VSV-ZEBOV Geneva Vaccine Trial

Phase 1

Completed

Conditions: Ebolavirus Disease

Interventions: Biological: VSV-ZEBOV

Registration Number: NCT02287480

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 115

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	VSV-ZEBOV	One intramuscular (deltoid) injection of normal saline (0.5 ml)
VSV-ZEBOV lower dose	VSV-ZEBOV	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
VSV-ZEBOV higher dose	VSV-ZEBOV	One intramuscular (deltoid) injection of a higher dose (5 x 10\^7 pfu) of VSV-ZEBOV. Study amendment (01.2015) : interrupted

Primary Outcome Measures

Name	Time	Method
Titers of ZEBOV-specific IgG Antibodies	Day 0 - 28	Primary immunogenicity outcome (required for dose selection)

Secondary Outcome Measures

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