Ebola Virus DiseasePhase 3EBO-PEPNCT06841614
EBOla Post-Exposure Prophylaxis
A Phase 3 study testing Ervebo and Inmazeb in people with Ebola Virus Disease, run by ANRS, Emerging Infectious Diseases at 4 sites in 4 countries.
Trial summary
EBO-PEP is a multicentre, multi-epidemic, phase III, comparative, controlled, randomised, strict superiority trial in two unblinded parallel arms. The trial will be open during EVD epidemics and will recruit asymptomatic participants at high risk of developing EVD. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Ebola Virus Disease
- What is being tested?
- Ervebo and Inmazeb
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Sep 2026to 1 Aug 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Last high-risk contact within the last 5 days
- No sign or symptoms of EVD
- Signed and dated informed consent from participants over the age of majority to participate in the trial or from a representative of parental authority for minor participants.
- Non-inclusion criteria
- History of vaccination with Ervebo or any other EVD vaccine within the last 5 years (self-reported by the participant)
- History of confirmed EVD within the last 5 years (self-reported by the participant)
Show all 9Show fewer
- Hypersensitivity to any of the experimental medical products (IMP) or their excipients (self-reported by the participant)
- Participation in another therapeutic or vaccine trial for EVD
- Any other reason that, at the investigator's discretion, could compromise the participant's safety and cooperation in the trial.
Who cannot join
None listed.
Trial locations and contacts
4 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 4 countries
Democratic Republic of the Congo1 site
National Institute for Biomedical Research (INRB)
Kinshasa
Placide Mbala, MD, MSPH, PhD, 822 851 584 ext. +243, mbalaplacide@gmail.com
Guinea1 site
Guinea Centre for Research and Training in Infectious Diseases (CERFIG)
Conakry
Abdoulaye Toure, MD, MSPH, PhD, 666 64 65 66 ext. +224, abdoulaye.toure@cerfig.org
Liberia1 site
National Public Health Institute of Liberia
Monrovia
Dougbeh Chris Nyan, MD, dnyan@doctor.com
Sierra Leone1 site
University of Sierra Leone College of Medicine and Allied Health Sciences
Freetown
Alhaji N'Jai, MD, PHD, +23278375157, alhaji.njai@gmail.com
About this study
Official title: Evaluation of the Efficacy of a Post-exposure Prophylaxis (PEP) Strategy in Contacts at High Risk of Developing Ebola Virus Disease (EVD)
EBO-PEP is a multicentre, multi-epidemic, phase III, comparative, controlled, randomised, strict superiority trial in two unblinded parallel arms.
The trial will be open during EVD epidemics and will recruit asymptomatic participants at high risk of developing EVD.
Read more
Participants will be randomized (1:1) into one of two trial arms:
- Arm 1 (ERV): Ervebo D0 (72 million PFU IM)
- Arm 2 (ERV+IMZ): Ervebo D0 (72 million PFU IM) + Inmazeb IV (150 mg/kg) D0 + Ervebo D56 (revaccination)
Definition of high-risk:
Direct contact with a person with EBOV PCR-confirmed EVD with diarrhea, vomiting or external bleeding ("wet symptoms"), or with their body fluids; Direct contact with the dead body of a person with confirmed or probable EVD; Needlestick with a syringe contaminated by the blood of a person with confirmed or probable EVD; Or a child born to or breastfed by an individual with EVD
Trial follow-up All participants are monitored daily for a minimum of 21 days.
Some visits are conducted in person at the investigation site, also called the Post-Exposure Prophylaxis (PEP) center:
- at Day 5, Day 10, and Day 21 for the ERV arm,
- at Day 5, Day 10, Day 21, and Day 56 for the ERV+IMZ arm. Other visits are conducted at home or by phone, in collaboration with the Ministry of Health's surveillance team.
Participants in the ERV+IMZ arm have an in-person visit at Day 56 to be revaccinated with the Ervebo vaccine to compensate for potential inhibition of the vaccine response when Ervebo is administered simultaneously with Inmazeb.
Participants in the ERV arm have a phone visit at Day 56. For all participants, a phone visit is scheduled at Day 60. It corresponds to the last visit for all trial participants.
Follow-up in Case of Hospitalisation In case of clinical signs suggestive of EVD, participants enter the suspected case management pathway at the Ebola Treatment Center (ETC).
If EVD is confirmed by EBOV PCR, participants are allowed at the ETC, and their study samples are discontinued. They continue to be followed by the research team, and daily data are collected throughout their stay at the ETC until they are discharged alive or deceased. The day of discharge from the ETC marks the end of follow-up in the study for these participants.
Of note, participants in the ERV+IMZ arm who have confirmed EVD are not revaccinated at day 56.
Of note, participants in the ERV+IMZ arm who have confirmed EVD are not revaccinated at day 56.
If EVD is not confirmed, participants continue to be followed up by the PEP center according to the protocol.
Read the detailed description
Since its discovery in the Democratic Republic of Congo (DRC) in 1976, the EBOV virus has been responsible for numerous epidemics. Outbreaks have occurred in the DRC, Gabon, Guinea, Liberia and Sierra Leone. Imported cases were also discovered in 1996 in South Africa, and in 2014 in Mali, Nigeria, Senegal, Italy, Spain, UK and USA (1). To date, the largest EVD epidemic occurred in West Africa between 2014 and 2016. It was responsible for over 28,000 infections and more than 11,000 deaths (2-4). Since this epidemic, EVD has emerged and re-emerged regularly in Sub-Saharan Africa (SSA).
Post-exposure prophylaxis (PEP) is the treatment of people at high risk of EVD. The main aim of PEP is to intervene during the asymptomatic incubation period (2-21 days) to prevent the development of EVD.
In addition to preventing the disease in individuals, an effective PEP strategy could reduce the rate of secondary attacks, thus interrupting transmission chains. If introduced rapidly, this tool could halt the spread of the disease and contribute to the fight against EVD epidemics (5). The particular vulnerability of healthcare personnel has been highlighted during several outbreaks, due to their close contact with infected patients and contaminated equipment (6). With an effective and accessible PEP tool, it will be possible to ensure the safety and protection of these essential personnel and minimize the risk of nosocomial transmission within healthcare establishments. PEP could also benefit contact tracing efforts by providing an appropriate preventive measure. By integrating PEP into comprehensive epidemic response strategies, it will be possible to improve countries' ability to control and mitigate the public health impact of EVD epidemics and prevent future outbreaks.
There is currently no comprehensive PEP strategy, i.e. one that combines several interventions. Several prophylactic interventions have been evaluated, including vaccination and mAb immunotherapy, each with its advantages and limitations (7-9). Although not intended for this use, Ervebo vaccine is currently administered as PEP during EVD epidemics, by being administered to contacts regardless of exposure levels.
MAbs have been administered as PEP on a compassionate basis, to healthcare workers following occupational exposure, in line with WHO expert advice from 2018 (10). In addition, mAbs are recommended as PEP for newborns of Ebola-infected mothers, within seven days of birth (11). PEP can prevent the risk of infection associated with a particular contact, but not the persistent risk of infection during an epidemic. A comprehensive strategy to protect high-risk contacts must therefore be put in place, including both a drug to prevent EVD after contact (mAb or antiviral) and a vaccine for long-term immunity, to guarantee both immediate and prolonged protection.
Inmazeb (REGN-EB3), developed by Regeneron, is a cocktail of 3 neutralizing humanized mAbs directed against 3 EBOV GP epitopes (atoltiviMab, maftiviMab and odesiviMab). It is indicated for the treatment of EVD in adult patients (including pregnant women) and in children, including neonates whose mothers have EVD at the time of delivery. Inmazeb inhibits viral entry into the target cell (12). This mechanism of action makes Inmazeb a promising candidate for PEP (34,40-44). In phase 1, the optimal dose was set at 150 mg/kg as a single intravenous (IV) dose, with good tolerability, except for moderate side effects such as headache and myalgia in 30% and 10% of participants respectively. The longest half-life of the three antibodies was 27.3 days (21.7 and 23.3 for the other two antibodies). At 180 days, the residual concentration of each antibody (administered at 150 mg/kg) is less than 10 mg/l (13). In the PALM trial, overall mortality after a single 150 mg/kg dose was estimated at 33.5% (versus 51.3% in the ZMapp control arm). However, the effect of treatment is strongly influenced by viral load. In patients with a high viral load at inclusion (NP Ct < 22), mortality was 63.6% (versus 86.2% in the Zmapp subgroup), while in patients with a low viral load at inclusion (NP Ct > 22), mortality was 11.2% (versus 25.8% in the Zmapp subgroup) (14). Following the PALM trial, Inmazeb was approved by the FDA for the treatment of EVD in adults and children (15).
A study conducted during the 10éme EVD epidemic in the DRC evaluated PEP with mAbs as part of a compassionate program (Post-Exposure Prophylaxis Monitored Emergency Used for Unregistered Intervention - PEP MEURI). In this study, 23 vaccine-naïve high-risk contacts received mAbs (21 Ebanga and 2 Inmazeb) after a median delay of one day between contact and PEP. At D14, none of the participants were symptom-free and their PCR was negative (16).
EBO-PEP is a multicentre, multi-epidemic, phase III, comparative, controlled, randomised, strict superiority trial in two unblinded parallel arms.
The trial will be open during EVD epidemics, and will recruit asymptomatic participants at high risk of developing EVD. Participants will be randomized (1:1) into one of two trial arms:
- Arm 1 (control arm): Ervebo D1 (72 million PFU IM)
- Arm 2: Ervebo D1 (72 million PFU IM) + Inmazeb IV (150 mg/kg) D1 + Ervebo D56 (revaccination)
Definition of high-risk:
Direct contact with a person with EBOV PCR-confirmed EVD with diarrhea, vomiting or external bleeding ("wet symptoms"), or with their body fluids; Direct contact with the dead body of a person with confirmed or probable EVD; Needlestick with a syringe contaminated by the blood of a person with confirmed or probable EVD; Or a child born to or breastfed by an individual with EVD
- Conditions
- Ebola Virus Disease
- Being tested
- Ervebo, Inmazeb
- Keywords
- Ebola Virus Disease, EBOV, High-Risk contact, Post-Exposure Prophylaxis
- 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.
ErveboBiological
Also called r-VSV-ZEBOV vaccine
Ebola Zaire vaccine (rVSV∆G-ZEBOV-GP, live, attenuated) ≥ 72 million PFU, composed of the Indiana strain of recombinant vesicular stomatitis virus (rVSV) with a deletion of the envelope glycoprotein (G) of VSV replaced by the surface glycoprotein (GP) of the Kikwit 1995 strain of Ebola virus Zaire (ZEBOV)
InmazebBiological
Also called REGN-EB3
Inmazeb (REGN-EB3), developed by Regeneron, is a cocktail of 3 neutralising humanised mAbs directed against 3 epitopes of the EBOV GP (atoltivimab, maftivimab and odesivimab). It is indicated for the treatment of EVD in adult patients (including pregnant women) and in children, including neonates born to mothers with confirmed EVD.
| Study group | Role | What they receive |
|---|---|---|
| Ervebo vaccine alone | Active comparator | Administration of Ervebo vaccine (72 million PFU IM) at day 1 Receives: Biological: Ervebo |
| Ervebo + Inmazeb | Experimental | Administration of Ervebo vaccine (72 million PFU IM) and Inmazeb IV (150 mg/kg) at day 1 and Inmazeb IV (150 mg/kg) at day 56 Receives: Biological: Ervebo; Biological: Inmazeb |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with EBOV PCR-confirmed symptomatic EVD
EVD rate
Measured: Between Day 1 and Day 21
Secondary outcomes (7)
Proportion of participants with EBOV PCR-confirmed symptomatic EVD
EVD rate
Measured: Between Day 1 and Day 60
Safety and tolerance
Proportion of participants with a grade 3 or higher Adverse Event
Measured: Between Day 1 and Day 60
Severity of EVD
Proportion of participants admitted to the Ebola Treatment Center with confirmed EVD meeting at least one of the following criteria:
- Nucleoprotein cycle threshold (NP Ct) < 22
- KDIGO stage 3
- ASAT or ALAT > 5N
- External bleeding
- AVPU score
- NEWS2 score ≥ 7
Measured: Between Day 1 and Day 60
Proportion of participants with asymptomatic EVD
Rate of PCR-confirmed EVD
Measured: Between Day 1 and Day 21
Proportion of deaths
Proportion of participants who died (all causes combined)
Measured: Between Day 1 and Day 60
Changes in viral load
NP Ct curve (nucleoprotein cycle threshold)
Measured: Between Day 1 and Day 21
Estimating cost-effectiveness
Incremental cost-effectiveness ratio (ICER) for ERV+IMZ arm vs ERV
Measured: Between Day 1 and up to Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2025
- Study startSep 2026 (estimated)
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)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
- Randomised
- Intervention model
- Parallel groups
- Model description
- The total follow-up duration for trial participants is 60 days. All participants are followed daily for a minimum of 21 days. Some visits are conducted in person at the investigation site, also called the Post-Exposure Prophylaxis (PEP) center: * at Day 5, Day 10, and Day 21 for the ERV arm, * at Day 5, Day 10, Day 21, and Day 56 for the ERV+IMZ arm. Other visits are conducted at home or by phone, in collaboration with the Ministry of Health's surveillance team. Participants in the ERV+IMZ arm have an in-person visit at Day 56 to be revaccinated with the Ervebo vaccine to compensate for potential inhibition of the vaccine response when Ervebo is administered simultaneously with Inmazeb. Participants in the ERV arm have a phone visit at Day 56. For all participants, a phone visit is scheduled at Day 60. It corresponds to the last visit for all trial participants.
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ANRS, Emerging Infectious Diseases
- Sponsor type
- Other government
- Collaborators
- Alliance for International Medical Action, Centre de Recherche et de Formation en Infectiologie de Guinée (CERFIG), Medecins Sans Frontieres, Netherlands, Barcelona Institute for Global Health, University of Bordeaux, INSERM UMR S 1136, Agence Nationale de Sécurité Sanitaire de Guinée (ANSS), Institut National de Recherche Biomedicale (INRB), Cheikh Anta Diop University, Senegal, PACCI Program, The PANdemic preparedness plaTform for Health and Emerging infectious Response, University of Sierra Leone, National Public Health Institute of Liberia
- Responsible party
- Sponsor
- Investigators
- Placide MBALA, MD, MSPH, PhD, Study chair, Institut National de Recherche Biomedicale (INRB)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06841614
- Sponsor's protocol ID
- ANRS 0515s EBO-PEP
- Acronym
- EBO-PEP
- Status last verified
- Jan 2026
- First submitted
- 28 Jan 2025
- Last updated
- 22 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huttner A, Agnandji ST, Combescure C, Fernandes JF, Bache EB, Kabwende L, Ndungu FM, Brosnahan J, Monath TP, Lemaitre B, Grillet S, Botto M, Engler O, Portmann J, Siegrist D, Bejon P, Silvera P, Kremsner P, Siegrist CA; VEBCON; VSV-EBOVAC; VSV-EBOPLUS Consortia. Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study. Lancet Infect Dis. 2018 Jul;18(7):738-748. doi: 10.1016/S1473-3099(18)30165-8. Epub 2018 Apr 5.
PubMed 29627147Isa F, Gonzalez Ortiz AM, Meyer J, Hamilton JD, Olenchock BA, Brackin T, Ganguly S, Forleo-Neto E, Faria L, Heirman I, Marovich M, Hutter J, Polakowski L, Irvin SC, Thakur M, Hooper AT, Baum A, Petro CD, Fakih FA, McElrath MJ, De Rosa SC, Cohen KW, Williams LD, Hellman CA, Odeh AJ, Patel AH, Tomaras GD, Geba GP, Kyratsous CA, Musser B, Yancopoulos GD, Herman GA; Trial Working Group. Effect of timing of casirivimab and imdevimab administration relative to mRNA-1273 COVID-19 vaccination on vaccine-induced SARS-CoV-2 neutralising antibody responses: a prospective, open-label, phase 2, randomised controlled trial. Lancet Infect Dis. 2025 Jan;25(1):52-67. doi: 10.1016/S1473-3099(24)00421-3. Epub 2024 Sep 2.
PubMed 39236733Cao L, Li Y, Yang S, Li G, Zhou Q, Sun J, Xu T, Yang Y, Liao R, Shi Y, Yang Y, Zhu T, Huang S, Ji Y, Cong F, Luo Y, Zhu Y, Luan H, Zhang H, Chen J, Liu X, Luo R, Liu L, Wang P, Yu Y, Xing F, Ke B, Zheng H, Deng X, Zhang W, Lin C, Shi M, Li CM, Zhang Y, Zhang L, Dai J, Lu H, Zhao J, Zhang X, Guo D. The adenosine analog prodrug ATV006 is orally bioavailable and has preclinical efficacy against parental SARS-CoV-2 and variants. Sci Transl Med. 2022 Sep 7;14(661):eabm7621. doi: 10.1126/scitranslmed.abm7621. Epub 2022 Sep 7.
PubMed 35579533Jaspard M, Juchet S, Serra B, Mayoum B, Kanta IM, Camara MS, Mbala P, Kojan R, Malvy D. Post-exposure prophylaxis following high-risk contact with Ebola virus, using immunotherapies with monoclonal antibodies, in the eastern Democratic Republic of the Congo: an emergency use program. Int J Infect Dis. 2021 Dec;113:166-167. doi: 10.1016/j.ijid.2021.09.053. Epub 2021 Sep 26.
PubMed 34587535PREVAC Study Team; Kieh M, Richert L, Beavogui AH, Grund B, Leigh B, D'Ortenzio E, Doumbia S, Lhomme E, Sow S, Vatrinet R, Roy C, Kennedy SB, Faye S, Lees S, Millimouno NP, Camara AM, Samai M, Deen GF, Doumbia M, Esperou H, Pierson J, Watson-Jones D, Diallo A, Wentworth D, McLean C, Simon J, Wiedemann A, Dighero-Kemp B, Hensley L, Lane HC, Levy Y, Piot P, Greenwood B, Chene G, Neaton J, Yazdanpanah Y. Randomized Trial of Vaccines for Zaire Ebola Virus Disease. N Engl J Med. 2022 Dec 29;387(26):2411-2424. doi: 10.1056/NEJMoa2200072. Epub 2022 Dec 14.
PubMed 36516078Sivapalasingam S, Kamal M, Slim R, Hosain R, Shao W, Stoltz R, Yen J, Pologe LG, Cao Y, Partridge M, Sumner G, Lipsich L. Safety, pharmacokinetics, and immunogenicity of a co-formulated cocktail of three human monoclonal antibodies targeting Ebola virus glycoprotein in healthy adults: a randomised, first-in-human phase 1 study. Lancet Infect Dis. 2018 Aug;18(8):884-893. doi: 10.1016/S1473-3099(18)30397-9. Epub 2018 Jun 18.
PubMed 29929783Pascal KE, Dudgeon D, Trefry JC, Anantpadma M, Sakurai Y, Murin CD, Turner HL, Fairhurst J, Torres M, Rafique A, Yan Y, Badithe A, Yu K, Potocky T, Bixler SL, Chance TB, Pratt WD, Rossi FD, Shamblin JD, Wollen SE, Zelko JM, Carrion R Jr, Worwa G, Staples HM, Burakov D, Babb R, Chen G, Martin J, Huang TT, Erlandson K, Willis MS, Armstrong K, Dreier TM, Ward AB, Davey RA, Pitt MLM, Lipsich L, Mason P, Olson W, Stahl N, Kyratsous CA. Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates. J Infect Dis. 2018 Nov 22;218(suppl_5):S612-S626. doi: 10.1093/infdis/jiy285.
PubMed 29860496Moso MA, Lim CK, Williams E, Marshall C, McCarthy J, Williamson DA. Prevention and post-exposure management of occupational exposure to Ebola virus. Lancet Infect Dis. 2024 Feb;24(2):e93-e105. doi: 10.1016/S1473-3099(23)00376-6. Epub 2023 Sep 15.
PubMed 37722397Crozier I, Britson KA, Wolfe DN, Klena JD, Hensley LE, Lee JS, Wolfraim LA, Taylor KL, Higgs ES, Montgomery JM, Martins KA. The Evolution of Medical Countermeasures for Ebola Virus Disease: Lessons Learned and Next Steps. Vaccines (Basel). 2022 Jul 29;10(8):1213. doi: 10.3390/vaccines10081213.
PubMed 36016101Fischer WA 2nd, Vetter P, Bausch DG, Burgess T, Davey RT Jr, Fowler R, Hayden FG, Jahrling PB, Kalil AC, Mayers DL, Mehta AK, Uyeki TM, Jacobs M. Ebola virus disease: an update on post-exposure prophylaxis. Lancet Infect Dis. 2018 Jun;18(6):e183-e192. doi: 10.1016/S1473-3099(17)30677-1. Epub 2017 Nov 15.
PubMed 29153266Bower H, Johnson S, Bangura MS, Kamara AJ, Kamara O, Mansaray SH, Sesay D, Turay C, Checchi F, Glynn JR. Exposure-Specific and Age-Specific Attack Rates for Ebola Virus Disease in Ebola-Affected Households, Sierra Leone. Emerg Infect Dis. 2016 Aug;22(8):1403-11. doi: 10.3201/eid2208.160163. Epub 2016 Aug 15.
PubMed 27144428Hoffmann Dahl E, Mbala P, Juchet S, Toure A, Montoyo A, Serra B, Kojan R, D'Ortenzio E, Blomberg B, Jaspard M. Improving Ebola virus disease outbreak control through targeted post-exposure prophylaxis. Lancet Glob Health. 2024 Oct;12(10):e1730-e1736. doi: 10.1016/S2214-109X(24)00255-9. Epub 2024 Sep 10.
PubMed 39270687Languon S, Quaye O. Filovirus Disease Outbreaks: A Chronological Overview. Virology (Auckl). 2019 Jun 21;10:1178122X19849927. doi: 10.1177/1178122X19849927. eCollection 2019.
PubMed 31258326
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy of a Post-exposure Prophylaxis (PEP) Strategy in Contacts at High Risk of Developing Ebola Virus Disease (EVD)
- ClinicalTrials.gov ID
- NCT06841614
- Acronym / sponsor ID
- EBO-PEP / ANRS 0515s EBO-PEP
- Conditions
- Ebola Virus Disease
- Keywords
- Ebola Virus Disease, EBOV, High-Risk contact, Post-Exposure Prophylaxis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- ANRS, Emerging Infectious DiseasesOther government
- Collaborators
- Alliance for International Medical Action, Centre de Recherche et de Formation en Infectiologie de Guinée (CERFIG), Medecins Sans Frontieres, Netherlands, Barcelona Institute for Global Health, University of Bordeaux, INSERM UMR S 1136, Agence Nationale de Sécurité Sanitaire de Guinée (ANSS), Institut National de Recherche Biomedicale (INRB), Cheikh Anta Diop University, Senegal, PACCI Program, The PANdemic preparedness plaTform for Health and Emerging infectious Response, University of Sierra Leone, National Public Health Institute of Liberia
- Study start
- Sep 2026 (estimated)
- Primary completion
- 1 Aug 2027 (estimated)
- Study completion
- 1 Aug 2028 (estimated)
- First posted
- 24 Feb 2025 (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.
EBO-PEP is a multicentre, multi-epidemic, phase III, comparative, controlled, randomised, strict superiority trial in two unblinded parallel arms.
The trial will be open during EVD epidemics and will recruit asymptomatic participants at high risk of developing EVD.
Participants will be randomized (1:1) into one of two trial arms:
- Arm 1 (ERV): Ervebo D0 (72 million PFU IM)
- Arm 2 (ERV+IMZ): Ervebo D0 (72 million PFU IM) + Inmazeb IV (150 mg/kg) D0 + Ervebo D56 (revaccination)
Definition of high-risk:
Direct contact with a person with EBOV PCR-confirmed EVD with diarrhea, vomiting or external bleeding ("wet symptoms"), or with their body fluids; Direct contact with the dead body of a person with confirmed or probable EVD; Needlestick with a syringe contaminated by the blood of a person with confirmed or probable EVD; Or a child born to or breastfed by an individual with EVD
Trial follow-up All participants are monitored daily for a minimum of 21 days.
Some visits are conducted in person at the investigation site, also called the Post-Exposure Prophylaxis (PEP) center:
- at Day 5, Day 10, and Day 21 for the ERV arm,
- at Day 5, Day 10, Day 21, and Day 56 for the ERV+IMZ arm. Other visits are conducted at home or by phone, in collaboration with the Ministry of Health's surveillance team.
Participants in the ERV+IMZ arm have an in-person visit at Day 56 to be revaccinated with the Ervebo vaccine to compensate for potential inhibition of the vaccine response when Ervebo is administered simultaneously with Inmazeb.
Participants in the ERV arm have a phone visit at Day 56. For all participants, a phone visit is scheduled at Day 60. It corresponds to the last visit for all trial participants.
Follow-up in Case of Hospitalisation In case of clinical signs suggestive of EVD, participants enter the suspected case management pathway at the Ebola Treatment Center (ETC).
If EVD is confirmed by EBOV PCR, participants are allowed at the ETC, and their study samples are discontinued. They continue to be followed by the research team, and daily data are collected throughout their stay at the ETC until they are discharged alive or deceased. The day of discharge from the ETC marks the end of follow-up in the study for these participants.
Of note, participants in the ERV+IMZ arm who have confirmed EVD are not revaccinated at day 56.
Of note, participants in the ERV+IMZ arm who have confirmed EVD are not revaccinated at day 56.
If EVD is not confirmed, participants continue to be followed up by the PEP center according to the protocol.
Detailed description
Since its discovery in the Democratic Republic of Congo (DRC) in 1976, the EBOV virus has been responsible for numerous epidemics. Outbreaks have occurred in the DRC, Gabon, Guinea, Liberia and Sierra Leone. Imported cases were also discovered in 1996 in South Africa, and in 2014 in Mali, Nigeria, Senegal, Italy, Spain, UK and USA (1). To date, the largest EVD epidemic occurred in West Africa between 2014 and 2016. It was responsible for over 28,000 infections and more than 11,000 deaths (2-4). Since this epidemic, EVD has emerged and re-emerged regularly in Sub-Saharan Africa (SSA).
Post-exposure prophylaxis (PEP) is the treatment of people at high risk of EVD. The main aim of PEP is to intervene during the asymptomatic incubation period (2-21 days) to prevent the development of EVD.
In addition to preventing the disease in individuals, an effective PEP strategy could reduce the rate of secondary attacks, thus interrupting transmission chains. If introduced rapidly, this tool could halt the spread of the disease and contribute to the fight against EVD epidemics (5). The particular vulnerability of healthcare personnel has been highlighted during several outbreaks, due to their close contact with infected patients and contaminated equipment (6). With an effective and accessible PEP tool, it will be possible to ensure the safety and protection of these essential personnel and minimize the risk of nosocomial transmission within healthcare establishments. PEP could also benefit contact tracing efforts by providing an appropriate preventive measure. By integrating PEP into comprehensive epidemic response strategies, it will be possible to improve countries' ability to control and mitigate the public health impact of EVD epidemics and prevent future outbreaks.
There is currently no comprehensive PEP strategy, i.e. one that combines several interventions. Several prophylactic interventions have been evaluated, including vaccination and mAb immunotherapy, each with its advantages and limitations (7-9). Although not intended for this use, Ervebo vaccine is currently administered as PEP during EVD epidemics, by being administered to contacts regardless of exposure levels.
MAbs have been administered as PEP on a compassionate basis, to healthcare workers following occupational exposure, in line with WHO expert advice from 2018 (10). In addition, mAbs are recommended as PEP for newborns of Ebola-infected mothers, within seven days of birth (11). PEP can prevent the risk of infection associated with a particular contact, but not the persistent risk of infection during an epidemic. A comprehensive strategy to protect high-risk contacts must therefore be put in place, including both a drug to prevent EVD after contact (mAb or antiviral) and a vaccine for long-term immunity, to guarantee both immediate and prolonged protection.
Inmazeb (REGN-EB3), developed by Regeneron, is a cocktail of 3 neutralizing humanized mAbs directed against 3 EBOV GP epitopes (atoltiviMab, maftiviMab and odesiviMab). It is indicated for the treatment of EVD in adult patients (including pregnant women) and in children, including neonates whose mothers have EVD at the time of delivery. Inmazeb inhibits viral entry into the target cell (12). This mechanism of action makes Inmazeb a promising candidate for PEP (34,40-44). In phase 1, the optimal dose was set at 150 mg/kg as a single intravenous (IV) dose, with good tolerability, except for moderate side effects such as headache and myalgia in 30% and 10% of participants respectively. The longest half-life of the three antibodies was 27.3 days (21.7 and 23.3 for the other two antibodies). At 180 days, the residual concentration of each antibody (administered at 150 mg/kg) is less than 10 mg/l (13). In the PALM trial, overall mortality after a single 150 mg/kg dose was estimated at 33.5% (versus 51.3% in the ZMapp control arm). However, the effect of treatment is strongly influenced by viral load. In patients with a high viral load at inclusion (NP Ct < 22), mortality was 63.6% (versus 86.2% in the Zmapp subgroup), while in patients with a low viral load at inclusion (NP Ct > 22), mortality was 11.2% (versus 25.8% in the Zmapp subgroup) (14). Following the PALM trial, Inmazeb was approved by the FDA for the treatment of EVD in adults and children (15).
A study conducted during the 10éme EVD epidemic in the DRC evaluated PEP with mAbs as part of a compassionate program (Post-Exposure Prophylaxis Monitored Emergency Used for Unregistered Intervention - PEP MEURI). In this study, 23 vaccine-naïve high-risk contacts received mAbs (21 Ebanga and 2 Inmazeb) after a median delay of one day between contact and PEP. At D14, none of the participants were symptom-free and their PCR was negative (16).
EBO-PEP is a multicentre, multi-epidemic, phase III, comparative, controlled, randomised, strict superiority trial in two unblinded parallel arms.
The trial will be open during EVD epidemics, and will recruit asymptomatic participants at high risk of developing EVD. Participants will be randomized (1:1) into one of two trial arms:
- Arm 1 (control arm): Ervebo D1 (72 million PFU IM)
- Arm 2: Ervebo D1 (72 million PFU IM) + Inmazeb IV (150 mg/kg) D1 + Ervebo D56 (revaccination)
Definition of high-risk:
Direct contact with a person with EBOV PCR-confirmed EVD with diarrhea, vomiting or external bleeding ("wet symptoms"), or with their body fluids; Direct contact with the dead body of a person with confirmed or probable EVD; Needlestick with a syringe contaminated by the blood of a person with confirmed or probable EVD; Or a child born to or breastfed by an individual with EVD
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The total follow-up duration for trial participants is 60 days. All participants are followed daily for a minimum of 21 days. Some visits are conducted in person at the investigation site, also called the Post-Exposure Prophylaxis (PEP) center: * at Day 5, Day 10, and Day 21 for the ERV arm, * at Day 5, Day 10, Day 21, and Day 56 for the ERV+IMZ arm. Other visits are conducted at home or by phone, in collaboration with the Ministry of Health's surveillance team. Participants in the ERV+IMZ arm have an in-person visit at Day 56 to be revaccinated with the Ervebo vaccine to compensate for potential inhibition of the vaccine response when Ervebo is administered simultaneously with Inmazeb. Participants in the ERV arm have a phone visit at Day 56. For all participants, a phone visit is scheduled at Day 60. It corresponds to the last visit for all trial participants.
| Arm | Type | Receives |
|---|---|---|
| Ervebo vaccine alone | Active comparator | Biological: ErveboAdministration of Ervebo vaccine (72 million PFU IM) at day 1 |
| Ervebo + Inmazeb | Experimental | Biological: Ervebo, Biological: InmazebAdministration of Ervebo vaccine (72 million PFU IM) and Inmazeb IV (150 mg/kg) at day 1 and Inmazeb IV (150 mg/kg) at day 56 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Last high-risk contact within the last 5 days
- No sign or symptoms of EVD
- Signed and dated informed consent from participants over the age of majority to participate in the trial or from a representative of parental authority for minor participants.
- Non-inclusion criteria
- History of vaccination with Ervebo or any other EVD vaccine within the last 5 years (self-reported by the participant)
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| ErveboAlso: r-VSV-ZEBOV vaccineEbola Zaire vaccine (rVSV∆G-ZEBOV-GP, live, attenuated) ≥ 72 million PFU, composed of the Indiana strain of recombinant vesicular stomatitis virus (rVSV) with a deletion of the envelope glycoprotein (G) of VSV replaced by the surface glycoprotein (GP) of the Kikwit 1995 strain of Ebola virus Zaire (ZEBOV) | Biological | Ervebo + Inmazeb, Ervebo vaccine alone |
| InmazebAlso: REGN-EB3Inmazeb (REGN-EB3), developed by Regeneron, is a cocktail of 3 neutralising humanised mAbs directed against 3 epitopes of the EBOV GP (atoltivimab, maftivimab and odesivimab). It is indicated for the treatment of EVD in adult patients (including pregnant women) and in children, including neonates born to mothers with confirmed EVD. | Biological | Ervebo + Inmazeb |
Primary outcome
Proportion of participants with EBOV PCR-confirmed symptomatic EVD
Time frame: Between Day 1 and Day 21
EVD rate
7 secondary outcomes
Proportion of participants with EBOV PCR-confirmed symptomatic EVD
Time frame: Between Day 1 and Day 60
Safety and tolerance
Time frame: Between Day 1 and Day 60
Severity of EVD
Time frame: Between Day 1 and Day 60
Proportion of participants with asymptomatic EVD
Time frame: Between Day 1 and Day 21
Proportion of deaths
Time frame: Between Day 1 and Day 60
Changes in viral load
Time frame: Between Day 1 and Day 21
Estimating cost-effectiveness
Time frame: Between Day 1 and up to Day 60
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
- Background: PubMed 29627147Huttner A, Agnandji ST, Combescure C, Fernandes JF, Bache EB, Kabwende L, Ndungu FM, Brosnahan J, Monath TP, Lemaitre B, Grillet S, Botto M, Engler O, Portmann J, Siegrist D, Bejon P, Silvera P, Kremsner P, Siegrist CA; VEBCON; VSV-EBOVAC; VSV-EBOPLUS Consortia. Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study. Lancet Infect Dis. 2018 Jul;18(7):738-748. doi: 10.1016/S1473-3099(18)30165-8. Epub 2018 Apr 5.
- Background: PubMed 39236733Isa F, Gonzalez Ortiz AM, Meyer J, Hamilton JD, Olenchock BA, Brackin T, Ganguly S, Forleo-Neto E, Faria L, Heirman I, Marovich M, Hutter J, Polakowski L, Irvin SC, Thakur M, Hooper AT, Baum A, Petro CD, Fakih FA, McElrath MJ, De Rosa SC, Cohen KW, Williams LD, Hellman CA, Odeh AJ, Patel AH, Tomaras GD, Geba GP, Kyratsous CA, Musser B, Yancopoulos GD, Herman GA; Trial Working Group. Effect of timing of casirivimab and imdevimab administration relative to mRNA-1273 COVID-19 vaccination on vaccine-induced SARS-CoV-2 neutralising antibody responses: a prospective, open-label, phase 2, randomised controlled trial. Lancet Infect Dis. 2025 Jan;25(1):52-67. doi: 10.1016/S1473-3099(24)00421-3. Epub 2024 Sep 2.
- Background: PubMed 35579533Cao L, Li Y, Yang S, Li G, Zhou Q, Sun J, Xu T, Yang Y, Liao R, Shi Y, Yang Y, Zhu T, Huang S, Ji Y, Cong F, Luo Y, Zhu Y, Luan H, Zhang H, Chen J, Liu X, Luo R, Liu L, Wang P, Yu Y, Xing F, Ke B, Zheng H, Deng X, Zhang W, Lin C, Shi M, Li CM, Zhang Y, Zhang L, Dai J, Lu H, Zhao J, Zhang X, Guo D. The adenosine analog prodrug ATV006 is orally bioavailable and has preclinical efficacy against parental SARS-CoV-2 and variants. Sci Transl Med. 2022 Sep 7;14(661):eabm7621. doi: 10.1126/scitranslmed.abm7621. Epub 2022 Sep 7.
- Background: PubMed 34587535Jaspard M, Juchet S, Serra B, Mayoum B, Kanta IM, Camara MS, Mbala P, Kojan R, Malvy D. Post-exposure prophylaxis following high-risk contact with Ebola virus, using immunotherapies with monoclonal antibodies, in the eastern Democratic Republic of the Congo: an emergency use program. Int J Infect Dis. 2021 Dec;113:166-167. doi: 10.1016/j.ijid.2021.09.053. Epub 2021 Sep 26.
- Background: PubMed 36516078PREVAC Study Team; Kieh M, Richert L, Beavogui AH, Grund B, Leigh B, D'Ortenzio E, Doumbia S, Lhomme E, Sow S, Vatrinet R, Roy C, Kennedy SB, Faye S, Lees S, Millimouno NP, Camara AM, Samai M, Deen GF, Doumbia M, Esperou H, Pierson J, Watson-Jones D, Diallo A, Wentworth D, McLean C, Simon J, Wiedemann A, Dighero-Kemp B, Hensley L, Lane HC, Levy Y, Piot P, Greenwood B, Chene G, Neaton J, Yazdanpanah Y. Randomized Trial of Vaccines for Zaire Ebola Virus Disease. N Engl J Med. 2022 Dec 29;387(26):2411-2424. doi: 10.1056/NEJMoa2200072. Epub 2022 Dec 14.
- Background: PubMed 29929783Sivapalasingam S, Kamal M, Slim R, Hosain R, Shao W, Stoltz R, Yen J, Pologe LG, Cao Y, Partridge M, Sumner G, Lipsich L. Safety, pharmacokinetics, and immunogenicity of a co-formulated cocktail of three human monoclonal antibodies targeting Ebola virus glycoprotein in healthy adults: a randomised, first-in-human phase 1 study. Lancet Infect Dis. 2018 Aug;18(8):884-893. doi: 10.1016/S1473-3099(18)30397-9. Epub 2018 Jun 18.
- Background: PubMed 29860496Pascal KE, Dudgeon D, Trefry JC, Anantpadma M, Sakurai Y, Murin CD, Turner HL, Fairhurst J, Torres M, Rafique A, Yan Y, Badithe A, Yu K, Potocky T, Bixler SL, Chance TB, Pratt WD, Rossi FD, Shamblin JD, Wollen SE, Zelko JM, Carrion R Jr, Worwa G, Staples HM, Burakov D, Babb R, Chen G, Martin J, Huang TT, Erlandson K, Willis MS, Armstrong K, Dreier TM, Ward AB, Davey RA, Pitt MLM, Lipsich L, Mason P, Olson W, Stahl N, Kyratsous CA. Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates. J Infect Dis. 2018 Nov 22;218(suppl_5):S612-S626. doi: 10.1093/infdis/jiy285.
- Background: PubMed 37722397Moso MA, Lim CK, Williams E, Marshall C, McCarthy J, Williamson DA. Prevention and post-exposure management of occupational exposure to Ebola virus. Lancet Infect Dis. 2024 Feb;24(2):e93-e105. doi: 10.1016/S1473-3099(23)00376-6. Epub 2023 Sep 15.
- Background: PubMed 36016101Crozier I, Britson KA, Wolfe DN, Klena JD, Hensley LE, Lee JS, Wolfraim LA, Taylor KL, Higgs ES, Montgomery JM, Martins KA. The Evolution of Medical Countermeasures for Ebola Virus Disease: Lessons Learned and Next Steps. Vaccines (Basel). 2022 Jul 29;10(8):1213. doi: 10.3390/vaccines10081213.
- Background: PubMed 29153266Fischer WA 2nd, Vetter P, Bausch DG, Burgess T, Davey RT Jr, Fowler R, Hayden FG, Jahrling PB, Kalil AC, Mayers DL, Mehta AK, Uyeki TM, Jacobs M. Ebola virus disease: an update on post-exposure prophylaxis. Lancet Infect Dis. 2018 Jun;18(6):e183-e192. doi: 10.1016/S1473-3099(17)30677-1. Epub 2017 Nov 15.
- Background: PubMed 27144428Bower H, Johnson S, Bangura MS, Kamara AJ, Kamara O, Mansaray SH, Sesay D, Turay C, Checchi F, Glynn JR. Exposure-Specific and Age-Specific Attack Rates for Ebola Virus Disease in Ebola-Affected Households, Sierra Leone. Emerg Infect Dis. 2016 Aug;22(8):1403-11. doi: 10.3201/eid2208.160163. Epub 2016 Aug 15.
- Background: PubMed 39270687Hoffmann Dahl E, Mbala P, Juchet S, Toure A, Montoyo A, Serra B, Kojan R, D'Ortenzio E, Blomberg B, Jaspard M. Improving Ebola virus disease outbreak control through targeted post-exposure prophylaxis. Lancet Glob Health. 2024 Oct;12(10):e1730-e1736. doi: 10.1016/S2214-109X(24)00255-9. Epub 2024 Sep 10.
- 2.WHO \| Regional Office for Africa \[Internet\]. 2024 \[cited 30 juill 2024\]. Ebola DiseaseLink provided by the sponsor.
- 11\. Therapeutics for Ebola virus disease \[Internet\]. \[cited 4 oct 2024\]Link provided by the sponsor.
- 22\. Implementation and management of contact tracing for Ebola virus disease \[Internet\]. \[cited 4 oct 2024\].Link provided by the sponsor.
- 25\. Study Details \| Pilot Study Evaluating the Impact of Delay Between Administration of Inmazeb Administration and Vaccination by Ervebo on Vaccine Immune Response on Healthy Volunteers \| ClinicalTrials.govLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Placide MBALA, MD, MSPH, PhD study chair
Institut National de Recherche Biomedicale (INRB)
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ervebo and Inmazeb in people with Ebola Virus Disease, run by ANRS, Emerging Infectious Diseases at 4 sites in 4 countries.
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 9 inclusion and 0 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: opening soon, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Democratic Republic of the Congo, Guinea, Liberia, Sierra Leone. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marie JASPARD, MD, PHD (0658809012 ext. +33, marie.jaspard@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with EBOV PCR-confirmed symptomatic EVD (time frame: Between Day 1 and Day 21). 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 NCT06841614, which also lists 13 linked publications.
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 22 Jan 2026.