Clinical trial NCT02287480: VSV-ZEBOV Geneva Vaccine Trial
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ebolavirus Disease
Keywords: Ebolavirus Vaccines
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: World Health Organization
name: Wellcome Trust
name: Universitätsklinikum Hamburg-Eppendorf
name: Philipps University Marburg
name: Albert Schweitzer Hospital
name: Institute of Tropical Medicine, University of Tuebingen
name: KEMRI-Wellcome Trust Collaborative Research Program
First posted: 2014-11-10
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Titers of ZEBOV-specific IgG Antibodies
timeFrame: Day 0 - 28
Secondary outcomes:
measure: Number of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms
timeFrame: Days 0 - 14
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Days 0 - 28
measure: Number of Participants With a Serious Adverse Event (SAE)
timeFrame: Days 0 - 365
measure: Magnitude (Copies/ml) of VSVΔG-ZEBOV Viremia
timeFrame: Days 1, 3 and 7
measure: Persistence of Titers of ZEBOV-specific IgG Antibodies
timeFrame: Day 168
measure: Titers of Neutralizing ZEBOV-specific IgG Antibodies
timeFrame: Days 0, 28 and 168
measure: Duration of VSVΔG-ZEBOV Viremia
timeFrame: Days 1, 3 and 7
measure: Number of Participants in Whom Shedding of VSVΔG-ZEBOV Was Detected in Urine and/or Saliva.
timeFrame: Days 1, 3 and 7
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: University Hospitals of Geneva
Study officials:
affiliation: University Hospita, Geneva
name: Claire-Anne Siegrist, MD
role: PRINCIPAL_INVESTIGATOR
References:
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