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VSV-ZEBOV Geneva Vaccine Trial (VSV-ZEBOV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02287480
Recruitment Status : Completed
First Posted : November 10, 2014
Last Update Posted : March 8, 2016
Sponsor:
Collaborators:
World Health Organization
Wellcome Trust
Universitätsklinikum Hamburg-Eppendorf
Philipps University Marburg Medical Center
Albert Schweitzer Hospital
Institute of Tropical Medicine, University of Tuebingen
KEMRI-Wellcome Trust Collaborative Research Program
Information provided by (Responsible Party):
Siegrist Claire-Anne, University Hospital, Geneva

Brief Summary:

The hemorrhagic fever resulting from Ebola infection is frequently fatal; the current Ebola outbreak, still in its ascendant phase, has a mortality rate over 50%. There is no proven therapy or prevention available at this time.

The vaccine candidate VSV-ZEBOV (BPSC1001) has shown promising safety and efficacy in preventing Ebola Zaire infections in non-human primates (NHP). Before it can be assessed in large Phase IIb/3 trials in affected areas, safety data from phase 1 first-in-human trials are needed. To accelerate this process, the World Health Organization (WHO) has constituted a consortium of Clinical Research Centers in Switzerland, Germany, and Africa that will use similar protocols to collectively include roughly 250 volunteers, the sample size required to identify a 2-fold difference in anti-ZEBOV IgG antibody titers following immunization with 2 different doses of BPSC1001.

The joint primary objectives of this single-center, double-blind, randomized placebo-controlled phase 1 dose-finding study are to assess the safety and tolerability of the VSV-ZEBOV vaccine when administered to healthy volunteers at a lower or higher vaccine dose and to define whether seroresponses differ significantly following immunization with the lower or higher vaccine dose.


Condition or disease Intervention/treatment Phase
Ebolavirus Disease Biological: VSV-ZEBOV Phase 1 Phase 2

Detailed Description:

This single-center, double-blind, randomized placebo-controlled phase 1 dose-finding study will have two randomization schemes. Volunteers who could later be exposed to Ebolavirus while working in epidemic areas ("deployable subjects") will be randomized to receive one of two vaccine doses. Non-deployable volunteers, with no identified risk of Ebola exposure in the near term, will be allocated to one of three groups and receive the lower or higher vaccine dose, or a placebo. A single immunization will be performed. All subjects will be observed in the clinical trials unit (CTU) for 1.5 hours after vaccine/placebo injection. Subjects will complete post-injection diaries for 7 days after injection, as well as post-injection follow-up visits (see below). On-site visits at the CTU will occur on days -90 to -1, 0, 1, 3, 7, 14, 28, 84, 168. Some subjects with a positive serologic response at 24 weeks may be requested to return for immune durability testing at 12 months.

One or more interim analyses will be undertaken to guide decisions on 1) the potential use of the vaccine in Ph2/3 trials in affected countries and 2) potential modification of the trial(s) through an amendment to evaluate a higher dose, if immunogenicity is poor, or a lower dose if the dosage levels selected are not safe and reasonably well tolerated.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 115 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase I/II Dose-finding Randomized, Single-center, Double-blind, Placebo-controlled Safety and Immunogenicity Trial of the Vesicular Stomatitis Virus-vectored Zaire Ebola Candidate Vaccine BPSC1001 (VSVΔG-ZEBOV) in Healthy Adults.
Study Start Date : November 2014
Actual Primary Completion Date : April 2015
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ebola Vaccines

Arm Intervention/treatment
Experimental: VSV-ZEBOV lower dose

One intramuscular (deltoid) injection of a lower dose (10^7 plaque-forming units) of VSV-ZEBOV.

Study amendment (01.2015) : One intramuscular (deltoid) injection of a markedly lower dose (3x 10^5 plaque-forming units) of VSV-ZEBOV

Biological: VSV-ZEBOV
See arm/group descriptions.
Other Name: BPSC1001

Experimental: VSV-ZEBOV higher dose

One intramuscular (deltoid) injection of a higher dose (5 x 10^7 pfu) of VSV-ZEBOV.

Study amendment (01.2015) : interrupted

Biological: VSV-ZEBOV
See arm/group descriptions.
Other Name: BPSC1001

Placebo Comparator: Placebo
One intramuscular (deltoid) injection of normal saline (0.5 ml)
Biological: VSV-ZEBOV
See arm/group descriptions.
Other Name: BPSC1001




Primary Outcome Measures :
  1. Incidence of adverse events with causal link to study intervention [ Time Frame: Days 0 - 14 ]
    Primary safety outcome

  2. Titers of ZEBOV-specific IgG antibodies [ Time Frame: Day 0 - 28 ]
    Primary immunogenicity outcome (required for dose selection)


Secondary Outcome Measures :
  1. Incidence of solicited local and systemic reactogenicity signs and symptoms [ Time Frame: Days 0 - 14 ]
    Day 0 is the day of the study intervention

  2. Incidence of unsolicited adverse events [ Time Frame: Days 0 - 28 ]
  3. Incidence of serious adverse events (SAE) [ Time Frame: Days 0 - 168 ]
  4. Magnitude (copies/ml) of VSVΔG-ZEBOV viremia [ Time Frame: Days 1, 3 and 7 ]
  5. Incidence of change(s) from baseline for safety laboratory measures [ Time Frame: Days 1, 3, 7 & 14 ]
  6. Persistence of titers of ZEBOV-specific IgG antibodies [ Time Frame: Days 168 ]
  7. Titers of neutralizing ZEBOV-specific IgG antibodies [ Time Frame: Days 0, 7, 14, 28 and 168 ]
    This outcome will be evaluated in a subset of the first 46 vaccinees.

  8. Pattern of ZEBOV-specific T cell responses [ Time Frame: Days 0, 7, 14, 28 and 168 ]
    This outcome will be evaluated in a subset of the first 46 vaccinees.

  9. Duration of VSVΔG-ZEBOV viremia [ Time Frame: Days 1, 3 and 7 ]
  10. Magnitude (copies/ml) of VSVΔG-ZEBOV shedding [ Time Frame: Days 1, 3 and 7 ]
    This outcome will be evaluated in a subset of vaccinees.


Other Outcome Measures:
  1. Pattern of vaccine-induced innate responses [ Time Frame: Day 7 ]
    This outcome will be evaluated in a subset of the first 46 vaccinees.

  2. Patterns of changes in B and T cell responses / repertoire induced by VSV-ZEBOV immunization [ Time Frame: Days 0, 7, 14, 28 and 168 ]
    This outcome will be evaluated in a subset of the first 46 vaccinees.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Has provided written informed consent before screening
  • Adult male or non-pregnant, non-lactating female, ages 18 to 65 (inclusive) at the time of screening
  • Free of clinically significant health problems, as determined by pertinent medical history and clinical examination at study screening
  • Females of childbearing potential who are willing to use an effective method of contraception, from at least 7 days prior to vaccination through the end of the study period, and a double method from day 0 through day 28
  • Males who are willing to use effective contraception from day 0 through day 28:
  • Be willing to minimize blood and body fluid exposure of others for 7 days after vaccination
  • Use of effective barrier prophylaxis, such as latex condoms, during penetrative sexual intercourse (avoiding the sharing of needles, razors, or toothbrushes, avoiding open-mouth kissing, be willing to refrain from blood donation during the course of the study)

Exclusion Criteria:

  • Prior receipt of an Ebolavirus or Marburgvirus vaccine, a VSV-vectored vaccine, or any other investigational vaccine likely to impact on interpretation of the trial data
  • Serologic evidence of prior Ebola exposure
  • Has a household contact (HHC) who is immunodeficient, HIV-positive, pregnant, has an unstable medical condition in the opinion of the investigator (e.g., New York Heart Association Class ≥ II heart failure, severe debilitating asthma and/or chronic obstructive pulmonary disease)
  • Works with livestock
  • 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 interventional clinical trial
  • Receipt of licensed vaccines within 14 days of planned study immunization (30 days for live vaccines) or ongoing participation in another clinical interventional trial
  • 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, and/or laboratory screening test
  • Any baseline laboratory screening tests which is outside of acceptable range as defined in the protocol: ALT, AST, creatinine, hemoglobin, platelet count, total white blood cell count, urine protein, urine occult blood, urine glucose
  • Serologic evidence of hepatitis C infection, evidence of active hepatitis B infection
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, asplenia, cytotoxic therapy in the previous 5 years, and/or diabetes
  • Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding febrile seizures as a child
  • Has a known history of Guillain-Barré Syndrome
  • Has an active malignancy or recent (< 10 years) history of metastatic or hematologic malignancy
  • Suspected or known alcohol and/or illicit drug abuse within the past 5 years
  • 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 30 days of enrollment or plans to donate within the study period
  • Administration of chronic (> 14 days) immunosuppressants or other immune-modifying drugs within 6 months of study entry
  • Any other significant finding that, in the opinion of the investigator, would increase the risk of the individual's having an adverse outcome by participating in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02287480


Locations
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Switzerland
University Hospitals of Geneva
Geneva, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
World Health Organization
Wellcome Trust
Universitätsklinikum Hamburg-Eppendorf
Philipps University Marburg Medical Center
Albert Schweitzer Hospital
Institute of Tropical Medicine, University of Tuebingen
KEMRI-Wellcome Trust Collaborative Research Program
Investigators
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Principal Investigator: Claire-Anne Siegrist, MD University Hospita, Geneva
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Siegrist Claire-Anne, Director of Center for Vaccinology, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT02287480    
Other Study ID Numbers: CCER 14-221
First Posted: November 10, 2014    Key Record Dates
Last Update Posted: March 8, 2016
Last Verified: March 2016
Keywords provided by Siegrist Claire-Anne, University Hospital, Geneva:
Ebolavirus Vaccines