Clinical trial NCT02378753: STRIVE (Sierra Leone Trial to Introduce a Vaccine Against Ebola)
Official title: [rVSVΔG-ZEBOV] Ebola Prevention Vaccine Evaluation in Sierra Leone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hemorrhagic Fever, Ebola
Keywords: Ebola
Sierra Leone
vaccine
rVSVΔG-ZEBOV
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: University of Sierra Leone
name: Ministry of Health and Sanitation, Sierra Leone
name: Department of Health and Human Services
name: eHealth Africa
First posted: 2015-03-04
Enrollment: 8651
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The 2014 outbreak of Ebola in West Africa is the largest in recorded history with widespread and intense transmission in Guinea, Liberia, and Sierra Leone. The high infectivity of blood and secretions, lack of appropriate personal protective equipment (PPE) and challenges in following infection control and prevention protocols put healthcare workers at high risk during outbreaks, and direct contact with the bodies of deceased Ebola victims can also sustain community transmission. This study will accelerate introduction and use of monovalent recombinant vesicular stomatitis virus Ebola vaccine (rVSVΔG-ZEBOV) among healthcare workers and frontline personnel involved in the Ebola outbreak response in Sierra Leone, while concurrently evaluating the safety and efficacy of the vaccine.

This is an unblinded, randomized trial with phased vaccine introduction in the target population. Participation in the study will be voluntary and open to adults 18 years of age and older who are at high risk of exposure to Ebola infection through their daily work and who work in a selected study area.

Detailed description: The Ebola outbreak was confirmed in March 2014 with widespread and intense transmission in Guinea, Liberia, and Sierra Leone. While there are no U.S. Food and Drug Administration (FDA)-approved pharmaceuticals to prevent or treat Ebola, two candidate vaccines are being tested in humans for dosing, tolerability, and safety. This study will evaluate monovalent recombinant vesicular stomatitis virus Ebola vaccine that remains replication competent (rVSVΔG-ZEBOV) in Sierra Leone.

The high infectivity of blood and secretions, lack of appropriate personal protective equipment (PPE) and challenges in following infection control and prevention protocols put healthcare workers at high risk during outbreaks, and direct contact with the bodies of deceased Ebola victims can also sustain community transmission.

This unblinded, randomized trial will evaluate vaccine efficacy (VE) and safety with phased vaccine introduction in the target population. Participation in the study will be voluntary and open to adults 18 years of age and older who are at high risk of exposure to Ebola infection through their daily work and who work in a selected study area. This includes: 1) personnel working in healthcare facilities where care is provided for Ebola patients; 2) personnel working in non-Ebola healthcare facilities who may have exposure to undiagnosed Ebola-infected individuals; and 3) personnel working in one of the following job categories: surveillance team, ambulance team, or laboratory worker responsible for swabbing deceased persons. Staff members involved in this study are also eligible to receive the vaccine under this protocol; study staff will be followed for 6 months post-vaccination to monitor for safety of rVSVΔG-ZEBOV.

Eligible participants within a healthcare facility or frontline team will be enrolled and individually randomized to either immediate or deferred vaccination. A single dose of rVSVΔG-ZEBOV will be administered intramuscularly. Immediate vaccination is defined as vaccination within 7 days of enrollment and deferred vaccination is defined as vaccination at the end of an 18-24 week follow-up period. Participants will not be blinded to the randomized assignment of immediate or deferred vaccination. All enrolled participants will have the opportunity to receive rVSVΔG-ZEBOV by the end of the study. Enrollment and vaccination will be phased over time.

Ebola events that occur during the 18-24 week post-enrollment will be included in the VE analysis, with the immediate vaccination arm contributing vaccinated follow-up time and the deferred vaccination arm contributing unvaccinated follow-up time. All participants, regardless of randomized assignment, will be followed for 6 months after vaccination to monitor for safety of rVSVΔG-ZEBOV.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older.
2. Member of target population at the time of enrollment:

   * active worker in an Ebola care, holding, or treatment center (may include physicians, nurses, nurse aides, lab technicians, pharmacists, pharmacy technicians, cleaners, and security and administrative staff);
   * active worker in a facility providing non-Ebola-related healthcare (may include physicians, nurses, nurse aides, lab technicians, pharmacists, pharmacy technicians, cleaners, and security and administrative staff);
   * active frontline worker in one of the following job categories: surveillance team, ambulance team, burial worker, or worker responsible for swabbing deceased persons.
3. Reasonably anticipates living in Sierra Leone for the 18-24 weeks following enrollment.
4. Reachable by phone throughout the 6 month post-vaccination safety follow-up period.
5. Willing to adhere to personal protective equipment (PPE) and infection control recommendations.
6. Able and willing to complete the informed consent process and study procedures.
7. Willing to receive vaccine in either the immediate or the deferred trial arms, according to random assignment.

Exclusion Criteria:

1. History of Ebola (self-report).
2. Prior receipt of experimental Ebola or Marburg vaccine.
3. History of human immunodeficiency virus (HIV) or clinically important immunodeficiency (self-report).
4. Any history of allergy or anaphylaxis to prior vaccines
5. Breast-feeding an infant or child.
6. Any reason the investigator suspects that data collected from this person would be incomplete or of poor quality.
7. Current pregnancy (a negative urine pregnancy test is required for women participants \<50 years of age who self-report as not pregnant).
8. Currently being followed for known exposure to Ebola.
9. Known experimental research agents or other vaccine within 28 days (4 weeks) before vaccination.
10. Fever ≥ 38.0°C (100.4°F) at time of vaccination.

Primary outcomes:
measure: Laboratory-confirmed Ebola (Study Diagnostics)
timeFrame: > 21 days following vaccination
measure: Number of Participants With Occurrence of Serious Adverse Events During the 6 Months Following the Vaccination
timeFrame: 6 months following vaccination
Secondary outcomes:
measure: Death Due to Laboratory-confirmed Ebola
timeFrame: 6 months following vaccination
measure: Ebola Confirmed by Non-study or Study Diagnostics
timeFrame: 6 months following vaccination
measure: Suspected, Probable or Laboratory-confirmed Ebola
timeFrame: 6 months following vaccination
measure: Number of Participants With Occurrence of Solicited Injection-site and Systemic Reactogenicity Signs and Symptoms, Including Fever, on Vaccination Day and During the 7 Days Following the Vaccination or Enrollment.
timeFrame: Vaccination day and for 7 days following vaccination
measure: Number of Participants With Occurrence of Solicited and Unsolicited AEs During the 28 Days Following the Vaccination or Enrollment
timeFrame: During 28 days following vaccination
Other outcomes:
Locations:
city: Freetown
country: Sierra Leone
facility: College of Medicine and Allied Health Sciences (COMAHS)
state: Western Area Urban
city: Bombali District
country: Sierra Leone
facility: Bombali
city: Port Loko District
country: Sierra Leone
facility: Port Loko
city: Tonkolili District
country: Sierra Leone
facility: Tonkolili
city: Western Area District
country: Sierra Leone
facility: Western Area Rural
Study officials:
affiliation: University of Sierra Leone
name: Mohamed Samai, MBChB,PhD
role: PRINCIPAL_INVESTIGATOR
References:
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