Placebo Controlled, Dose Response, Safety and Immunogenicity Study of Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-004)

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 Ebola virus 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 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 viruses (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 replicating vesicular stomatitis virus (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, Multi-Center, Double-Blind, Placebo-Controlled, Dose-Response Study to Evaluate the Safety and Immunogenicity of the BPSC-1001 (VSVΔG-ZEBOV) Ebola Virus Vaccine Candidate in Healthy Adult Subjects

Conditions
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Ebola Virus

Intervention / Treatment
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* Biological: V920 Vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult male or non-pregnant, non-lactating adult female, ages 18 to 60 (inclusive) at the time of screening Have provided written informed consent prior to screening procedures Free of clinically significant health problems, as determined by pertinent medical history, physical examination and clinical judgment of the investigator. Available, able, and willing to participate for all study visits and procedures. Males and females who are willing to practice abstinence from sexual intercourse with the opposite sex, or willing to use effective methods of contraception, from at least 30 days prior to vaccination until study end. Be willing to minimize blood and body fluid exposure of others for 7 days after vaccination by: Using effective barrier prophylaxis, such as latex condoms, during penetrative sexual intercourse Avoiding the sharing of needles, razors, or toothbrushes Avoiding open-mouth kissing Resides in the geographic area of a clinical study site for 1 year after vaccination without risk of deployment outside the U.S. Exclusion Criteria: History of prior infection with a filovirus or prior participation in a filovirus vaccine trial History of prior infection with VSV or receipt of a VSV vectored vaccine Has been involved in the care in any capacity of a patient with Ebola virus infection within the previous 21 days Is a healthcare worker who has direct contact with patients (nurse, physician, dentist, emergency medical technician, dental hygienist) Has a house-hold contact (HHC) who is immunodeficient, on immunosuppressive medications, human immunodeficiency virus (HIV)-positive, pregnant, has an unstable medical condition Has an HHC, or is a childcare worker who has direct contact with children, 5 years of age or younger Direct hands-on job preparing food in the food industry History of employment in an industry involved in contact with ruminant animals, veterinary sciences, or other potential exposure to VSV History of employment or activity which involves potential contact with filoviruses 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 randomization or ongoing participation in another clinical trial Receipt of licensed non-live vaccines within 14 days of planned study immunization (30 days for live vaccines) Ability to observe possible local reactions at the eligible injections sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art 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 examination, and/or laboratory screening test. This would include a known hemoglobinopathy or coagulation abnormality. Any baseline laboratory screening test which in the opinion of the investigator, is considered clinically significant Any serologic evidence of hepatitis B or C infection Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV-1, HIV-2 infection, cytotoxic therapy in the previous 5 years, and/or diabetes Any chronic or active neurologic disorder, including migraines, seizures, and epilepsy, excluding a single febrile seizure as a child Have a known history of Guillain-Barré Syndrome Have an 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 >100.4°F within 1 week prior to vaccination (can be rescheduled) Pregnant or lactating female, or female who intends to become pregnant during the study period Administration of IgGs 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 Administration of chronic (defined as more than 14 days) immunosuppressants or other immune modifying drugs within 6 months of study entry For corticosteroids, this includes prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day Intranasal, topical, and intra-articular steroids are allowed Unwilling to allow storage and use of blood for future vaccine research 28. Research staff or the immediate family of research staff directly involved with the clinical study. 29. Unwilling to undergo diagnostic evaluation of joint signs and symptoms, which may include arthrocentesis if clinically indicated based on presence of effusion and if the procedure is acceptable to the subject at the time (Cohort 2 only) 30. Unwilling to undergo diagnostic evaluation of skin rash, to include punch biopsy if clinically indicated and if the procedure is acceptable to the subject at the time (Cohort 2 only) 31. Research staff or the immediate family of research staff directly involved in the clinical study 32. 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 33. Elective surgery or hospitalization planned during the period of study participation 34. Has traveled to an area where the World Health Organization has declared as an Ebola outbreak zone 35. History of chronic inflammatory disease (e.g., rheumatoid arthritis, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Crohn's disease, ulcerative colitis, and gout), symptomatic osteoarthritis, or any other autoimmune or autoinflammatory disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Interventional Model Description: The study comprised two separate cohorts. Cohort 1 consisted of the 4 lower V920 dose groups (3x10^3 pfu, 3x10^4 pfu, 3x10^5 pfu, and 3x10^6 pfu). Cohort 2 consisted of the 3 higher V920 dose groups (9x10^6 pfu, 2x10^7 pfu, 1x10^8 pfu) plus a bridging group that received vaccine at the highest dose evaluated in Cohort 1 (i.e. 3x10^6 pfu). Both Cohorts 1 and 2 had a placebo group.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3x10^3 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^3 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^4 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^4 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^5 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^5 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^6 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^6 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 9x10^6 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 9x10^6 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 2x10^7 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 2x10^7 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 1x10^8 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 1x10^8 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Placebo Comparator: Placebo Cohort 1<br>Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0. | Other: Placebo<br>* 0.9% Saline<br>|
| Experimental: 3x10^6 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^3 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Placebo Comparator: Placebo Cohort 2<br>Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0. | Other: Placebo<br>* 0.9% Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With One or More Solicited Injection-site Adverse Events by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Injection-site AEs prompted on the Vaccination Report Card (VRC) were erythema, pain, tenderness and swelling. AEs were assessed for severity by the investigator according to a toxicity grading scale based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least 1 solicited injection-site AE was summarized by grade. | Up to 14 days postvaccination | 
| Percentage of Participants With One or More Solicited Systemic Adverse Events by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Systemic AEs included subjective and objective fever, shivering/chills, sweats, myalgia, arthralgia, joint swelling, joint tenderness, fatigue, headache, gastrointestinal symptoms (nausea, vomiting, abdominal pain, and diarrhea), mucosal lesion, and skin lesion (including any blisters). AEs were assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least one systemic AE was summarized by grade. | Up to 14 days postvaccination | 
| Percentage of Participants With One or More Unsolicited Vaccine-related Adverse Event by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Unsolicited vaccine-related AEs were those events not specifically listed as either an injection-site (local) or systemic in the VRC and were reported as at least possibly related to the study vaccine or placebo. The AEs were further assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least one unsolicited vaccine-related AE was summarized by grade.. | Up to 56 days postvaccination | 
| Percentage of Participants With One or More Serious Adverse Event (SAE) by Severity | An adverse event is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with 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. SAEs were assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening; 5=Fatal. The percentage of participants that experienced at least 1 SAE was summarized by grade. | Up to 360 days postvaccination | 
| Geometric Mean Titers (GMTs) of Zaire Ebola Virus- (ZEBOV)-Specific Immunoglobulin-G (IgG) Antibody | Blood was drawn on Day 28 to assess the GMTs of ZEBOV-specific IgG antibodies as determined by Enzyme-linked immunosorbent assay (ELISA). | 28 days postvaccination | 
| Optimum Dose for General Use Prophylaxis With V920 | The optimum dose for general use prophylaxis with V920 was determined following the review of all immunogenicity and safety data. | Day 360 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Copies of Vector Ribonucleic Acid (RNA) for Participants With a V920 Polymerase Chain Reaction (PCR) Result ≥ Lower Limit of Quantification (LLOQ) | Participants had blood, assessed for evidence of V920 via polymerase chain reaction (PCR). Mean copies of RNA was reported for all participants who had reading ≥ the LLOQ (62.5 copies/mL) | Days 1, 2, 3, 4, 7, 14 and 28 post-vaccination | 
| Percentage of Participants With Seroconversion for ZEBOV-specific IgG | Blood was drawn on Days 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days to assess the GMTs via ELISA. Seroconversion was defined as a post-vaccination titer ≥ 200 ELISA Units/mL that was also at least a 4-fold increase in titer compared to baseline. | 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination | 
| Percentage of Participants With Seroconversion for ZEBOV Neutralizing Antibodies | Blood was drawn on Days 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days to assess the GMTs of Zaire ebolavirus neutralizing antibodies as determined plaque reduction neutralization titer (reciprocal of the dilution that resulted in a 60% decrease in plaques) (PRNT60). | 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination |