VRC 313: A Trivalent Virus-like Particle (VLP) Encephalitis Vaccine (WEVEE) in Healthy Adults

Brief Title

VRC 313: A Trivalent Virus-like Particle (VLP) Encephalitis Vaccine (WEVEE) in Healthy Adults

Official Title

A Phase 1 Open Label, Dose-Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of a Trivalent Virus-Like Particle (VLP) Encephalitis Vaccine, VRC-WEVVLP073-00-VP, in Healthy Adults

Brief Summary

      Western Equine Encephalitis Virus (WEEV), Eastern Equine Encephalitis Virus (EEEV), and
      Venezuelan Equine Encephalitis Virus (VEEV) are transmitted to humans by infected mosquitoes
      and can cause encephalitis (swelling of the brain) and other neurological manifestations,
      including fever, chills, discomfort, feeling sick, muscle pain and then headache, vomiting,
      restlessness, irritability, seizures, coma, and death.

      Vaccines teach the body to prevent or fight an infection. When the body learns to fight an
      infection, this is called an immune response. Researchers developed a vaccine against
      Western, Eastern and Venezuelan equine encephalitis viruses to help the body make an immune
      response. There are no live or killed viruses in the vaccine, so you cannot get infected with
      any of these 3 viruses from getting the vaccine.

      The experimental trivalent encephalitis vaccine, VRC-WEVVLP073-00-VP, is composed of Western
      equine encephalitis (WEE), Eastern equine encephalitis (EEE), and Venezuelan equine
      encephalitis (VEE) virus-like particles (VLP).

      The purpose of this study is to test three doses (6 mcg, 30 mcg, and 60 mcg) of this
      experimental vaccine against Western, Eastern and Venezuelan equine encephalitis viruses.
    

Detailed Description

      This is a Phase 1, randomized, open-label, dose-escalation study to examine the safety,
      tolerability, and immune response of three doses (6 mcg, 30 mcg, and 60 mcg) of the WEVEE
      vaccine (VRC-WEVVLP073-00-VP) alone or with alum adjuvant (VRC-GENMIX083-AL-VP) in a
      2-product administration regimen.

      Eligible subjects were randomized to WEVEE alone (Groups 1, 3, and 5) or WEVEE plus alum
      (Groups 2, 4, and 6, respectively) in each dose group. No more than 1 subject was randomized
      and vaccinated per day for the first 3 subjects at each dose. If the 6 mcg dose of WEVEE was
      assessed as not showing safety concerns by a Protocol Safety Review Team (PSRT),
      randomization began for Groups 3 and 4 (30 mcg WEVEE without alum and with alum,
      respectively). In a second safety review conducted on the first 3 subjects to receive 30 mcg,
      if the 30 mcg dose of WEVEE was assessed as not showing safety concerns by the PSRT,
      randomization began for Groups 5 and 6 (60 mcg WEVEE without and with alum, respectively).

      The product was administered in the upper arm muscle as an intramuscular (IM) injection via
      needle and syringe at Day 0 and 8 weeks later.

      For all groups, solicited reactogenicity was evaluated using a 7-day diary card. Assessment
      of vaccine safety included clinical observation and monitoring of hematological and chemical
      parameters at clinical visits throughout the study.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Number of Subjects Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration

Secondary Outcome

 Antigen-specific Neutralizing Antibody Geometric Mean Titers (GMTs) at 4 Weeks After the Last Product Administration of VRC-WEVVLP073-00-VP (WEVEE) Alone Or With Alum Adjuvant

Condition

Venezuelan Equine Encephalitis

Intervention

VRC-WEVVLP073-00-VP

Study Arms / Comparison Groups

 Group 1: 6 mcg WEVEE vaccine
Description:  6 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) administered IM on Day 0 and Week 8

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

30

Start Date

April 2, 2019

Completion Date

February 26, 2020

Primary Completion Date

February 26, 2020

Eligibility Criteria

        Inclusion Criteria:

        A volunteer must have met all of the following criteria:

          -  Age 18 to 50 years

          -  Available for clinical follow-up through 36 weeks after randomization

          -  Able to provide proof of identity to the satisfaction of the study clinician
             completing the enrollment process

          -  Able and willing to complete the informed consent process

          -  Willing to donate blood for sample storage to be used for future research

          -  In good general health, without clinically significant medical history, and has
             satisfactorily completed screening

          -  Physical examination and laboratory results without clinically significant findings
             within the 28 days prior to randomization

        Laboratory Criteria within 28 days prior to randomization:

          -  Hemoglobin within institutional normal range or accompanied by Principal Investigator
             (PI) or designee approval

          -  White blood cell (WBC) and differential either within institutional normal range or
             accompanied by PI or designee approval

          -  Total lymphocyte count: ≥800 cells/mm3

          -  Platelets: 125,000-500,000/mm3

          -  Alanine aminotransferase (ALT): ≤ 1.25 x upper limit of normal range

          -  Serum creatinine: ≤1.1 x upper limit of normal

          -  Negative for HIV infection by an FDA-approved method of detection

        Criteria applicable to women of childbearing potential:

          -  Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on
             day of randomization before receiving the study product

          -  Agrees to use an effective method of birth control, if sexually active, from at least
             21 days prior to randomization through the last study visit.

        Exclusion Criteria:

        A volunteer was excluded if one or more of the following conditions applied:

        Female-Specific Criteria

        • Breast-feeding or planning to become pregnant while participating in the study

        Volunteer received any of the following:

          -  More than 10 days of systemic immunosuppressive medications or cytotoxic medications
             within the 4 weeks prior to randomization or any within the 14 days prior to
             randomization

          -  Blood products within 16 weeks prior to randomization

          -  Immunoglobulin within 8 weeks prior to randomization

          -  Prior vaccinations with an investigational alphavirus vaccine

          -  Investigational research agents within 4 weeks prior to randomization or planning to
             receive investigational products while on study

          -  Live attenuated vaccines within 4 weeks prior to randomization

          -  Inactivated vaccines within 2 weeks prior initial study vaccine administration unless
             approved by the PI

          -  Current anti-tuberculosis (TB) prophylaxis or therapy

        Volunteer has a history of any of the following clinically significant conditions:

          -  A history of confirmed or suspected viral encephalitis infection

          -  Serious reactions to vaccines that preclude receipt of study vaccinations as
             determined by the investigator

          -  Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema

          -  Asthma that is not well controlled

          -  Diabetes mellitus (type I or type II) with the exception of gestational diabetes

          -  Thyroid disease that is not well controlled

          -  Hypertension that is not well controlled

          -  Evidence of autoimmune disease or immunodeficiency

          -  Idiopathic urticaria within the last year

          -  Malignancy that is active or history of malignancy that is likely to recur during the
             study

          -  Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions) or significant bruising or bleeding
             difficulties with intramuscular (IM) product administration or blood draws

          -  Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol
             withdrawal more than 3 years ago, or 3) seizures or treatment for a seizure disorder
             within the last 3 years

          -  Asplenia, functional asplenia or any condition resulting in absence or removal of the
             spleen

          -  Psychiatric condition that precludes compliance with the protocol; past or present
             psychoses; or within 5 years prior to randomization, a history of suicide plan or
             attempt

          -  Any other chronic or clinically significant medical, psychiatric or social condition
             that, in the judgement of the investigator is a contraindication to protocol
             participation or impairs a volunteer's ability to give informed consent.
      

Gender

All

Ages

18 Years - 50 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Julie E Ledgerwood, DO, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03879603

Organization ID

VRC 313


Responsible Party

Sponsor

Study Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)


Study Sponsor

Julie E Ledgerwood, DO, Study Chair, VRC/NIAID/NIH


Verification Date

March 2021