VSV-ZEBOV Geneva Vaccine Trial

Study Overview
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Brief Summary
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The hemorrhagic fever resulting from Ebola infection is frequently fatal; the current Ebola outbreak, still in its ascendant phase, has a mortality rate over 50%. There is no proven therapy or prevention available at this time. The vaccine candidate VSV-ZEBOV (BPSC1001) has shown promising safety and efficacy in preventing Ebola Zaire infections in non-human primates (NHP). Before it can be assessed in large Phase IIb/3 trials in affected areas, safety data from phase 1 first-in-human trials are needed. To accelerate this process, the World Health Organization (WHO) has constituted a consortium of Clinical Research Centers in Switzerland, Germany, and Africa that will use similar protocols to collectively include roughly 250 volunteers, the sample size required to identify a 2-fold difference in anti-ZEBOV IgG antibody titers following immunization with 2 different doses of BPSC1001. The joint primary objectives of this single-center, double-blind, randomized placebo-controlled phase 1 dose-finding study are to assess the safety and tolerability of the VSV-ZEBOV vaccine when administered to healthy volunteers at a lower or higher vaccine dose and to define whether seroresponses differ significantly following immunization with the lower or higher vaccine dose.

Detailed Description
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This single-center, double-blind, randomized placebo-controlled phase 1 dose-finding study will have two randomization schemes. Volunteers who could later be exposed to Ebolavirus while working in epidemic areas (deployable subjects) will be randomized to receive one of two vaccine doses. Non-deployable volunteers, with no identified risk of Ebola exposure in the near term, will be allocated to one of three groups and receive the lower or higher vaccine dose, or a placebo. A single immunization will be performed. All subjects will be observed in the clinical trials unit (CTU) for 1.5 hours after vaccine/placebo injection. Subjects will complete post-injection diaries for 7 days after injection, as well as post-injection follow-up visits (see below). On-site visits at the CTU will occur on days -90 to -1, 0, 1, 3, 7, 14, 28, 84, 168. Some subjects with a positive serologic response at 24 weeks may be requested to return for immune durability testing at 12 months. One or more interim analyses will be undertaken to guide decisions on 1) the potential use of the vaccine in Ph2/3 trials in affected countries and 2) potential modification of the trial(s) through an amendment to evaluate a higher dose, if immunogenicity is poor, or a lower dose if the dosage levels selected are not safe and reasonably well tolerated.

Official Title
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A Phase I/II Dose-finding Randomized, Single-center, Double-blind, Placebo-controlled Safety and Immunogenicity Trial of the Vesicular Stomatitis Virus-vectored Zaire Ebola Candidate Vaccine BPSC1001 (VSVΔG-ZEBOV) in Healthy Adults.

Conditions
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Ebolavirus Disease

Intervention / Treatment
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* Biological: VSV-ZEBOV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has provided written informed consent before screening Adult male or non-pregnant, non-lactating female, ages 18 to 65 (inclusive) at the time of screening Free of clinically significant health problems, as determined by pertinent medical history and clinical examination at study screening Females of childbearing potential who are willing to use an effective method of contraception, from at least 7 days prior to vaccination through the end of the study period, and a double method from day 0 through day 28 Males who are willing to use effective contraception from day 0 through day 28: Be willing to minimize blood and body fluid exposure of others for 7 days after vaccination Use of effective barrier prophylaxis, such as latex condoms, during penetrative sexual intercourse (avoiding the sharing of needles, razors, or toothbrushes, avoiding open-mouth kissing, be willing to refrain from blood donation during the course of the study) Exclusion Criteria: Prior receipt of an Ebolavirus or Marburgvirus vaccine, a VSV-vectored vaccine, or any other investigational vaccine likely to impact on interpretation of the trial data Serologic evidence of prior Ebola exposure Has a household contact (HHC) who is immunodeficient, HIV-positive, pregnant, has an unstable medical condition in the opinion of the investigator (e.g., New York Heart Association Class ≥ II heart failure, severe debilitating asthma and/or chronic obstructive pulmonary disease) Works with livestock History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions Known allergy to the components of the BPSC1001 vaccine product Receipt of investigational product up to 30 days prior to enrollment or ongoing participation in another interventional clinical trial Receipt of licensed vaccines within 14 days of planned study immunization (30 days for live vaccines) or ongoing participation in another clinical interventional trial Acute or chronic, clinically significant psychiatric, hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the Investigator based on medical history, physical exam, and/or laboratory screening test Any baseline laboratory screening tests which is outside of acceptable range as defined in the protocol: ALT, AST, creatinine, hemoglobin, platelet count, total white blood cell count, urine protein, urine occult blood, urine glucose Serologic evidence of hepatitis C infection, evidence of active hepatitis B infection Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, asplenia, cytotoxic therapy in the previous 5 years, and/or diabetes Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding febrile seizures as a child Has a known history of Guillain-Barré Syndrome Has an active malignancy or recent (< 10 years) history of metastatic or hematologic malignancy Suspected or known alcohol and/or illicit drug abuse within the past 5 years Pregnant or lactating female, or female who intends to become pregnant during the study period 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 30 days of enrollment or plans to donate within the study period Administration of chronic (> 14 days) immunosuppressants or other immune-modifying drugs within 6 months of study entry Any other significant finding that, in the opinion of the investigator, would increase the risk of the individual's having an adverse outcome by participating in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VSV-ZEBOV lower dose<br>One intramuscular (deltoid) injection of a lower dose (10^7 plaque-forming units) of VSV-ZEBOV. Study amendment (01.2015) : One intramuscular (deltoid) injection of a markedly lower dose (3x 10^5 plaque-forming units) of VSV-ZEBOV | Biological: VSV-ZEBOV<br>* See arm/group descriptions.<br>* Other names: BPSC1001;|
| Experimental: VSV-ZEBOV higher dose<br>One intramuscular (deltoid) injection of a higher dose (5 x 10^7 pfu) of VSV-ZEBOV. Study amendment (01.2015) : interrupted | Biological: VSV-ZEBOV<br>* See arm/group descriptions.<br>* Other names: BPSC1001;|
| Placebo Comparator: Placebo<br>One intramuscular (deltoid) injection of normal saline (0.5 ml) | Biological: VSV-ZEBOV<br>* See arm/group descriptions.<br>* Other names: BPSC1001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers of ZEBOV-specific IgG Antibodies | Primary immunogenicity outcome (required for dose selection) | Day 0 - 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms | Number of participants with solicited local and systemic reactogenicity signs and symptoms. Day 0 is the day of the study intervention. | Days 0 - 14 | 
| Number of Participants With Unsolicited Adverse Events | Number of participants with unsolicited adverse events in the 28 days following injection | Days 0 - 28 | 
| Number of Participants With a Serious Adverse Event (SAE) | Number of participants with a serious adverse event (SAE) in the 365 days (1 year) following injection. | Days 0 - 365 | 
| Magnitude (Copies/ml) of VSVΔG-ZEBOV Viremia | Magnitude (copies/ml) of VSVΔG-ZEBOV viremia as expressed by median VSV RNA concentrations after vaccination. | Days 1, 3 and 7 | 
| Persistence of Titers of ZEBOV-specific IgG Antibodies | The percentage of participants maintaining positive ZEBOV-specific IgG antibody titers at 168 days after vaccination. | Day 168 | 
| Titers of Neutralizing ZEBOV-specific IgG Antibodies | Geometric mean titers of neutralizing ZEBOV-specific IgG antibodies. | Days 0, 28 and 168 | 
| Duration of VSVΔG-ZEBOV Viremia | Percentage of participants with any detectable viremia on days 1, 3 and 7 | Days 1, 3 and 7 | 
| Number of Participants in Whom Shedding of VSVΔG-ZEBOV Was Detected in Urine and/or Saliva. | This outcome was evaluated in a subset of vaccinees. | Days 1, 3 and 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ebolavirus Vaccines