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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Encephalitis
- Sponsor
- SRI International
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Number of subjects reporting serious adverse events
- Last Updated
- 5 years ago
Overview
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
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female between the ages of 18 and
- •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/m
- •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.
Exclusion Criteria
- •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
Outcomes
Primary Outcomes
Number of subjects reporting serious adverse events
Time Frame: Through the study duration of 44 weeks
• 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.
Number of subjects reporting treatment-emergent adverse events
Time Frame: Through the study duration of 44 weeks
• 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.
Number of subjects reporting solicited systemic adverse events
Time Frame: Through the study duration of 44 weeks
• 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.
Number of subjects with abnormal complete blood counts
Time Frame: Through the study duration of 44 weeks
• 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.
Number of subjects reporting solicited local adverse events
Time Frame: Through the study duration of 44 weeks
• 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.
Number of subjects with abnormalities in serum creatinine concentrations
Time Frame: Through the study duration of 44 weeks
• 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.
Number of subjects with abnormal serum alanine aminotransferase concentrations
Time Frame: Through the study duration of 44 weeks
• 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.
Secondary Outcomes
- The magnitude of neutralizing antibodies as assessed by a plaque reduction neutralization test (PRNT50)(Through the study duration of 44 weeks)
- 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)