Safety and Immunogenicity of Prime-Boost Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-002)

Study Overview
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Brief Summary
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Ebola virus has infected and killed people, mostly in Africa. In 2014, the Zaire ebolavirus (ZEBOV) has affected several thousand people. There is no approved effective way to treat or prevent Ebola. Researchers are trying to develop a vaccine for it. This is a study of the anti-Ebola vaccine vesicular stomatitis virus (VSV) ZEBOV (V920; BPSC-1001) to see if it is safe and to see how it affects people's immune system.

Detailed Description
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Between 1994 and the present, there have been many Ebola virus (EBOV) outbreaks affecting mostly central Africa. However, the 2014 West African outbreak significantly exceeds all previous outbreaks in geographic range, number of individuals affected and in disruption of typical activities of civil society. This is a Phase 1 safety and tolerability study to evaluate a novel vaccine to Ebola using a live VSV replacing the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Zaire strain of Ebola (VSVΔG-ZEBOV also known as V920 and BPSC-1001).

Official Title
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A Phase 1 Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of Prime-Boost VSV Ebola Vaccine in Healthy Adults

Conditions
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Ebola Viruses

Intervention / Treatment
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* Other: Placebo
* Biological: V920


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Healthy male or females, ages 18 to 65 (inclusive) at the time of screening Females of childbearing potential and all males, must be willing to use effective methods of contraception, from at least 14 days prior to vaccination through Day 56 which would include: Oral contraceptives, either combined or progestogen alone injectable progestogen implants of etonogestrel or levonorgestrel oestrogenic vaginal ring percutaneous contraceptive patches intrauterine device or intrauterine system male partner sterilization male condom combined with a spermicide Must be willing to minimize blood and body fluid exposure of others for at least 7 days after vaccination, which includes: Use of effective barrier prophylaxis, such as latex condoms, during any sexual interaction (regardless of childbearing status or sexual orientation) Avoiding the sharing of needles, razors, eating utensils, drinking from the same cup, or toothbrushes Avoiding open-mouth kissing Must be willing to forgo blood donation for one year Must agree not to enroll in another study of an investigational agent prior to completion of Day 56 and not participate in an investigational vaccine study until the last required protocol visit on Day 365 Ability to provide informed consent EXCLUSION CRITERIA: FACTORS THAT INCREASE RISK TO THE SUBJECT: Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to: A process that would affect the immune response A process that would require medication that affects the immune response Any contraindication to repeated injections or blood draws A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being during the study period A condition or process for which signs or symptoms could be confused with reactions to vaccine Any condition specifically listed among the exclusion criteria below Active malignancy Asplenia History of Guillain-Barré Syndrome History of neurological or neuropsychiatric disorder that may either increase risk (history of encephalitis, narcolepsy, stroke, depression, bipolar disorder, seizure, etc.) or could interfere with the assessment of safety (e.g., frequent headaches) History of autoimmune disease History of hemoglobinopathy or a coagulopathy Women who are breast-feeding Positive urine or serum pregnancy test Abnormal chemistry panel; defined as: Defined as any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table Evaluating only creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and estimated glomerular filtration rate Abnormal complete blood count (CBC) defined as: Defined as any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table Evaluating only the white blood cell (WBC), hemoglobin, hematocrit, and platelets Abnormal urinalysis defined as: Defined as any Grade 3 or greater toxicity (regardless of clinical significance) by the toxicity table Evaluating red blood cells (RBC), protein, and glucose only Positive serology for hepatitis B surface antigen Positive serology for hepatitis C Positive serology for human immunodeficiency virus (HIV) Known allergy to the components of the VSVΔG-ZEBOV vaccine (V920) vaccine product (VSV, albumin, tris) History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions FACTORS THAT MAY LIMIT VSV REPLICATION OR MAKE INTERPRETATION OF IMMUNOGENICITY DIFFICULT: History of prior infection with a filovirus or prior participation in a filovirus vaccine trial Veterinarian or ranchers exposed to livestock known to be infected with VSV History of prior infection with VSV or receipt of a VSV vectored vaccine FACTORS THAT WOULD INCREASE RISK TO OTHERS DUE TO VSV VIRAL SHEDDING: Is a healthcare worker who will have direct contact with patients within 14 days of each vaccination Is an animal care worker, who will have direct contact with animals (livestock or domestic, besides subjects family pet) within 14 days of each vaccination Has a house-hold contact (HHC) who is immunodeficient (in the opinion of the investigator), pregnant, has an unstable medical condition, or is under the age of 5 years Is a childcare worker who has direct contact with children 5 years of age or younger FACTORS THAT COULD IMPAIR INTERPRETATION OR EXECUTION OF THE STUDY: Receipt of any investigational drug within 5 half-lives or 30 days, whichever is longer, prior to study drug administration (i.e., Day 0) Receipt of licensed vaccines 14 days before the planned study immunization Receipt of immunoglobulins and/or any blood products within the 120 days preceding study entry or that are planned during the study period Immunosuppressive medications received within 168 days before first vaccination. (Not including: [1] corticosteroid nasal spray for allergic rhinitis; [2] topical corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral corticosteroids given for non-chronic conditions not expected to recur [length of therapy 10 days or less with completion at least 30 days prior to vaccination(s)].) Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled through Day 56 Participants who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3x10^6 plaque-forming units (pfu) Vaccine Cohort<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^6 pfu in the deltoid on Day 0 and Day 28. | Biological: V920<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^6, 2x10^7, or 1x10^8 pfu.<br>|
| Experimental: 2x10^7 pfu Vaccine Cohort<br>Participants will receive a 1-mL intramuscular injection of V920 2x10^7 pfu in the deltoid on Day 0 and Day 28. | Biological: V920<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^6, 2x10^7, or 1x10^8 pfu.<br>|
| Experimental: 1x10^8 pfu Vaccine Cohort<br>Participants will receive a 1-mL intramuscular injection of V920 1x10^8 pfu in the deltoid on Day 0 and Day 28. | Biological: V920<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^6, 2x10^7, or 1x10^8 pfu.<br>|
| Placebo Comparator: Placebo Cohort<br>Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0 and Day 28. | Other: Placebo<br>* Normal saline placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With 1 or More Unsolicited AE : Vaccination 1 | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An unsolicited AE was an AE other than those specifically designated local or systemic. The percentage of participants that experienced at least 1 unsolicited AE was summarized. | Up to 28 days post vaccination 1 (From Day 1 up to Day 28) | 
| Percentage of Participants With 1 or More Unsolicited AE : Vaccination 2 | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An unsolicited AE was an AE other than those specifically designated local or systemic. The percentage of participants that experienced at least 1 unsolicited AE was summarized. | Up to 28 days post vaccination 2 (From Day 29 to Day 56) | 
| Percentage of Participants With 1 or More Solicited Systemic Adverse Event (AE) by Severity: Vaccination 1 | A solicited AE was a predetermined specific event. The solicited systemic AEs for this study were the following: redness, swelling, or pain at site of injection, subjective and objective fever, chills, sweats, myalgia, arthralgia, fatigue, headache and gastrointestinal symptoms (nausea, vomiting, abdominal pain, and/or diarrhea). All AEs were assessed for severity by the investigator according to the Food and Drug Administration(FDA's) Guidance Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials and were classified into 4 categories: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) and Potentially Life-Threatening (Grade 4). The percentage of participants that experienced at least 1 solicited systemic AE were summarized by grade. | Up to 14 days post vaccination 1 (From Day 1 up to Day 14) | 
| Percentage of Participants With 1 or More Solicited Systemic AE by Severity: Vaccination 2 | A solicited AE was a predetermined specific event. The solicited systemic AEs for this study were the following: redness, swelling, or pain at site of injection, subjective and objective fever, chills, sweats, myalgia, arthralgia, fatigue, headache and gastrointestinal symptoms (nausea, vomiting, abdominal pain, and/or diarrhea). All AEs were assessed for severity by the investigator according to the Food and Drug Administration(FDA's) Guidance Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials and were classified into 4 categories: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) and Potentially Life-Threatening (Grade 4). The percentage of participants that experienced at least 1 solicited systemic AE were summarized by grade. | Up to 14 days post vaccination 2 (Day 29 up to Day 42) | 
| Percentage of Participants With One or More Serious Adverse Event | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. An SAE is an AE that results in death, is life-threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event. The percentage of participants that experienced 1 or more SAEs was summarized. | Up to Day 56 (Day 1 up to Day 56) | 
| Percentage of Participants With 1 or More Solicited Local Injection-site AE by Severity: Vaccination 1 | A solicited AE was a predetermined specific event. The solicited local AEs for this study were the following: Local reactogenicity signs and symptoms include pain, erythema (redness), and induration (swelling). All AEs were assessed for severity by the investigator according to the Food and Drug Administration(FDA's) Guidance Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials and were classified into 4 categories: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) and Potentially Life-Threatening (Grade 4). The percentage of participants that experienced at least 1 solicited local AE was summarized by grade. | Up to 14 days post vaccination 1 (Day 1 to Day 14) | 
| Percentage of Participants With 1 or More Solicited Local Injection-site AE by Severity: Vaccination 2 | A solicited AE was a predetermined specific event. The solicited local AEs for this study were the following: Local reactogenicity signs and symptoms include pain, erythema (redness), and induration (swelling). All AEs were assessed for severity by the investigator according to the Food and Drug Administration(FDA's) Guidance Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials and were classified into 4 categories: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) and Potentially Life-Threatening (Grade 4). The percentage of participants that experienced at least 1 solicited local AE was summarized by grade. | Up to 14 days post vaccination 2 (Day 29 up to Day 42) | 
| Percentage of Participants With Early Discontinuation of Vaccination | The percentage of participants that had vaccination discontinued for any reason was summarized. | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Zaire Ebolavirus-(ZEBOV)-Specific Immunoglobin G (IgG) Antibodies: Day 28 | Blood was drawn on Day 28 to assess the GMTs of ZEBOV-specific IgG antibodies as determined by enzyme-linked immunosorbent assay (ELISA). | Day 28 | 
| Geometric Mean Titers of ZEBOV-specific IgG Antibodies: Day 56 | Blood was drawn on Day 56 to assess the GMTs of ZEBOV-specific IgG antibodies as determined by Enzyme-linked immunosorbent assay (ELISA). | Day 56 (28 days post vaccination 2) | 
| Geometric Mean Titers of ZEBOV-specific Neutralizing Antibodies: Day 28 | Blood was drawn on Day 28 to assess the GMTs of Zaire ebolavirus neutralizing antibodies as determined by Pseudovirion neutralizing assay (PsVNA). Titers are reported for PsVNA50 values, which was derived from the reciprocal of the dilution that resulted in a 50% decrease in luciferase activity. | Day 28 (28 days post vaccination 1) | 
| Geometric Mean Titers of ZEBOV-specific Neutralizing Antibodies: Day 56 | Blood was drawn on Day 56 to assess the GMTs of Zaire ebolavirus neutralizing antibodies as determined by Pseudovirion neutralizing assay (PsVNA). Titers are reported for PsVNA50 values, which was derived from the reciprocal of the dilution that resulted in a 50% decrease in luciferase activity. | Day 56 (28 days post vaccination 2) | 
| Percentage of Participants Who Seroconvert: Day 28 | GMTs for Zebov-specific antibodies were determined via ELISA. Seroconversion was defined as a post-vaccination titer ≥ 200 that is also at least a 4-fold increase in titer compared to baseline. | Day 28 (28 days post vaccination 1) | 
| Percentage of Participants Who Seroconvert: Day 56 | GMTs for Zebov-specific antibodies were determined via ELISA. Seroconversion was defined as a post-vaccination titer ≥ 200 that is also at least a 4-fold increase in titer compared to baseline. | Day 56 (28 days post vaccination 2) | 
| Percentage of Participants With Viremia on Day 3 and Day 7: Vaccination 1 | Blood was drawn on Days 3 and 7 to assess the presence of V920 via polymerase chain reaction (PCR) assay. The percentage of participants that were positive for V920 in serum was summarized. | Day 3 and Day 7 post vaccination 1 | 
| Percentage of Participants With Viremia on Day 3 and Day 7: Vaccination 2 | Blood was drawn on Days 3 and 7 to assess the presence of V920 via polymerase chain reaction (PCR) assay. The percentage of participants that were positive for V920 in serum was summarized. | Day 3 and Day 7 post vaccination 2 (Day 31 and Day 35) |