Clinical trial NCT02269423: Vaccine Treatment for Ebola Virus in Healthy Adults (V920-001)
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
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: United States Department of Defense
First posted: 2014-10-21
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants With One or More Solicited Local Treatment-Emergent Adverse Events (TEAE)
timeFrame: Up to 14 days postvaccination
measure: Number of Participants With One or More Solicited Local Treatment-Emergent Adverse Events (TEAE) by Severity
timeFrame: Up to 14 days postvaccination
measure: Number of Participants With One or More Solicited Systemic Treatment-Emergent Adverse Events (TEAE)
timeFrame: Up to 14 days postvaccination
measure: Number of Participants With One or More Solicited Systemic Treatment-Emergent Adverse Events (TEAE) by Severity
timeFrame: Up to 14 days postvaccination
measure: Number of Participants With One or More Unsolicited Treatment-Emergent Adverse Events (TEAE)
timeFrame: Up to 28 days postvaccination
measure: Number of Participants With One or More Vaccination-Related Unsolicited Treatment-Emergent Adverse Events (TEAE)
timeFrame: Up to 28 days postvaccination
measure: Number of Participants With One or More Vaccination-Related Unsolicited Treatment-Emergent Adverse Events (TEAE) by Severity
timeFrame: Up to 28 days postvaccination
measure: Number of Participants With Early Study Discontinuation Due to an Adverse Event
timeFrame: Up to 28 days postvaccination
measure: Number of Participants With One or More Serious Adverse Event
timeFrame: Up to 180 days postvaccination
Secondary outcomes:
measure: Geometric Mean Titers of ZEBOV Envelope Glycoprotein-specific Binding Antibodies
timeFrame: Baseline, Days 7, 14, 28, 56, 84 and 180 post-vaccination
measure: Geometric Mean Titers of ZEBOV-specific Neutralizing Antibodies
timeFrame: Baseline, Days 7, 14, 28, 56, and 180 post-vaccination
measure: Number of Participants With Vaccine Viremia
timeFrame: Days 1, 3, 7, and 14 post-vaccination
measure: Number of Participants With Vaccine Shedding/Excretion in Saliva or Urine
timeFrame: Days 1, 3, 7, and 14 post-vaccination
measure: Mean Copy Number of Vector RNA (Vector Viremia)
timeFrame: Up to 14 days postvaccination
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.
citation: Regules JA, Beigel JH, Paolino KM, Voell J, Castellano AR, Hu Z, Munoz P, Moon JE, Ruck RC, Bennett JW, Twomey PS, Gutierrez RL, Remich SA, Hack HR, Wisniewski ML, Josleyn MD, Kwilas SA, Van Deusen N, Mbaya OT, Zhou Y, Stanley DA, Jing W, Smith KS, Shi M, Ledgerwood JE, Graham BS, Sullivan NJ, Jagodzinski LL, Peel SA, Alimonti JB, Hooper JW, Silvera PM, Martin BK, Monath TP, Ramsey WJ, Link CJ, Lane HC, Michael NL, Davey RT Jr, Thomas SJ; rVSVDeltaG-ZEBOV-GP Study Group. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine. N Engl J Med. 2017 Jan 26;376(4):330-341. doi: 10.1056/NEJMoa1414216. Epub 2015 Apr 1.