Vaccine Treatment for Ebola Virus in Healthy Adults (V920-001)

Study Overview
=================
Brief Summary
-----------------
This is a study of the anti-Ebola vaccine vesicular stomatitis virus (VSV) ZEBOV (Zaire ebolavirus) also known as V920 and BPSC-1001. The purpose of this study is to test how safe the vaccine is in humans and how well it makes the human immune system cause an immune- or defense-response to Ebola virus. This vaccine will be studied at different doses.

Detailed Description
-----------------
This study is being conducted to assess whether this vaccine is safe, and if it causes the body to create an infection-fighting response. Between 1994 and the present, there have been many Ebola virus outbreaks caused by 4 different strains of the virus, affecting mostly people living in central Africa and the health care providers trying to treat them. Ebola viruses are members of the filoviridae virus family, which also includes the dangerous Marburg virus. Ebola virus causes severe and often deadly infection called a viral hemorrhagic fever, characterized by organ failure, bleeding, and death. To date, the virus is found primarily in Central and West Africa. It is not clear where these viruses come from, but it is thought that bats are the most likely source of the human outbreaks that occur. Once an outbreak occurs, the virus is spread from person to person through direct contact with infected blood or body fluids with an infected individual. Given the recent increase in Ebola virus infections occurring in Africa, there is interest in making an effective vaccine to protect against the infection. V920/BPSC-1001 is an experimental Ebola vaccine candidate demonstrating protection against Ebola virus in animal experiments. This is a Phase 1 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). This phase 1 protocol provides a first-in-human study to evaluate the safety and toxicity of V920/BPSC-1001 in healthy adult participants. Participants will be randomized to receive V920/BPSC-1001 or Placebo by intramuscular injection. Three dose levels will be assessed with follow-up visits through 180 days after the injection.

Official Title
-----------------
A Phase 1 Randomized, Single-Center, Double-Blind, Placebo Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the BPSC-1001 (VSVΔG-ZEBOV) Ebola Virus Vaccine Candidate in Healthy Adult Subjects

Conditions
-----------------
Ebola Virus

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult male or non-pregnant, non-lactating female, ages 18 to 50 (inclusive) at the time of screening Have provided written informed consent before screening Free of clinically significant health problems, as determined by pertinent medical history and clinical examination prior to entry into the study Available, able, and willing to participate for all study visits and procedures Males and females who are willing to practice abstinence from sexual intercourse, 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 Score at least 80% on the Comprehension Assessment test 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 Is a healthcare worker who has direct contact with patients Has a house-hold contact (HHC) who is immunodeficient, Human Immunodeficiency Virus (HIV)-positive, 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 Directly prepares 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 Planned or frequent contact with animals at-risk of VSV infection (e.g. cattle, horses, pigs, mules, etc.) 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 enrollment or ongoing participation in another clinical trial Receipt of licensed vaccines within 30 days of planned study immunization Ongoing participation in another clinical trial 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 exam, electrocardiogram, and/or laboratory screening test. This would include a known hemoglobinopathy or coagulation abnormality. Any baseline laboratory screening tests which is outside of acceptable range as defined in the protocol.: alanine aminotransferase, aspartate aminotransferase, creatinine, hemoglobin, platelet count, total white blood cell count, urine protein, urine occult blood, urine glucose Any serologic evidence of hepatitis B or C infection Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV 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 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 >100.4F within one week prior to vaccination 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 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 will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day, Intranasal and topical steroids are allowed) Unwilling to allow storage and use of blood for future vaccine research 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
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


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 one deltoid and a 1-mL intramuscular injection of placebo in the contralateral deltoid on Day 0. | Biological: V920<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;Other: Placebo<br>* Normal saline placebo.<br>|
| Experimental: 2x10^7 pfu Vaccine Cohort<br>Participants will receive a 1-mL intramuscular injection of V920 2x10^7 pfu in one deltoid and a 1-mL intramuscular injection of placebo in the contralateral deltoid on Day 0. | Biological: V920<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;Other: Placebo<br>* Normal saline placebo.<br>|
| Experimental: 1x10^8 pfu Vaccine Cohort<br>Participants will receive a 1-mL intramuscular injection of V920 1x10^8 pfu in one deltoid and a 1-mL intramuscular injection of placebo in the contralateral deltoid on Day 0. | Biological: V920<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;Other: Placebo<br>* Normal saline placebo.<br>|
| Placebo Comparator: Placebo Cohort<br>Participants will receive a 1-mL intramuscular injection of placebo in each deltoid on Day 0. | Other: Placebo<br>* Normal saline placebo.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Solicited Local Treatment-Emergent Adverse Events (TEAE) | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. A treatment-emergent adverse event (TEAE) is defined as an AE that starts or worsens on or after the date and time of the study vaccination. Local reactogenicity signs and symptoms include pain, erythema (redness), and induration (swelling). The number of participants that experienced at least one solicited local TEAE was assessed. Solicited TEAEs occurred from the time of each injection through 14 days following the procedure, facilitated with the use of a memory aid to record participant observations. | Up to 14 days postvaccination | 
| Number of Participants With One or More Solicited Local Treatment-Emergent Adverse Events (TEAE) by Severity | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. A TEAE is defined as an AE that starts or worsens on or after the date and time of the study vaccination. Local reactogenicity signs and symptoms include pain, erythema (redness), and induration (swelling). AEs were assessed for severity by the investigator according to a toxicity grading scale based on the FDA's 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 number of participants that experienced at least one solicited local TEAE was summarized by grade. Solicited TEAEs occurred from the time of each injection through 14 days following the procedure, facilitated with the use of a memory aid to record participant observations. | Up to 14 days postvaccination | 
| Number of Participants With One or More Solicited Systemic Treatment-Emergent Adverse Events (TEAE) | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. A treatment-emergent adverse event is defined as an AE that starts or worsens on or after the date and time of the study vaccination. Systemic reactogenicity signs and symptoms include pyrexia (subjective and objective fever), chills, hyperhidrosis (sweats), myalgia, arthralgia, fatigue, headache, and gastrointestinal symptoms including nausea, vomiting, abdominal pain, and/or diarrhea. The number of participants that experienced at least one solicited systemic TEAE was assessed. Solicited TEAEs occurred from the time of each injection through 14 days following the procedure, facilitated with the use of a memory aid to record participant observations. | Up to 14 days postvaccination | 
| Number of Participants With One or More Solicited Systemic Treatment-Emergent Adverse Events (TEAE) by Severity | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. A TEAE is defined as an AE that starts or worsens on or after the date and time of the study vaccination. Systemic reactogenicity signs and symptoms include pyrexia (subjective and objective fever), chills, hyperhidrosis (sweats), myalgia, arthralgia, fatigue, headache, and gastrointestinal symptoms including nausea, vomiting, abdominal pain, and/or diarrhea. 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 number of participants that experienced at least 1 solicited systemic TEAE was summarized by grade. Solicited TEAEs occurred from the time of each injection through 14 days following the procedure, facilitated with the use of a memory aid to record participant observations. | Up to 14 days postvaccination | 
| Number of Participants With One or More Unsolicited Treatment-Emergent Adverse Events (TEAE) | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. A treatment-emergent adverse event is defined as an AE that starts or worsens on or after the date and time of the study vaccination. The number of participants that experienced at least one unsolicited TEAE was assessed. Unsolicited AEs occurred from the time of injection through 28 days following injection. | Up to 28 days postvaccination | 
| Number of Participants With One or More Vaccination-Related Unsolicited Treatment-Emergent Adverse Events (TEAE) | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. A treatment-emergent adverse event is defined as an AE that starts or worsens on or after the date and time of the study vaccination. A related TEAE is defined as a TEAE that was possibly, probably, or definitely related to the vaccination as assessed by the investigator. The number of participants that experienced at least one unsolicited TEAE related to study vaccination was assessed. | Up to 28 days postvaccination | 
| Number of Participants With One or More Vaccination-Related Unsolicited Treatment-Emergent Adverse Events (TEAE) by Severity | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. A treatment-emergent adverse event is defined as an AE that starts or worsens on or after the date and time of the study vaccination. A related TEAE is defined as a TEAE that was possibly, probably, or definitely related to the vaccination as assessed by the investigator. AEs were assessed for severity by the investigator according to a toxicity grading scale based on the FDA's 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 number of participants that experienced at least one unsolicited TEAE related to study vaccination was summarized by grade. | Up to 28 days postvaccination | 
| Number of Participants With Early Study Discontinuation Due to an Adverse Event | An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. The number of participants prematurely withdrawing from the study due to an AE was assessed. | Up to 28 days postvaccination | 
| Number of Participants With One or More Serious Adverse Event | An adverse event is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. A serious adverse event (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 number of participants that experienced one or more SAE was summarized. | Up to 180 days postvaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of ZEBOV Envelope Glycoprotein-specific Binding Antibodies | The Geometric Mean Titers (GMT) of ZEBOV-specific Immunoglobulin G antibodies were measured by unqualified ZEBOV immunoglobulin (IgG) enzyme-linked immunosorbent assay (ELISA). For titers expressed in ELISA Units/mL, the lower level of quantitation (LLOQ) was 58.84. ZEBOV IgG titers at baseline (Day 0) and analysis Days 7, 14, 28, 56, 84, and 180 were summarized by V920 vaccine dose level and placebo as the mean of log10 titers, transformed into GMT. The geometric standard deviation (GSD) for the GMT at each visit was obtained by exponentiating the standard deviation for the mean of log (base 10) transformed titers. | Baseline, Days 7, 14, 28, 56, 84 and 180 post-vaccination | 
| Geometric Mean Titers of ZEBOV-specific Neutralizing Antibodies | The Geometric Mean Titers (GMT) of ZEBOV-specific neutralizing antibodies were measured by pseudovirion neutralization assays (PsVNA). Titers were reported for PsVNA50 values which were derived from the reciprocal of the dilution that resulted in a 50% decrease in luciferase activity. The LLOQ for the PsVNA was 20. If the PsVNA was reported ≤20, the numeric portion of the titer was divided by 2 for statistical purposes, which could result in a reported GMT <20.0. PsVNA50 titers at baseline (Day 0) and analysis Days 7, 14, 28, 56, and 180 were summarized by V920 vaccine dose level and placebo as the mean of log10 titers, transformed into GMT. The geometric standard deviation (GSD) for the GMT at each visit was obtained by exponentiating the standard deviation for the mean of log (base 10) transformed titers. | Baseline, Days 7, 14, 28, 56, and 180 post-vaccination | 
| Number of Participants With Vaccine Viremia | The number of participants with viremia detected by recombinant vesicular stomatitis virus (rVSV) reverse transcription polymerase chain reaction (PCR) of blood specimens was assessed. | Days 1, 3, 7, and 14 post-vaccination | 
| Number of Participants With Vaccine Shedding/Excretion in Saliva or Urine | The number of participants with viremia detected by rVSV reverse transcription PCR of saliva or urine specimens was assessed. | Days 1, 3, 7, and 14 post-vaccination | 
| Mean Copy Number of Vector RNA (Vector Viremia) | Although the protocol specified a secondary endpoint that included the mean copy number of vector RNA (vector viremia), the Polymerase Chain Reaction (PCR) test used for the study reported a qualitative rather than a quantitative outcome, so the proportion of participants with viremia is reported instead of the mean copy number of vector RNA. Qualitative results are therefore reported in Outcome Measures 12 and 13. | Up to 14 days postvaccination |