Phase 1 Trial of Ebola Vaccine in Mali

Brief Title

Phase 1 Trial of Ebola Vaccine in Mali

Official Title

A Phase 1b, Dose-escalating Safety and Immunogenicity Trial of the Novel Monovalent Ebola Zaire Candidate Vaccine, cAd3-EBO Z and the Heterologous Prime-boost Candidate Vaccine Regimen of cAD3-EBO Z Followed by MVA-BN® Filo in Malian Adults Aged 18-50 Years.

Brief Summary

      Ebola virus causes an infection known as Ebola virus disease (EVD). This is generally a
      severe disease which can also lead to death. The 2014 outbreak of EVD in West Africa is the
      largest ever. Researchers want to develop a vaccine to prevent Ebola infection. It is
      impossible for someone to get an Ebola infection from this vaccine.
    

Detailed Description

      This is a Phase 1b (1b implies that the trial is occurring in a geographic region where cases
      of the disease against which the vaccine is directed, i.e. Ebola disease, may occur before,
      during or after the clinical trial), open label, dose-escalation study to examine the safety,
      tolerability and immunogenicity of an investigational Ebola virus vaccine, cAD3-EB) Z, in
      Malian healthy adults. The vaccine is a recombinant chimpanzee adenovirus Type-3 vectored
      Ebola Zaire vaccine (cAd3-EBO Z) and consists of a recombinant replication-deficient
      adenovirus chimpanzee serotype 3 (cAd3) vector expressing wild-type (WT) Ebola glycoprotein
      (GP) from the Zaire strain.

      A revision of the protocol on 14Dec2014 added a booster dose with MVA-BN® Filo or placebo in
      56 subjects in groups 1 (except for first 5 vaccines), 2, 3A and 4. The multivalent vectored
      vaccine MVA-BN® Filo contains an insert for the Zaire Ebola virus glycoprotein, as well as
      the Sudan strain Ebola virus glycoprotein, the Musoke strain Marburg virus glycoprotein, and
      a nucleoprotein from the Tai-Forest Ebola virus.

      Forty volunteers will be enrolled into two dosage groups. Another group of 40 volunteers
      (Groups 3A-C) with group 3A receiving 1.0x10(10)vp. All study participants will receive one
      dose of the study vaccine by intramuscular injection. Group 4 was added to include another 11
      volunteers to receive 1.-X10(11)vp. A total of 91 volunteers have been included.

      Group 1 will include 20 participants who will receive the lower dose of the vaccine at 2.5 x
      10(10) vp

      Group 2 will include 20 participants who will receive the higher does of vaccine at 5 x
      10(10) vp.

      Group 3A will include 10 participants to receive 1.0X10(10) vp

      Group 3B will include 15 participants to receive 2.5X10(10) vp

      Group 3C will include 15 participants to receive 5X10(10) vp (participants will be randomly
      allocated to Group 3B or 3C)

      Group 4 will include 11 participants to receive1x10(11) vp. The goal of vaccinating this
      group is to see if there is any added benefit to the immunogenicity of this vaccine by using
      a higher dose. This dosage level of the monovalent vaccine has already been studied at
      VRC/NIH in September and at CVD in Baltimore this month in November. This dosage level was
      not studied in Oxford nor in Bamako. Having data on West African subjects given this dosage
      will be very helpful in designing the final formulation for the field trials in Q1 of 2015.
      The decision will be made based on three sets of data: clinical dose-response; immunologic
      dose-response (as a proxy for expected protection); and manufacturing yield and cost of goods
      considerations.

      For safety reasons, the first Malian volunteer to receive a vaccine dose in Group 1 will be
      vaccinated alone and we will wait 24 hours before vaccinating subsequent volunteers in this
      dose group. Two further Group 1 volunteers may be vaccinated 24 hours after the first, and
      then at least another 24 hours gap will be left before vaccinating further subjects receiving
      that dose of vaccine. After 5 volunteers in Group 1 have been vaccinated and followed up for
      7 days, an interim safety review (ISR1) will be performed by the DSMB. Enrollment of the rest
      of this group may proceed only if the DSMB assesses the data and indicates that it is safe to
      do so.

      Group 2 volunteers will be vaccinated without the stepwise procedure. This decision was made
      by the DSMB after review of safety data for 5X10(10) from the UK trial and approval by the
      Institutional Review Boards.

      Group 3A, who will receive a lower dosage level than Groups 1 or 2, can be vaccinated as soon
      as logistically possible after all subjects in Group 2 have been vaccinated. Groups 3B and
      Group 3C will be similarly vaccinated over a period of three days at the rate of 10 subjects
      per day.

      Group 4 will vaccinate and additional 11 participants with 1X10(11) and will be vaccinated
      over 2 days (5 subjects one day followed by another 6 subjects the next day.

      Heterologous boosting dose of MVA-BN® Filo or placebo in 56 subjects in groups 1 (except for
      first 5 vaccinees), 2, 3A and 4 will commence in January 2015 with random allocation to
      either vaccine or placebo.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Occurrence of solicited local and systemic reactogenicity signs and symptoms

Secondary Outcome

 Antibody responses as measured by ELISA and neutralization assays

Condition

Ebola Virus Disease

Intervention

Ebola Chimpanzee Adenovirus Vector Vaccine (cAd3-EBO Z

Study Arms / Comparison Groups

 2.5 x 10(10) vp
Description:  Ebola Chimpanzee Adenovirus Vector Vaccine (cAd3-EBO Z) 2.5 x 10(10):

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

91

Start Date

October 2014

Completion Date

April 20, 2016

Primary Completion Date

April 20, 2016

Eligibility Criteria

        Inclusion Criteria:

        Healthy adults aged 18 to 50 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
             his/her health care provider

          -  For females only, willingness to practice continuous effective contraception (see
             section 6.4.3) during the study and a negative urine pregnancy test on the day(s) of
             screening and vaccination

          -  Agreement to refrain from blood donation during the course of the study

          -  Provide written informed consent

        Exclusion Criteria:

          -  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, a chimpanzee adenovirus
             vectored vaccine, MVA vectored vaccine or any other investigational vaccine likely to
             impact on interpretation of the trial data

          -  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

          -  Administration of immunoglobulins and/or any blood products within the three months
             preceding the planned administration of the vaccine candidate

          -  Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV
             infection; asplenia; recurrent, severe infections and chronic (more than 14 days)
             immunosuppressant medication within the past 6 months (inhaled and topical steroids
             are allowed)

          -  History of allergic disease or reactions likely to be exacerbated by any component of
             the vaccine, including urticaria, respiratory difficulty or abdominal pain

          -  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

          -  Bleeding disorder (eg. Factor deficiency, coagulopathy or platelet disorder), or prior
             history of significant bleeding or bruising following IM injections or venipuncture

          -  Any known history of cardiac disease

          -  Any other serious chronic illness requiring hospital specialist supervision

          -  Current anti-tuberculosis prophylaxis or therapy

          -  Suspected or known current alcohol abuse as defined by an alcohol intake of greater
             than 42 units every week

          -  Suspected or known injecting drug abuse in the 5 years preceding enrolment

          -  Seropositive for hepatitis B surface antigen (HBsAg)

          -  Travel to an Ebola or Marburg endemic region during the study period or within the
             previous six months or history of recovery from Ebola or Marburg virus disease.

          -  Any clinically significant abnormal finding on screening biochemistry or haematology
             blood tests or urinalysis

          -  Any other significant disease, disorder or finding which may significantly increase
             the risk to the volunteer because of participation in the study, affect the ability of
             the volunteer to participate in the study or impair interpretation of the study data
      

Gender

All

Ages

18 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Myron M Levine, MD, DTPH, , 

Location Countries

Mali

Location Countries

Mali

Administrative Informations


NCT ID

NCT02267109

Organization ID

HP-00061513


Responsible Party

Principal Investigator

Study Sponsor

University of Maryland, Baltimore

Collaborators

 Wellcome Trust

Study Sponsor

Myron M Levine, MD, DTPH, Study Director, University of Maryland, Baltimore


Verification Date

September 2019