Clinical trial NCT02314923: Placebo Controlled, Dose Response, Safety and Immunogenicity Study of Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-004)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ebola Virus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: BioProtection Systems Corporation
name: Department of Health and Human Services
First posted: 2014-12-11
Enrollment: 513
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. Healthy adult male or non-pregnant, non-lactating adult female, ages 18 to 60 (inclusive) at the time of screening
2. Have provided written informed consent prior to screening procedures
3. Free of clinically significant health problems, as determined by pertinent medical history, physical examination and clinical judgment of the investigator.
4. Available, able, and willing to participate for all study visits and procedures.
5. 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.
6. Be willing to minimize blood and body fluid exposure of others for 7 days after vaccination by:

   1. Using effective barrier prophylaxis, such as latex condoms, during penetrative sexual intercourse
   2. Avoiding the sharing of needles, razors, or toothbrushes
   3. Avoiding open-mouth kissing
7. 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:

1. History of prior infection with a filovirus or prior participation in a filovirus vaccine trial
2. History of prior infection with VSV or receipt of a VSV vectored vaccine
3. Has been involved in the care in any capacity of a patient with Ebola virus infection within the previous 21 days
4. Is a healthcare worker who has direct contact with patients (nurse, physician, dentist, emergency medical technician, dental hygienist)
5. Has a house-hold contact (HHC) who is immunodeficient, on immunosuppressive medications, human immunodeficiency virus (HIV)-positive, pregnant, has an unstable medical condition
6. Has an HHC, or is a childcare worker who has direct contact with children, 5 years of age or younger
7. Direct hands-on job preparing food in the food industry
8. History of employment in an industry involved in contact with ruminant animals, veterinary sciences, or other potential exposure to VSV
9. History of employment or activity which involves potential contact with filoviruses
10. History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions
11. Known allergy to the components of the BPSC1001 vaccine product
12. Receipt of investigational product up to 30 days prior to randomization or ongoing participation in another clinical trial
13. Receipt of licensed non-live vaccines within 14 days of planned study immunization (30 days for live vaccines)
14. 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
15. 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.
16. Any baseline laboratory screening test which in the opinion of the investigator, is considered clinically significant
17. Any serologic evidence of hepatitis B or C infection
18. Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV-1, HIV-2 infection, cytotoxic therapy in the previous 5 years, and/or diabetes
19. Any chronic or active neurologic disorder, including migraines, seizures, and epilepsy, excluding a single febrile seizure as a child
20. Have a known history of Guillain-Barré Syndrome
21. Have an active malignancy or history of metastatic or hematologic malignancy
22. Suspected or known alcohol and/or illicit drug abuse within the past 5 years
23. Moderate or severe illness and/or fever \>100.4°F within 1 week prior to vaccination (can be rescheduled)
24. Pregnant or lactating female, or female who intends to become pregnant during the study period
25. Administration of IgGs and/or any blood products within the 120 days preceding study entry or planned administration during the study period
26. History of blood donation within 60 days of enrollment or plans to donate within the study period
27. Administration of chronic (defined as more than 14 days) immunosuppressants or other immune modifying drugs within 6 months of study entry

    1. For corticosteroids, this includes prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day
    2. Intranasal, topical, and intra-articular steroids are allowed
28. 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

Primary outcomes:
measure: Percentage of Participants With One or More Solicited Injection-site Adverse Events by Severity
timeFrame: Up to 14 days postvaccination
measure: Percentage of Participants With One or More Solicited Systemic Adverse Events by Severity
timeFrame: Up to 14 days postvaccination
measure: Percentage of Participants With One or More Unsolicited Vaccine-related Adverse Event by Severity
timeFrame: Up to 56 days postvaccination
measure: Percentage of Participants With One or More Serious Adverse Event (SAE) by Severity
timeFrame: Up to 360 days postvaccination
measure: Geometric Mean Titers (GMTs) of Zaire Ebola Virus- (ZEBOV)-Specific Immunoglobulin-G (IgG) Antibody
timeFrame: 28 days postvaccination
measure: Optimum Dose for General Use Prophylaxis With V920
timeFrame: Day 360
Secondary outcomes:
measure: Mean Copies of Vector Ribonucleic Acid (RNA) for Participants With a V920 Polymerase Chain Reaction (PCR) Result ≥ Lower Limit of Quantification (LLOQ)
timeFrame: Days 1, 2, 3, 4, 7, 14 and 28 post-vaccination
measure: Percentage of Participants With Seroconversion for ZEBOV-specific IgG
timeFrame: 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination
measure: Percentage of Participants With Seroconversion for ZEBOV Neutralizing Antibodies
timeFrame: 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.