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