VSV-ZEBOV Geneva Vaccine Trial

NCT02287480 | Completed Phase 1 Results DMC

• 1 other identifier: CCER 14-221
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 1

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.

Conditions

Ebolavirus Disease

Keywords

Ebolavirus Vaccines

Outcome Measures

Primary Outcomes (1)

• Titers of ZEBOV-specific IgG Antibodies

  Primary immunogenicity outcome (required for dose selection)

  Day 0 - 28

Secondary Outcomes (8)

• Number of Participants With Solicited Local and Systemic Reactogenicity Signs and Symptoms

  Days 0 - 14

• Number of Participants With Unsolicited Adverse Events

  Days 0 - 28

• Number of Participants With a Serious Adverse Event (SAE)

  Days 0 - 365

• Magnitude (Copies/ml) of VSVΔG-ZEBOV Viremia

  Days 1, 3 and 7

• Persistence of Titers of ZEBOV-specific IgG Antibodies

  Day 168

Study Arms (3)

VSV-ZEBOV lower dose

EXPERIMENTAL

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

VSV-ZEBOV higher dose

EXPERIMENTAL

One intramuscular (deltoid) injection of a higher dose (5 x 10\^7 pfu) of VSV-ZEBOV. Study amendment (01.2015) : interrupted

Biological: VSV-ZEBOV

Placebo

PLACEBO COMPARATOR

One intramuscular (deltoid) injection of normal saline (0.5 ml)

Biological: VSV-ZEBOV

Interventions

VSV-ZEBOV BIOLOGICAL

See arm/group descriptions.

Also known as: BPSC1001

Placebo; VSV-ZEBOV higher dose; VSV-ZEBOV lower dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Geneva: lead
• World Health Organization: collaborator
• Wellcome Trust: collaborator
• Universitätsklinikum Hamburg-Eppendorf: collaborator
• Philipps University Marburg: collaborator
• Albert Schweitzer Hospital: collaborator
• Institute of Tropical Medicine, University of Tuebingen: collaborator
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator

Study Sites (1)

University Hospitals of Geneva

Geneva, 1211, Switzerland

Location

Related Publications (5)

• Agnandji ST, Huttner A, Zinser ME, Njuguna P, Dahlke C, Fernandes JF, Yerly S, Dayer JA, Kraehling V, Kasonta R, Adegnika AA, Altfeld M, Auderset F, Bache EB, Biedenkopf N, Borregaard S, Brosnahan JS, Burrow R, Combescure C, Desmeules J, Eickmann M, Fehling SK, Finckh A, Goncalves AR, Grobusch MP, Hooper J, Jambrecina A, Kabwende AL, Kaya G, Kimani D, Lell B, Lemaitre B, Lohse AW, Massinga-Loembe M, Matthey A, Mordmuller B, Nolting A, Ogwang C, Ramharter M, Schmidt-Chanasit J, Schmiedel S, Silvera P, Stahl FR, Staines HM, Strecker T, Stubbe HC, Tsofa B, Zaki S, Fast P, Moorthy V, Kaiser L, Krishna S, Becker S, Kieny MP, Bejon P, Kremsner PG, Addo MM, Siegrist CA. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. N Engl J Med. 2016 Apr 28;374(17):1647-60. doi: 10.1056/NEJMoa1502924. Epub 2015 Apr 1.

  PMID: 25830326 RESULT

• Huttner A, Dayer JA, Yerly S, Combescure C, Auderset F, Desmeules J, Eickmann M, Finckh A, Goncalves AR, Hooper JW, Kaya G, Krahling V, Kwilas S, Lemaitre B, Matthey A, Silvera P, Becker S, Fast PE, Moorthy V, Kieny MP, Kaiser L, Siegrist CA; VSV-Ebola Consortium. The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial. Lancet Infect Dis. 2015 Oct;15(10):1156-1166. doi: 10.1016/S1473-3099(15)00154-1. Epub 2015 Aug 4.

  PMID: 26248510 RESULT

• Huttner A, Agnandji ST, Combescure C, Fernandes JF, Bache EB, Kabwende L, Ndungu FM, Brosnahan J, Monath TP, Lemaitre B, Grillet S, Botto M, Engler O, Portmann J, Siegrist D, Bejon P, Silvera P, Kremsner P, Siegrist CA; VEBCON; VSV-EBOVAC; VSV-EBOPLUS Consortia. Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study. Lancet Infect Dis. 2018 Jul;18(7):738-748. doi: 10.1016/S1473-3099(18)30165-8. Epub 2018 Apr 5.

  PMID: 29627147 DERIVED

• 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.

  PMID: 28647166 DERIVED

• Medaglini D, Harandi AM, Ottenhoff TH, Siegrist CA; VSV-Ebovac Consortium. Ebola vaccine R&D: Filling the knowledge gaps. Sci Transl Med. 2015 Dec 9;7(317):317ps24. doi: 10.1126/scitranslmed.aad3106.

  PMID: 26659569 DERIVED

Results Point of Contact

• Title: Prof. Claire-Anne Siegrist
• Organization: Geneva University Hospitals

claire-anne.siegrist@unige.ch

0041 22 379 5778

Study Officials

• Claire-Anne Siegrist, MD

  University Hospita, Geneva

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Center for Vaccinology

Study Record Dates

• First Submitted: November 2, 2014
• First Posted: November 10, 2014
• Study Start: November 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: January 1, 2016
• Last Updated: May 10, 2023
• Results First Posted: May 10, 2023

Record last verified: 2023-05

Locations

CH (1)