EBOla Post-Exposure Prophylaxis

NCT06841614 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: ANRS 0515s EBO-PEP
• Study Type: interventional
• Target: 160
• Locations: 4 countries
• Sites: 4

Brief 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. 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.

Conditions

Ebola Virus Disease

Keywords

Ebola Virus Disease; EBOV; High-Risk contact; Post-Exposure Prophylaxis

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with EBOV PCR-confirmed symptomatic EVD

  EVD rate

  Between Day 1 and Day 21

Secondary Outcomes (7)

• Proportion of participants with EBOV PCR-confirmed symptomatic EVD

  Between Day 1 and Day 60

• Safety and tolerance

  Between Day 1 and Day 60

• Severity of EVD

  Between Day 1 and Day 60

• Proportion of participants with asymptomatic EVD

  Between Day 1 and Day 21

• Proportion of deaths

  Between Day 1 and Day 60

Study Arms (2)

Ervebo vaccine alone

ACTIVE COMPARATOR

Administration of Ervebo vaccine (72 million PFU IM) at day 1

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

Biological: Ervebo; Biological: Inmazeb

Interventions

Inmazeb BIOLOGICAL

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.

Also known as: REGN-EB3

Ervebo + Inmazeb

Ervebo BIOLOGICAL

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)

Also known as: r-VSV-ZEBOV vaccine

Ervebo + Inmazeb; Ervebo vaccine alone

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)
• 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.

Sponsors & Collaborators

• Alliance for International Medical Action: collaborator
• Centre de Recherche et de Formation en Infectiologie de Guinée (CERFIG): collaborator
• Medecins Sans Frontieres, Netherlands: collaborator
• Barcelona Institute for Global Health: collaborator
• University of Bordeaux: collaborator
• INSERM UMR S 1136: collaborator
• National Institute for Biomedical Research DRC: collaborator
• PACCI Program: collaborator
• The PANdemic preparedness plaTform for Health and Emerging infectious Response: collaborator
• University of Sierra Leone College of Medicine and Allied Health Sciences: collaborator
• National Public Health Institute of Liberia: collaborator
• ANRS, Emerging Infectious Diseases: lead
• Agence Nationale de Sécurité Sanitaire de Guinée (ANSS): collaborator
• Cheikh Anta Diop University, Senegal: collaborator

Study Sites (4)

National Institute for Biomedical Research (INRB)

Kinshasa, Democratic Republic of the Congo

Location

Guinea Centre for Research and Training in Infectious Diseases (CERFIG)

Conakry, Guinea

Location

National Public Health Institute of Liberia

Monrovia, Liberia

Location

University of Sierra Leone College of Medicine and Allied Health Sciences

Freetown, Sierra Leone

Location

Related Publications (13)

• 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.

  PMID: 29627147 BACKGROUND

• Isa 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.

  PMID: 39236733 BACKGROUND

• Cao 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.

  PMID: 35579533 BACKGROUND

• Jaspard 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.

  PMID: 34587535 BACKGROUND

• PREVAC 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.

  PMID: 36516078 BACKGROUND

• Sivapalasingam 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.

  PMID: 29929783 BACKGROUND

• Pascal 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.

  PMID: 29860496 BACKGROUND

• Moso 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.

  PMID: 37722397 BACKGROUND

• Crozier 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.

  PMID: 36016101 BACKGROUND

• Fischer 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.

  PMID: 29153266 BACKGROUND

• Bower 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.

  PMID: 27144428 BACKGROUND

• Hoffmann 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.

  PMID: 39270687 BACKGROUND

• Languon S, Quaye O. Filovirus Disease Outbreaks: A Chronological Overview. Virology (Auckl). 2019 Jun 21;10:1178122X19849927. doi: 10.1177/1178122X19849927. eCollection 2019.

  PMID: 31258326 BACKGROUND

Related Links

• 2.WHO \| Regional Office for Africa \[Internet\]. 2024 \[cited 30 juill 2024\]. Ebola Disease
• 3.CDC. Ebola. 2024 \[cited 4 oct 2024\]. Outbreak History.
• 11\. Therapeutics for Ebola virus disease \[Internet\]. \[cited 4 oct 2024\]
• 22\. Implementation and management of contact tracing for Ebola virus disease \[Internet\]. \[cited 4 oct 2024\].
• 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.gov

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Interventions

atoltivimab, maftivimab, and odesivimab-ebgn drug combination

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Study Officials

• Placide MBALA, MD, MSPH, PhD

  INRB

  STUDY CHAIR

Central Study Contacts

Marie JASPARD, MD, PHD

CONTACT

0658809012; marie.jaspard@aphp.fr

Alice MONTOYO, PharmD

CONTACT

0660162965; alice.montoyo@alima.coral.ngo

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: February 24, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

SI (1); LI (1); GU (1); DE (1)