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

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

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.

Study Overview

• Status: Completed
• Conditions: Chikungunya Virus
• Intervention / Treatment: Biological: Placebo; Biological: CHIKV VLP/adjuvant

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sufia Muhammad, MD; Phone Number: (346) 732-7331; Email: muhammads@ebsi.com
• Study Contact Backup: Name: Patrick Ajiboye, MD; Phone Number: (240) 841-1378; Email: ajiboyep@ebsi.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33173
      • Suncoast Research Associates, LLC
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • Saint Petersburg, Florida, United States, 33705
      • Global Clinical Research Professionals (GCP)
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • AMR Kansas City
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Texas
    • Houston, Texas, United States, 77065
      • DM Clinical Research CyFair
    • San Antonio, Texas, United States, 78249
      • BHFC Research
    • Tomball, Texas, United States, 77375
      • DM Clinical Research Tomball
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

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

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: Emergent BioSolutions; Catalyst Clinical Research, LLC

Publications and helpful links

General Publications

• Bennett SR, McCarty JM, Ramanathan R, Mendy J, Richardson JS, Smith J, Alexander J, Ledgerwood JE, de Lame PA, Royalty Tredo S, Warfield KL, Bedell L. Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial. Lancet Infect Dis. 2022 Sep;22(9):1343-1355. doi: 10.1016/S1473-3099(22)00226-2. Epub 2022 Jun 13.

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2022
• Primary Completion (Actual): June 19, 2023
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 27, 2022

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: vaccine; immunogenicity; chikungunya; virus like particle (VLP); PXVX0317
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Alphavirus Infections; Togaviridae Infections; Chikungunya Fever
• Other Study ID Numbers: EBSI-CV-317-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No