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.
