Phase I Trial to Assess the Safety, Tolerability and Immunogenicity of a Ebola Virus Vaccine (rVSVΔG-ZEBOV-GP)

Study Overview
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Brief Summary
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The study is designed to establish safety, tolerability and immunogenicity of rVSVΔG-ZEBOV-GP (BPSC1001), an Ebola Virus Vaccine candidate (recombinant vesicular stomatitis virus (VSV) expressing the envelope glycoprotein of Ebola Virus Zaire), investigated at three different dose levels in 30 healthy adults in Germany. This study is part of the WHO led VEBCON consortium that is aiming to generate harmonized data for the rVSVΔG-ZEBOV-GP (BPSC1001) vaccine candidate to allow optimized rapid decisions on dose and safety.

Detailed Description
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This study is being conducted to assess safety and immunogenicity of an experimental ebola vaccine. An outbreak due to the Ebola Zaire (ZEBOV) strain of unprecedented magnitude and scope and with a high mortality continues to spread across West Africa. No vaccine is currently licensed. The specific opportunity at hand with rVSVΔG-ZEBOV-GP (BPSC1001) is to achieve long-lasting protective immunity to ZEBOV on a time scale of weeks in humans upon a single-shot vaccination, offering a discrete benefit over prime-boost vaccination protocols. The current outbreak represents a global health emergency and the need for access to therapeutic intervention and vaccines is paramount. The vaccine investigated in this study might provide a critical tool to suppress future out-breaks of EVD in areas at risk. This study is 1 of 4 clinical trials currently conducted as part of the WHO-led VEBCON consortium, aiming to generate harmonized data for the rVSVΔG-ZEBOV-GP (BPSC1001) vaccine candidate to allow optimized rapid decisions on dose and safety.

Official Title
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An Open Label, Single Center, Dose Escalation Phase I Trial to Assess the Safety, Tolerability and Immunogenicity of a Single Ascending Dose of the Ebola Virus Vaccine rVSVΔG-ZEBOV-GP (BPSC1001)

Conditions
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Hemorrhagic Fever, Ebola

Intervention / Treatment
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* Biological: rVSVΔ-ZEBOV-GP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the subject information and to personally sign the informed consent Provided written informed consent. Healthy females and males aged 18 - 55 years . No clinically significant health problems Body mass index 18.5 - 30.0 kg/m2 and weight >50 kg at screening. Females of childbearing potential who agree to comply with the applicable contraceptive requirements of the protocol or females who are permanently sterilized. Males who agree to comply with the applicable contraceptive requirements of the protocol Subjects must be willing to minimize blood and body fluid exposure of others for 7 days after vaccination Be willing to refrain from blood donation during the course of the study. The subject is co-operative and available for the entire study. Exclusion Criteria: Prior receipt of an Ebolavirus or Marburgvirus vaccine or VSV-vectored vaccine. Receipt of any vaccine in the 2 weeks prior to the trial vaccination (4 weeks for live vaccines) or planned receipt of any vaccine in the 3 weeks following the trial vaccination. Known allergy to the components of the BPSC1001 vaccine product or history of life-threatening reactions to vaccine containing the same substances. Participation in a clinical trial or use of an investigational product within 30 days or five times the half-life of the investigational drug -prior to receiving the first dose within this study Evidence in the subject's medical history or in the medical examination that might influence either the safety of the subject or the absorption, distribution, metabolism or excretion of the investigational product under investigation. Any positive result for HIV1/2, HCV antibody or HBs antigen testing. Pregnant or lactating females, or females who intend to become pregnant during the study period. Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic therapy in the previous 5 years, and/or diabetes Subjects with inflammatory, infectious and neuroinflammatory underlying disease which could cause an expected impairment of the blood brain barrier such as meningitis, multiple sclerosis, epilepsy, or Alzheimer's. Any household contact who is immunodeficient, HIV positive or pregnant Working with livestock Any chronic or active neurologic disorder, including migraines, seizures, and epilepsy, exclud-ing a single febrile seizure as a child Known history of Guillain-Barré Syndrome Active malignancy or history of metastatic or hematologic malignancy Suspected or known alcohol and/or illicit drug abuse within the past 5 years Moderate or severe illness and/or fever >38°C within 1 week prior to vaccination Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period History of blood donation within 60 days of enrollment or plans to donate within the study period Receipt of chronic immune suppressants or other immune-modifying drugs within 6 months of study inclusion Subjects with skin lesions close to the injection site or active oral lesions will be excluded. Thrombocytopenia, contraindicating intramuscular vaccination based on investigator's judgment Subjects with a significant infection or known inflammation. History of relevant cardiovascular disorders or evidence of hyper- or hypotension Subjects who are known or suspected not to comply with the study directives. Any other significant finding that in the opinion of the investigator would increase the risk of the individual having an adverse outcome from participating in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rVSVΔ-ZEBOV-GP (BPSC1001)<br>Subjects will be allocated to three cohorts of 10 subjects each receiving one single vaccine injection administered as an i.m. injection. | Biological: rVSVΔ-ZEBOV-GP<br>* single dose of rVSVΔ-ZEBOV-GP (3x10^6 pfu, 2x10^7 pfu or 3x10^5)<br>* Other names: BPSC1001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of adverse events associated with the rVSVΔ-ZEBOV-GP (BPSC1001) vaccine will be collected and measured |  | Vaccination (day 0) to day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ZEBOV-GP-specific antibody responses | Humoral immunity: Magnitude of ZEBOV-GP-specific antibody responses as assayed by ELISA in a centralized laboratory. | Vaccination (day 0) to day 180 | 
| To evaluate vaccine viremia and excretion | Vaccine viremia and viral shedding: concentration of rVSV in peripheral blood, urine and saliva as detected by qRT-PCR | Vaccination (day 0) to day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ebola virus, vaccination, phase I, healthy volunteers