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

NCT03879603 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: VRC 313
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Venezuelan Equine Encephalitis; Western Equine Encephalitis; Eastern Equine Encephalitis; Alphavirus Infections

Keywords

Alphavirus; VEE; WEE; EEE; Vaccine; Virus-like particles

Outcome Measures

Primary Outcomes (5)

• 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).

  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).

  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.

  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.

  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.

  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

  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

  4 weeks after the last product administration, at Week 12

Study Arms (6)

Group 1: 6 mcg WEVEE vaccine

EXPERIMENTAL

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

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

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

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

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

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

Biological: VRC-WEVVLP073-00-VP; Other: VRC-GENMIX083-AL-VP

Interventions

VRC-WEVVLP073-00-VP BIOLOGICAL

VRC-WEVVLP073-00-VP is composed of 1:1:1 ratio of WEE, EEE, and VEE virus-like particles (VLP)

Also known as: WEVEE

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-VP OTHER

VRC-GENMIX083-AL-VP is an adjuvant

Also known as: Aluminum Hydroxide Suspension, Alum

Group 2: 6 mcg WEVEE vaccine + alum; Group 4: 30 mcg WEVEE vaccine + alum; Group 6: 60 mcg WEVEE vaccine + alum

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

The Hope Clinic of the Emory Vaccine Center

Decatur, Georgia, 30030, United States

Location

Related Publications (3)

• 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.

  PMID: 25132507 BACKGROUND

• Akahata 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.

  PMID: 20111039 BACKGROUND

• Coates 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.

  PMID: 35568049 DERIVED

MeSH Terms

Conditions

Encephalomyelitis, Venezuelan Equine; Encephalomyelitis, Western Equine; Encephalomyelitis, Eastern Equine; Alphavirus Infections

Interventions

aluminum sulfate

Condition Hierarchy (Ancestors)

Encephalomyelitis, Equine; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Encephalomyelitis; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Encephalitis, Arbovirus; Mosquito-Borne Diseases; Virus Diseases; Togaviridae Infections; RNA Virus Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Results Point of Contact

• Title: Julie E. Ledgerwood, DO (Study Chair)
• Organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

ledgerwood@mail.nih.gov

301-594-8502

Study Officials

• Julie E Ledgerwood, DO

  VRC/NIAID/NIH

  STUDY CHAIR

• Grace Chen, MD

  VRC/NIAID/NIH

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: March 19, 2019
• Study Start: April 2, 2019
• Primary Completion: February 26, 2020
• Study Completion: February 26, 2020
• Last Updated: March 24, 2021
• Results First Posted: March 19, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)