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

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.

• Chikungunya (Biological): Virus Like Particle

Primary outcomes

• Percentage of Participants With 4-fold Rise in Anti-CHIKV Neutralizing Antibody Response [Day 22 (21 days after vaccination)]: 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.

Secondary outcomes

• Geometric Mean Titer of Anti-CHIKV Neutralizing Antibody Response [Day 1, 8, 22, 29, 57, 182]: 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.
• Percentage of Participants With 4-fold Rise in Anti-CHIKV Neutralizing Antibody Response [Day 8, 29, 57, 182]: Evaluation of seroconversion rate of Anti-CHIKV neutralizing antibodies, determined by luciferase-based assay (NT80), in prior alphavirus vaccine recipients versus alphavirus-naïve controls.
• Percentage of Participants With Anti-CHIKV Neutralizing Antibody at or Above Selected Thresholds [Day 1, 8, 22, 29, 57, 182]: 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.
• Geometric Mean Titer of Anti-CHIKV Total Antibody Response [Day 1, 22, 29]: Evaluation of Geometric Mean Titer of Anti-CHIKV total antibodies, determined by immunoassay (ELISA), in prior alphavirus vaccine recipients versus alphavirus-naïve controls.
• Percentage of Participants With 4-fold Rise in Anti-CHIKV Total Antibody Response [Day 22, 29]: 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.
• Geometric Mean Titer of Anti-VEEV Neutralizing Antibody Response [Day 1, 22, 29]: 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
• Number of Participants With Anti-CHIKV Total Antibody Titers of at Least 40,160 or 640 [Days 1, 22, and 29]: 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.
• Percentage of Participants With 4-fold Rise in Anti-VEEV Neutralizing Antibody Response [Day 22 and 29]: 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.
• Percentage of Participants With Anti-VEEV PRNT Neutralizing Activity at or Above Selected Thresholds [Day 1, 22, 29]: 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.
• Geometric Mean Titer of Anti-VEEV Total Antibody Response [Day 1, 22, 29]: 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.
• Percentage of Participants With 4-fold Rise in Total ELISA IgG Antibody Against VEEV [Day 22, 29]: 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.
• Number of Participants With Anti-VEEV Total Antibody Titers of at Least 40,160 or 640 [Days 1, 22, and 29]: 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.

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• Percentage of Participants With 4-fold Rise in Anti-CHIKV Neutralizing Antibody Response (Primary), Number, percentage of participants: Experimental: Prior Alpha 100 (88.6 to 100); Control: Naive Alpha 100 (88.6 to 100) (p 1)
• Geometric Mean Titer of Anti-CHIKV Neutralizing Antibody Response (Secondary), Geometric mean, titers: Experimental: Prior Alpha 9.21 (7.80 to 10.87); Control: Naive Alpha 7.69 (NA to NA)
• Percentage of Participants With 4-fold Rise in Anti-CHIKV Neutralizing Antibody Response (Secondary), Number, percentage of participants: Experimental: Prior Alpha 93.3 (78.7 to 98.2); Control: Naive Alpha 66.7 (48.8 to 80.8) (p 0.0211)
• Percentage of Participants With Anti-CHIKV Neutralizing Antibody at or Above Selected Thresholds (Secondary), Number, percentage of participants: Experimental: Prior Alpha 3.3 (0.6 to 16.7); Control: Naive Alpha 0 (0.0 to 11.4) (p >0.9999)
• Geometric Mean Titer of Anti-CHIKV Total Antibody Response (Secondary), Geometric mean, titers: Experimental: Prior Alpha 39.03 (29.85 to 51.03); Control: Naive Alpha 25.77 (19.71 to 33.70) (p 0.0277)
• Percentage of Participants With 4-fold Rise in Anti-CHIKV Total Antibody Response (Secondary), Number, percentage of participants: Experimental: Prior Alpha 100 (88.6 to 100); Control: Naive Alpha 100 (86.6 to 100) (p 1.00)
• Geometric Mean Titer of Anti-VEEV Neutralizing Antibody Response (Secondary), Geometric mean, titers: Experimental: Prior Alpha 449.82 (262.84 to 769.80); Control: Naive Alpha 9.96 (NA to NA)
• Number of Participants With Anti-CHIKV Total Antibody Titers of at Least 40,160 or 640 (Secondary), Count of participants, Participants: Experimental: Prior Alpha 15; Control: Naive Alpha 4
• Percentage of Participants With 4-fold Rise in Anti-VEEV Neutralizing Antibody Response (Secondary), Number, percentage of participants: Experimental: Prior Alpha 0 (0.0 to 11.4); Control: Naive Alpha 0 (0.0 to 11.4) (p 1.0000)
• Percentage of Participants With Anti-VEEV PRNT Neutralizing Activity at or Above Selected Thresholds (Secondary), Number, percentage of participants: Experimental: Prior Alpha 90.0 (74.4 to 96.5); Control: Naive Alpha 0 (0.0 to 11.4) (p <0.0001)
• Geometric Mean Titer of Anti-VEEV Total Antibody Response (Secondary), Geometric mean, titers: Experimental: Prior Alpha 324.36 (195.37 to 538.52); Control: Naive Alpha 14.03 (8.45 to 23.30) (p <0.0001)
• Percentage of Participants With 4-fold Rise in Total ELISA IgG Antibody Against VEEV (Secondary), Number, percentage of participants: Experimental: Prior Alpha 86.7 (70.3 to 94.7); Control: Naive Alpha 0 (0.0 to 11.4) (p <0.0001)
• Number of Participants With Anti-VEEV Total Antibody Titers of at Least 40,160 or 640 (Secondary), Count of participants, Participants: Experimental : Prior Alpha 27; Control: Naive Alpha 0

Adverse events

Time frame: Local and systemic post-injection solicited events were collected through Day 8. Unsolicited adverse events were collected through Day 29. Serious adverse events and adverse events leading to withdrawal were collected through Day 183 end of study visit.

Serious adverse events by term

Other adverse events by term

• Results publication: Hamer MJ, McCarty JM, Pierson BC, Regules JA, Mendy J, Sanborn AD, Gardner CL, Haller JM, Gregory MK, Liggett DL, Glass PJ, Ghosh N, Royalty Tredo S, Warfield KL, Burke CW, Lee C, Saunders D, Bedell L, Richardson JS. Safety and immunogenicity of an adjuvanted chikungunya virus virus-like particle (CHIKV VLP) vaccine in previous recipients of other alphavirus vaccines versus alphavirus vaccine-naive controls: an open-label, parallel-group, age-matched, sex-matched, phase 2 randomised controlled study. Lancet Microbe. 2025 Apr;6(4):101000. doi: 10.1016/j.lanmic.2024.101000. Epub 2025 Feb 12. PMID 39954701

• Study Protocol (PDF, 2021-01-25)
• Statistical Analysis Plan (PDF, 2021-03-01)
• Informed Consent Form (PDF, 2019-10-10)

• James McCarty, MD, Study director, Emergent BioSolutions