Clinical Trials Logo

Clinical Trial Summary

The aim of this study is to investigate the persistence of the vaccine induced immune response between 24 - 60 months following primary vaccination.

The study consists of three cohorts:

Cohort 1: volunteers from the Phase 1 study of the various prime/boost regimes with two viral vectored Ebola vaccines: Ad26-ZEBOV and MVA-BN-Filo vaccines

Cohort 2: volunteers who have been vaccinated previously with Ebola vaccine r-VSV-ZEBOV

Cohort 3: volunteers from the Phase 2 study of 3 prime/boost regimes with Ad26.ZEBOV and MVA-BN-Filo vaccines (VAC52150EBL2001: EVOLVE).


Clinical Trial Description

The Ebola Virus Disease (EVD), is caused by the viruses belonging to the genus Ebola virus. The disease occurs in sporadic outbreaks in the endemic zones of Africa and results in high mortality. During an outbreak, human to human to transmission occurs by contact with the body fluids of an infected individual. In the inter-endemic period the disease is zoonotically sustained in the environment. Prevention or control of future endemic outbreaks in the high risk areas of Africa will require effective preventative strategies including immunisation.

Cohort 1:

The Phase 1 study with the multiple heterologous prime boost regimes of the Ad26-ZEBOV and the MVA-BN-Filo vaccines demonstrated a substantive immunogenicity and safety of the vaccines. A combined immune response of humoral and cellular immunity was observed in the study participants. Furthermore, persistence of the immune response was evident at one year following the primary vaccination. It is not known whether the immune response persists beyond this time point. The duration of the immunological response is important as it will inform the clinical utility of the vaccines and whether or not additional booster dosage will be required and if so, at what interval.

In this study we will invite the 56 participants from the Phase 1 study at two time points: 24 - 30 months and 36 - 48 months after receiving the primary vaccination. Following consenting and enrolment into the study, the participants will undergo a blood test. We will assess the humoral immunity by estimating the level of binding antibody to the Ebola virus envelope glycoprotein. Cellular immunity will be assessed by estimating the functional CD4+ and the CD8+ T cells secreting the pro-inflammatory cytokines. We will undertake this assessment by intracellular staining of the peripheral blood mononuclear cells (PBMC) and using flowcytometry technique to identify the positively stained cells. A second assessment of the cellular immunity will be carried out by an in-house ELISpot technique subject to availability of additional funding.

Cohort 2:

In October 2015, contacts of a laboratory-confirmed case of Ebola virus diseases (EVD) in the U.K. were given the rVSV-EBOV vaccine as a part of clinical preventative care. Subsequently, these recipients of the rVSV-EBOV vaccine were enrolled and followed up for safety and immune response until one year post vaccination in the Glasgow Ebola Vaccine Follow-up Study (REC reference 15/WS/0251). The duration of persistence of the immune response to rVSV-EBOV beyond 360 days is unknown and may impact on the use of the vaccine in any future Ebola outbreaks. This study provides an opportunity to study the immune response beyond 1 year from the prime vaccination and to compare those results with the response to MVA-BN-Filo and Ad26-ZEBOV vaccines. This study will also allow for a further period of safety follow-up for this cohort.

Twenty-six individuals were vaccinated with the r-VSV-EBOV Ebola vaccine in Glasgow following possible exposure to a patient with confirmed Ebola virus disease as a part of preventative clinical care. All 26 individuals will be invited to take part in this study.

Cohort 3:

This cohort consists of participants from the Phase 2 study of 3 prime/boost regimes with Ad26.ZEBOV and MVA-BN-Filo vaccines (VAC52150EBL2001: EVOLVE). This was a randomized, observer-blind, placebo-controlled, parallel-group, multicentre, Phase 2 study to evaluate the safety, tolerability and immunogenicity of 3 heterologous prime-boost regimens which differed in the timing of the boost vaccination. The dose of each study vaccine (Ad26.ZEBOV, MVA-BN-Filo or placebo) and the sequence of vaccination were identical in each group. The prime/boost regimens were commenced in July 2015 and completed in February 2016.

Recruitment of participants in Group 1 (unblinded) of EVOLVE into the PRISM study can commence once all approvals are in place. However, for participants in Group 2 (blinded) of the EVOLVE study, recruitment and enrolment will not commence until after EVOLVE has been unblinded (anticipated to occur in Q4 2018 - Q1 2019). ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03140774
Study type Observational
Source University of Oxford
Contact
Status Completed
Phase
Start date May 17, 2017
Completion date July 10, 2020

See also
  Status Clinical Trial Phase
Completed NCT00374309 - Experimental Vaccine for Prevention of Ebola Virus Infection Phase 1
Completed NCT03098862 - PREVAIL VI: Identification of Host Genetic Factors Underlying Ebola Virus Disease Risk, Mortality, Long-term Sequelae, Viral RNA Persistence, Humoral Immunity, and Ebola Vaccine Response
Completed NCT02509494 - Staged Phase 3 Study to Assess the Safety and Immunogenicity of Ebola Candidate Vaccines Ad26.ZEBOV and MVA-BN-Filo Phase 3
Recruiting NCT06093646 - Addressing Medium- to Long-term EBOLA Associated Psychological Distress and Psychosocial Problems in Central Uganda N/A
Completed NCT02495246 - A Study to Assess Ebola Vaccines ChAd3-EBO-Z and Ad26.ZEBOV Phase 1
Completed NCT04906629 - INO-4201 as Booster in Healthy VSV-ZEBOV Vaccinees Phase 1
Completed NCT05064956 - Ad26.ZEBOV Booster in HIV+ Adults Previously Vaccinated With Ad26.ZEBOV/MVA-BN-Filo (EBOVAC HIV+ Booster Study) Phase 2
Withdrawn NCT04268966 - An Open-Label Study , Safety and Tolerability of Brincidofovir for Post Exposure Prophylaxis of Ebola Phase 2
Completed NCT02267109 - Phase 1 Trial of Ebola Vaccine in Mali Phase 1
Not yet recruiting NCT04822376 - Prophylaxis Vaccine Antibodies Ebola Phase 2
Recruiting NCT02333578 - Clinical Trial to Evaluate the Efficacy and Safety of Convalescent Plasma for Ebola Treatment N/A
Completed NCT02662855 - Efficacy of Favipiravir Against Severe Ebola Virus Disease Phase 2
Active, not recruiting NCT04152486 - Effectiveness and Safety of a Heterologous, Two-dose Ebola Vaccine in the DRC Phase 3
Terminated NCT04250168 - Piloting Clinical Bacteriology in the Ebola Virus Disease Care Response
Completed NCT03161366 - Providing Additional Information on the Safety and Effectiveness of an Ebola Vaccine Phase 3
Not yet recruiting NCT06100913 - Immunology of Ebola Vaccine Phase 2
Suspended NCT03462004 - Evaluating the Live-Attenuated Human Parainfluenza Virus Type 3 Vectored Vaccine Candidate Expressing Ebolavirus Zaire Glycoprotein as the Sole Envelope Glycoprotein Phase 1
Active, not recruiting NCT02876328 - Partnership for Research on Ebola VACcinations Phase 2
Not yet recruiting NCT06126822 - Safety and Immunogenicity of Ervebo® and Zabdeno® Booster Vaccines Against Ebola Virus Following Previous Vaccination With the Zabdeno/Mvabea® or Ervebo® Vaccine Schedules in DRC Phase 3
Not yet recruiting NCT05202288 - Pilot Study Evaluating the Impact of Delay Between Administration of Inmazeb Administration and Vaccination by Ervebo on Vaccine Immune Response on Healthy Volunteers Phase 2