Safety and Immunogenicity of Prime-Boost Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-002)
- Conditions
- Ebola Viruses
- Interventions
- Biological: V920Other: Placebo
- Registration Number
- NCT02280408
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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
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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 3x10^6 plaque-forming units (pfu) Vaccine Cohort V920 Participants will receive a 1-mL intramuscular injection of V920 3x10\^6 pfu in the deltoid on Day 0 and Day 28. 1x10^8 pfu Vaccine Cohort V920 Participants will receive a 1-mL intramuscular injection of V920 1x10\^8 pfu in the deltoid on Day 0 and Day 28. Placebo Cohort Placebo Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0 and Day 28. 2x10^7 pfu Vaccine Cohort V920 Participants will receive a 1-mL intramuscular injection of V920 2x10\^7 pfu in the deltoid on Day 0 and Day 28.
- Primary Outcome Measures
Name Time Method Percentage of Participants With One or More Serious Adverse Event Up to Day 56 (Day 1 up to Day 56) 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.
Percentage of Participants With 1 or More Solicited Local Injection-site AE by Severity: Vaccination 2 Up to 14 days post vaccination 2 (Day 29 up to Day 42) 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.
Percentage of Participants With 1 or More Solicited Local Injection-site AE by Severity: Vaccination 1 Up to 14 days post vaccination 1 (Day 1 to Day 14) 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.
Percentage of Participants With Early Discontinuation of Vaccination Up to Day 28 The percentage of participants that had vaccination discontinued for any reason was summarized.
Percentage of Participants With 1 or More Unsolicited AE : Vaccination 1 Up to 28 days post vaccination 1 (From Day 1 up to Day 28) 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.
Percentage of Participants With 1 or More Unsolicited AE : Vaccination 2 Up to 28 days post vaccination 2 (From Day 29 to Day 56) 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.
Percentage of Participants With 1 or More Solicited Systemic Adverse Event (AE) by Severity: Vaccination 1 Up to 14 days post vaccination 1 (From Day 1 up to Day 14) 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.
Percentage of Participants With 1 or More Solicited Systemic AE by Severity: Vaccination 2 Up to 14 days post vaccination 2 (Day 29 up to Day 42) 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.
- Secondary Outcome Measures
Name Time Method Geometric Mean Titers of ZEBOV-specific Neutralizing Antibodies: Day 28 Day 28 (28 days post vaccination 1) 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.
Geometric Mean Titers of ZEBOV-specific Neutralizing Antibodies: Day 56 Day 56 (28 days post vaccination 2) 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.
Percentage of Participants With Viremia on Day 3 and Day 7: Vaccination 1 Day 3 and Day 7 post 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.
Geometric Mean Titers of Zaire Ebolavirus-(ZEBOV)-Specific Immunoglobin G (IgG) Antibodies: Day 28 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).
Geometric Mean Titers of ZEBOV-specific IgG Antibodies: Day 56 Day 56 (28 days post vaccination 2) Blood was drawn on Day 56 to assess the GMTs of ZEBOV-specific IgG antibodies as determined by Enzyme-linked immunosorbent assay (ELISA).
Percentage of Participants Who Seroconvert: Day 56 Day 56 (28 days post vaccination 2) 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.
Percentage of Participants With Viremia on Day 3 and Day 7: Vaccination 2 Day 3 and Day 7 post vaccination 2 (Day 31 and Day 35) 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.
Percentage of Participants Who Seroconvert: Day 28 Day 28 (28 days post vaccination 1) 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.