Ebola Virus DiseasePhase 3NCT04152486
Effectiveness and Safety of a Heterologous, Two-dose Ebola Vaccine in the DRC
A Phase 3 study testing Ad26.ZEBOV, MVA-BN-Filo vaccine in people with Ebola Virus Disease, run by London School of Hygiene and Tropical Medicine at 1 site in Democratic Republic of the Congo.
Trial summary
A single arm, open-label, non-randomized, interventional phase 3 study to measure safety and effectiveness of a heterologous, two dose preventative vaccine (Ad26. ZEBOV, MVA-BN®-Filo) against Ebola Virus Disease. Read more about this study
- Who is it for?
- Ages 1 year and olderHealthy volunteers can take part
- Conditions the study is for
- Ebola Virus Disease
- What is being tested?
- Ad26.ZEBOV, MVA-BN-Filo vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20,426 participants
- Where
- 1 siteDemocratic Republic of the Congo
- Study dates
- 14 Nov 2019to 28 Feb 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Must provide a written or witnessed (if illiterate) informed consent form indicating that he or she understands the reasons for the study and is willing to participate in the study and be vaccinated. If less than 18 years old, must have a parent or guardian that is able to meet this criterion.
- Must be aged 1 year or older.
- Must be healthy in the investigator's clinical judgment as assessed on the day of vaccination.
- Must be willing to have a photograph taken.
- Participant must be available and willing to participate for duration of study visits and follow up.
Who cannot join
- Known history of Ebola virus disease.
- Has received any experimental Ebola vaccine less than one month prior to Visit 1.
- Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products, egg and egg proteins or gentamicin.
- Presence of acute illness (excluding minor illnesses such as mild diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC at Visit 1 (dose 1 visit). Participants with such symptoms will be temporarily excluded from vaccination at that time but may be rescheduled for vaccination at a later date if feasible.
- Presence of significant conditions or clinically significant findings at the vaccination visit for which, in the opinion of the investigator, vaccination would not be in the best interest of the participant.
- History of recurrent generalized hives.
Trial locations and contacts
1 site in 1 country.
Democratic Republic of the Congo1 site
L'Institut National de Recherche Biomédicale RDC
Kinshasa
About this study
Official title: Evaluation of a Heterologous, Two-dose Preventive Ebola Vaccine for Effectiveness and Safety in the Democratic Republic of the Congo
A single arm, open-label, non-randomized, interventional phase 3 study to measure safety and effectiveness of a heterologous, two dose preventative vaccine (Ad26. ZEBOV, MVA-BN®-Filo) against Ebola Virus Disease.
Read the detailed description
Ebola Virus Disease (EVD) is an acute, systemic, febrile syndrome caused by Ebola viruses. EVD has a case fatality ranging from 30% to 90% and spreads by direct contact with body fluids of symptomatic patients.
During the 2013-16 Ebola outbreak in Guinea, a Phase 3 cluster-randomised ring-vaccination trial using single-dose rVSV-ZEBOV-GP investigational vaccine reported 100% efficacy in protection against EVD. In 2016, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended the rapid deployment of rVSV-ZEBOV-GP in case of an EVD outbreak under an Expanded Access (compassionate use) protocol, with informed consent and Good Clinical Practice (GCP) compliance.
A new EVD outbreak started in North Kivu and Ituri provinces in the Democratic Republic of Congo in July 2018. Despite extensive control measures, including vaccination with rVSV-ZEBOV-GP in active outbreak areas, the outbreak has continued and WHO declared the outbreak a Public Health Emergency of International Concern on 17 July 2019. The ongoing outbreak has prompted consideration of additional vaccine candidates that might assist in preventing the spread of this infection to currently unaffected communities.
This study will investigate population-level vaccination with a two-dose prophylactic vaccine against Ebola, the Ad26.ZEBOV, MVA-BN-Filo vaccine that has been extensively studied in 11 previous safety and immunogenicity trials. This will be done by offering vaccination first to communities that neighbour the outbreak area or that are located on transport routes from the edge of the outbreak area to major centres like Goma.
In this study, approximately 500,000 healthy adults and children will be given the two-dose candidate vaccine regimen VAC52150 that consists of two vaccines, Ad26.ZEBOV and MVA-BN®-Filo, administered at an interval of 56 days (-14 day +28 day). Safety will be assessed in a safety subset of 1000 individuals and a pregnancy subset of up to 500 pregnant women will be followed to delivery. The first 100 infants born to these pregnant participants will be given a clinical examination at 3 months post-delivery. The study will estimate vaccine coverage of dose 1 and dose 2 overall and in different target groups and will also examine the knowledge and perceptions of persons eligible for large-scale delivery of a preventative Ebola vaccine with a two-dose vaccine strategy. The effectiveness of the vaccination on EVD will be determined through a test-negative case control study. The target sample size for the primary effectiveness evaluation is 110 laboratory-confirmed EVD cases.
An exploratory objective is to assess the immune response at before the second dose and 21 days after the second dose (MVN-BN-Filo) in a subgroup of 50 adults and 50 children who receive dose 2 beyond the recommended 56-day interval.
- Conditions
- Ebola Virus Disease
- Being tested
- Ad26.ZEBOV, MVA-BN-Filo vaccine
- Medical subject headings
- Hemorrhagic Fever, Ebola
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad26.ZEBOV, MVA-BN-Filo vaccineBiological
Ad26.ZEBOV: a monovalent vaccine expressing the full-length glycoprotein (GP) from Ebola virus (EBOV) Mayinga. The vaccine is produced in the human cell line PER.C6®.
MVA-mBN226B: further referred to as Modified Vaccinia Ankara (MVA)-BN®-Filo. This is a multivalent vaccine expressing the EBOV GP, the Sudan virus (SUDV) GP, the Marburg virus (MARV) Musoke GP, and the Taï Forest virus (TAFV, formerly known as Côte d'Ivoire ebolavirus) nucleoprotein (NP). The EBOV GP expressed by MVA BN Filo has 100% homology with the one expressed by Ad26.ZEBOV.
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | The vaccine Ad26.ZEBOV (5x10^10 viral particles (vp)) will be given as the first dose and the vaccine MVA-BN-Filo (1x10^8 infectious units (Inf U)) will be given as the second dose 56 (-14 day +28 day) days later. Receives: Biological: Ad26.ZEBOV, MVA-BN-Filo vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Numbers and odds of vaccination status in Ebola Virus Diseases cases and in EVD-negative controls.
Test negative case control study of 110 laboratory confirmed EVD cases matched to controls who test negative for EVD. Effectiveness is derived from the odds ratio for vaccination in cases compared to controls to calculate vaccine effectiveness.
Measured: Through study completion, an average of 2 years.
Secondary outcomes (4)
Number and proportion of adults and children with solicited and unsolicited serious adverse events.
Data on SAEs within one month post-dose 2 that are considered related to vaccination with Ad26. ZEBOV, MVA-BN®-Filo vaccine in adults and children.
Measured: From date of first vaccination to the one month post-dose 2 assessment of the last vaccinated participant.
Number and proportion of adults and children receiving dose 1.
Vaccine uptake
Measured: From date of first vaccination up to month 12.
Number and proportion of adults and children receiving dose 2.
Vaccine coverage
Measured: From date of first vaccination up to month 12.
Number of participants participating in in-depth interviews and focus group discussions
Focus group discussions and in-depth interviews on participant and community perceptions of the trial and on vaccine acceptability.
Measured: Through to study completion at month 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2019
- Study start14 Nov 2019
- Primary completion31 Jan 2022 (estimated)
- Study completion28 Feb 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ebola Virus DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, open-label, non-randomized interventional trial of the two dose, Ad26.ZEBOV, MVA-BN-Filo Ebola preventative vaccine
- Masking
- None (open label)
- Enrolment
- 20,426 participants (actual)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Epicentre, Ministère de la Santé de la RDC, Médecins Sans Frontières, France, Coalition for Epidemic Preparedness Innovations, Janssen Vaccines & Prevention B.V., Public Health England
- Responsible party
- Sponsor
- Investigators
- Jean-Jacques Muyembe-Tamfum, MD, PhD, Principal investigator, L'Institut National de Recherche Biomédicale RDCDaniel Bausch, MD, PhD, Principal investigator, London School of Hygiene and Tropical MedicineDeborah Watson-Jones, MD, PhD, Principal investigator, London School of Hygiene and Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04152486
- Sponsor's protocol ID
- DRC-EB-001
- Status last verified
- Jun 2021
- First submitted
- 25 Oct 2019
- Last updated
- 23 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual level data (de-identified) that underlie results in a publication.
Publications
Watson-Jones D, Kavunga-Membo H, Grais RF, Ahuka S, Roberts N, Edmunds WJ, Choi EM, Roberts CH, Edwards T, Camacho A, Lees S, Leyssen M, Spiessens B, Luhn K, Douoguih M, Hatchett R, Bausch DG, Muyembe JJ; DRC-EB-001 protocol writing team. Protocol for a phase 3 trial to evaluate the effectiveness and safety of a heterologous, two-dose vaccine for Ebola virus disease in the Democratic Republic of the Congo. BMJ Open. 2022 Mar 8;12(3):e055596. doi: 10.1136/bmjopen-2021-055596.
PubMed 35260458
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of a Heterologous, Two-dose Preventive Ebola Vaccine for Effectiveness and Safety in the Democratic Republic of the Congo
- ClinicalTrials.gov ID
- NCT04152486
- Acronym / sponsor ID
- DRC-EB-001
- Conditions
- Ebola Virus Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20,426 participants (actual)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- Epicentre, Ministère de la Santé de la RDC, Médecins Sans Frontières, France, Coalition for Epidemic Preparedness Innovations, Janssen Vaccines & Prevention B.V., Public Health England
- Study start
- 14 Nov 2019 (actual)
- Primary completion
- 31 Jan 2022 (estimated)
- Study completion
- 28 Feb 2022 (estimated)
- First posted
- 5 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A single arm, open-label, non-randomized, interventional phase 3 study to measure safety and effectiveness of a heterologous, two dose preventative vaccine (Ad26. ZEBOV, MVA-BN®-Filo) against Ebola Virus Disease.
Detailed description
Ebola Virus Disease (EVD) is an acute, systemic, febrile syndrome caused by Ebola viruses. EVD has a case fatality ranging from 30% to 90% and spreads by direct contact with body fluids of symptomatic patients.
During the 2013-16 Ebola outbreak in Guinea, a Phase 3 cluster-randomised ring-vaccination trial using single-dose rVSV-ZEBOV-GP investigational vaccine reported 100% efficacy in protection against EVD. In 2016, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended the rapid deployment of rVSV-ZEBOV-GP in case of an EVD outbreak under an Expanded Access (compassionate use) protocol, with informed consent and Good Clinical Practice (GCP) compliance.
A new EVD outbreak started in North Kivu and Ituri provinces in the Democratic Republic of Congo in July 2018. Despite extensive control measures, including vaccination with rVSV-ZEBOV-GP in active outbreak areas, the outbreak has continued and WHO declared the outbreak a Public Health Emergency of International Concern on 17 July 2019. The ongoing outbreak has prompted consideration of additional vaccine candidates that might assist in preventing the spread of this infection to currently unaffected communities.
This study will investigate population-level vaccination with a two-dose prophylactic vaccine against Ebola, the Ad26.ZEBOV, MVA-BN-Filo vaccine that has been extensively studied in 11 previous safety and immunogenicity trials. This will be done by offering vaccination first to communities that neighbour the outbreak area or that are located on transport routes from the edge of the outbreak area to major centres like Goma.
In this study, approximately 500,000 healthy adults and children will be given the two-dose candidate vaccine regimen VAC52150 that consists of two vaccines, Ad26.ZEBOV and MVA-BN®-Filo, administered at an interval of 56 days (-14 day +28 day). Safety will be assessed in a safety subset of 1000 individuals and a pregnancy subset of up to 500 pregnant women will be followed to delivery. The first 100 infants born to these pregnant participants will be given a clinical examination at 3 months post-delivery. The study will estimate vaccine coverage of dose 1 and dose 2 overall and in different target groups and will also examine the knowledge and perceptions of persons eligible for large-scale delivery of a preventative Ebola vaccine with a two-dose vaccine strategy. The effectiveness of the vaccination on EVD will be determined through a test-negative case control study. The target sample size for the primary effectiveness evaluation is 110 laboratory-confirmed EVD cases.
An exploratory objective is to assess the immune response at before the second dose and 21 days after the second dose (MVN-BN-Filo) in a subgroup of 50 adults and 50 children who receive dose 2 beyond the recommended 56-day interval.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, open-label, non-randomized interventional trial of the two dose, Ad26.ZEBOV, MVA-BN-Filo Ebola preventative vaccine
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Biological: Ad26.ZEBOV, MVA-BN-Filo vaccineThe vaccine Ad26.ZEBOV (5x10^10 viral particles (vp)) will be given as the first dose and the vaccine MVA-BN-Filo (1x10^8 infectious units (Inf U)) will be given as the second dose 56 (-14 day +28 day) days later. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Must provide a written or witnessed (if illiterate) informed consent form indicating that he or she understands the reasons for the study and is willing to participate in the study and be vaccinated. If less than 18 years old, must have a parent or guardian that is able to meet this criterion.
- Must be aged 1 year or older.
- Must be healthy in the investigator's clinical judgment as assessed on the day of vaccination.
- Must be willing to have a photograph taken.
- Participant must be available and willing to participate for duration of study visits and follow up.
Key exclusion criteria (6 listed)
- Known history of Ebola virus disease.
- Has received any experimental Ebola vaccine less than one month prior to Visit 1.
- Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products, egg and egg proteins or gentamicin.
- Presence of acute illness (excluding minor illnesses such as mild diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC at Visit 1 (dose 1 visit). Participants with such symptoms will be temporarily excluded from vaccination at that time but may be rescheduled for vaccination at a later date if feasible.
- Presence of significant conditions or clinically significant findings at the vaccination visit for which, in the opinion of the investigator, vaccination would not be in the best interest of the participant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ad26.ZEBOV, MVA-BN-Filo vaccineAd26.ZEBOV: a monovalent vaccine expressing the full-length glycoprotein (GP) from Ebola virus (EBOV) Mayinga. The vaccine is produced in the human cell line PER.C6®. MVA-mBN226B: further referred to as Modified Vaccinia Ankara (MVA)-BN®-Filo. This is a multivalent vaccine expressing the EBOV GP, the Sudan virus (SUDV) GP, the Marburg virus (MARV) Musoke GP, and the Taï Forest virus (TAFV, formerly known as Côte d'Ivoire ebolavirus) nucleoprotein (NP). The EBOV GP expressed by MVA BN Filo has 100% homology with the one expressed by Ad26.ZEBOV. | Biological | Intervention arm |
Primary outcome
Numbers and odds of vaccination status in Ebola Virus Diseases cases and in EVD-negative controls.
Time frame: Through study completion, an average of 2 years.
Test negative case control study of 110 laboratory confirmed EVD cases matched to controls who test negative for EVD. Effectiveness is derived from the odds ratio for vaccination in cases compared to controls to calculate vaccine effectiveness.
4 secondary outcomes
Number and proportion of adults and children with solicited and unsolicited serious adverse events.
Time frame: From date of first vaccination to the one month post-dose 2 assessment of the last vaccinated participant.
Number and proportion of adults and children receiving dose 1.
Time frame: From date of first vaccination up to month 12.
Number and proportion of adults and children receiving dose 2.
Time frame: From date of first vaccination up to month 12.
Number of participants participating in in-depth interviews and focus group discussions
Time frame: Through to study completion at month 24.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2021.
- Derived from this study: PubMed 35260458Watson-Jones D, Kavunga-Membo H, Grais RF, Ahuka S, Roberts N, Edmunds WJ, Choi EM, Roberts CH, Edwards T, Camacho A, Lees S, Leyssen M, Spiessens B, Luhn K, Douoguih M, Hatchett R, Bausch DG, Muyembe JJ; DRC-EB-001 protocol writing team. Protocol for a phase 3 trial to evaluate the effectiveness and safety of a heterologous, two-dose vaccine for Ebola virus disease in the Democratic Republic of the Congo. BMJ Open. 2022 Mar 8;12(3):e055596. doi: 10.1136/bmjopen-2021-055596.
- Individual participant dataSharing planned: Yes. Individual level data (de-identified) that underlie results in a publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Jacques Muyembe-Tamfum, MD, PhD principal investigator
L'Institut National de Recherche Biomédicale RDC
Daniel Bausch, MD, PhD principal investigator
London School of Hygiene and Tropical Medicine
Deborah Watson-Jones, MD, PhD principal investigator
London School of Hygiene and Tropical Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ad26.ZEBOV, MVA-BN-Filo vaccine in people with Ebola Virus Disease, run by London School of Hygiene and Tropical Medicine at 1 site in Democratic Republic of the Congo.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Democratic Republic of the Congo. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Numbers and odds of vaccination status in Ebola Virus Diseases cases and in EVD-negative controls. (time frame: Through study completion, an average of 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04152486, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2021.