM injection on Day 1 and Day 57. Participants will also receive a dose of MenACWY at the 6-months post-dose-2 visit. | Biological: MenACWY<br>* Participants will receive 0.5 mL IM injection of MenACWY.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Study: Percentage of Participants With Solicited Local and Systemic Adverse Events (AEs) up to 7 Days Post-dose 1 | 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. | From dose 1 (Day 1) up to 7 days post-dose 1 (Day 8) | 
| Main Study: Percentage of Participants With Solicited Local and Systemic AEs up to 7 Days Post-dose 2 | 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. | From dose 2 (Day 57) up to 7 days post-dose 2 (Day 64) | 
| Main Study: Percentage of Participants With Unsolicited AEs up to 28 Days Post-dose 1 | 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. | From dose 1 (Day 1) up to 28 days post-dose 1 (Day 29) | 
| Main Study: Percentage of Participants With Unsolicited AEs up to 28 Days Post-dose 2 | 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. | From dose 2 (Day 57) up to 28 days post-dose 2 (Day 85) | 
| Main Study: Percentage of Participants With Serious Adverse Events (SAEs) up to 6 Months Post Dose-2 on Day 57 | 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. | Up to 6 months post dose-2 on Day 57 (Up to 8 months) | 
| 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. | Up to Day 365 | 

Secondary Outcome Measures

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