Ebola CVD-Mali #2000 (Bivalent) VRC-EBOAdc069-00-vp (cAd3-EBO)

Brief Title

Ebola CVD-Mali #2000 (Bivalent) VRC-EBOAdc069-00-vp (cAd3-EBO)

Official Title

A PHASE IB, DOUBLE-BLIND, CLINICAL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY AND IMMUNOGENICITY OF TWO DIFFERENT DOSAGE LEVELS OF EBOLA CHIMPANZEE ADENOVIRUS VECTOR VACCINE "VRC-EBOADC069-00-VP (cAd3-EBO)" AND THE HETEROLOGOUS PRIME-BOOST CANDIDATE VACCINE REGIMEN OF cAD3-EBO FOLLOWED BY MVA-VECTORED VACCINE IN HEALTHY ADULTS, 18-65 YEARS OF AGE, IN BAMAKO, MALI

Brief Summary

      Ebola virus causes an infection known as Ebola virus disease (EVD). This it 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.

      This study will assess the safety of a single dose of the bivalent Ebola Zaire candidate
      vaccine VRC-EBOADC069-00-VP (cAD3-EBO) when administered to healthy Malian adult volunteers,
      age 18-65 years (mostly health care workers and other front line workers [e.g., individuals
      who incinerate contaminated materials]), at one of 2 dosage levels, 2.0 x 10(10) vp or 2 x
      10(11) vp. It is impossible for someone to get an Ebola infection from this vaccine.

      Heterologous booster dose allocation - Each participant will be offered the opportunity to be
      included in the booster step of this study. After obtaining consent and the additional review
      of pertinent medical history, participants in each group will be randomized to receive the
      candidate booster vaccine, MVA-EbolaZ or placebo.

      This will be the first clinical trial in Mali with bivalent cAd3-based Ebola vaccine and the
      first where the dosage level contains > 10(11) vp. It follows completion of a Phase Ib trial
      in Malian health care workers that tested three dosage levels of monovalent cAd3-EBO Z
      vaccine. The data generated in West Africans (Mali) on the tolerability and immunogenicity of
      the bivalent vaccine will be compared to clinical and immunologic responses documented in in
      parallel studies in East African subjects (Uganda) and North American subjects (NIH,
      Bethesda, MD, USA).

      Objectives:

        -  To see if an Ebola vaccine is safe and to study immune responses to it.

        -  To study the effect of the MVA-EbolaZ booster on the immune response

      Eligibility:

      - Healthy adults ages 18-65.
    

Detailed Description

      This is a phase 1B, double-blind, randomized study to examine the safety, tolerability and
      immunogenicity of two different dosage levels of investigational Ebola vaccine.

      The vaccine is a recombinant chimpanzee adenovirus Type 3-vectored Ebolavirus vaccine
      (cAd3-EBO), VRC-EBOADC069-00-VP. The vaccine encodes wild type (WT) glycoproteins (GP) from
      Zaire and Sudan species of Ebola virus. The primary objective is to assess the safety of a
      single dose intramuscular injection of the bivalent vaccine at one of 2 dosage levels, 2.0 X
      10(10) vp or 2 x 10(11) vp and to assess the safety of the heterologous prime boost regimen
      of cAd3-EBO followed by MVA-EbolaZ or Phosphate Buffered Saline (PBS) placebo. A secondary
      objective is to assess the immunogenicity generated by 2 different dosage levels of the
      bivalent Ebola candidate vaccine.

      Enrolment of Group 1 participants:

      The first 20 Malian volunteers will be vaccinated in a staggered fashion. For safety reasons,
      the first 10 Malian subjects to receive a vaccine dose in Group 1 will be vaccinated on day 1
      and we will wait 24 hours before vaccinating 10 subsequent volunteers. After these 20
      volunteers in Group 1 have been vaccinated and followed up for 7 days, an interim safety
      review (ISR1) will be performed by the DSMB. Enrolment of subjects into Group 2 will commence
      only after the DSMB has assessed the data and indicated that it is safe to do so.

      Half of Group 1 participants will be randomly assigned to receive the low dose and the
      remaining 10 will be randomized to receive the high dose.

      Enrolment of Group 2 participants:

      The 40 subjects in Group 2 will be accrued as rapidly as possible. The 40 Malian volunteers
      in Group 2 will be vaccinated over several days to limit wastage of the available doses of
      cAd3 EBO. As a result, a proposed scheme would be 10 per vaccination day. This could be
      adjusted as needed to limit wastage but no more than 20 participants would be vaccinated in 1
      day. After the total of 40 volunteers in Group 2 have been vaccinated and followed up for 7
      days, an interim safety review (ISR2) will be performed by the DSMB.

      Prime Boost Vaccine Randomization 4-16 weeks after priming dose: Each participant will be
      offered the opportunity to be included in the booster step of this study. After obtaining
      consent and the additional review of pertinent medical history, participants in each group
      will be randomized to receive the candidate booster vaccine, MVA-EbolaZ or PBS placebo
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Solicited local reactogenicity - Number of participants with the specific outcome

Secondary Outcome

 Ebolavirus specific immunogenicity

Condition

Ebola Virus Disease

Intervention

VRC-EBOADC069-00-vp

Study Arms / Comparison Groups

 Group 1
Description:  VRC-EBOADC069-00 VP (cAd3-EBO bivalent (Zaire plus Sudan) vaccine (2 x 10(10) vp (n=10) or VRC-EBOADC069-00 VP (cAd3-EBO bivalent (Zaire plus Sudan) vaccine (2 x 10(11) vp (n=10). Randomization to booster of MVA-EbolaZ or PBS placebo will be completed 4 to 16 weeks after priming dose.

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

60

Start Date

March 2015

Completion Date

September 27, 2016

Primary Completion Date

September 27, 2016

Eligibility Criteria

        Inclusion Criteria:

          -  Healthy adults aged 18 to 65 years

          -  Able and willing (in the Investigator's opinion) to comply with all study requirements

          -  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

        Laboratory criteria within 30 days prior to enrollment:

          -  Hemoglobin ≥ 11.0 g/dL for women; ≥12.5 g/dL for men.

          -  White blood cells (WBC) = 2,500-11,000 cells/mm3.

          -  Neutrophil count = 1200 - 7000 cells/mm3

          -  Lymphocyte count ≥ 800 cells/mm3

          -  Eosinophil count = 0 - 500 cells/mm3

          -  Platelets = 125,000 - 400,000/mm3

          -  Alanine aminotransferase (ALT) = 10-45 IU/L

          -  Serum creatinine = 54-145 umol/L.

          -  HIV-uninfected as evidenced by a negative HIV diagnostic test.

          -  Seronegative for hepatitis B surface antigen (HBsAg)

          -  Negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day
             of enrollment if woman is presumed to be of reproductive potential.

          -  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.

        Exclusion Criteria:

          -  Recent exposure to Ebola virus infection (this is not a post-exposure vaccine)

          -  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 (for booster study) 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 (for the booster portion of the study only)

          -  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

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

          -  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 - 65 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Myrons M Levine, MD DTPH, , 

Location Countries

Mali

Location Countries

Mali

Administrative Informations


NCT ID

NCT02368119

Organization ID

HP-00062548


Responsible Party

Principal Investigator

Study Sponsor

University of Maryland, Baltimore

Collaborators

 National Institute of Allergy and Infectious Diseases (NIAID)

Study Sponsor

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


Verification Date

September 2019