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Persistence of the Immune Response After Immunisation With Ebola Virus Vaccines (PRISM)

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ClinicalTrials.gov Identifier: NCT03140774
Recruitment Status : Completed
First Posted : May 4, 2017
Last Update Posted : July 15, 2020
Sponsor:
Collaborator:
University of Glasgow
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date May 2, 2017
First Posted Date May 4, 2017
Last Update Posted Date July 15, 2020
Actual Study Start Date May 17, 2017
Actual Primary Completion Date July 10, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 17, 2018)
Humoral Immunity [ Time Frame: 24 to 60 months following the primary vaccination ]
Binding antibody to the Ebola viral glycoprotein (GP) antigen assessed by ELISA
Original Primary Outcome Measures
 (submitted: May 3, 2017)
Humoral Immunity [ Time Frame: 24 to 30 months following the primary vaccination ]
Binding antibody to the Ebola viral glycoprotein antigen assessed by ELISA
Change History
Current Secondary Outcome Measures
 (submitted: October 17, 2018)
Cellular Immunity [ Time Frame: 24 to 60 months following the primary vaccination ]
Pro-inflammatory cytokine response of T cells, by using intracellular staining technique and multicolour flow cytometer
Original Secondary Outcome Measures
 (submitted: May 3, 2017)
Cellular Immunity [ Time Frame: 24 to 30 months following the primary vaccination ]
Pro-inflammatory cytokine response of T cells, by using intracellular staining technique and multicolour flow cytometer
Current Other Pre-specified Outcome Measures
 (submitted: October 17, 2018)
Cellular Immunity by alternative method [ Time Frame: 24 to 60 months following the primary vaccination ]
Interferon-gamma (INF-gamma) release by Ebola GP specific activated T cells as measured by ELISpot
Original Other Pre-specified Outcome Measures
 (submitted: May 3, 2017)
Cellular Immunity by alternative method [ Time Frame: 24 to 30 months following the primary vaccination ]
INF-gamma release by Ebola GP specific activated T cells as measured by ELISpot
 
Descriptive Information
Brief Title Persistence of the Immune Response After Immunisation With Ebola Virus Vaccines
Official Title Evaluating the Long Term Immunogenicity of Ebola Virus Vaccines Ad26-ZEBOV, MVA-BN-Filo and rVSV-ZEBOV
Brief 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).

Detailed 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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
We will seek consent for storage of excess blood samples in the Biobank. Participants will be separately consented for this.
Sampling Method Non-Probability Sample
Study Population

Cohort 1: 56 Phase 1 study participants who have received both Ad26-ZEBOV and the MVA-BN-Filo vaccines and who meet the inclusion and exclusion criteria as listed above .

Cohort 2: 26 participants who received r-VSV-ZEBOV vaccine as a part of clinical preventative care.

Cohort 3: 148 Phase 2 study participants who have received both Ad26-ZEBOV and the MVA-BN-Filo vaccines and who meet the inclusion and exclusion criteria as listed above

Condition Ebola Virus Disease
Intervention Biological: Previously exposed to Ebola vaccine
Exposure of interest: participants must have had one or more previous Ebola vaccines, Ad26.ZEBOV , MVA-BN-Filo or r-VSV-ZEBOV to enter the study.
Study Groups/Cohorts
  • Cohort 1: Phase 1 participants
    Previously exposed to Ebola vaccine Ad26-ZEBOV and MVA-BN-Filo.
    Intervention: Biological: Previously exposed to Ebola vaccine
  • Cohort 2: Received r-VSV-ZEBOV vaccine
    Previously exposed to Ebola vaccine rVSV-EBOV.
    Intervention: Biological: Previously exposed to Ebola vaccine
  • Cohort 3: Phase 2 participants
    Previously exposed to Ebola vaccine Ad26-ZEBOV and MVA-BN-Filo
    Intervention: Biological: Previously exposed to Ebola vaccine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: December 4, 2019)
126
Original Estimated Enrollment
 (submitted: May 3, 2017)
56
Actual Study Completion Date July 10, 2020
Actual Primary Completion Date July 10, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Participant is willing and able to give informed consent for participation in the study.
  2. Aged 18 years or above.
  3. Subject must have received both vaccines in the phase 1 trial (Cohort 1) the r-VSV-ZEBOV vaccine (Cohort 2), or both vaccines in the Phase 2 trial (Cohort 3)
  4. Agree to allow his or her General Practitioner and or Consultant if appropriate, to be notified of participation in the study, if required.

Exclusion Criteria:

  1. History of malignancy and receipt of immunosuppressive therapy
  2. Post organ or stem cell transplantation with or without follow-on immunosuppressive therapy
  3. Receipt of adeno virus or MVA virus based vaccine since the Phase 1 or Phase 2 study (Cohort 1 and 3) or since receiving the r-VSV-ZEBOV vaccine (Cohort 2)
  4. Chronic or recurrent use of medication which modify host immune response
  5. A visit to an Ebola endemic area since the Phase 1 or Phase 2 study (Cohort 1 and 3) or since receiving the r-VSV-ZEBOV vaccine (Cohort 2)
  6. Any contraindication to venepuncture, as determined by clinical judgement
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT03140774
Other Study ID Numbers OVG2016/04
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University of Oxford
Study Sponsor University of Oxford
Collaborators University of Glasgow
Investigators
Principal Investigator: Matthew Snape, FRCPH, MD Oxford Vaccine Group, University of Oxford
PRS Account University of Oxford
Verification Date December 2019