- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02509494
Staged Phase 3 Study to Assess the Safety and Immunogenicity of Ebola Candidate Vaccines Ad26.ZEBOV and MVA-BN-Filo (EBOVAC-Salone)
June 22, 2022 updated by: Janssen Vaccines & Prevention B.V.
A Staged Phase 3 Study, Including a Double-Blinded Controlled Stage to Evaluate the Safety and Immunogenicity of Ad26.ZEBOV and MVA-BN-Filo as Candidate Prophylactic Vaccines for Ebola
The purpose of this study is the evaluation of the safety and immunogenicity of two candidate Ebola vaccines Ad26.ZEBOV and MVA-BN-Filo, in a 2-dose heterologous regimen.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is staged Phase 3 study to gather information on the safety and immunogenicity of a 2-dose heterologous regimen.
In this regimen, Ad26.ZEBOV will be administered as a Dose 1 vaccination followed by the candidate vaccine MVA-BN-Filo (Dose 2 56 days later) and a booster dose of A26.ZEBOV will be administered 2 years post Dose 1 vaccination to participants in Stage 1 who consent to this.
The study will take place in Sierra Leone and will consist of a screening phase, an active phase (vaccination) and a follow-up phase.
The active phase of the study will be conducted initially in two stages.
In the first stage approximately 40 adults aged 18 years or older will be vaccinated to gain information about the safety and immunogenicity of the 2-dose heterologous vaccine regimen.
In stage 2 a larger group of approximately 976 individuals will be vaccinated to further evaluate the safety and immunogenicity of the 2 dose heterologous vaccine regimen across different age groups.
In this stage, children aged 1 year or older, adolescents and adults will be included.
Solicited local and systemic adverse events will be collected until 7 days after the Dose 1 and Dose 2 vaccination.
Unsolicited adverse events will be collected from signing of the informed consent form (ICF) onwards until 56 days after the Dose 2 vaccination in Stage 1 and then again from the day of the booster vaccination until 28 days after the booster vaccination, and until 28 days after each vaccination in stage 2. Serious adverse events will be collected from signing of the ICF onwards until 12 and 36 months after the Dose 1 vaccination in Stage 2 and Stage 1, respectively.
These data will be reviewed by an independent data monitoring committee (IDMC) to assess whether initiation of vaccination in the next stage or age group can be provided.
Safety evaluations will include assessment of adverse events, which will be monitored throughout the study.
Participants in Stage 2 will be followed up for safety and immunogenicity until 12 months (children and adolescents) or 24 months (adults) after the Dose 1 vaccination.
Participants in Stage 1 will be followed up for safety and immunogenicity until 36 months after the Dose 1 vaccination or until 1 year after the booster vaccination.
Study Type
Interventional
Enrollment (Actual)
1023
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Freetown, Sierra Leone
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
3 months and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria Stage 1 and 2:
- Documented community engagement from community leader and a signed inform consent form (ICF) from each participant must be available
- Participant Stage 1 must be 18 years or older at screening and be resident in selected study community with no intention to move from study area within the next 5 months
- Participant must be healthy with no abnormalities in laboratory screening tests within 28 days before Dose 1 vaccination
- Female participants of childbearing potential must use adequate birth control measures and must have a negative pregnancy test at screening and immediately prior to each study vaccination
- Participant must pass the test of understanding (TOU)
Additional Inclusion criteria Stage 2:
- One year or older at screening (children of enrolled parents are eligible)
- Parent/legal guardian (for children) must pass the TOU before signing the ICF
- Subjects aged 7 years and older will be asked to give positive assent in the presence of a witness
Exclusion Criteria:
- Diagnosed with EVD or under quarantine/exposed to Ebola or body temperature equal of >= 38 degree Celsius (fever)
- Having an acute illness (mild in nature that can be treated at home) or any clinically significant acute/chronic medical condition or having a decreased number of red blood cells/hemoglobin in the blood (anemia)
- Previously participated in another Ebola interventional study or received any Ad26/MVA-based candidate vaccine
- Vaccinated with live attenuated vaccines within 30 days or with inactivated vaccines 15 days before Dose 1 vaccination
- Treated with an immunosuppressive drug at the time of screening
Additional exclusion criteria:
- Children up to 5 years of age with severe malnutrition (underweight or Z-score weight <2)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Stage 1: Active vaccination
Ad26.ZEBOV will be administered as a 0.5 milliliter (mL) intramuscular (IM) injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2).
The booster vaccination using Ad26.ZEBOV will be administered as a 0.5 mL IM injection (2 years post Dose 1).
|
Ebola Zaire vaccine, replication incompetent vaccine, sterile suspension of 0.5 milliliter (mL) intramuscular (IM) injection of 5*10^10 viral particles.
MVA-BN-Filo- is a non-replicating vaccine, 0.5 mL IM injection of 1*10^8 Infectious Unit (Inf.
U.).
|
Experimental: Stage 2: Active vaccination
Ad26.ZEBOV will be administered as a 0.5 mL IM injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2).
|
Ebola Zaire vaccine, replication incompetent vaccine, sterile suspension of 0.5 milliliter (mL) intramuscular (IM) injection of 5*10^10 viral particles.
MVA-BN-Filo- is a non-replicating vaccine, 0.5 mL IM injection of 1*10^8 Infectious Unit (Inf.
U.).
|
Experimental: Stage 2: Active vaccination for children
Ad26.ZEBOV will be administered as a 0.5 mL IM injection (Dose 1); MVA-BN-Filo will be administered as a 0.5 mL IM injection (Dose 2).
Children aged less than 2 years at randomization will receive a booster dose of vaccination at 3 months post Dose 2 with Placebo.
|
Ebola Zaire vaccine, replication incompetent vaccine, sterile suspension of 0.5 milliliter (mL) intramuscular (IM) injection of 5*10^10 viral particles.
MVA-BN-Filo- is a non-replicating vaccine, 0.5 mL IM injection of 1*10^8 Infectious Unit (Inf.
U.).
|
Active Comparator: Stage 2: Control vaccination
MenACWY will be administered as a 0.5 mL IM injection on Day 1 (Dose 1) and placebo on Day 57 (Dose 2).
|
MenACWY is a WHO-prequalified Meningococcal Group A, C, W135 and Y conjugate vaccine.
0.9% saline for injection.
|
Active Comparator: Stage 2: Control vaccination for children
MenACWY will be administered as a 0.5 mL IM injection on Day 1 (Dose 1) and placebo on Day 57 (Dose 2).
Children aged less than 2 years at randomization will receive a booster dose of MenACWY vaccination at 3 months post Dose 2 with MenACWY.
|
MenACWY is a WHO-prequalified Meningococcal Group A, C, W135 and Y conjugate vaccine.
0.9% saline for injection.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stages 1 and 2: Number of Participants With Solicited Local Adverse Events (AEs) (Day 8)
Time Frame: 7 days post dose 1 (Day 8)
|
Number of participants with solicited local AEs were reported.
Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination.
Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.
|
7 days post dose 1 (Day 8)
|
Stages 1 and 2: Number of Participants With Solicited Local AEs (Day 64)
Time Frame: 7 days post dose 2 (Day 64)
|
Number of participants with solicited local AEs were reported.
Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination.
Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.
|
7 days post dose 2 (Day 64)
|
Stage 1: Number of Participants With Solicited Local AEs (Day 738)
Time Frame: 7 days post dose 3 (Day 738)
|
Number of participants with solicited local AEs were reported.
Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination.
Solicited local AEs were: injection site pain/tenderness, erythema, induration/swelling, itching at the vaccination site.
|
7 days post dose 3 (Day 738)
|
Stages 1 and 2: Number of Participants With Solicited Systemic AEs (Day 8)
Time Frame: 7 days post dose 1 (Day 8)
|
Number of participants with solicited systemic AEs were reported.
Solicited systemic AEs included body temperature, vomiting, reduced activity, somnolence, fatigue, irritability/fussiness/crying/screaming, and loss of appetite (for preverbal children/infants) and body temperature, nausea/vomiting, fatigue/malaise, muscle pain, chills, joint pain and headache (for young children, adolescents, and adults).
|
7 days post dose 1 (Day 8)
|
Stages 1 and 2: Number of Participants With Solicited Systemic AEs (Day 64)
Time Frame: 7 days post dose 2 (Day 64)
|
Number of participants with solicited systemic AEs were reported.
Solicited systemic AEs included body temperature, vomiting, reduced activity, somnolence, fatigue, irritability/fussiness/crying/screaming, and loss of appetite (for preverbal children/infants) and body temperature, nausea/vomiting, fatigue/malaise, muscle pain, chills, joint pain and headache (for young children, adolescents, and adults).
|
7 days post dose 2 (Day 64)
|
Stage 1: Number of Participants With Solicited Systemic AEs (Day 738)
Time Frame: 7 days post dose 3 (Up to Day 738)
|
Number of participants with solicited systemic AEs were reported.
Solicited systemic AEs included body temperature, vomiting, reduced activity, somnolence, fatigue, irritability/fussiness/crying/screaming, and loss of appetite (for preverbal children/infants) and body temperature, nausea/vomiting, fatigue/malaise, muscle pain, chills, joint pain and headache (for young children, adolescents, and adults).
|
7 days post dose 3 (Up to Day 738)
|
Stages 1: Number of Participants With Serious Adverse Events (SAEs)
Time Frame: Up to 36 months
|
Number of Participants with SAEs were reported.
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.
|
Up to 36 months
|
Stages 2: Number of Participants With SAEs
Time Frame: Up to 24 months
|
Number of Participants with SAEs were reported.
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.
|
Up to 24 months
|
Stage 1: Number of Participants With Unsolicited AEs (Day 759)
Time Frame: 28 days post booster dose (Day 759)
|
Number of participants with unsolicited AEs were reported.
Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary.
|
28 days post booster dose (Day 759)
|
Stage 1: Number of Participants With Unsolicited AEs (Day 29)
Time Frame: 28 days post dose 1 (Day 29)
|
Number of participants with unsolicited AEs were reported.
Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary.
|
28 days post dose 1 (Day 29)
|
Stage 2: Number of Participants With Unsolicited AEs (Day 29)
Time Frame: 28 days post dose 1 (Day 29)
|
Number of participants with unsolicited AEs were reported.
Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary.
|
28 days post dose 1 (Day 29)
|
Stage 1: Number of Participants With Unsolicited AEs (Day 85)
Time Frame: 28 days post dose 2 (Day 85)
|
Number of participants with unsolicited AEs were reported.
Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary.
|
28 days post dose 2 (Day 85)
|
Stage 2: Number of Participants With Unsolicited AEs (Day 85)
Time Frame: 28 days post dose 2 (Day 85)
|
Number of participants with unsolicited AEs were reported.
Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary.
|
28 days post dose 2 (Day 85)
|
Stage 1: Number of Participants With Deaths
Time Frame: Up to 36 months
|
Number of participants with deaths were reported.
|
Up to 36 months
|
Stage 2: Number of Participants With Deaths (Children and Adolescents)
Time Frame: Up to 12 months
|
Number of participants (children and adolescents) with deaths were reported.
|
Up to 12 months
|
Stage 2: Number of Participants With Deaths (Adults)
Time Frame: Up to 24 months
|
Number of participants (adults) with deaths were reported.
|
Up to 24 months
|
Stage 1: Number of Participants With Immediate Reportable Event (IREs)
Time Frame: Up to 36 months
|
Number of participants with IREs were reported.
The following list of neuroinflammatory disorders are categorized as IREs: Cranial nerve disorders, including paralyses/paresis, optic neuritis, multiple sclerosis, transverse myelitis, guillain-Barré syndrome, acute disseminated encephalomyelitis, including site specific variants, myasthenia gravis and Lambert-Eaton myasthenic syndrome, immune-mediated peripheral neuropathies and plexopathies, narcolepsy, isolated paresthesia of greater than (>) 7 days duration.
|
Up to 36 months
|
Stage 2: Number of Participants With IREs (Children and Adolescents)
Time Frame: Up to 12 months
|
Number of participants (children and adolescents) with IREs were reported.
The following list of neuroinflammatory disorders are categorized as IREs: Cranial nerve disorders, including paralyses/paresis, optic neuritis, multiple sclerosis, transverse myelitis, guillain-Barré syndrome, acute disseminated encephalomyelitis, including site specific variants, myasthenia gravis and Lambert-Eaton myasthenic syndrome, immune-mediated peripheral neuropathies and plexopathies, narcolepsy, isolated paresthesia of greater than (>) 7 days duration.
|
Up to 12 months
|
Stage 2: Number of Participants With IREs (Adults)
Time Frame: Up to 24 months
|
Number of participants (adults) with IREs were reported.
The following list of neuroinflammatory disorders are categorized as IREs: Cranial nerve disorders, including paralyses/paresis, optic neuritis, multiple sclerosis, transverse myelitis, guillain-Barré syndrome, acute disseminated encephalomyelitis, including site specific variants, myasthenia gravis and Lambert-Eaton myasthenic syndrome, immune-mediated peripheral neuropathies and plexopathies, narcolepsy, isolated paresthesia of greater than (>) 7 days duration.
|
Up to 24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stages 1 and 2: Geometric Mean Concentrations (GMCs) of Binding Antibody Levels Against Ebola Virus Glycoprotein (EBOV GP) Measured Using Enzyme-linked Immunosorbent Assay (ELISA)
Time Frame: 21 days post-dose 2 (Day 78)
|
GMCs of antibodies binding to EBOV GP using ELISA were reported and were measured in ELISA units per milliliter (EU/mL).
Serum samples were collected for analysis of binding antibodies against EBOV GP using ELISA to determine humoral responses following vaccination.
For ELISA binding antibody responses, values below the lower limit of quantification (LLOQ) (36.11
ELISA units/mL).
|
21 days post-dose 2 (Day 78)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Ishola D, Manno D, Afolabi MO, Keshinro B, Bockstal V, Rogers B, Owusu-Kyei K, Serry-Bangura A, Swaray I, Lowe B, Kowuor D, Baiden F, Mooney T, Smout E, Kohn B, Otieno GT, Jusu M, Foster J, Samai M, Deen GF, Larson H, Lees S, Goldstein N, Gallagher KE, Gaddah A, Heerwegh D, Callendret B, Luhn K, Robinson C, Leyssen M, Greenwood B, Douoguih M, Leigh B, Watson-Jones D; EBL3001 study group. Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial. Lancet Infect Dis. 2022 Jan;22(1):97-109. doi: 10.1016/S1473-3099(21)00125-0. Epub 2021 Sep 13.
- Afolabi MO, Ishola D, Manno D, Keshinro B, Bockstal V, Rogers B, Owusu-Kyei K, Serry-Bangura A, Swaray I, Lowe B, Kowuor D, Baiden F, Mooney T, Smout E, Kohn B, Otieno GT, Jusu M, Foster J, Samai M, Deen GF, Larson H, Lees S, Goldstein N, Gallagher KE, Gaddah A, Heerwegh D, Callendret B, Luhn K, Robinson C, Greenwood B, Leyssen M, Douoguih M, Leigh B, Watson-Jones D; EBL3001 study group. Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2022 Jan;22(1):110-122. doi: 10.1016/S1473-3099(21)00128-6. Epub 2021 Sep 13.
- Mooney T, Smout E, Leigh B, Greenwood B, Enria L, Ishola D, Manno D, Samai M, Douoguih M, Watson-Jones D. EBOVAC-Salone: Lessons learned from implementing an Ebola vaccine trial in an Ebola-affected country. Clin Trials. 2018 Oct;15(5):436-443. doi: 10.1177/1740774518780678. Epub 2018 Jun 12.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 30, 2015
Primary Completion (Actual)
June 28, 2019
Study Completion (Actual)
July 3, 2019
Study Registration Dates
First Submitted
June 24, 2015
First Submitted That Met QC Criteria
July 27, 2015
First Posted (Estimate)
July 28, 2015
Study Record Updates
Last Update Posted (Actual)
July 18, 2022
Last Update Submitted That Met QC Criteria
June 22, 2022
Last Verified
June 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CR107372
- VAC52150EBL3001 (Other Identifier: Janssen Vaccines & Prevention B.V.)
- 115854 EBOVAC1 (Other Grant/Funding Number: The Trial is financed within the IMI-2 Ebola program)
- 2019-000691-42 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated device product
No
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