VSV-ZEBOV Geneva Vaccine Trial (VSV-ZEBOV)

May 9, 2023 updated by: Siegrist Claire-Anne, University Hospital, Geneva

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

115

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Geneva, Switzerland, 1211
        • University Hospitals of Geneva

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Titers of ZEBOV-specific IgG Antibodies
Time Frame: Day 0 - 28
Primary immunogenicity outcome (required for dose selection)
Day 0 - 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms
Time Frame: Days 0 - 14
Number of participants with solicited local and systemic reactogenicity signs and symptoms. Day 0 is the day of the study intervention.
Days 0 - 14
Number of Participants With Unsolicited Adverse Events
Time Frame: Days 0 - 28
Number of participants with unsolicited adverse events in the 28 days following injection
Days 0 - 28
Number of Participants With a Serious Adverse Event (SAE)
Time Frame: Days 0 - 365
Number of participants with a serious adverse event (SAE) in the 365 days (1 year) following injection.
Days 0 - 365
Magnitude (Copies/ml) of VSVΔG-ZEBOV Viremia
Time Frame: Days 1, 3 and 7
Magnitude (copies/ml) of VSVΔG-ZEBOV viremia as expressed by median VSV RNA concentrations after vaccination.
Days 1, 3 and 7
Persistence of Titers of ZEBOV-specific IgG Antibodies
Time Frame: Day 168
The percentage of participants maintaining positive ZEBOV-specific IgG antibody titers at 168 days after vaccination.
Day 168
Titers of Neutralizing ZEBOV-specific IgG Antibodies
Time Frame: Days 0, 28 and 168
Geometric mean titers of neutralizing ZEBOV-specific IgG antibodies.
Days 0, 28 and 168
Duration of VSVΔG-ZEBOV Viremia
Time Frame: Days 1, 3 and 7
Percentage of participants with any detectable viremia on days 1, 3 and 7
Days 1, 3 and 7
Number of Participants in Whom Shedding of VSVΔG-ZEBOV Was Detected in Urine and/or Saliva.
Time Frame: Days 1, 3 and 7
This outcome was evaluated in a subset of vaccinees.
Days 1, 3 and 7

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pattern of vaccine-induced innate responses
Time Frame: Day 7
This outcome will be evaluated in a subset of the first 46 vaccinees.
Day 7
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.
Days 0, 7, 14, 28 and 168

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Geneva

Collaborators

Wellcome Trust
KEMRI-Wellcome Trust Collaborative Research Program
World Health Organization
Universitätsklinikum Hamburg-Eppendorf
Philipps University Marburg Medical Center
Albert Schweitzer Hospital
Institute of Tropical Medicine, University of Tuebingen

Investigators

  • Principal Investigator: Claire-Anne Siegrist, MD, University Hospita, Geneva

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

November 2, 2014

First Submitted That Met QC Criteria

November 7, 2014

First Posted (Estimate)

November 10, 2014

Study Record Updates

Last Update Posted (Actual)

May 10, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • CCER 14-221

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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