Phase 2 Open-label Study of Alum-adjuvanted Chikungunya Virus-like Particle Vaccine (PXVX0317) (WRAIR)

A Phase 2 Open-label Study to Assess the Safety and Immunogenicity of an Alum-adjuvanted Chikungunya Virus-like Particle Vaccine (PXVX0317) in Prior Recipients of Other Alphavirus Vaccines Versus Alphavirus Naïve Controls.

This was a phase 2 parallel-group age- and gender-matched open label study in healthy adults 18-65 years of age to assess the safety and immunogenicity of an alum-adjuvanted chikungunya virus-like particle vaccine (PXVX0317; CHIKV VLP vaccine) in prior recipients of other alphavirus vaccines versus alphavirus naïve controls.

Study Overview

• Status: Completed
• Conditions: Chikungunya
• Intervention / Treatment: Biological: Chikungunya

Detailed Description

It is currently unknown whether prior exposure to heterologous alphaviruses will enhance or interfere with immune responses to chikungunya virus (CHIKV) exposure or vaccination. The objective of this study was to evaluate the safety and immunogenicity of the chikungunya vaccine candidate PXVX0317 when administered to prior recipients of experimental alphavirus vaccines versus alphavirus naïve gender- and age-matched controls.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Fort Deterick, Maryland, United States, 21702
      • United States Army Medical Research Institute of Infectious Diseases
    • Silver Spring, Maryland, United States, 20910
      • Walter Reed Army Institute of Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18 to 65 years old (inclusive)
• For women of childbearing potential, a negative pregnancy test at screening and on vaccination day, practicing highly effective contraception for at least 30 days prior to vaccination, and willing to use a highly effective method of contraception through study completion.
• Able and willing to provide informed consent for study participation prior to screening procedures.
• Free of obvious health problems as established by medical history and clinical examination at screening and enrollment.
• Available to participate for the duration of the study (approximately 8 months).
• For the cohort of prior alphavirus vaccine recipients, a documented history of prior alphavirus vaccination.

Exclusion Criteria:

• Acute disease or febrile illness at the time of screening or enrollment.
• Clinically significant cardiac, respiratory, rheumatologic or other medical or psychiatric condition that, in the opinion of the Investigator, places the subject at increased risk or affects their ability to understand and comply with study procedures.
• Abnormal screening lab test result that, in the opinion of the investigator, obscures interpretation of the safety data or suggests a clinically significant cardiac, respiratory, rheumatologic or other medical condition that places the subject at increased risk.
• Pregnant, lactating or planning to become pregnant during the study period.
• Laboratory evidence of infection with Hepatitis B, C or HIV.
• History of naturally (non-laboratory) acquired chikungunya or other alphavirus infection or travel to a WHO-designated chikungunya-endemic region within 30 days prior to Day 1.
• History of acute allergic reaction to any component of CHIKV VLP vaccine or Alhydrogel®.
• Current (30 days prior to Day 1) or anticipated use of systemic immunomodulatory or immunosuppressive medications.
• History of splenectomy, immunosuppressive condition, autoimmune disease, or immunodeficient condition.
• Family history of congenital or hereditary immunodeficiency.
• Suspected or known current alcohol abuse that, in the opinion of the Investigator, would interfere with the subject's ability to understand and comply with study procedures.
• Current intravenous drug use.
• Prior receipt of an investigational chikungunya vaccine.
• Receipt or planned receipt of any licensed vaccine from 30 days prior to Day 1 through Day 29 study visit.
• Participation in another clinical trial during the study period in which an investigational product is administered.
• For the alphavirus naïve group, history of prior alphavirus vaccination is exclusionary.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prior Alpha; All study participants received the same Investigational Product according to the same schedule. Participants were prior recipients of experimental alphavirus vaccines.	Biological: Chikungunya; Virus Like Particle
Active Comparator: Control: Naïve Alpha; All study participants received the same Investigational Product according to the same schedule. The alphavirus vaccine naïve participants will serve as controls for determining the effect of pre-existing alphavirus immunity on vaccine safety and immunogenicity.	Biological: Chikungunya; Virus Like Particle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With 4-fold Rise in Anti-CHIKV Neutralizing Antibody Response	Seroconversion, defined as a 4-fold or greater rise in neutralizing antibody against chikungunya virus, as determined by luciferase-based assay (NT80), induced by PXVX0317. PXVX0317 was administered to prior alphavirus vaccine recipients versus gender- and age-matched controls.	Day 22 (21 days after vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titer of Anti-CHIKV Neutralizing Antibody Response	Evaluation of Geometric Mean Titer of Anti-CHIKV neutralizing antibodies, determined by luciferase-based assay (NT80), in prior alphavirus vaccine recipients versus alphavirus-naïve controls.	Day 1, 8, 22, 29, 57, 182
Percentage of Participants With 4-fold Rise in Anti-CHIKV Neutralizing Antibody Response	Evaluation of seroconversion rate of Anti-CHIKV neutralizing antibodies, determined by luciferase-based assay (NT80), in prior alphavirus vaccine recipients versus alphavirus-naïve controls.	Day 8, 29, 57, 182
Percentage of Participants With Anti-CHIKV Neutralizing Antibody at or Above Selected Thresholds	Evaluation of Anti-CHIKV neutralizing antibody response, as determined by luciferase-based assay (NT80), via proportion of participants with titers of at least 40, 160 or 640 on Days 1, 8, 22, 29, 57 and 182.	Day 1, 8, 22, 29, 57, 182
Geometric Mean Titer of Anti-CHIKV Total Antibody Response	Evaluation of Geometric Mean Titer of Anti-CHIKV total antibodies, determined by immunoassay (ELISA), in prior alphavirus vaccine recipients versus alphavirus-naïve controls.	Day 1, 22, 29
Percentage of Participants With 4-fold Rise in Anti-CHIKV Total Antibody Response	Evaluation of seroconversion rate of Anti-CHIKV total antibodies, determined by immunoassay, on Days 22 and 29, where seroconversion was a 4-fold rise in titer over baseline.	Day 22, 29
Geometric Mean Titer of Anti-VEEV Neutralizing Antibody Response	Evaluation of Geometric Mean Titer of Anti-VEEV neutralizing antibodies, determined by Plaque-Reduction Neutralization Test (PRNT80), in prior alphavirus vaccine recipients versus alphavirus-naïve controls	Day 1, 22, 29
Number of Participants With Anti-CHIKV Total Antibody Titers of at Least 40,160 or 640	Evaluation of Anti-CHIKV total antibody titer, as determined by immunoassay (ELISA), via proportion of participants with titers of at least 40, 160 or 640 on Days 1, 22, and 29.	Days 1, 22, and 29
Percentage of Participants With 4-fold Rise in Anti-VEEV Neutralizing Antibody Response	Evaluation of seroconversion rate of anti-VEEV neutralizing antibodies on Days 22 and 29 as determined by Plaque-Reduction Neutralization Test (PRNT80), where seroconversion is a 4-fold rise in titer over baseline.	Day 22 and 29
Percentage of Participants With Anti-VEEV PRNT Neutralizing Activity at or Above Selected Thresholds	Evaluation of Anti-VEEV neutralizing antibody response, as determined by Plaque-Reduction Neutralization Test (PRNT80), via proportion of participants with titers of at least 40, 160 or 640 on Days 1, 22 and 29.	Day 1, 22, 29
Geometric Mean Titer of Anti-VEEV Total Antibody Response	Evaluation of Geometric Mean Titer of Anti-VEEV total antibody as determined by an immunoassay (ELISA) in prior alphavirus vaccine recipients versus alphavirus-naïve controls.	Day 1, 22, 29
Percentage of Participants With 4-fold Rise in Total ELISA IgG Antibody Against VEEV	Evaluation of seroconversion rate of Anti-VEEV total antibody, as determined by immunoassay (ELISA), on Days 22 and 29, where seroconversion is a 4-fold rise in titer over baseline.	Day 22, 29
Number of Participants With Anti-VEEV Total Antibody Titers of at Least 40,160 or 640	Evaluation of Anti-VEEV total antibody titer, as determined by immunoassay (ELISA), via proportion of participants with titers of at least 40, 160, or 640 on Days 1, 22, and 29.	Days 1, 22, and 29

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: Walter Reed Army Institute of Research (WRAIR); Emergent BioSolutions
• Investigators: Study Director: James McCarty, MD, Emergent BioSolutions

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Actual): January 19, 2021
• Study Completion (Actual): January 19, 2021

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 20, 2019

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• 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-317-002

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