Venezuelan Equine EncephalitisPhase 1NCT03879603
VRC 313: A Trivalent Virus-like Particle (VLP) Encephalitis Vaccine (WEVEE) in Healthy Adults
A Phase 1 study testing VRC-WEVVLP073-00-VP and VRC-GENMIX083-AL-VP in people with Venezuelan Equine Encephalitis and Western Equine Encephalitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Venezuelan Equine Encephalitis, Western Equine Encephalitis, Eastern Equine Encephalitis
- What is being tested?
- VRC-WEVVLP073-00-VP and VRC-GENMIX083-AL-VP
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Apr 2019to 26 Feb 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 19Show fewer
- 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.
Who cannot join
- 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
Show all 28Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Hope Clinic of the Emory Vaccine Center
Decatur, Georgia, 30030
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Venezuelan Equine Encephalitis, Western Equine Encephalitis, Eastern Equine Encephalitis, Alphavirus Infections
- Being tested
- VRC-WEVVLP073-00-VP, VRC-GENMIX083-AL-VP
- Keywords
- Alphavirus, VEE, WEE, EEE, Vaccine, Virus-like particles
- Medical subject headings
- Encephalomyelitis, Venezuelan Equine, Encephalomyelitis, Western Equine, Encephalomyelitis, Eastern Equine, Alphavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VRC-WEVVLP073-00-VPBiological
Also called WEVEE
VRC-WEVVLP073-00-VP is composed of 1:1:1 ratio of WEE, EEE, and VEE virus-like particles (VLP)
VRC-GENMIX083-AL-VPOther
Also called Aluminum Hydroxide Suspension, Alum
VRC-GENMIX083-AL-VP is an adjuvant
| Study group | Role | What they receive |
|---|---|---|
| Group 1: 6 mcg WEVEE vaccine | Experimental | 6 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) administered IM on Day 0 and Week 8 Receives: Biological: VRC-WEVVLP073-00-VP |
| Group 2: 6 mcg WEVEE vaccine + alum | Experimental | 6 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) and 500 mcg of Alum (VRC-GENMIX083-AL-VP) administered IM on Day 0 and Week 8 Receives: Biological: VRC-WEVVLP073-00-VP; Other: VRC-GENMIX083-AL-VP |
| Group 3: 30 mcg WEVEE vaccine | Experimental | 30 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) administered IM on Day 0 and Week 8 Receives: Biological: VRC-WEVVLP073-00-VP |
| Group 4: 30 mcg WEVEE vaccine + alum | Experimental | 30 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) and 500 mcg of Alum (VRC-GENMIX083-AL-VP) administered IM on Day 0 and Week 8 Receives: Biological: VRC-WEVVLP073-00-VP; Other: VRC-GENMIX083-AL-VP |
| Group 5: 60 mcg WEVEE vaccine | Experimental | 60 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) administered IM on Day 0 and Week 8 Receives: Biological: VRC-WEVVLP073-00-VP |
| Group 6: 60 mcg WEVEE vaccine + alum | Experimental | 60 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) and 500 mcg of Alum (VRC-GENMIX083-AL-VP) administered IM on Day 0 and Week 8 Receives: Biological: VRC-WEVVLP073-00-VP; Other: VRC-GENMIX083-AL-VP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (modified from FDA Guidance - September 2007).
Measured: 7 days after each product administration, at approximately Week 1 and Week 9
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (modified from FDA Guidance - September 2007).
Measured: 7 days after each product administration, at approximately Week 1 and Week 9
Number of Subjects With Abnormal Laboratory Measures of Safety
Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety laboratory parameters included hematology (hemoglobin, hemoglobin change from baseline, hematocrit, mean corpuscular volume (MCV), platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC), differential, platelet, and ALT results were collected at screening (≤ 28 days before enrollment), Day 0 prior to study product administration (baseline), and at Days 14, 28, 56, 70, 84, 168 and 252. Creatinine results were collected at screening, Day 0 and Day 56. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (modified from FDA Guidance, September 2007) were used.
Measured: Day 0 through Day 252
Number of Subjects With One or More Unsolicited Non-Serious Adverse Events (AEs)
Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 4 weeks after each study product administration. At other time periods between study product administrations and when greater than 4 weeks after the last study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Measured: Day 0 through 4 weeks of each study product administration, up to Week 12
Number of Subjects With Serious Adverse Events (SAEs)
SAEs were reported from receipt of first study product administration through the last expected study visit at Day 252. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Measured: Day 0 through Day 252
Secondary outcomes (2)
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
WEVEE antigen-specific antibody responses as evaluated by virus-specific neutralization assays. Eastern Equine Encephalitis Virus (EEEV), Venezuelan Equine Encephalitis Virus (VEEV) and Western Equine Encephalitis Virus (WEEV) neutralizing titers were assessed using a plaque reduction neutralization test (PRNT) at baseline and 4 weeks after the second study injection. Geometric mean titers of the individual PRNT80 (80% plaque reduction neutralization) titer values are reported.
Measured: 4 weeks after the last product administration, at Week 12
Percentage of Positive Responders at 4 Weeks After the Last Product Administration of VRC-WEVVLP073-00-VP (WEVEE) Alone Or With Alum Adjuvant
A subject was a responder or met the threshold of a positive response if the post vaccination anti-Eastern Equine Encephalitis Virus (EEEV), Venezuelan Equine Encephalitis Virus (VEEV) or Western Equine Encephalitis Virus (WEEV) antibody titer was 10 or greater.
Measured: 4 weeks after the last product administration, at Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2019
- Study start2 Apr 2019
- Primary completion26 Feb 2020
- Study completion26 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Venezuelan Equine EncephalitisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Subjects were randomized into: WEVEE vaccine alone (Group 1, Group 3, and Group 5) or, WEVEE vaccine mixed with alum (Group 2, Group 4, and Group 6, respectively). The study started by randomizing subjects to get a dose of 6 mcg in Group 1 or Group 2. Safety data were reviewed after 2 weeks to make sure this vaccine dose had no safety concerns before subjects were randomized to get the next dose of 30 mcg in Group 3 or Group 4. Safety data were reviewed again to make sure the 30 mcg vaccine dose had no safety concerns before subjects were randomized to the 60 mcg dose in Group 5 or Group 6. A total of 30 subjects were randomized among the 6 groups.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Julie E Ledgerwood, DO, Study chair, VRC/NIAID/NIHGrace Chen, MD, Study chair, VRC/NIAID/NIH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03879603
- Sponsor's protocol ID
- VRC 313
- Status last verified
- Mar 2021
- First submitted
- 8 Mar 2019
- Last updated
- 24 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chang LJ, Dowd KA, Mendoza FH, Saunders JG, Sitar S, Plummer SH, Yamshchikov G, Sarwar UN, Hu Z, Enama ME, Bailer RT, Koup RA, Schwartz RM, Akahata W, Nabel GJ, Mascola JR, Pierson TC, Graham BS, Ledgerwood JE; VRC 311 Study Team. Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial. Lancet. 2014 Dec 6;384(9959):2046-52. doi: 10.1016/S0140-6736(14)61185-5. Epub 2014 Aug 14.
PubMed 25132507Akahata W, Yang ZY, Andersen H, Sun S, Holdaway HA, Kong WP, Lewis MG, Higgs S, Rossmann MG, Rao S, Nabel GJ. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nat Med. 2010 Mar;16(3):334-8. doi: 10.1038/nm.2105. Epub 2010 Jan 28.
PubMed 20111039Coates EE, Edupuganti S, Chen GL, Happe M, Strom L, Widge A, Florez MB, Cox JH, Gordon I, Plummer S, Ola A, Yamshchikov G, Andrews C, Curate-Ingram S, Morgan P, Nagar S, Collins MH, Bray A, Nguyen T, Stein J, Case CL, Kaltovich F, Wycuff D, Liang CJ, Carlton K, Vazquez S, Mascola JR, Ledgerwood JE; VRC 313 Study Team. Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial. Lancet Infect Dis. 2022 Aug;22(8):1210-1220. doi: 10.1016/S1473-3099(22)00052-4. Epub 2022 May 11.
PubMed 35568049
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03879603
- Acronym / sponsor ID
- VRC 313
- Conditions
- Venezuelan Equine Encephalitis, Western Equine Encephalitis, Eastern Equine Encephalitis, Alphavirus Infections
- Keywords
- Alphavirus, VEE, WEE, EEE, Vaccine, Virus-like particles
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 2 Apr 2019 (actual)
- Primary completion
- 26 Feb 2020 (actual)
- Study completion
- 26 Feb 2020 (actual)
- First posted
- 19 Mar 2019 (actual)
- Results
- Posted 19 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Subjects were randomized into: WEVEE vaccine alone (Group 1, Group 3, and Group 5) or, WEVEE vaccine mixed with alum (Group 2, Group 4, and Group 6, respectively). The study started by randomizing subjects to get a dose of 6 mcg in Group 1 or Group 2. Safety data were reviewed after 2 weeks to make sure this vaccine dose had no safety concerns before subjects were randomized to get the next dose of 30 mcg in Group 3 or Group 4. Safety data were reviewed again to make sure the 30 mcg vaccine dose had no safety concerns before subjects were randomized to the 60 mcg dose in Group 5 or Group 6. A total of 30 subjects were randomized among the 6 groups.
| Arm | Type | Receives |
|---|---|---|
| Group 1: 6 mcg WEVEE vaccine | Experimental | Biological: VRC-WEVVLP073-00-VP6 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) administered IM on Day 0 and Week 8 |
| Group 2: 6 mcg WEVEE vaccine + alum | Experimental | Biological: VRC-WEVVLP073-00-VP, Other: VRC-GENMIX083-AL-VP6 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) and 500 mcg of Alum (VRC-GENMIX083-AL-VP) administered IM on Day 0 and Week 8 |
| Group 3: 30 mcg WEVEE vaccine | Experimental | Biological: VRC-WEVVLP073-00-VP30 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) administered IM on Day 0 and Week 8 |
| Group 4: 30 mcg WEVEE vaccine + alum | Experimental | Biological: VRC-WEVVLP073-00-VP, Other: VRC-GENMIX083-AL-VP30 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) and 500 mcg of Alum (VRC-GENMIX083-AL-VP) administered IM on Day 0 and Week 8 |
| Group 5: 60 mcg WEVEE vaccine | Experimental | Biological: VRC-WEVVLP073-00-VP60 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) administered IM on Day 0 and Week 8 |
| Group 6: 60 mcg WEVEE vaccine + alum | Experimental | Biological: VRC-WEVVLP073-00-VP, Other: VRC-GENMIX083-AL-VP60 mcg of WEVEE vaccine (VRC-WEVVLP073-00-VP) and 500 mcg of Alum (VRC-GENMIX083-AL-VP) administered IM on Day 0 and Week 8 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (28 listed)
- Female-Specific Criteria
- Breast-feeding or planning to become pregnant while participating in the study
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VRC-WEVVLP073-00-VPAlso: WEVEEVRC-WEVVLP073-00-VP is composed of 1:1:1 ratio of WEE, EEE, and VEE virus-like particles (VLP) | Biological | Group 1: 6 mcg WEVEE vaccine, Group 2: 6 mcg WEVEE vaccine + alum, Group 3: 30 mcg WEVEE vaccine, Group 4: 30 mcg WEVEE vaccine + alum, Group 5: 60 mcg WEVEE vaccine, Group 6: 60 mcg WEVEE vaccine + alum |
| VRC-GENMIX083-AL-VPAlso: Aluminum Hydroxide Suspension, AlumVRC-GENMIX083-AL-VP is an adjuvant | Other | Group 2: 6 mcg WEVEE vaccine + alum, Group 4: 30 mcg WEVEE vaccine + alum, Group 6: 60 mcg WEVEE vaccine + alum |
Primary outcome
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration
Time frame: 7 days after each product administration, at approximately Week 1 and Week 9
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of subjects reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (modified from FDA Guidance - September 2007).
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration
Time frame: 7 days after each product administration, at approximately Week 1 and Week 9
Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of subjects reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (modified from FDA Guidance - September 2007).
Number of Subjects With Abnormal Laboratory Measures of Safety
Time frame: Day 0 through Day 252
Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety laboratory parameters included hematology (hemoglobin, hemoglobin change from baseline, hematocrit, mean corpuscular volume (MCV), platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT) and creatinine). Complete blood count (CBC), differential, platelet, and ALT results were collected at screening (≤ 28 days before enrollment), Day 0 prior to study product administration (baseline), and at Days 14, 28, 56, 70, 84, 168 and 252. Creatinine results were collected at screening, Day 0 and Day 56. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (modified from FDA Guidance, September 2007) were used.
Number of Subjects With One or More Unsolicited Non-Serious Adverse Events (AEs)
Time frame: Day 0 through 4 weeks of each study product administration, up to Week 12
Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 4 weeks after each study product administration. At other time periods between study product administrations and when greater than 4 weeks after the last study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.
Number of Subjects With Serious Adverse Events (SAEs)
Time frame: Day 0 through Day 252
SAEs were reported from receipt of first study product administration through the last expected study visit at Day 252. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.
2 secondary outcomes
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
Time frame: 4 weeks after the last product administration, at Week 12
Percentage of Positive Responders at 4 Weeks After the Last Product Administration of VRC-WEVVLP073-00-VP (WEVEE) Alone Or With Alum Adjuvant
Time frame: 4 weeks after the last product administration, at Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25132507Chang LJ, Dowd KA, Mendoza FH, Saunders JG, Sitar S, Plummer SH, Yamshchikov G, Sarwar UN, Hu Z, Enama ME, Bailer RT, Koup RA, Schwartz RM, Akahata W, Nabel GJ, Mascola JR, Pierson TC, Graham BS, Ledgerwood JE; VRC 311 Study Team. Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial. Lancet. 2014 Dec 6;384(9959):2046-52. doi: 10.1016/S0140-6736(14)61185-5. Epub 2014 Aug 14.
- Background: PubMed 20111039Akahata W, Yang ZY, Andersen H, Sun S, Holdaway HA, Kong WP, Lewis MG, Higgs S, Rossmann MG, Rao S, Nabel GJ. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nat Med. 2010 Mar;16(3):334-8. doi: 10.1038/nm.2105. Epub 2010 Jan 28.
- Derived from this study: PubMed 35568049Coates EE, Edupuganti S, Chen GL, Happe M, Strom L, Widge A, Florez MB, Cox JH, Gordon I, Plummer S, Ola A, Yamshchikov G, Andrews C, Curate-Ingram S, Morgan P, Nagar S, Collins MH, Bray A, Nguyen T, Stein J, Case CL, Kaltovich F, Wycuff D, Liang CJ, Carlton K, Vazquez S, Mascola JR, Ledgerwood JE; VRC 313 Study Team. Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial. Lancet Infect Dis. 2022 Aug;22(8):1210-1220. doi: 10.1016/S1473-3099(22)00052-4. Epub 2022 May 11.
- Individual participant dataSharing planned: No
Related trials for Venezuelan Equine Encephalitis
Not yet recruitingPhase 1
A Phase 1 Study Evaluating the Safety, Tolerability, and Immunogenicity of V4020 Vaccine in Healthy Volunteers
Venezuelan Equine Encephalitis, Venezuelan Equine Encephalitis Virus Infection
Not yet recruitingPhase 2
Safety and Immunogenicity Study of Venezuelan Equine Encephalomyelitis (VEE) Vaccine as Booster Vaccine in Adults
Venezuelan Equine Encephalomyelitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julie E Ledgerwood, DO study chair
VRC/NIAID/NIH
Grace Chen, MD study chair
VRC/NIAID/NIH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VRC-WEVVLP073-00-VP and VRC-GENMIX083-AL-VP in people with Venezuelan Equine Encephalitis and Western Equine Encephalitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms For 7 Days After Each Product Administration (time frame: 7 days after each product administration, at approximately Week 1 and Week 9). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03879603, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2021.