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

NCT02314923 | Completed Phase 1 Results DMC

• 2 other identifiers: V920-004NLG0507
• Study Type: interventional
• Target: 513
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Ebola Virus

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• Mean Copies of Vector Ribonucleic Acid (RNA) for Participants With a V920 Polymerase Chain Reaction (PCR) Result ≥ Lower Limit of Quantification (LLOQ)

  Days 1, 2, 3, 4, 7, 14 and 28 post-vaccination

• Percentage of Participants With Seroconversion for ZEBOV-specific IgG

  7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination

• Percentage of Participants With Seroconversion for ZEBOV Neutralizing Antibodies

  7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination

Study Arms (10)

3x10^3 pfu Vaccine Cohort 1

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 3x10\^3 pfu in the deltoid on Day 0.

Biological: V920 Vaccine

3x10^4 pfu Vaccine Cohort 1

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 3x10\^4 pfu in the deltoid on Day 0.

Biological: V920 Vaccine

3x10^5 pfu Vaccine Cohort 1

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 3x10\^5 pfu in the deltoid on Day 0.

Biological: V920 Vaccine

3x10^6 pfu Vaccine Cohort 1

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 3x10\^6 pfu in the deltoid on Day 0.

Biological: V920 Vaccine

9x10^6 pfu Vaccine Cohort 2

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 9x10\^6 pfu in the deltoid on Day 0.

Biological: V920 Vaccine

2x10^7 pfu Vaccine Cohort 2

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 2x10\^7 pfu in the deltoid on Day 0.

Biological: V920 Vaccine

1x10^8 pfu Vaccine Cohort 2

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 1x10\^8 pfu in the deltoid on Day 0.

Biological: V920 Vaccine

Placebo Cohort 1

PLACEBO COMPARATOR

Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0.

Other: Placebo

3x10^6 pfu Vaccine Cohort 2

EXPERIMENTAL

Participants will receive a 1-mL intramuscular injection of V920 3x10\^3 pfu in the deltoid on Day 0.

Biological: V920 Vaccine

Placebo Cohort 2

PLACEBO COMPARATOR

Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0.

Other: Placebo

Interventions

V920 Vaccine BIOLOGICAL

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.

Also known as: BPSC-1001

1x10^8 pfu Vaccine Cohort 2; 2x10^7 pfu Vaccine Cohort 2; 3x10^3 pfu Vaccine Cohort 1; 3x10^4 pfu Vaccine Cohort 1; 3x10^5 pfu Vaccine Cohort 1; 3x10^6 pfu Vaccine Cohort 1; 3x10^6 pfu Vaccine Cohort 2; 9x10^6 pfu Vaccine Cohort 2

Placebo OTHER

0.9% Saline

Placebo Cohort 1; Placebo Cohort 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• BioProtection Systems Corporation: collaborator
• Department of Health and Human Services: collaborator

Related Publications (2)

• Heppner DG Jr, Kemp TL, Martin BK, Ramsey WJ, Nichols R, Dasen EJ, Link CJ, Das R, Xu ZJ, Sheldon EA, Nowak TA, Monath TP; V920-004 study team. Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study. Lancet Infect Dis. 2017 Aug;17(8):854-866. doi: 10.1016/S1473-3099(17)30313-4. Epub 2017 Jun 9.

  PMID: 28606591 RESULT

• Coller BG, Blue J, Das R, Dubey S, Finelli L, Gupta S, Helmond F, Grant-Klein RJ, Liu K, Simon J, Troth S, VanRheenen S, Waterbury J, Wivel A, Wolf J, Heppner DG, Kemp T, Nichols R, Monath TP. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic. Vaccine. 2017 Aug 16;35(35 Pt A):4465-4469. doi: 10.1016/j.vaccine.2017.05.097. Epub 2017 Jun 21.

  PMID: 28647166 DERIVED

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 8, 2014
• First Posted: December 11, 2014
• Study Start: December 5, 2014
• Primary Completion: June 23, 2016
• Study Completion: June 23, 2016
• Last Updated: February 5, 2020
• Results First Posted: January 2, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share