Long-term Follow-up Study to Evaluate Safety and Immunogenicity of PXVX0317 Single or Booster Vaccination

A Long-term Follow-up Study to Evaluate Safety and Immunogenicity of a Chikungunya Virus Virus-like Particle Vaccine (PXVX0317) in Healthy Adults and Adolescents After Either a Single or Booster Vaccination Dosing Regimen

The purpose of this phase 3 multicenter, randomized, double-blind, placebo-controlled rollover study is to evaluate the safety and long-term immunogenicity of CHIKV VLP vaccine in adult and adolescent participants and to evaluate CHIKV VLP booster vaccine induced serum neutralizing antibody (SNA) response at 3, 4, or 5 years post-initial CHIKV VLP vaccination.

Study Overview

• Status: Active, not recruiting
• Conditions: Chikungunya Virus Infection
• Intervention / Treatment: Biological: Placebo booster; Biological: CHIKV VLP vaccine booster

Detailed Description

Primary Objectives:

• To evaluate the long-term immunogenicity of CHIKV VLP vaccine in healthy adult and adolescent participants as measured by proportion of participants maintaining an anti-CHIKV serum neutralizing antibody (SNA) titer ≥100 (seroresponse rate, also considered the presumptive seroprotection rate) at yearly intervals up to 5 years postvaccination in feeder studies EBSI-CV-317-004 (NCT05072080) and EBSI-CV-317-005 (NCT05349617).
• To assess the vaccine-induced SNA titers by a booster dose of CHIKV VLP vaccine at 3, 4, or 5 years post-initial vaccination in feeder studies EBSI-CV- 317-004 and EBSI-CV-317-005.
• To evaluate the safety and tolerability of CHIKV VLP vaccine in all participants.
• To evaluate the safety and tolerability of a booster vaccination and compare with safety and tolerability reported post-initial vaccination of CHIKV VLP vaccine under feeder studies EBSI-CV-317-004 and EBSI-CV-317-005 in healthy adults and adolescents.

Secondary Objectives:

• To evaluate the long-term immunogenicity of CHIKV VLP vaccine in healthy adult and adolescent participants as measured by anti-CHIKV SNA geometric mean titers (GMTs) at yearly intervals up to 5 years post-initial vaccination in feeder studies EBSI-CV-317-004 and EBSI-CV-317-005.
• To evaluate the immune response to a booster vaccination and compare this response to that reported post-initial vaccination of CHIKV VLP vaccine under feeder studies EBSI-CV-317-004 and EBSI-CV-317-005 in healthy adults and adolescents.

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Alliance for Multispecialty Research, LLC
  • Arizona
    • Tempe, Arizona, United States, 85281
      • Alliance for Multispecialty Research, LLC
  • Florida
    • Melbourne, Florida, United States, 32934
      • Optimal Research, LLC
    • Miami, Florida, United States, 33173
      • Suncoast Research Associates, LLC
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Synexus Clinical Research US, Inc.
    • Peoria, Illinois, United States, 61614
      • Optimal Research, LLC
  • Kansas
    • Newton, Kansas, United States, 67114
      • Alliance for Multispecialty Research, LLC
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Alliance for Multispecialty Research, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty Research, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Alliance for Multispecialty Research, LLC
    • Las Vegas, Nevada, United States, 89106
      • Wr-Crcn, Llc
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, LLC
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research Inc.
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Velocity Clinical Research, Cleveland
  • Oklahoma
    • Norman, Oklahoma, United States, 73072
      • Lynn Institute of Norman
  • Oregon
    • Medford, Oregon, United States, 97504
      • Velocity Clinical Research, Medford
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research, Providence
  • Texas
    • Cedar Park, Texas, United States, 78613
      • Velocity Clinical Research, Austin
    • Houston, Texas, United States, 77081
      • DM Clinical Research
    • San Antonio, Texas, United States, 78249
      • BFHC Research, LLC
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research, Salt Lake City
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Alliance for Multispecialty Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Only within the EBSI-CV-317-004 feeder study informed consent form (ICF) (and/or assent form, as applicable), the participant voluntarily signed and agreed to be contacted or did not indicate they were not to be contacted for potential screening and enrollment in a future study (ie, EBSI-CV-317-008).
• Able and willing to provide informed consent (and assent, as applicable) voluntarily signed by participant (and guardian, as applicable) for participation in this rollover study EBSI-CV-317-008, including possible receipt of a booster dose of CHIKV VLP vaccine.
• Males or females, 12 years of age or older at the time of enrollment in the feeder study.
• Received a single dose of CHIKV VLP vaccine in one of the feeder studies, EBSI-CV-317-004 or EBSI-CV-317-005.
• Demonstrated compliance to the feeder study conduct (ie, rollover participant was without protocol deviations that excluded them from immunogenicity analysis in feeder study EBSI-CV-317-004 or EBSI-CV-317-005) without discontinuation or early withdrawal.
• Generally healthy, in the opinion of the investigator, based on medical history and physical examination.

Additional inclusion criteria to be assessed at Prerandomization Visit (Visit 5), before Randomization A (Visit 6), and before Randomization B (Visit 8 for Group 2 and Visit 10 for Group 3) to determine eligibility for a booster dose of CHIKV VLP vaccine or placebo:

- Women who are either: i. Not of childbearing potential (CBP): premenarche, surgically sterile (at least six weeks postbilateral tubal ligation or bilateral total salpingectomy, 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). For women who are postmenopausal, documented follicle stimulating hormone (FSH) level of ≥40 mIU/mL must be obtained. If the FSH is <40 mIU/mL, the participant must agree to use an acceptable form of contraception. or: ii. Meet all the below criteria:

• Negative serum pregnancy test at Prerandomization and Prebooster Visits
• Negative urine pregnancy test immediately prior to booster dose administration
• Use one of these acceptable methods of contraception (if women of CBP) for at least six months after booster:
• Hormonal contraceptives (eg, implants, pills, patches) initiated ≥30 days prior to booster dose administration
• Intrauterine device (IUD) inserted ≥30 days prior to booster dose administration
• Double barrier type of birth control (male condom with female diaphragm, male condom with cervical cap)
• Abstinence is acceptable only for adolescents (12-<18 years of age) who are not sexually active.

Women participants of CBP must use an acceptable method of contraception from ≥30 days prior to Randomization A or assignment to Group 1; those who are randomized to Groups 2 or 3 at year 3 can discontinue contraception until 30 days prior to booster dose administration, if desired. Women participants of CBP must use an acceptable method of contraception from ≥30 days prior to Randomization B through six-months postbooster vaccination dose (if applicable).

Note: Contraception requirements do not apply for participants in exclusively same-sex relationships and these participants should have no plans to become pregnant by any other means during the same time period as women of CBP are required to use contraception. Contraception requirements do not apply to Group 4 participants (unrandomized or unboosted).

Exclusion Criteria:

• Received placebo treatment in the feeder study.
• Measurable anti-CHIKV SNA at Day 1 in the feeder study.
• History of severe allergic reaction or anaphylaxis to any component of the investigational product (IP).
• Receipt of either an investigational or licensed CHIKV vaccine (excluding prior receipt of CHIKV VLP vaccine).
• New onset/diagnosis of any disease falling within the feeder study exclusion criteria including: i. 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) or ii. Clinically significant cardiac, pulmonary, rheumatologic, or other chronic disease, in the opinion of the investigator. This may include chronic illness requiring hospitalization during the feeder study.
• Evidence of substance abuse that, in the opinion of the investigator, could adversely impact the individual's participation or the conduct of the study.
• Any other medical condition or general reason that, in the opinion of the investigator, could adversely impact the individual's participation or the conduct of the study.
• Bavarian Nordic staff members and their families, contractors, agents, business partners, and anyone with a financial interest in the outcome of the study.

Additional exclusion criteria to be assessed at Prerandomization Visit (Visit 5), before Randomization A (Visit 6), and before Randomization B (Visit 8 for Group 2 and Visit 10 for Group 3) to determine eligibility for a booster dose of CHIKV VLP vaccine or placebo:

• Participation or planned participation in an investigational clinical trial, excluding feeder studies EBSI-CV-317-004 or EBSI-CV-317-005 (eg, vaccine, drug, medical device, or medical procedure) for the following time periods:

Group 1: 30 days prior to Randomization A or assignment to Group 1 at Visit 6 through Visit 7 Group 2: 30 days prior to Randomization A at Visit 6 until the Randomization A visit and 30 days prior to booster dose at Visit 8 through Visit 9 Group 3: 30 days prior to Randomization A at Visit 6 until the Randomization A visit and 30 days prior to booster dose at Visit 10 through EOS Visit Group 4: 30 days prior to Randomization A at Visit 6 until the Randomization A visit Note: Participation in an observational trial or follow-up phase of a trial may be allowed; however, these instances should be discussed with this study's medical monitor (MM).

• Currently breastfeeding.
• Positive laboratory evidence of current infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV).
• Prior receipt or anticipated use of systemic immunomodulatory or immunosuppressive medications from six months prior to Prebooster Visit through 21 days after booster dose. 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 Prebooster Visit through 21 days postbooster dose 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 Prebooster Visit through 21 days postbooster dose.
• Acute disease within the last 14 days prior to booster dose (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).
• Receipt or anticipated receipt of any vaccine from 30 days prior to booster dose through 21 days postbooster.

Note: Participants that are ineligible or decline booster will be included in Group 4 (unrandomized or unboosted) for follow-up unless consent/assent for follow-up is withdrawn.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1b; Placebo booster, 3 years post initial vaccination	Biological: Placebo booster; Placebo is comprised of formulation buffer supplied as a single dose of 0.8 mL in a pre-filled syringe administered via IM injection in the deltoid muscle.
Placebo Comparator: Group 2b; Placebo booster, 4 years post initial vaccination	Biological: Placebo booster; Placebo is comprised of formulation buffer supplied as a single dose of 0.8 mL in a pre-filled syringe administered via IM injection in the deltoid muscle.
Placebo Comparator: Group 3b; Placebo booster, 5 years post initial vaccination	Biological: Placebo booster; Placebo is comprised of formulation buffer supplied as a single dose of 0.8 mL in a pre-filled syringe administered via IM injection in the deltoid muscle.
No Intervention: Group 4; Unrandomized or unboosted participants, for any reason
Active Comparator: Group 1a; CHIKV VLP vaccine booster, 3 years post initial vaccination	Biological: CHIKV VLP vaccine booster; CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP) 40mg, aluminum hydroxide 2% adjuvant, and formulation buffer supplied as a single dose of 0.8 mL in a pre-filled syringe, to be administered via intramuscular (IM) injection in the deltoid muscle.; Other Names: PXVX0317
Active Comparator: Group 2a; CHIKV VLP vaccine booster, 4 years post initial vaccination	Biological: CHIKV VLP vaccine booster; CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP) 40mg, aluminum hydroxide 2% adjuvant, and formulation buffer supplied as a single dose of 0.8 mL in a pre-filled syringe, to be administered via intramuscular (IM) injection in the deltoid muscle.; Other Names: PXVX0317
Active Comparator: Group 3a; CHIKV VLP vaccine booster, 5 years post initial vaccination	Biological: CHIKV VLP vaccine booster; CHIKV VLP vaccine is comprised of chikungunya virus virus-like particles (CHIKV VLP) 40mg, aluminum hydroxide 2% adjuvant, and formulation buffer supplied as a single dose of 0.8 mL in a pre-filled syringe, to be administered via intramuscular (IM) injection in the deltoid muscle.; Other Names: PXVX0317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants maintaining a preboost anti-CHIKV SNA titer ≥100 at yearly intervals up to 5 years post-initial vaccination	For all groups using the immunogenicity evaluable population (IEP) the proportion of participants maintaining a preboost anti-CHIKV SNA titer ≥100 (seroresponse rate, also considered the presumptive seroprotection rate) at yearly intervals up to 5 years post-initial vaccination in one of the feeder studies; only prebooster data will be summarized.	5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV317-005 until booster
Proportion of vaccine boosted participants with composite booster response at 21 days after booster vaccination	For IEP participants who receive a CHIKV VLP vaccine booster (Groups 1a, 2a, and 3a), proportion of participants with a boost response is defined as a composite of: ≥4-fold rise in anti-CHIKV SNA titer from prebooster to postbooster measured at 21 days after booster for participants with a prebooster titer ≥100 OR; Anti-CHIKV SNA titer ≥100 and ≥4-fold increase in anti-CHIKV SNA titer from prebooster to postbooster measured at 21 days after booster vaccination for participants with a prebooster titer <100. Note: Prebooster is the last SNA sample prior to booster dose, ideally the sample on boost day prior to booster dose administration but can be the time point prior if the boost day sample is missed or incorrectly processed.	21 days after booster vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-CHIKV SNA GMTs at 21 days postboost	Anti-CHIKV SNA GMTs in Groups 1a, 2a, and 3a (PXVX0317 IEP booster population), at 21 days postboost.	21 days postboost for Groups 1a, 2a, and 3a
Anti-CHIKV SNA Geometric Mean Titers (GMTs) at yearly intervals	For all groups using the IEP, anti-CHIKV SNA GMTs preboost at yearly intervals up to 5 years post-initial CHIKV VLP vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005; only prebooster data will be summarized.	5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005 until booster
Anti-CHIKV SNA Geometric Mean Fold Increase (GMFI) Prebooster to Postbooster	For IEP participants who receive a CHIKV VLP vaccine booster (Groups 1a, 2a, and 3a) and have a 21-day postbooster SNA titer, GMFI from prebooster anti-CHIKV SNA titer to 21 days postbooster anti-CHIKV SNA titer and at yearly intervals up to 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005.	21 days after booster vaccination and 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005
Booster Response at 21 Days Relative to 21-day Response in Feeder Study EBSI-CV-317-004 or EBSI-CV-317-005	For IEP participants who receive a CHIKV VLP vaccine booster (Groups 1a, 2a, and 3a) and have a 21-day postboost SNA titer, GMFI from feeder study EBSI-CV-317-004 or EBSI-CV-317-005 Day 22 SNA titer to 21-day postbooster SNA titer in the rollover study.	21 days after booster vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of vaccine boosted participants with local or systemic solicited adverse events (AEs) within 7 days after booster vaccination	Proportion of participants with local or systemic solicited AEs of increased frequency or severity after a booster vaccination of PXVX0317 (Groups 1a, 2a, and 3a) as compared with those reported by the same participants after initial vaccination of PXVX0317 under the feeder study (EBSI-CV-317-004) in healthy adults and adolescents.	7 days after booster vaccination
Proportion of vaccine or placebo boosted participants with of unsolicited Adverse Events (AEs)	Occurrence of unsolicited AEs within 28 days postbooster (Groups 1, 2, and 3).	28 days after booster vaccination
Proportion of vaccine or placebo boosted participants with of Adverse Events of Special Interest (AESI)	Occurrence of AESI, through the duration of the study for all participants.	5 years post-initial vaccination in the feeder study for Groups 1, 2 and 4; 5.5 years post-initial vaccination in the feeder study for Group 3
Proportion of vaccine or placebo boosted participants with Medically Attended Adverse Event (MAAE)	Occurrence of MAAE, through the duration of the study for all participants.	5 years post-initial vaccination in the feeder study for Groups 1, 2 and 4; 5.5 years post-initial vaccination in the feeder study for Group 3
Proportion of participants with Serious Adverse Events (SAEs)	Occurrence of SAEs through the duration of the study for all participants.	5 years post-initial vaccination in the feeder study for Groups 1, 2 and 4; 5.5 years post-initial vaccination in the feeder study for Group 3

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2023
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: August 18, 2023
• First Submitted That Met QC Criteria: August 18, 2023
• First Posted (Actual): August 23, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Vaccine; Immunogenicity; Chikungunya; PXVX0317; CHIKV VLP
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Alphavirus Infections; Togaviridae Infections; Chikungunya Fever
• Other Study ID Numbers: EBSI-CV-317-008

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
• product manufactured in and exported from the U.S.: No