A Clinical Trial on the Candidate Vaccine cAd3-EBOZ in Healthy Adults in Switzerland

NCT02289027 | Completed Phase 1 DMC

• 1 other identifier: cAd3-EBOZ Lau
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this trial is to assess in healthy adults the safety and reactogenicity of a new candidate vaccine, cAd3-EBOZ, made of a chimpanzee Adenovirus vector encoding the glycoprotein of Zaire Ebola virus. The secondary objectives will be to assess the immunogenicity of the candidate vaccine and find the most suitable dose for further deployment in epidemic areas in Africa. The 120 planned study subjects will be composed of possibly exposed volunteers owning to organisations such as "Médecins sans frontières" and susceptible to be deployed in the outbreak zone (named as "possibly exposed volunteers"). The other volunteers will be adults with no planned travels to the epidemic zone (named as "not exposed volunteers"). The first group will be randomly allocated to two different groups (low dose = single injection of 2.5x10e10 viral particles (vp), high dose = single injection of 5x10e10 vp). The second group will be randomly allocated to three different groups (low dose = single injection of 2.5x10e10 viral particles (vp), high dose = single injection of 5x10e10 vp or placebo = single injection of vaccine diluent). The design will be double-blind. Follow-up visits will take place at Day 1, 7, 14, 28, 90 and 180.

Conditions

Ebola Vaccines

Keywords

Ebola, Ebolavirus

Outcome Measures

Primary Outcomes (4)

• Solicited local and systemic reactogenicity signs and symptoms

  Solicited local signs and symptoms include: pain at injection site; erythema at injection site; swelling at injection site. They will be assessed according to a preestablished scale (grade 1 to 3). Solicited systemic signs and symptoms include: fever; tachycardia; bradycardia; systolic hypertension; distolic hypertension; systolic hypotension. They will be assessed according to a preestablished scale (grade 1 to 3).

  Daily for 7 days following the vaccination

• Unsolicited adverse events of all severities

  Unsolicited adverse events will be assessed according to a severity grading scale (grade 1 to 3).

  Through 28 days after the vaccination

• Change from baseline for safety laboratory measures

  Safety laboratory measures include: hemoglobin; white blood cells count; neutrophil count; lymphocyte count; platelets; total bilirubin; alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase; creatinine; urea; sodium; potassium; partial thromboplastin time (aPTT). They will be assessed according to a severity grading scale (grade 1 to 3).

  Through 6 months after the vaccination

• Occurrence of serious adverse events and suspected unexpected serious adverse reactions

  SAE are defined as AE that result in any of the following outcomes, whether or not considered related to the study intervention: * Death * Life-threatening event * Persistent or significant disability or incapacity * Hospitalisation * An important medical event (that may not cause death, be life threatening, or require hospitalisation) that may, based upon appropriate medical judgment, jeopardise the volunteer and/or require medical or surgical intervention to prevent one of the outcomes listed above. * Congenital anomaly or birth defect. A SUSAR is a suspected unexpected serious adverse reaction thought to be possibly, probably or definitely related to an IMP. No category of SAE has been defined as 'expected'.

  Through 6 months after the vaccination

Secondary Outcomes (2)

• Antibody responses as measured by ELISA (anti-EBOZ immunoglobulins titers) and by antigen-specific neutralization assays

  Through 6 months after the vaccination

• T cell immune responses as measured by ex-vivo ELISPOT

  Through 6 months after the vaccination

Other Outcomes (4)

• T cell immune responses as measured by intracellular cytokine staining assays (ICS)

  Through 6 months after the vaccination

• T cell immune responses as measured by 6-day culture cytokine production by Multiplex and flow cytometry

  Through 6 months after the vaccination

• HLA typing

  On Day 0 (day of vaccination)

Study Arms (5)

Deployed volunteers - Group 1

EXPERIMENTAL

Low dose cAd3-EBOZ (2.5x10e10 vp)

Biological: cAd3-EBOZ vaccine

Deployed volunteers - Group 2

EXPERIMENTAL

High dose cAd3-EBOZ (5x10e10 vp)

Biological: cAd3-EBOZ vaccine

Not deployed volunteers - Group 3

EXPERIMENTAL

Low dose cAd3-EBOZ (2.5x10e10 vp)

Biological: cAd3-EBOZ vaccine

Not deployed volunteers - Group 4

EXPERIMENTAL

High dose cAd3-EBOZ (5x10e10 vp)

Biological: cAd3-EBOZ vaccine

Not deployed volunteers - Group 5

PLACEBO COMPARATOR

Biological: Placebo (for cAd3-EBOZ vaccine)

Interventions

cAd3-EBOZ vaccine BIOLOGICAL

Deployed volunteers - Group 1; Deployed volunteers - Group 2; Not deployed volunteers - Group 3; Not deployed volunteers - Group 4

Placebo (for cAd3-EBOZ vaccine) BIOLOGICAL

Diluent

Not deployed volunteers - Group 5

Eligibility Criteria

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

You may qualify if:

• Healthy adults aged 18 to 65 years
• Able and willing (in the Investigator's opinion) to comply with all study requirements
• Willing to allow the investigators to discuss the volunteer's medical history with their general practitioner
• For females of reproductive capacity and males, having practiced continuous effective contraception for 21 days prior to enrolment, and willing to practice continuous effective contraception for 3 months post vaccination
• For females of reproductive capacity, having a negative pregnancy test on the day(s) of screening and vaccination if \>7 days interval
• Agreement to refrain from blood donation during the course of the study
• Provide written informed consent

You may not qualify if:

• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
• Prior receipt of an investigational Ebola or Marburg vaccine or a chimpanzee adenovirus vectored vaccine
• Receipt of any live, attenuated vaccine within 28 days prior to enrolment
• Receipt of any subunit or killed vaccine within 14 days prior to enrolment (influenza vaccination is encouraged prior to participation)
• Receipt of any investigational vaccine within 3 months prior to enrollment
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Any confirmed or suspected immunosuppressed or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressive medication within the past 6 months (inhaled and topical steroids are allowed)
• History of allergic reactions likely to be exacerbated by any component of the vaccine,
• Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
• Any history of anaphylaxis in reaction to vaccination
• Pregnancy, lactation or willingness/intention to become pregnant during the study
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of serious psychiatric condition
• Poorly controlled asthma or thyroid disease
• Seizure in the past 3 years or treatment for seizure disorder in the past 3 years

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead
• Infectious Disease Service, CHUV, Lausanne: collaborator
• Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland: collaborator
• University of Lausanne Hospitals: collaborator
• Swiss Tropical & Public Health Institute: collaborator
• University of Lausanne: collaborator
• GlaxoSmithKline: collaborator
• World Health Organization: collaborator
• Immunology and Allergy Service, CHUV, Lausanne: collaborator

Study Sites (1)

Clinical Trial Unit Lausanne

Lausanne, 1011, Switzerland

Location

Related Publications (1)

• De Santis O, Audran R, Pothin E, Warpelin-Decrausaz L, Vallotton L, Wuerzner G, Cochet C, Estoppey D, Steiner-Monard V, Lonchampt S, Thierry AC, Mayor C, Bailer RT, Mbaya OT, Zhou Y, Ploquin A, Sullivan NJ, Graham BS, Roman F, De Ryck I, Ballou WR, Kieny MP, Moorthy V, Spertini F, Genton B. Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study. Lancet Infect Dis. 2016 Mar;16(3):311-20. doi: 10.1016/S1473-3099(15)00486-7. Epub 2015 Dec 23.

  PMID: 26725450 DERIVED

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Study Officials

• Blaise Genton, MD PhD

  CHUV and PMU

  PRINCIPAL INVESTIGATOR

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: Head physician Immunology and Allergy

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: November 13, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 28, 2016

Record last verified: 2016-01

Locations

CH (1)