Venezuelan Equine Encephalitis Monovalent Virus-Like Particle Vaccine

NCT03776994 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: SRI-VEEV-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to evaluate the safety and immunogenicity of non-adjuvanted and adjuvanted monovalent VEE VLP Vaccine in healthy adults (ages 18-50 years) when administered via intramuscular (IM) injection at escalating doses of 2 μg, 10 μg, and 20 μg as a 2-dose primary series (Day 0, Day 28) with a Day 140 booster dose. The secondary objective of the study is to evaluate immunogenicity of the vaccine at the aforementioned time points

Conditions

Encephalitis; Encephalitis, Viral; Infectious Encephalitis; Virus Diseases; Encephalomyelitis, Venezuelan Equine; Brain Diseases; Central Nervous System Diseases; Central Nervous System Viral Diseases; Alphavirus Infections; Togaviridae Infections; RNA Virus Infections; Central Nervous System Infections; Encephalomyelitis; Physiological Effects of Drugs; Vaccines; Encephalomyelitis, Equine; Nervous System Diseases

Keywords

Venezuelan Equine Encephalitis, vaccine; Intramuscular; Phase 1 clinical study

Outcome Measures

Primary Outcomes (7)

• Number of subjects reporting solicited local adverse events

  • The solicited local adverse events (SLAEs) are specified and collected in daily diary questionnaires for 1 week after each vaccination in each arm of the study (Days 0-7, 28-35, and 140-147). These SLAEs include pain, tenderness, induration or swelling, and erythema. Symptoms are counted once if subjects experienced the symptom at any severity during the reporting period. The number of local symptoms is the total of one or more local symptom at any severity. The severity of the SLAEs will be graded as Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) or Potentially Life Threatening (Grade 4). SLAEs will be characterized according to the "Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine trials" FDA Guidance for Industry (Sept 2007). The frequency of SLAEs will each be expressed as the number of subjects experiencing these adverse events for the 3 vaccinations within each of the 6 arms of the study.

  Through the study duration of 44 weeks

• Number of subjects reporting solicited systemic adverse events

  • The solicited systemic adverse events (SSAEs) are specified and collected in daily diary questionnaires for 1 week after each vaccination in each arm of the study (Days 0-7, 28-35, and 140-147). These SSAEs are fever, malaise, myalgia, arthralgia, headache, chills, fever, nausea, and rash. Symptoms are counted once if subjects experienced the symptom at any severity during the reporting period. The number of systemic symptoms is the total of one or more systemic symptom at any severity. The severity of the SSAEs will be graded as Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3) or Potentially Life Threatening (Grade 4). SSAEs will be characterized according to the "Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine trials" FDA Guidance for Industry (Sept 2007). The frequency of SSAEs will each be expressed as the number of subjects experiencing these adverse events for the 3 vaccinations within each of the 6 arms of the study.

  Through the study duration of 44 weeks

• Number of subjects reporting treatment-emergent adverse events

  • Unsolicited treatment-emergent adverse events (collected for 28 days after each vaccination or Days 0-28, Days 28-56, and Days 140-168) will be collected and tabulated. MedDRA version 21.0 will be used for coding. The number of subjects experiencing the unsolicited treatment-emergent adverse events within the 28 days after the three vaccinations will be reported for each of the six arms.

  Through the study duration of 44 weeks

• Number of subjects reporting serious adverse events

  • Serious adverse events will be collected throughout the study. The frequency of these solicited adverse events will each be expressed as the number of subjects experiencing these adverse events for the three vaccinations within each of the six arms of the study.

  Through the study duration of 44 weeks

• Number of subjects with abnormalities in serum creatinine concentrations

  • Serum creatinine is measured on Days 0, 7, 28, 35, 56, 140, 147, 168 and 308. The normal range for adults aged 18-50 years for men is 0.6 - 1.35 mg/dL and women 0.50 - 1.10 mg/dL. The abnormal serum creatinine values are characterized as follows: Grade 1 (1.5 - 1.7 mg/dL), Grade 2 (1.8 - 2.0 mg/dL), Grade 3 (2.1 - 2.5 mg/dL), and grade 4 (\>2.5 mg/dL or requires dialysis) according to the "Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine trials" FDA Guidance for Industry (September 2007). The frequency and severity of these adverse events will be expressed as the number of subjects with any abnormal result for the three vaccinations within each of the six arms of the study.

  Through the study duration of 44 weeks

• Number of subjects with abnormal serum alanine aminotransferase concentrations

  • Serum alanine aminotransferase is measured on Days 0, 7, 28, 35, 56, 140, 147, 168 and 308.The normal range for adults ages 18-50 years for men is 9 - 46 mg/dL and women 6 - 29 mg/dL. The grading is characterized as follows: Grade 1 (1.1 - 2.5 x upper limits of normal \[ULN\]), Grade 2 (2.6 - 5.0 ULN), Grade 3 (5.1 - 10 x ULN) and Grade 4 (\>10 x ULN) according to the "Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine trials" FDA Guidance for Industry (September 2007). The frequency and severity of these adverse events will be expressed as the number of subjects with any abnormal result for the three vaccinations within each of the six arms of the study.

  Through the study duration of 44 weeks

• Number of subjects with abnormal complete blood counts

  • Complete blood count is measured on Days 0, 7, 28, 35, 56, 140, 147, 168 and 308. The changes (either increases or decreases) in components of the complete blood count (e.g., hemoglobin, hematocrit, total white blood cell to and differential, and platelet count) are tabulated according to Grades 1- 4 in the "Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine trials" FDA Guidance for Industry (September 2007). The frequency and severity of any abnormal results will be expressed as the number of subjects with any abnormal result for the three vaccinations within each of the six arms of the study.

  Through the study duration of 44 weeks

Secondary Outcomes (3)

• Number of subjects with neutralizing antibody titers as assessed by a plaque reduction neutralization test (PRNT50)

  Through the study duration of 44 weeks

• The duration of detectable neutralizing antibody titers as assessed by the plaque reduction neutralization test (PRNT50)

  Through the study duration of 44 weeks

• The magnitude of neutralizing antibodies as assessed by a plaque reduction neutralization test (PRNT50)

  Through the study duration of 44 weeks

Study Arms (6)

Group 1A 2 µg VEE Vaccine Alone

EXPERIMENTAL

Subgroup 1A, 2 µg VEE VLP Vaccine Alone Venezuelan equine encephalitis VLP Vaccine candidate Vaccinations on Day 0, Day 28, and Day 140

Biological: Vaccinations on Day 0, Day 28, and Day 140

Group 2A 10 µg VEE Vaccine Alone

EXPERIMENTAL

Venezuelan equine encephalitis VLP Vaccine candidate Subgroup 2A, 10 µg VLP Vaccine Alone Vaccinations on Day 0, Day 28, and Day 140

Biological: Vaccinations on Day 0, Day 28, and Day 140

Group 3A 20 µg VEE Vaccine Alone

EXPERIMENTAL

Venezuelan equine encephalitis VLP Vaccine candidate Subgroup 3A, 20 µg VEE VLP Vaccine Alone Vaccinations on Day 0, Day 28, and Day 140

Biological: Vaccinations on Day 0, Day 28, and Day 140

Group 1B 2 µg VEE Vaccine and Adjuvant

EXPERIMENTAL

Venezuelan equine encephalitis VLP Vaccine candidate with Adjuvant Subgroup 1B, 2 µg VEE VLP Vaccine with Adjuvant (Adjuvant - Aluminum hydroxide, 5 mg/mL) Vaccinations on Day 0, Day 28, and Day 140

Biological: Vaccinations on Day 0, Day 28, and Day 140

Group 2B 10 µg VEE Vaccine with Adjuvant

EXPERIMENTAL

Venezuelan equine encephalitis VLP Vaccine candidate with Adjuvant Subgroup 2B, 10 µg VEE VLP Vaccine with Adjuvant (Adjuvant - Aluminum hydroxide, 5 mg/mL) Vaccinations on Day 0, Day 28, and Day 140

Biological: Vaccinations on Day 0, Day 28, and Day 140

Group 3B 20 µg VEE Vaccine with Adjuvant

EXPERIMENTAL

Venezuelan equine encephalitis VLP Vaccine candidate with Adjuvant Subgroup 3B, 20 µg VEE VLP Vaccine with Adjuvant (Adjuvant - Aluminum hydroxide, 5 mg/mL) Vaccinations on Day 0, Day 28, and Day 140

Biological: Vaccinations on Day 0, Day 28, and Day 140

Interventions

Vaccinations on Day 0, Day 28, and Day 140 BIOLOGICAL

The monovalent VEE VLP vaccine (the same VEE VLP study agent which comprises the VEE portion of the NIAID trivalent alphaviral VLP vaccine) will use the same vaccination regimen (Day 0, Week 4 \[Day 28\], and Week 20 \[Day 140\]) and the vaccine dosages (2 μg, 10 μg, and 20 μg)

Group 1A 2 µg VEE Vaccine Alone; Group 1B 2 µg VEE Vaccine and Adjuvant; Group 2A 10 µg VEE Vaccine Alone; Group 2B 10 µg VEE Vaccine with Adjuvant; Group 3A 20 µg VEE Vaccine Alone; Group 3B 20 µg VEE Vaccine with Adjuvant

Eligibility Criteria

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

You may qualify if:

• Male or female between the ages of 18 and 50.
• Understanding of the requirements of the study, provision of written informed consent, and agreement to abide by the study restrictions.
• In good general health (no chronic health condition) and an acceptable medical history, physical examination and screening laboratory studies within 28 days of enrollment on the study (specific laboratory requirements are listed below).
• Negative urine screen for drugs of abuse at screening.
• Body weight ≥ 49.8 kg and ≤ 110 kg. If body weight is over 110 kg, then body mass index (BMI) will be considered and must be \< 40 kg/m2. The National Institutes of Health National Heart, Lung, and Blood Institute BMI calculator will be used to make this determination (https://www.nhlbi.nih.gov/health/educational/lose\_wt/BMI/bmi-m.htm).
• Available for entire clinical study duration of 44 weeks.
• Individual agrees to not receive non-study vaccines during study unless urgent medical indication (i.e., tetanus booster, rabies vaccine).
• Females must be of non-childbearing potential or agree to use two types of an acceptable form of FDA-approved contraception through the duration of the study and must not be pregnant or lactating. If volunteers are sexually abstinent, they are not required to use additional forms of birth control. Non-childbearing potential is defined as being post-menopausal (absence of menses for 12 consecutive months not caused by drugs or hormones), status after bilateral tubal ligation for at least 1 year, status after bilateral oophorectomy, or status after hysterectomy. Examples of acceptable forms of birth control include but are not limited to barrier methods, Depo-Provera®, Norplant®, Nova Ring®, Ortho Evra® (birth control patch), and oral contraceptives. Absence of pregnancy in women of child-bearing potential (WOCBP) is indicated by a negative history of current pregnancy, a negative urine pregnancy test at screening, and a negative urine pregnancy test performed within 1 day before each administration of study vaccine.

You may not qualify if:

• Laboratory Studies:
• Any clinically significant hematology, chemistry, coagulation, serology, or urinalysis value on screening labs (some examples are listed below):
• Hemoglobin \<11.5 g/dL for women; \<12.0 g/dL for men
• White blood cell (WBC) Count \<3,000 or \>13,000/mm3
• Total lymphocyte count \<800 cell/ mm3
• Platelets \<125,000 or \>500,000/mm3
• Alanine aminotransferase (ALT) \>1.2 upper limits of normal
• Serum creatinine not greater than the upper limits of normal
• Prothrombin Time (PT) \>12.5 seconds
• International Normalized Ratio (INR) \>1.32
• Partial Thromboplastin Time (PTT) \>36.5 seconds
• Positive urine pregnancy test
• HBsAg positive, or serologic evidence of infection with Hepatitis C (HCV) or Human Immunodeficiency Virus (HIV)
• Subject has a history of any of the following:
• Active substance or alcohol abuse (within the previous 2 years as per the judgment of the investigator).

Sponsors & Collaborators

• SRI International: lead
• US Army Medical Research Institute of Infectious Diseases: collaborator

Study Sites (1)

SRI Biosciences Clinical Trials Unit

Plymouth, Michigan, 48170, United States

Location

Related Publications (3)

• Hoke CH Jr. History of U.S. military contributions to the study of viral encephalitis. Mil Med. 2005 Apr;170(4 Suppl):92-105. doi: 10.7205/milmed.170.4s.92.

  PMID: 15916288 BACKGROUND

• Tyler KL. Acute Viral Encephalitis. N Engl J Med. 2018 Aug 9;379(6):557-566. doi: 10.1056/NEJMra1708714. No abstract available.

  PMID: 30089069 BACKGROUND

• Paessler S, Weaver SC. Vaccines for Venezuelan equine encephalitis. Vaccine. 2009 Nov 5;27 Suppl 4:D80-5. doi: 10.1016/j.vaccine.2009.07.095.

  PMID: 19837294 BACKGROUND

MeSH Terms

Conditions

Encephalitis; Encephalitis, Viral; Infectious Encephalitis; Virus Diseases; Encephalomyelitis, Venezuelan Equine; Brain Diseases; Central Nervous System Diseases; Central Nervous System Viral Diseases; Alphavirus Infections; Togaviridae Infections; RNA Virus Infections; Central Nervous System Infections; Encephalomyelitis; Encephalomyelitis, Equine; Nervous System Diseases

Condition Hierarchy (Ancestors)

Neuroinflammatory Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Encephalitis, Arbovirus; Mosquito-Borne Diseases

Study Officials

• Sascha Goonewardena, MD

  SRI International

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects will be blinded to receiving the non-adjuvanted versus adjuvanted vaccines, but will not be blinded to the vaccine dosage. Vaccines will be brought into the subject rooms in a concealed container, and subjects will be asked to turn away from the dosing arm so that the SRI Clinical Trials' Unit (CTU) staff can prepare and administer the dose. Subjects may be unblinded if subject experiences a Serious Adverse Event (SAE) and upon notification to the data review team, called Protocol Safety Review Team (PSRT).
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To assess the safety and immunogenicity of a monovalent Venezuelan Equine Encephalitis (VEE) Virus-like Particle (VLP) Vaccine in healthy adults for protection against exposure to VEE virus (VEEV).

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: December 17, 2018
• Study Start: July 17, 2018
• Primary Completion: July 27, 2020
• Study Completion: April 1, 2021
• Last Updated: February 23, 2021

Record last verified: 2021-02

Locations

US (1)