Monitoring Serious Adverse Events in the Sierra Leone Trial to Introduce a Vaccine Against Ebola

The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) was a randomized, controlled trial of rVSVΔG-ZEBOV-GP vaccine in healthcare and frontline workers during the 2014-2016 Ebola epidemic. Overall safety findings have been previously reported; there were no vaccine-related serious adverse events (SAEs). Here we describe the safety monitoring system established for STRIVE and the health conditions that resulted in reported SAEs, as well as factors affecting SAE incidence. Participants were randomized to immediate (≤7 days) or deferred (18-24 weeks later) vaccination and were monitored for safety for 6 months (immediate-vaccinated group) or until vaccination (deferred [unvaccinated] group). Once vaccinated, the latter group was termed crossover-vaccinated and monitored for 6 additional months. Of the 8577 STRIVE participants with safety follow-up data, 4172 were in the immediate-vaccinated group and 4398 were in the unvaccinated group, of whom 3787 received crossover vaccination. Overall, 143 SAEs were reported among 132 participants. Of the 143 SAEs, 130 (90.9%) resulted in hospitalization, and 24 (18.2%) participants with an SAE died. Infections were the most common SAEs; malaria was the most common single diagnosis and the most common cause of death. STRIVE built local capacity for vaccine safety monitoring in future clinical trials and research and in the national immunization program. This information about serious health conditions that resulted in hospitalization or death among a population of relatively young, healthy adults in Sierra Leone could help inform improved delivery of preventive and therapeutic health services

Health Conditions in an Adult Population in Sierra Leone: Data Reported from the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)

The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE), a clinical trial of the investigational recombinant vesicular stomatitis virus-based Ebola virus vaccine (rVSVΔZEBOV-GP; Merck), provided an opportunity to assess health conditions in a cohort of healthy Sierra Leonean adults before vaccination. Of the 8793 healthcare and frontline Ebola response workers screened for study enrollment, 7 (0.1%) self-reported human immunodeficiency virus infection or another significant immunodeficiency disorder and 11 of 3190 (0.3%) women 18-49 years old had a positive urine pregnancy test. Of the 440 participants included in a safety substudy, 124 (28.2%) reported at least 1 medical condition at baseline, most commonly drug hypersensitivity (11.6%), arthralgia (3.9%), arthropathy (2.7%), or gastric (3.0%) or peptic (2.7%) ulcer disease. We calculated the incidence per 100 person-years (PY) and 95% confidence intervals (CIs) of new medical conditions among the 4297 participants followed for 18-24 weeks from enrollment to scheduled vaccination. The most commonly reported conditions were headache (32.4 PY [95% CI, 29.7-35.3 PY]), pain (unspecified) (17.3 PY [95% CI, 15.4-19.4 PY]), arthralgia (9.3 PY [95% CI, 7.9-10.8 PY]), and abdominal pain (9.1 PY [95% CI, 7.7-10.7 PY]). Nasopharyngitis (7.0 PY [95% CI, 5.8-8.4 PY]) and malaria (1.9 PY [95% CI, 1.3-2.7 PY]) were the most commonly reported infectious conditions. Several cases of hypertension, diabetes mellitus, and cancer were also reported

The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSVΔG-ZEBOV-GP Vaccine Tolerability and Safety during the West Africa Ebola Outbreak

The West Africa Ebola epidemic stimulated rapid implementation of Ebola vaccine trials in the 3 highly affected countries. In Sierra Leone, we studied the recombinant vesicular stomatitis virus Ebola vaccine (rVSVΔG-ZEBOV-GP) safety and efficacy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) was a randomized, unblinded Phase 2/3 trial with phased vaccine introduction, no placebo, and concurrent evaluation of vaccine safety and efficacy. Healthcare and frontline response workers in 5 districts were randomized to immediate or deferred (18-24 weeks later) vaccination and followed for 6 months postvaccination. We enrolled 8651 participants from April through August 2015; 7998 were vaccinated. No participants developed Ebola virus disease so an efficacy assessment was not possible. Overall, 132 (1.5%) participants experienced serious adverse events (SAEs); none were vaccine-related. In a detailed safety substudy (N = 436), vaccinated participants reported significantly more systemic adverse events (AEs) within 7 days than unvaccinated participants including fever higher than 38°C (20.5% vs 3.9%), headache (71.2% vs 22.1%), fatigue (50.7% vs 10.4%), and joint pain (31.7% vs 6.5%); most AEs were mild to moderate severity and resolved within 5 days. During days 5-28, vaccinated participants more commonly reported joint pain (17.0% vs 4.8%) and rash (7.8% vs 1.7%) (P<.05 for both comparisons). Vaccinated participants also more commonly reported skin vesicles (2.0% vs 0%) and mouth ulcers (2.0% vs 0%) but only during days 8-14 (P<.05 for both comparisons). Among almost 8000 high-risk workers vaccinated during the Sierra Leone Ebola epidemic, rVSVΔG-ZEBOV-GP was generally well tolerated with no vaccine-related SAEs. Reported joint pain, rash, skin vesicles, and mouth ulcers postvaccination are consistent with conditions associated with transient viral replication described among participants in other trials