A Phase 1 Randomized, Blinded, Placebo Controlled, Dose-Escalation and Dosing Regimen Selection Study to Evaluate the Safety and Immunogenicity of rVSV-Vectored Lassa Virus Vaccine in Healthy Adults at Multiple Sites in West Africa (Lassa Fever Phase 1 Trial)

September 12, 2022 | Completed Project | Reading time: 6 min

Introduction
Kintampo Health Research Centre (KHRC) has successfully completed this Lassa Fever Phase 1 Vaccine Trial that tested a candidate vaccine for Lassa fever called EBS LASV on humans for the very first time. This trial was conducted to investigate the vaccine’s safety and ability to help the body produce an immune response, to protect against Lassa fever. This study was funded by Emergent Bio-Solutions.

Investigators

Dr. Seyram Kaali, Dr. Samuel Harrison, Dr. Prince Darko Agyapong, Dr. Cynthia Yaa Bema, Dr. Felicia Serwah.

Background

Lassa fever is a viral disease that is prevalent in rodents (Mastomys Natalensis) and is common in many West African countries. There have been confirmed cases of Lassa fever in Nigeria, Mali, Ghana, Benin, Guinea, Sierra Leone, Togo, Cote D’Ivoire and Liberia. People can catch Lassa fever by touching or inhaling rodent droppings, eating meat from an infected animal, or coming into contact with the bodily fluids of an infected person. It has been identified as an emerging outbreak pathogen by the World Health Organization and the UK Health Security Agency classifies it as a high consequence infectious disease.

Despite its dangerous effects, there is currently no approved therapeutic treatment or prophylactic vaccine for the prevention of LASV infection or Lassa fever. To address this unmet medical need, this first-in-human (FIH) study has been conducted to evaluate the safety and immunogenicity of the candidate vaccine, EBS LASV. The target population were healthy adults ≥18 to ≤50 years of age.

Given the significance of the infection, the potential long-term consequences for the survivors and number of people at risk of this disease, it is important we find a vaccine to help protect against the disease.

Objective
The objectives of the study were divided into two main parts.

Safety objective
1. To evaluate safety and tolerability of increasing dose levels of EBS-LASV vaccine administered as a single dose or two-dose series

2. To evaluate in vivo replication, bio distribution, and shedding of EBS-LASV vaccine.

Primary Immunogenicity Objective;
1. To evaluate humoral immune responses to EBS-LASV vaccine at various dose levels and dosing schedules for the purpose of selecting two regimens (dose and schedule) for further evaluation in a Phase 2 study.

Exploratory Immunogenicity Objective;
1. To evaluate the cellular immune response to EBS-LASV vaccine.

Study Methodology

This study was a Phase 1, first in human (FIH) clinical study. The target population were healthy adults 18 to 50 years of age. The goals for the study were to assess the safety and tolerability of a low, medium, and high dose of EBS-LASV when administered as a two-dose series. Healthy adult volunteers were identified from selected communities and invited to the study clinic, where they underwent consenting and screening procedures. Participants were enrolled into three cohorts in a sequential dose escalation manner. The Randomization ratio was 3:1 to either the active treatment arm or the placebo arm. The duration of participation was 28 weeks for each enrolled participant.

Expected Outcome
The expected outcomes for the Lassa fever phase 1 study were to show that the candidate vaccine (EBS-LASV) is both safe and capable of producing enough antibodies to protect against the virus. The study also sought to prove how the vaccine performs at different dose levels, demonstrating its safety and effectiveness in causing an immune response.

Key Findings

Key findings from the study showed that while the EBS-LASV candidate vaccine was safe, it did not cause the immune response needed to protect against the Lassa fever virus. This means that participants who received the vaccine did not produce the required levels of antibodies to defend against future infections.

The difference in antibody levels between participants who received the vaccine and those who were given a placebo (a substance without any active ingredients) was minimal. Also, none of the participants in the three dosage groups, also known as cohorts, produced the required antibody levels to fight the virus effectively.

Participants in Cohort 1 received a low dose of the vaccine, those in Cohort 2 received a medium dose, and Cohort 3 participants received a high dose. Despite the lack of immune response, there were no serious adverse effects reported among participants.

Ten (10) individuals were unable to join the study due to screening failures. This included participants who tested positive for hepatitis B surface antigen, HIV, or had positive drug tests in their urine, making them ineligible for the study.

Funders:Emergent Bio-Solutions

Study Duration: Two (2) Years

Start Date: 12th July 2022

End Date: 4th May 2024