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.

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3258
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
      • Optimal Research, LLC
    • Mobile, Alabama, United States, 36608
      • Alliance for Multispecialty Research - Mobile
  • Arizona
    • Tempe, Arizona, United States, 85281
      • Alliance for Multispecialty Research, LLC
  • California
    • Banning, California, United States, 92220
      • Velocity Clinical Research, Banning
    • San Diego, California, United States, 92108
      • Optimal Research, LLC
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Lynn Institute of the Rockies
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Lake Mary, Florida, United States, 32746
      • Accel Research Sites-DeLand Clinical Research Unit
    • Melbourne, Florida, United States, 32934
      • Optimal Research, LLC
    • Miami, Florida, United States, 33173
      • Suncoast Research Associates, LLC
    • Pinellas Park, Florida, United States, 33781
      • Synexus Clinical Research US, Inc.
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Velocity Clinical Research, Boise
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Synexus Clinical Research US, Inc.
    • Peoria, Illinois, United States, 61614
      • Optimal Research LLC
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clintrials
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty Research, LLC
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research - Wichita East
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Alliance for Multispecialty Research, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Alliance for Multispecialty Research, LLC
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Optimal Research, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty Research - Kansas City
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
    • Saint Louis, Missouri, United States, 63141
      • Synexus Clinical Research US, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Wr-Crcn, Llc
    • Las Vegas, Nevada, United States, 89119
      • Alliance for Multispecialty Research, LLC.
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center - The Gamble Vaccine Research Center
    • Cleveland, Ohio, United States, 44122
      • Velocity Clinical Rsearch, Inc.
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc.
  • Oklahoma
    • Norman, Oklahoma, United States, 73072
      • Lynn Institute of Norman
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Oregon
    • Medford, Oregon, United States, 97504
      • Velocity Clinical Research, Medford
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research-Providence
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Synexus Clinical Research US, Inc.
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research, LLC
  • Texas
    • Cedar Park, Texas, United States, 78613
      • Velocity Clinical Research, Austin
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development, Inc.
    • Plano, Texas, United States, 75093
      • Research Your Health
    • San Antonio, Texas, United States, 78249
      • BFHC Research
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Alliance for Multispecialty Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 64 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 4; Group 4 - Placebo	Biological: Placebo; Placebo is comprised of formulation buffer
Experimental: Group 1; Group 1 - PXVX0317 lot A (Lot 104)	Biological: CHIKV VLP/adjuvant; CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%
Experimental: Group 2; Group 2 - PXVX0317 lot B (Lot 105)	Biological: CHIKV VLP/adjuvant; CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%
Experimental: Group 3; Group 3 - PXVX0317 lot C (Lot 106)	Biological: CHIKV VLP/adjuvant; CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide adjuvant 2%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Solicited Adverse Events (AE)	Incidence of solicited AEs through Day 8 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).	7 days post-vaccination
Incidence of Unsolicited AEs	Incidence of unsolicited AEs through Day 29 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).	28 days post-vaccination
Incidence of Adverse Events of Special Interest (AESI)	Incidence of AESIs, through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).	182 days post-vaccination
Incidence of Medically Attended Adverse Event (MAAE)	Incidence of MAAEs through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).	182 days post-vaccination
Incidence of Serious Adverse Event (SAE)	Incidence of SAEs through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).	182 days post-vaccination
Anti-CHIKV Serum Neutralizing Antibody (SNA) Seroresponse Rates at Day 22	Anti-CHIKV SNA seroresponse rates for PXVX0317 (CHIKV VLP vaccine) and placebo, difference (PXVX0317 minus placebo), and associated 95% confidence interval (CI) at Day 22 for the immunogenicity evaluable population (IEP), all age strata combined.	21 days post-vaccination
Anti-CHIKV Serum Neutralizing Antibody (SNA) Seroresponse Rates at Day 22 (Data Reported Per Arm)	Anti-CHIKV SNA seroresponse rates and associated 95% confidence interval for PXVX0317 (CHIKV VLP vaccine) and placebo at Day 22 for the immunogenicity evaluable population (IEP), all age strata combined.	21 days post-vaccination
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22	Anti-CHIKV SNA GMTs and associated 95% CIs at Day 22 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined.	21 days post-vaccination
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (Data Reported Per Arm - All Age Strata)	Anti-CHIKV SNA GMTs and associated 95% CIs at Day 22 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined.	21 days post-vaccination
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (for Lot Comparison)	Anti-CHIKV SNA GMTs and associated 95% CIs between all three pairs of PXVX0317 (CHIKV VLP vaccine) lots (104:105, 104:106, 105:106) in adults 18 to <46 years of age in the IEP at Day 22. Placebo group 4 is not relevant for this lot-to-lot consistency analysis. Reported GMT estimates and 95% CIs are derived from an ANOVA model that includes site and product lot as fixed effects assuming normality of log titers.	21 days post-vaccination
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (Data Reported Per Arm - Adults 18 to <46)	Anti-CHIKV SNA GMTs and associated 95% CIs for PXVX0317 (CHIKV VLP vaccine) and placebo in adults 18 to <46 years of age in the IEP at Day 22.	21 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-CHIKV SNA Seroresponse Rates at Days 15, 183, and 8	Anti-CHIKV SNA seroresponse rates for PXVX0317 (CHIKV VLP vaccine) and placebo, difference (PXVX0317 minus placebo), and associated 95% CIs at Day 15, Day 183, and Day 8, in that order, for the IEP, all age strata combined. Number analyzed is number of participants with a sample result available at the indicated visit.	Day 15, 183, and 8 (14, 182, and 7 days post-vaccination, respectively)
Anti-CHIKV SNA Seroresponse Rates at Days 15, 183, and 8 (Data Reported Per Arm)	Anti-CHIKV SNA seroresponse rates and associated 95% CIs for PXVX0317 (CHIKV VLP vaccine) and placebo at Day 15, Day 183, and Day 8, in that order, for the IEP, all age strata combined. Number analyzed is number of participants with a sample result available at the indicated visit.	Day 15, 183, and 8 (14, 182, and 7 days post-vaccination, respectively)
Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183	Anti-CHIKV SNA GMTs with associated 95% CIs at Day 8, Day 15, and Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined. Number analyzed is number of participants with a sample result available at the indicated visit.	Day 8, 15, and 183 (7, 14, and 182 days post-vaccination, respectively)
Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183 (Data Reported Per Arm)	Anti-CHIKV SNA GMTs with associated 95% CIs at Day 8, Day 15, and Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined. Number analyzed is number of participants with a sample result available at the indicated visit	Day 8, 15, and 183 (7, 14, and 182 days post-vaccination, respectively)
Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titers From Day 1 to Days 8, 15, 22, and 183	Geometric mean fold increase (GMFI) in anti-CHIKV SNA titers from Day 1 to Day 8, Day 15, Day 22, and Day 183 for the IEP for all age strata combined. Fold rise in geometric mean titer is the ratio of the post-baseline value to the baseline value (e.g. number of 2 represents a post-baseline doubling of geometric mean titer). Number analyzed is number of participants with a sample result available at both Day 1 and the indicated visit.	Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively)
Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titers From Day 1 to Days 8, 15, 22, and 183 (Data Reported Per Arm)	Geometric mean fold increase (GMFI) in anti-CHIKV SNA titers from Day 1 to Day 8, Day 15, Day 22, and Day 183 for the IEP for all age strata combined. Fold rise in geometric mean titer is the ratio of the post-baseline value to the baseline value (e.g. number of 2 represents a post-baseline doubling of geometric mean titer). Number analyzed is number of participants with a sample result available at both Day 1 and the indicated visit.	Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively)
Number and Percentage of Participants With Anti-CHIKV SNA Titer ≥15 and 4-fold Rise Over Baseline at Days 8, 15, 22, and 183	Number and percentage of participants with anti-CHIKV SNA titers ≥15 and 4-fold rise over baseline at Day 8, Day 15, Day 22, and Day 183 for the IEP for all age strata combined. Number analyzed is number of participants with a sample result available at the indicated visit.	Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively)
Number and Percentage of Participants With Anti-CHIKV SNA Titer ≥15 and 4-fold Rise Over Baseline at Days 8, 15, 22, and 183 (Data Reported Per Arm)	Number and percentage of participants with anti-CHIKV SNA titers ≥15 and 4-fold rise over baseline at Day 8, Day 15, Day 22, and Day 183 for the IEP for all age strata combined. Number analyzed is number of participants with a sample result available at the indicated visit.	Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively)

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: Emergent BioSolutions
• Investigators: Study Director: Patrick Ajiboye, MD, Bavarian Nordic

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): September 29, 2021
• Primary Completion (Actual): April 3, 2023
• Study Completion (Actual): April 3, 2023

Study Registration Dates

• First Submitted: September 28, 2021
• First Submitted That Met QC Criteria: September 28, 2021
• First Posted (Actual): October 8, 2021

Study Record Updates

• Last Update Posted (Actual): August 30, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: vaccine; immunogenicity; CHIKV; Chikungunya; PXVX0317; VLP
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Alphavirus Infections; Togaviridae Infections; Mosquito-Borne Diseases; Chikungunya Fever
• Other Study ID Numbers: EBSI-CV-317-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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