Venezuelan Equine Encephalitis Monovalent Virus-Like Particle Vaccine

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

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).

Inclusion Criteria:

1. Male or female between the ages of 18 and 50.
2. Understanding of the requirements of the study, provision of written informed consent, and agreement to abide by the study restrictions.
3. 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).
4. Negative urine screen for drugs of abuse at screening.
5. 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).
6. Available for entire clinical study duration of 44 weeks.
7. Individual agrees to not receive non-study vaccines during study unless urgent medical indication (i.e., tetanus booster, rabies vaccine).
8. 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
• 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:

1. Active substance or alcohol abuse (within the previous 2 years as per the judgment of the investigator).
2. 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.
3. 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.
4. Recipient of an organ transplant (solid or hematopoietic)

Subject has received any of the following substances:

1. Administration of blood products within 16 weeks and immunoglobulin products within 8 weeks preceding enrollment or planned vaccine administration during the study period.
2. Prior alphaviral vaccines (VEE, Eastern equine encephalitis (EEE), western equine encephalitis (WEE), or chikungunya) or VEE subunit vaccinations.
3. Investigational vaccine in the previous 6 months before receiving the initial vaccine dose of this study (or plans to receive during the study).
4. 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.
5. Marketed attenuated vaccines (i.e., measles, rubella) within 28 days after or within 28 days before any study vaccine doses.
6. Investigational drug within 30 days of enrollment.
7. Current tuberculosis prophylaxis or therapy or current HIV prophylaxis.
8. 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:

1. History of a serious reaction to vaccines that preclude receipt of study vaccine as determined by the investigator
2. Allergy to vaccine, vaccine components or aluminum compounds.
3. History of serious allergic reactions or anaphylaxis (e.g., vaccines, insect stings, food, drugs, or other biological products).
4. 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.
5. 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).
6. 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.
7. Blood donation within 60 days of enrollment. -