Safety and Immunogenicity of CHIKV VLP Vaccine PXVX0317 in Adults ≥65 Years

Study Overview
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Brief Summary
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The purpose of this phase 3, randomized, double-blind, placebo-controlled study is to evaluate the safety and immunogenicity to PXVX0317 in adults ≥65 years of age.

Detailed Description
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Co-primary Objectives: To compare the anti-CHIKV serum neutralizing antibody (SNA) response to PXVX0317 and placebo at Day 22, as measured by geometric mean titer (GMT) and clinically relevant difference in seroresponse rate (PXVX0317 minus placebo) in adults ≥65 years of age. To evaluate the safety of PXVX0317 in adults ≥65 years of age Secondary Objectives: To compare the anti-CHIKV SNA response to PXVX0317 and placebo at Day 15 and Day 183, as measured by GMT and seroresponse rate. To compare the anti-CHIKV SNA response to PXVX0317 and placebo in participants ≥65 to <75 and ≥75 years of age as measured by GMT and seroresponse rate.

Official Title
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A Phase 3 Safety and Immunogenicity Trial of the VLP-Based Chikungunya Virus Vaccine PXVX0317 in Adults ≥65 Years of Age

Conditions
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Chikungunya Virus

Intervention / Treatment
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* Biological: CHIKV VLP/adjuvant
* Biological: Placebo


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. Must verbalize understanding of the general procedures of, and reason for the study. Males or females, ≥65 years of age. Able to complete all scheduled visits and comply with all study procedures. Women who are not of childbearing potential (CBP): 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 post menopausal sex-hormonal treatment). Participants must be in stable health in the opinion of the investigator for at least 30 days prior to screening (eg, no hospital admission for acute illness in the last 30 days prior to screening). Exclusion Criteria: Participation or planned participation in an investigational clinical trial (eg, vaccine, drug, medical device, or medical procedure) within 30 days of Day 1 and for the duration of the study. Note: Participation in an observational trial or follow-up phase of a trial may be allowed; however, these instances should be discussed with the sponsor's medical monitor (MM) prior to enrollment. Prior receipt of any CHIKV vaccine. Positive laboratory evidence of current infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV). Body mass index (BMI) ≥35 kg/m^2 History of any known or suspected allergy or history of anaphylaxis to any component of the investigational product (IP). History of any known congenital or acquired immunodeficiency or immunosuppressive condition that could impact response to vaccination (eg, leukemia, lymphoma, malignancy, functional or anatomic asplenia, alcoholic cirrhosis). Note: History of basal cell and squamous cell carcinoma of the skin or carcinoma in situ of the cervix considered cured would not be exclusionary. History of a malignancy considered cured from over five years from the date of screening with minimal risk of recurrence is not exclusionary. Prior or anticipated use of systemic immunomodulatory or immunosuppressive medications from six months prior to screening through Day 22. Note: Systemic corticosteroid use at a dose or equivalent dose of 20 mg of prednisone daily for 14 days or more within 90 days of screening through Day 22 is exclusionary. The use of inhaled, intranasal, topical, or ocular steroids is allowed. Bleeding disorder or receipt of anticoagulants in the 21 days prior to screening, contraindicating intramuscular (IM) vaccination, as judged by the investigator. Moderate or severe acute illness with or without fever (oral temperature ≥100.4°F or 38.0°C). Receipt or anticipated receipt of immunoglobulin from 180 days prior to screening through Day 22. Medical condition (such as dementia) that, in the opinion of the investigator, could adversely impact the participant's participation in or conduct of the study. Evidence of substance abuse that, in the opinion of the investigator, could adversely impact the participant's participation in or conduct of the study. Identified as an investigator or employee of an Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse) of the investigator or employee with direct involvement in the proposed study. Receipt or anticipated receipt of any vaccine from 30 days prior to Day 1 through Day 22. Receipt or anticipated receipt of blood or blood-derived products from 90 days prior to screening through Day 22. Any planned elective surgery that may interfere with study participation or conduct. Any other medical condition that, in the opinion of the investigator, could adversely impact the participant's participation in or conduct of the study.

Ages Eligible for Study
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Minimum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized in a 1:1 ratio to receive PXVX0317 or placebo within each age stratum. Participants will be stratified in two age subgroups (≥65 to <75 and ≥75 years of age). This study will be conducted in the US, using up to 10 sites.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - PXVX0317<br> | Biological: CHIKV VLP/adjuvant<br>* PXVX0317 vaccine is comprised of chikungunya virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%<br>|
| Placebo Comparator: Group 2 - Placebo<br> | Biological: Placebo<br>* Placebo is comprised of formulation buffer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-CHIKV SNA seroresponse rates at Day 22 in baseline seronegative participants | Difference in anti-CHIKV SNA seroresponse rate (PXVX0317 minus placebo) and associated 95% confidence interval (CI) at Day 22. | 21 days post vaccination | 
| Anti-CHIKV SNA GMTs at Day 22 | Anti-CHIKV SNA GMT and associated 95% CIs at Day 22 for PXVX0317 and placebo. | 21 days post vaccination | 
| Incidence of solicited adverse events (AE) | Incidence of solicited AEs through Day 8 | 7 days post vaccination | 
| Incidence of unsolicited AEs | Incidence of unsolicited AEs through Day 29 | 28 days post vaccination | 
| Incidence of Serious Adverse Events (SAE) | Incidence of SAEs through Day 183 | 182 days post vaccination | 
| Incidence of Medically Attended Adverse Events (MAAE) | Incidence of MAAEs through Day 183 | 182 days post vaccination | 
| Incidence of Adverse Events of Special Interest (AESI) | Incidence of AESI through Day 183 | 182 days post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-CHIKV SNA seroresponse rates at Days 15 and 183 | Difference in anti-CHIKV SNA seroresponse rate (PXVX0317 minus placebo) with associated 95% CIs at Day 15 and Day 183. | 182 days post vaccination | 
| Anti-CHIKV SNA GMTs at Days 15 and 183 | Anti-CHIKV SNA GMTs by study arm with associated 95% CIs at Day 15 and Day 183. | 182 days post vaccination | 
| Anti-CHIKV SNA Geometric Mean Fold Increase (GMFI) | Geometric mean fold increase (GMFI) from Day 1 to subsequent collection time points. | 182 days post vaccination | 
| Subjects with anti-CHIKV SNA titer ≥15 and 4-fold rise over baseline | Number and percentage of participants with an anti-CHIKV SNA titer ≥15 and 4-fold rise over baseline. | 182 days post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chikungunya, virus like particle (VLP), PXVX0317, vaccine, immunogenicity