Study to Evaluate the Immunogenicity and Safety of a Heterologous Vaccine Regimen Against Ebola

NCT04186000 | Completed Phase 2

• 2 other identifiers: VAC52150EBL2007EDMS-ERI-176345633
• Study Type: interventional
• Target: 699
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 2 study aims to improve preparedness for future Ebola outbreaks by vaccination of a well-known population at risk, ie, a cohort of health care providers (HCP) (such as primary, emergency, and community health care workers) who may be exposed to Ebola in the event of a future outbreak in the Democratic Republic of the Congo (DRC). This study will enhance the immunogenicity database by investigating the kinetics of the humoral immune response. The study will contribute to the safety database (serious adverse events) for VAC52150 following a heterologous vaccine regimen with Ad26.ZEBOV as first vaccine followed by second dose with MVA-BN-Filo administered 56 days later (Day 57). Additionally, after randomization (1:1), a booster vaccination with Ad26.ZEBOV will be executed at 1 year post first dose or 2 years post first dose.

Conditions

Ebola Virus Disease

Keywords

Ad26.ZEBOV; MVA-BN-Filo; DRC; health care providers

Outcome Measures

Primary Outcomes (1)

• Binding antibody responses post-dose 2 vaccination with MVA-BN-Filo

  To assess binding antibody levels against the EBOV GP using FANG ELISA

  21 days post-dose 2 vaccination

Secondary Outcomes (2)

• Safety of a heterologous vaccine regimen utilizing Ad26.ZEBOV as dose 1, MVA-BN-Filo as dose 2 and Ad26.ZEBOV as booster dose 3

  The entire clinical study for SAE reporting and until 7 days post booster for solicited local and system adverse events

• Binding antibody responses after booster vaccination with Ad26.ZEBOV

  7 days post-booster vaccination

Study Arms (2)

group 1

EXPERIMENTAL

Booster vaccine with AD26.ZEBOV after 1 year

Biological: Ad26.ZEBOV vaccine

group 2

EXPERIMENTAL

Booster vaccine with AD26.ZEBOV after 2 years

Biological: Ad26.ZEBOV vaccine

Interventions

Ad26.ZEBOV vaccine BIOLOGICAL

The booster vaccination with Ad26.ZEBOV (5x10\^10 vp, same dosage as during the first dose) will be given at 1 year after the first dose or 2 years post-first dose.

group 1; group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant must pass the Test of Understanding (TOU).
• Each participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. In case the participant cannot read or write, the procedures must be explained and informed consent must be witnessed by a trusted literate third party not involved with the conduct of the study.
• Participant must be a man or woman aged 18 years or older.
• Participant must be a documented health care provider in DRC.
• Participant must be healthy in the investigator's clinical judgment and on the basis of vital signs assessed at day 1 screening.
• Before vaccination, a woman must be either:
• Of childbearing potential and practicing (or intending to practice) a highly effective method of birth control consistent with local regulations and/or local culture regarding the use of birth control methods for participants in clinical studies, beginning at least 28 days prior to vaccination and during the study up to at least 3 months after the first (or only) vaccination (Ad26.ZEBOV) and 1 month after the MVA-BN-Filo vaccination (if applicable); and then starting again 14 days before the booster vaccination until 3 months after the booster vaccination.
• OR Not of childbearing potential: postmenopausal (amenorrhea for at least 12 months without alternative medical cause); permanently sterilized (eg, bilateral tubal occlusion \[which includes tubal ligation procedures as consistent with local regulations\], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); OR otherwise be incapable of pregnancy.
• Woman of childbearing potential must have a negative urine β-human chorionic gonadotropin (β-hCG) pregnancy test immediately prior to each study vaccine administration.
• Participant must be available and willing to participate for the duration of the study.
• Participant must be willing and able to comply with the protocol requirements, including the prohibitions and restrictions specified in Section 4.3.
• Participant must be willing to provide verifiable identification.
• Participant must have a means to be contacted.

You may not qualify if:

• Known history of Ebola virus disease.
• Having received any experimental candidate Ebola vaccine less than 3 months prior to the screening at the first visit.
• Having received any experimental candidate Ad26-vaccine in the past. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines \[eg, polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-histidine for Ad26.ZEBOV vaccine; and tris (hydroxymethyl)-amino methane (THAM) for MVA BN-Filo vaccine\]), including known allergy to egg, egg products and aminoglycosides.
• Presence of acute illness (this does not include minor illnesses such as mild diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC on Day 1. Participants with such symptoms will be excluded from enrollment at that time, but may be rescheduled for enrollment at a later date if feasible.
• Pregnant or breastfeeding women, or women planning to become pregnant while enrolled in this study until at least 3 months after the Ad26.ZEBOV vaccination or 1 month after MVA-BN-Filo.
• Presence of significant conditions or clinically significant findings at screening or vital signs for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Major surgery (per the investigator's judgment) within the 4 weeks prior to screening, or planned major surgery during the study (from the start of screening onwards).
• Post-organ and/or stem cell transplant whether or not with chronic immunosuppressive therapy.
• Received an investigational drug or investigational vaccines or used an invasive investigational medical device within 3 months prior to screening, or current or planned participation in another clinical study during the study.
• History of chronic urticaria (recurrent hives).

Sponsors & Collaborators

• Universiteit Antwerpen: lead
• Johnson & Johnson: collaborator
• Ace Africa: collaborator
• Innovative Medicines Initiative: collaborator
• Coalition for Epidemic Preparedness Innovations: collaborator
• University of Kinshasa: collaborator

Study Sites (1)

Hôpital Général de Référence de Boende

Boende, Province de La Tshuapa, Democratic Republic of the Congo

Location

Related Publications (14)

• Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keita S, De Clerck H, Tiffany A, Dominguez G, Loua M, Traore A, Kolie M, Malano ER, Heleze E, Bocquin A, Mely S, Raoul H, Caro V, Cadar D, Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Gunther S. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 2014 Oct 9;371(15):1418-25. doi: 10.1056/NEJMoa1404505. Epub 2014 Apr 16.

  PMID: 24738640 RESULT

• Baden LR, Walsh SR, Seaman MS, Tucker RP, Krause KH, Patel A, Johnson JA, Kleinjan J, Yanosick KE, Perry J, Zablowsky E, Abbink P, Peter L, Iampietro MJ, Cheung A, Pau MG, Weijtens M, Goudsmit J, Swann E, Wolff M, Loblein H, Dolin R, Barouch DH. First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001). J Infect Dis. 2013 Jan 15;207(2):240-7. doi: 10.1093/infdis/jis670. Epub 2012 Nov 2.

  PMID: 23125444 RESULT

• Friedrich BM, Trefry JC, Biggins JE, Hensley LE, Honko AN, Smith DR, Olinger GG. Potential vaccines and post-exposure treatments for filovirus infections. Viruses. 2012 Sep;4(9):1619-50. doi: 10.3390/v4091619. Epub 2012 Sep 21.

  PMID: 23170176 RESULT

• Kohl KS, Walop W, Gidudu J, Ball L, Halperin S, Hammer SJ, Heath P, Varricchio F, Rothstein E, Schuind A, Hennig R; Brighton Collaboration Local Reaction Working Group for Swelling at or near Injection Site. Swelling at or near injection site: case definition and guidelines for collection, analysis and presentation of immunization safety data. Vaccine. 2007 Aug 1;25(31):5858-74. doi: 10.1016/j.vaccine.2007.04.056. Epub 2007 May 11. No abstract available.

  PMID: 17548132 RESULT

• Kohl KS, Walop W, Gidudu J, Ball L, Halperin S, Hammer SJ, Heath P, Hennig R, Rothstein E, Schuind A, Varricchio F; Brighton Collaboration Local Reactions Working Group for Induration at or near Injection Site. Induration at or near injection site: case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2007 Aug 1;25(31):5839-57. doi: 10.1016/j.vaccine.2007.04.062. Epub 2007 May 8. No abstract available.

  PMID: 17553602 RESULT

• Marcy SM, Kohl KS, Dagan R, Nalin D, Blum M, Jones MC, Hansen J, Labadie J, Lee L, Martin BL, O'Brien K, Rothstein E, Vermeer P; Brighton Collaboration Fever Working Group. Fever as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation. Vaccine. 2004 Jan 26;22(5-6):551-6. doi: 10.1016/j.vaccine.2003.09.007. No abstract available.

  PMID: 14741143 RESULT

• Stittelaar KJ, Kuiken T, de Swart RL, van Amerongen G, Vos HW, Niesters HG, van Schalkwijk P, van der Kwast T, Wyatt LS, Moss B, Osterhaus AD. Safety of modified vaccinia virus Ankara (MVA) in immune-suppressed macaques. Vaccine. 2001 Jun 14;19(27):3700-9. doi: 10.1016/s0264-410x(01)00075-5.

  PMID: 11395204 RESULT

• Verheust C, Goossens M, Pauwels K, Breyer D. Biosafety aspects of modified vaccinia virus Ankara (MVA)-based vectors used for gene therapy or vaccination. Vaccine. 2012 Mar 30;30(16):2623-32. doi: 10.1016/j.vaccine.2012.02.016. Epub 2012 Feb 17.

  PMID: 22342706 RESULT

• Hoff NA, Mukadi P, Doshi RH, Bramble MS, Lu K, Gadoth A, Sinai C, Spencer D, Nicholson BP, Williams R, Mossoko M, Ilunga-Kebela B, Wasiswa J, Okitolonda-Wemakoy E, Alfonso VH, Steffen I, Muyembe-Tamfum JJ, Simmons G, Rimoin AW. Serologic Markers for Ebolavirus Among Healthcare Workers in the Democratic Republic of the Congo. J Infect Dis. 2019 Jan 29;219(4):517-525. doi: 10.1093/infdis/jiy499.

  PMID: 30239838 RESULT

• Lariviere Y, Matuvanga TZ, Osang'ir BI, Milolo S, Meta R, Kimbulu P, Robinson C, Katwere M, McLean C, Lemey G, Matangila J, Maketa V, Mitashi P, Van Geertruyden JP, Van Damme P, Muhindo-Mavoko H. Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccine regimen plus Ad26.ZEBOV booster at 1 year versus 2 years in health-care and front-line workers in the Democratic Republic of the Congo: secondary and exploratory outcomes of an open-label, randomised, phase 2 trial. Lancet Infect Dis. 2024 Jul;24(7):746-759. doi: 10.1016/S1473-3099(24)00058-6. Epub 2024 Mar 26.

  PMID: 38552653 DERIVED

• Lariviere Y, Matuvanga TZ, Lemey G, Osang'ir BI, Vermeiren PP, Milolo S, Meta R, Kimbulu P, Esanga E, Matangila J, Van Geertruyden JP, Van Damme P, Maketa V, Muhindo-Mavoko H, Mitashi P. Conducting an Ebola vaccine trial in a remote area of the Democratic Republic of the Congo: Challenges, mitigations, and lessons learned. Vaccine. 2023 Dec 12;41(51):7587-7597. doi: 10.1016/j.vaccine.2023.11.030. Epub 2023 Nov 22.

  PMID: 37993355 DERIVED

• Zola Matuvanga T, Lariviere Y, Lemey G, De Bie J, Milolo S, Meta R, Esanga E, Vermeiren PP, Thys S, Van Geertruyden JP, Van Damme P, Maketa V, Matangila J, Mitashi P, Muhindo-Mavoko H. Setting-up an Ebola vaccine trial in a remote area of the Democratic Republic of the Congo: Challenges, mitigations, and lessons learned. Vaccine. 2022 May 31;40(25):3470-3480. doi: 10.1016/j.vaccine.2022.04.094. Epub 2022 May 9.

  PMID: 35550847 DERIVED

• Lariviere Y, Zola T, Stoppie E, Maketa V, Matangila J, Mitashi P, De Bie J, Muhindo-Mavoko H, Van Geertruyden JP, Van Damme P. Open-label, randomised, clinical trial to evaluate the immunogenicity and safety of a prophylactic vaccination of healthcare providers by administration of a heterologous vaccine regimen against Ebola in the Democratic Republic of the Congo: the study protocol. BMJ Open. 2021 Sep 28;11(9):e046835. doi: 10.1136/bmjopen-2020-046835.

  PMID: 34588237 DERIVED

• Zola Matuvanga T, Johnson G, Lariviere Y, Esanga Longomo E, Matangila J, Maketa V, Lapika B, Mitashi P, Mc Kenna P, De Bie J, Van Geertruyden JP, Van Damme P, Muhindo Mavoko H. Use of Iris Scanning for Biometric Recognition of Healthy Adults Participating in an Ebola Vaccine Trial in the Democratic Republic of the Congo: Mixed Methods Study. J Med Internet Res. 2021 Aug 9;23(8):e28573. doi: 10.2196/28573.

  PMID: 34378545 DERIVED

Related Links

• IMVANEX suspension for injection. UK Summary of Product Characteristics.
• MVA-BN® (Modified Vaccinia Ankara - Bavarian Nordic).
• WHO Fact Sheet No103 Ebola Virus Disease 2014

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Condition Hierarchy (Ancestors)

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

Study Officials

• Hypolite Mavoko Muhindo, Dr.

  University of Kinshasa, Tropical Medicine Department

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical professor

Model Details: All participants receive a heterologous vaccine regimen with Ad26.ZEBOV as first vaccine followed by second dose with MVA-BN-Filo administered 56 days later (Day 57). After randomization (1:1), a booster vaccination with Ad26.ZEBOV will be executed at 1 year post first dose or 2 years post first dose.

Study Record Dates

• First Submitted: December 1, 2019
• First Posted: December 4, 2019
• Study Start: December 18, 2019
• Primary Completion: April 25, 2020
• Study Completion: October 12, 2022
• Last Updated: January 4, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)