Ad26.ZEBOV Booster in HIV+ Adults Previously Vaccinated With Ad26.ZEBOV/MVA-BN-Filo (EBOVAC HIV+ Booster Study)
Condition: Ebola Virus Disease; Ebola; Hiv
MeSH terms: Virus Diseases; Hemorrhagic Fever, Ebola
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an open label study to evaluate the safety and immune response to a booster dose of
      Ad26.ZEBOV Ebola vaccine in HIV+ adults from Kenya and Uganda. Only participants who have
      received the 2-dose Ebola vaccine regimen "Ad26.ZEBOV/MVA-BN-Filo " in the VAC52150EBL2002
      vaccine trial about 4 years ago are eligible to take part.

      Approximately 50 healthy HIV+ adults, aged 18 - 50 years at the time of the parent trial,
      will be invited. Participants will first be asked to provide consent to participate in this
      study. Upon receiving the booster vaccination, participants will be followed up for
      approximately 28 days (+/- 3 days) to collect information on side effects and provide blood
      samples for antibody measurement.

      This study is designed to provide descriptive information regarding vaccine safety and
      immunogenicity. There is no formal treatment comparisons and no formal testing of statistical
      hypothesis.
    

Detailed description: 
      TITLE

      An open label, Phase 2 study to evaluate the safety and immunogenicity of an Ad26.ZEBOV
      booster dose in Human Immunodeficiency Virus positive (HIV+) adults previously vaccinated
      with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen.

      RATIONALE

      In previous Phase 2 and 3 trials, HIV+ adult participants were vaccinated with a 2-dose Ebola
      vaccine regimen of adenovirus serotype 26 expressing the Ebola virus Mayinga glycoprotein
      (Ad26.ZEBOV) followed by Modified Vaccinia Ankara Bavarian Nordic vector expressing multiple
      filovirus proteins (MVA-BN-Filo). This Ebola vaccine regimen elicited humoral immune
      responses in HIV+ adults comparable to those in HIV-negative adults 21-days after dose 2.
      However, the durability of vaccine-induced humoral responses was not known.

      PRIMARY OBJECTIVES

        -  To assess the safety and tolerability of a Ad26.ZEBOV booster dose in HIV+ adults
           previously vaccinated with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen.

        -  To assess humoral responses induced by the booster dose against EBOV glycoprotein (GP),
           as measured by Filovirus Animal Non-Clinical Group (FANG) Enzyme-Linked Immunosorbent
           Assay (ELISA) at 7 and 21 days.

      STUDY DESIGN

      This is an open label study to evaluate the immune response to a booster dose of Ad26.ZEBOV
      administered to HIV+ participants who previously received the 2-dose Ebola vaccine regimen
      with Ad26.ZEBOV followed by MVA-BN-Filo 28 days or 56 days later in the VAC52150EBL2002
      vaccine trial. The Ad26.ZEBOV will be administered as a booster dose in this population
      approximately 4 years from the time participants received MVA-BN-Filo. Approximately 50 HIV+
      adult participants, aged 18 - 50 years at randomisation in the parent trial, VAC52150EBL2002,
      from Kenya and Uganda will be invited to participate in this trial. Subjects will be asked to
      consent to participate in this study. Upon receiving the booster vaccination, participants
      will be followed up for immunogenicity and safety for approximately 28 days (+/- 3 days).

      SUBJECT POPULATION

      Participants must be healthy (based on physical examination, medical history, and clinical
      judgment) HIV+ adults who participated in the VAC52150EBL2002 trial. Participants will have
      to be virologically suppressed and immunologically controlled on highly active antiretroviral
      therapy (HAART) regimen (HIV viral load < 50 copies/millilitres (mL) and CD4+ T cell count
      >/= 350 cells/microlitres (uL) within 28 days of study vaccination). The study will be
      conducted at VAC52150EBL2002 sites in Kenya and Uganda.

      PROHIBITIONS AND RESTRICTIONS

        1. Travel to an area with active Ebola outbreak during the study period

        2. Sexually active female subjects of childbearing potential should use adequate birth
           control measures from at least 14 days before and 28 days after vaccination

        3. No disallowed concomitant therapies are being used

      INVESTIGATIONAL PRODUCT, DOSAGE AND ADMINISTRATION

      Ad26.ZEBOV is a replication-incompetent monovalent vaccine against Ebola. It consists of an
      adenovirus serotype 26 vector expressing the full-length Ebola virus (EBOV, formerly known as
      Zaire ebolavirus) Mayinga GP. A single dose of Ad26.ZEBOV at a dose of 5x10^10 viral
      particles (vp) will be administered intramuscularly.

      SAFETY EVALUATIONS

      Solicited local (i.e. injection site) and systemic adverse events (AEs) will be assessed on
      the day of vaccination and using a diary for a period of seven days following the booster
      vaccination. Unsolicited adverse events will be tracked for 28 days following booster
      vaccination, while serious adverse events will be tracked for the duration of the study. The
      Principal Investigators, together with the sponsor's medical safety officer, will be
      responsible for the safety monitoring of the study.

      Solicited local AEs to be collected in this study include:

        -  Injection Site Tenderness

        -  Injection Site Erythema

        -  Injection Site Swelling

        -  Itching

      Solicited systemic AEs to be collected in this study include:

        -  body temperature

        -  fatigue/malaise

        -  chills

        -  headache

        -  nausea/vomiting

        -  muscle pain

        -  joint pain

      IMMUNOGENICITY EVALUATIONS

      Blood will be drawn for assessments of immune responses at Day 1 (prior to vaccination), Day
      8 and Day 22. The site staff will perform sample collection and processing according to
      current versions of approved standard operating procedures.

      Future scientific research may be conducted to further investigate Ebola vaccine- and
      disease-related questions and to study other infections of public health importance in Kenya
      and Uganda, and neighboring countries. This may include the development of new, or the
      improvement of existing, techniques to characterise EBOV-directed immune responses or
      diagnostic tests. No additional samples will be taken for these analyses, however, residual
      samples from the study tests may be retained for these purposes and analysed after the end of
      the study.

      INDEPENDENT DATA AND MONITORING COMMITTEE (IDMC)

      The safety of the Ad26.ZEBOV vaccine has already been shown in HIV+ adults in previous
      studies. Therefore, the role of the IDMC will be designated to an Independent Medical
      Reviewer (IMR) to provide medical oversight and detect trends in safety signals. The IMR will
      periodically review the safety data collected and call for ad hoc safety meetings should any
      of the pre-specified pausing rules are met or in any situation that could affect participant
      safety.

      PAUSING RULES

        1. Death of a participant, considered related to study vaccine or if the causal
           relationship to the study vaccine cannot be excluded; OR

        2. One or more participants experience an serious adverse event (SAE; solicited or
           unsolicited) that is determined to be related to study vaccine; OR

        3. One or more participants experience anaphylaxis or generalised urticaria within 24 hours
           of vaccination, clearly not attributable to other causes than the study vaccine.

      QUALITY ASSURANCE (QA) AND MONITORING

      Systematic QA and monitoring of study activities during the clinical study will serve to
      assure the data reliability and validity, as well as ensure the close adherence to the
      protocol, Good Clinical Practice (GCP) and contribute to protecting the participant's safety.
      Automatic data queries will be generated by the Sponsor Data Manager. These queries will be
      posted in the electronic Data Capture system or sent to the site Investigators via email, if
      necessary. The QA Committee and external monitors will periodically review these queries and
      follow up with the sites to ensure resolution. External monitors will also conduct on-site
      monitoring visits to perform 100% source document verification.
    

Intervention name(s): Ad26.ZEBOV
Intervention type(s): Biological
Intervention description(s): Ad26.ZEBOV is a non-replicating, monovalent vaccine expressing the full-length Mayinga glycoprotein (GP) of the Ebola virus (formerly known as Zaire ebolavirus), and is produced in human cell line.
Participants will receive a 0.5mL intramuscular injection of Ad26.ZEBOV, at a concentration of 1x10^11 vp/mL, into the anterolateral deltoid muscle.
Other intervention name(s): Zabdeno®
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Ebola; Vaccine; HIV; Safety; Immunogenicity