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EncephalitisPhase 1VEEVNCT03776994

Venezuelan Equine Encephalitis Monovalent Virus-Like Particle Vaccine

A Phase 1 study testing Vaccinations on Day 0, Day 28, and Day 140 in people with Encephalitis and Encephalitis, Viral, run by SRI International at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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)… Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
What is being tested?
Vaccinations on Day 0, Day 28, and Day 140
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteUnited States
Study dates
17 Jul 2018to Apr 2021
Phase
Phase 1
Are there results?
None posted in the registry

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

  • 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.

Who cannot join

  • 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
Show all 35Show fewer
  • 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).
  • History of any psychiatric condition (e.g., past or present psychoses) that could jeopardize the subject's safety or the subject's ability to comply with the protocol.
  • History of a significant medical condition that could jeopardize the subject's safety or the subject's ability to comply with the protocol. Exclusionary medical conditions include (but not limited to) significant endocrine disorders (e.g., diabetes mellitus, type I or II), gastrointestinal disorders (e.g., active peptic ulcer disease, hepatitis), hematological disease (e.g., thrombocytopenia, diathesis, coagulopathy, asplenia or functional asplenia), renal disease (e.g., acute or chronic), neurological disease (e.g., seizure disorder other than a history of febrile seizures, or seizures secondary to alcohol withdrawal >3years ago, or seizures that have not required treatment within the last 3 years, history of Guillain-Barré syndrome), pulmonary disease (e.g., including asthma or chronic obstructive pulmonary disease (COPD) that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years and that is expected to require the use of oral or intravenous corticosteroids), autoimmune disorders, active malignancy (or previous malignancy and at risk for disease recurrence or malignancy for which there is no reasonable assurance of sustained cure, or likely to recur during the period of the study), cardiac disorders (e.g., congestive heart failure), and other significant conditions as deemed by the investigator to be an exclusion from the study.
  • Recipient of an organ transplant (solid or hematopoietic)
  • Subject has received any of the following substances:
  • Administration of blood products within 16 weeks and immunoglobulin products within 8 weeks preceding enrollment or planned vaccine administration during the study period.
  • Prior alphaviral vaccines (VEE, Eastern equine encephalitis (EEE), western equine encephalitis (WEE), or chikungunya) or VEE subunit vaccinations.
  • Investigational vaccine in the previous 6 months before receiving the initial vaccine dose of this study (or plans to receive during the study).
  • Marketed medically indicated subunit or inactivated vaccines (i.e., influenza, pneumococcal vaccines) or allergy antigen injections) within 28 days after or within 28 days before any study vaccine doses.
  • Marketed attenuated vaccines (i.e., measles, rubella) within 28 days after or within 28 days before any study vaccine doses.
  • Investigational drug within 30 days of enrollment.
  • Current tuberculosis prophylaxis or therapy or current HIV prophylaxis.
  • Systemic immunosuppressive or cytotoxic medications within 12 weeks prior to enrollment [does not exclude individuals who received a short course of corticosteroids (<10 days duration or a single injection) for a self-limited condition greater than at least 2 weeks prior to enrollment].
  • Subject has a history of the following:
  • History of a serious reaction to vaccines that preclude receipt of study vaccine as determined by the investigator
  • Allergy to vaccine, vaccine components or aluminum compounds.
  • History of serious allergic reactions or anaphylaxis (e.g., vaccines, insect stings, food, drugs, or other biological products).
  • Febrile illness or significant infection at the time of vaccination (may be rescheduled for enrollment). Must be afebrile for 72 hours prior to receiving vaccine as reported by the subject to the SRI Clinical Trials' Unit (CTU) staff.
  • A confirmed or suspected history of VEEV or other alphaviral infection (i.e., eastern equine encephalitis (EEE), western equine encephalitis (WEE), chikungunya) or other encephalitis infection or a history of employment in a laboratory that worked with VEE virus (VEEV).
  • Bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or history of significant bruising or bleeding difficulties with IM injections or blood draws.
  • Blood donation within 60 days of enrollment. -

Trial locations and contacts

1 site in 1 country.

United States1 site

  • SRI Biosciences Clinical Trials Unit

    Plymouth, Michigan, 48170

Other trials in United States

About this study

Official title: A Phase 1 Dose Escalation Study to Assess the Safety and Immunogenicity of a Monovalent Virus-Like Particle (VLP) Venezuelan Equine Encephalitis Vaccine in Healthy Adults

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

Read the detailed description

This Phase 1 dose escalation study will evaluate safety and immunogenicity of both non-adjuvanted and adjuvanted VEE VLP vaccine in three dose groups (2 μg, 10 μg, and 20 μg) given as a 2-dose primary series IM injection (Days 0 and Week 4 [Day 28]) followed by a booster dose injection (Week 20 [Day 140]). Each group will consist of 30 subjects, for a total of 90 study subjects. Each group of 30 subjects will be randomized to receive either non-adjuvanted vaccine (Subgroup A; n=15) or adjuvanted vaccine (Subgroup B; n=15). Subjects will be blinded to receiving the non-adjuvanted versus adjuvanted vaccine, but will not be blinded to the vaccine dosage. Enrollment will utilize a sentinel dose design, with only one subject receiving a vaccine dose the initial day, 2 subjects the following day, and 3 subjects the subsequent day, before proceeding with further enrollments in that group. Subjects in each Group will be randomized to receive the vaccine dose either without adjuvant (Subgroup A) or with adjuvant (Subgroup B).

Being tested
Vaccinations on Day 0, Day 28, and Day 140
Keywords
Venezuelan Equine Encephalitis, vaccine, Intramuscular, Phase 1 clinical study
Medical subject headings
Encephalitis, Encephalitis, Viral, Infectious Encephalitis, Virus Diseases, Encephalomyelitis, Venezuelan Equine, Brain Diseases, Central Nervous System Diseases, Central Nervous System Viral Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    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)

Study groups in NCT03776994
Study groupRoleWhat they receive
Group 1A 2 µg VEE Vaccine AloneExperimentalSubgroup 1A, 2 µg VEE VLP Vaccine Alone Venezuelan equine encephalitis VLP Vaccine candidate Vaccinations on Day 0, Day 28, and Day 140
Receives: Biological: Vaccinations on Day 0, Day 28, and Day 140
Group 2A 10 µg VEE Vaccine AloneExperimentalVenezuelan equine encephalitis VLP Vaccine candidate Subgroup 2A, 10 µg VLP Vaccine Alone Vaccinations on Day 0, Day 28, and Day 140
Receives: Biological: Vaccinations on Day 0, Day 28, and Day 140
Group 3A 20 µg VEE Vaccine AloneExperimentalVenezuelan equine encephalitis VLP Vaccine candidate Subgroup 3A, 20 µg VEE VLP Vaccine Alone Vaccinations on Day 0, Day 28, and Day 140
Receives: Biological: Vaccinations on Day 0, Day 28, and Day 140
Group 1B 2 µg VEE Vaccine and AdjuvantExperimentalVenezuelan 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
Receives: Biological: Vaccinations on Day 0, Day 28, and Day 140
Group 2B 10 µg VEE Vaccine with AdjuvantExperimentalVenezuelan 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
Receives: Biological: Vaccinations on Day 0, Day 28, and Day 140
Group 3B 20 µg VEE Vaccine with AdjuvantExperimentalVenezuelan 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
Receives: Biological: Vaccinations on Day 0, Day 28, and Day 140

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Through the study duration of 44 weeks

  2. 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.

    Measured: Through the study duration of 44 weeks

  3. 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.

    Measured: Through the study duration of 44 weeks

  4. 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.

    Measured: Through the study duration of 44 weeks

  5. 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.

    Measured: Through the study duration of 44 weeks

  6. 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.

    Measured: Through the study duration of 44 weeks

  7. 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.

    Measured: Through the study duration of 44 weeks

Secondary outcomes (3)

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

    • The number of subjects with detectable titers of neutralization antibodies will be measured with the plaque reduction neutralization test (PRNT50) at four weeks after the second injection (Week 8), four weeks after the third injection (Week 24) and at the end of the study (Week 44). The titers of the anti-VEEV neutralizing antibodies will be expressed as a geometric mean titer for the three vaccinations within each of the six arms of the study

    Measured: Through the study duration of 44 weeks

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

    • The duration of detectable titers of neutralization antibodies in subjects will be measured with the plaque reduction neutralization test (PRNT50) at four weeks after the second injection (Week 8), four weeks after the third injection (Week 24) and at the end of the study (Week 44, Day 308). The titers of the anti-VEEV neutralizing antibodies will be expressed as a geometric mean titer for the three vaccinations within each of the six arms of the study

    Measured: Through the study duration of 44 weeks

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

    • The magnitude of detectable titers of neutralization antibodies in subjects will be measured with the plaque reduction neutralization test (PRNT50) at four weeks after the second injection (Week 8), four weeks after the third injection (Week 24) and at the end of the study (Week 44, Day 308). The titers of the anti-VEEV neutralizing antibodies will be expressed as a geometric mean titer for the three vaccinations within each of the six arms of the study

    Measured: Through the study duration of 44 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2018
  2. Study start17 Jul 2018
  3. Primary completion27 Jul 2020
  4. Study completionApr 2021 (estimated)

Resources

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
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).
Masking
Single blind
Who is masked
Participant
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03776994
Sponsor's protocol ID
SRI-VEEV-01
Acronym
VEEV
Status last verified
Feb 2021
First submitted
7 Nov 2018
Last updated
23 Feb 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 15916288

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

    PubMed 30089069

  • 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.

    PubMed 19837294

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vaccinations on Day 0, Day 28, and Day 140 in people with Encephalitis and Encephalitis, Viral, run by SRI International 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 8 inclusion and 35 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: status not confirmed, as of the sponsor's last update on 23 Feb 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?

Results are not available in the source record.

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 solicited local adverse events (time frame: Through the study duration of 44 weeks). The study lists 7 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 NCT03776994, 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 23 Feb 2021.

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