A Phase 3 Trial of the VLP-Based Chikungunya Vaccine PXVX0317 (CHIKV VLP Vaccine)

A Phase 3 Safety, Immunogenicity, and Lot-Consistency Trial of the VLP-Based Chikungunya Vaccine PXVX0317 in Healthy Adults and Adolescents

The goal of this multi-center, randomized, double blind, placebo controlled study is to evaluate the safety and immunogenicity of PXVX0317 (CHIKV VLP vaccine) in healthy adult and adolescent subjects.

Coprimary Objectives:

1. To evaluate the safety of PXVX0317 (CHIKV VLP vaccine) in healthy adult and adolescent participants 12 to <65 years of age.
2. To compare the anti-CHIKV serum neutralizing antibody (SNA) response to PXVX0317 (CHIKV VLP vaccine) and placebo at Day 22, as measured by geometric mean titer (GMT) and clinically relevant difference in seroresponse rate (PXVX0317 minus placebo).
3. To demonstrate the consistency of the anti-CHIKV SNA response across three consecutively manufactured lots of PXVX0317 (CHIKV VLP vaccine) at Day 22 as measured by GMT.

Secondary Objectives:

1. To compare the anti-CHIKV SNA response to PXVX0317 (CHIKV VLP vaccine) and placebo at Day 15, Day 183, and Day 8 as measured by GMT and seroresponse rate.
2. To compare the GMT fold increase in anti-CHIKV SNA response and number and percentage of participants with an anti-CHIKV SNA titer ≥15 and 4-fold rise over baseline, both at Day 8, 15, 22, and 183.

Inclusion Criteria:

• Able and willing to provide informed consent (and assent, as applicable) voluntarily signed by participant (and guardian, as applicable).
• Males or females, 12 to <65 years of age.
• Generally healthy, in the opinion of the investigator, based on medical history, physical examination, and screening laboratory assessments.
• Women who are either: (i) Not of childbearing potential (CBP): pre-menarche, surgically sterile (at least six weeks post bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or postmenopausal (defined as a history of ≥12 consecutive months without menses prior to randomization in the absence of other pathologic or physiologic causes, following cessation of exogenous sex-hormonal treatment) or (ii) Meeting all the below criteria: Negative serum pregnancy test at screening visit, Negative urine pregnancy test immediately prior to dosing at Day 1, Using an acceptable method of contraception (if women of CBP) for the duration of participation, such as hormonal contraceptives (eg, implants, pills, patches) initiated ≥30 days prior to dosing, intrauterine device (IUD) inserted ≥30 days prior to dosing, double barrier type of birth control (male condom with female diaphragm, male condom with cervical cap), Abstinence is acceptable only for adolescents (12 to <18 years old) who are not sexually active.

Exclusion Criteria:

• Currently pregnant, breastfeeding, or planning to become pregnant during the study.
• Body Mass Index (BMI) ≥35 kg/m2.
• Positive laboratory evidence of current infection with human immunodeficiency virus (HIV-1, HIV-2), hepatitis C virus (HCV) or hepatitis B virus (HBV).
• History of severe allergic reaction or anaphylaxis to any component of the vaccine.
• History of any known congenital or acquired immunodeficiency that could impact response to vaccination (eg, leukemia, lymphoma, generalized malignancy, functional or anatomic asplenia, alcoholic cirrhosis).
• Prior receipt or anticipated use of systemic immunomodulatory or immunosuppressive medications from six months prior to screening through Day 22. Note: For systemic corticosteroids, use at a dose or equivalent dose of 20 mg of prednisone daily for 14 days or more within three months of screening through Day 22 is exclusionary. The use of inhaled, intranasal, topical, ocular, or intraocular steroids is allowed.
• Receipt or anticipated receipt of blood or blood-derived products from 90 days prior to screening through Day 22.
• Acute disease within the last 14 days (participants with an acute mild febrile illness can be considered for a deferral of vaccination two weeks after the illness has resolved and treatment has been completed).
• Clinically significant cardiac, pulmonary, rheumatologic, or other chronic disease, in the opinion of the investigator. This may include chronic illness requiring hospitalization in the last 30 days prior to screening.
• Enrollment in an interventional study and/or receipt of another investigational product from 30 days prior to screening through the duration of study participation.
• Receipt or anticipated receipt of any vaccine from 30 days prior to Day 1 through Day 22.
• Evidence of substance abuse that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study.
• Prior receipt of an investigational CHIKV vaccine/product.
• Any other medical condition that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study.