A Study to Assess the Safety and Immunogenicity of PXVX0317 Chikungunya Virus Virus-Like Particle Vaccine

Study Overview
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Brief Summary
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The objective of this study is to assess the safety and immunogenicity of PXVX0317 (Chikungunya Virus Virus-Like Particle Vaccine [CHIKV VLP], aluminum hydroxide adjuvanted).

Detailed Description
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Primary Objectives: To assess the induction of anti-CHIKV neutralizing antibody responses following a single adjuvanted dose of PXVX0317 (40 µg CHIKV VLP, alum-adjuvanted) as measured 21 days (Day 22) after vaccination. To assess the induction of anti-CHIKV neutralizing antibody responses following a single adjuvanted dose of PXVX0317 as measured 7 days (Day 8), 14 days (Day 15), and 56 days (Day 57) after vaccination. Secondary Objectives: 1. To assess safety of a single adjuvanted dose of PXVX0317 in healthy adults.

Official Title
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A Phase 2 Open-Label Study to Assess the Safety and Immunogenicity of PXVX0317 (Chikungunya Virus Virus-Like Particle Vaccine [CHIKV VLP], Aluminum Hydroxide Adjuvanted)

Conditions
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Chikungunya Virus

Intervention / Treatment
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* Biological: CHIKV VLP, adjuvanted


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to provide informed consent voluntarily signed by participant. Any gender, 18 to 45 years of age (inclusive). 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, anatomically sterile, or post-menopausal (defined as ≥12 months without menses) or (ii). Meeting all the following criteria: Negative urine pregnancy test at screening visit; and Negative urine pregnancy test immediately prior to dosing at Day 1; and using an acceptable method of contraception (if female of childbearing potential) for the duration of participation, such as: Hormonal contraceptives (e.g., implants, pills, patches) initiated ≥ 30 days prior to dosing or; Intrauterine device (IUD) inserted ≥30 days prior to dosing or; double barrier type of birth control (male condom with female diaphragm, male condom with cervical cap). 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 investigational product (IP). History of known congenital or acquired immunodeficiency that could impact response to vaccination (e.g., leukemia, lymphoma, generalized malignancy, functional or anatomic asplenia, alcoholic cirrhosis). Prior or anticipated receipt of immunomodulatory or immunosuppressive therapy from six months prior to screening through Day 64. Receipt or anticipated receipt of blood or blood-derived products from 90 days prior to screening through Day 64. 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, respiratory, rheumatologic, or other chronic disease, in the opinion of the Investigator. This may include chronic illness requiring hospitalization in the last one month 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 screening through Day 64. Prior receipt of an investigational CHIKV vaccine/product. Detectable baseline anti-CHIKV IgG antibody as determined by ELISA. Any other condition that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study, creates an unacceptable risk to the participant, or may interfere with the conduct of the study or validity of the data. Restricted venous access that would prevent the collection of plasma and serum necessary for participation. Weight <110 pounds.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Open Label Safety and Immunogenicity
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PXVX0317 (CHIKV VLP, alum-adjuvanted) vaccine<br>All study participants will receive the same Investigational Product (40 µg CHIKV VLP, alum-adjuvanted according to the same single dose schedule on Day 1). | Biological: CHIKV VLP, adjuvanted<br>* Adjuvanted formulation includes aluminum hydroxide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CHIKV SNA (Serum Neutralizing Antibody) Seroresponse Rate at Day 22 | CHIKV SNA Seroresponse Rate (Titer >=40) and Associated 95% Confidence Interval (CI) at Day 22 | 21 days post vaccination | 
| CHIKV SNA GMT (Geometric Mean Titer) at Day 22 | CHIKV SNA GMT and Associated 95% CI at Day 22 | 21 days post vaccination | 
| CHIKV SNA Seroresponse Rates at Days 8, 15, and 57 | CHIKV SNA Seroresponse Rates with Associated 95% CIs at Days 8, 15, and 57 | 56 days post vaccination | 
| CHIKV SNA GMTs at Days 8, 15, and 57 | CHIKV SNA GMTs with Associated 95% CIs at Days 8, 15, and 57 | 56 days post vaccination | 
| CHIKV ELISA (Enzyme-Linked Immunosorbent Assay) IgG GMTs at Days 8, 15, 22, and 57 | CHIKV ELISA IgG GMTs with Associated 95% CIs at Days 8, 15, 22, and 57 | 56 days post vaccination | 
| CHIKV ELISA IgM GMTs at Days 8, 15, 22, and 57 | CHIKV ELISA IgM GMTs with Associated 95% CIs at Days 8, 15, 22, and 57 | 56 days post vaccination | 
| Geometric Mean Fold Increase (GMFI) in CHIK SNA Titers at Days 8, 15, 22, and 57 | GMFI in CHIK SNA Titers from Day 1 to Days 8, 15, 22, and 57 | 56 days post vaccination | 
| GMFI in CHIK ELISA IgG at Days 8, 15, 22, and 57 | GMFI in CHIK ELISA IgG from Day 1 to Days 8, 15, 22, and 57 | 56 days post vaccination | 
| GMFI in CHIK ELISA IgM at Days 8, 15, 22, and 57 | GMFI in CHIK ELISA IgM from Day 1 to Days 8, 15, 22, and 57 | 56 days post vaccination | 
| Number and Percentage of Participants With a CHIKV SNA Titer at or Above Threshold Values at Days 8, 15, 22, and 57 | Number and Percentage of Participants with a CHIKV SNA Titer ≥15, 40, 60, 80, 100, 160, 640, and 4-fold Rise Over Baseline Thresholds at Days 8, 15, 22, and 57 | 56 days post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Solicited Adverse Events (AE) Through Day 8 | Incidence of Solicited AEs Through Day 8 | 7 days post vaccination | 
| Incidence of Unsolicited AEs Through Day 29 | Incidence of Unsolicited AEs Through Day 29 | 28 days post vaccination | 
| Incidence of Adverse Events of Special Interest (AESI) Through Day 183 | Incidence of AESIs Through Day 183 | 182 days post vaccination | 
| Incidence of Serious Adverse Events (SAEs) Through Day 183 | Incidence of SAEs Through Day 183 | 182 days post vaccination |