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

Study Overview
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Brief Summary
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The purpose of this phase 3 multicenter, randomized, double-blind, placebo-controlled rollover study is to evaluate the safety and long-term immunogenicity of PXVX0317 in adult and adolescent participants and to evaluate PXVX0317 booster vaccine induced serum neutralizing antibody (SNA) response at 3, 4, or 5 years post-initial PXVX0317 vaccination.

Detailed Description
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Primary Objectives: To evaluate the long-term immunogenicity of PXVX0317 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 study EBSI-CV-317-004 (NCT05072080). To assess the vaccine-induced SNA titers by a booster dose of PXVX0317 vaccine at 3, 4, or 5 years post-initial vaccination in feeder study EBSI-CV- 317-004. To evaluate the safety and tolerability of PXVX0317 in all participants. To evaluate the safety and tolerability of a booster vaccination and compare with safety and tolerability reported post-initial vaccination of PXVX0317 under feeder study EBSI-CV-317-004 in healthy adults and adolescents. Secondary Objectives: To evaluate the long-term immunogenicity of PXVX0317 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 study EBSI-CV-317-004. To evaluate the immune response to a booster vaccination and compare this response to that reported post-initial vaccination of PXVX0317 under feeder study EBSI-CV-317-004 in healthy adults and adolescents.

Official Title
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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

Conditions
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Chikungunya Virus Infection

Intervention / Treatment
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* Biological: PXVX0317 vaccine booster
* Biological: Placebo booster


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Within the 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 PXVX0317. Males or females, 12 to <65 years of age at the time of enrollment in the feeder study. Received a single dose of PXVX0317 vaccine in the feeder study. Demonstrated compliance to the feeder study conduct (ie, rollover participant was without protocol deviations that excluded them from analysis in feeder study EBSI-CV-317-004) 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 PXVX0317 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; 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 PXVX0317). 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 PXVX0317 or placebo: Participation or planned participation in an investigational clinical trial, excluding EBSI-CV-317-004 feeder study (eg, vaccine, drug, medical device, or medical procedure) for the following time periods: Group 1: 30 days prior to Randomization A 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. Experienced a related safety event in the feeder study that, in the investigator's judgement, precludes receipt of booster. 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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 67 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants still in the study at the Year 3 timepoint (time point relative to initial vaccination in feeder study EBSI-CV-317-004) will be randomized 1:1:1 to Year 3, 4, or 5 and 1:1 to PXVX0317 booster or placebo booster.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1a<br>PXVX0317 vaccine booster, 3 years post initial vaccination | Biological: PXVX0317 vaccine booster<br>* PXVX0317 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.<br>* Other names: CHIKV VLP;|
| Placebo Comparator: Group 1b<br>Placebo booster, 3 years post initial vaccination | Biological: Placebo booster<br>* 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.<br>|
| Active Comparator: Group 2a<br>PXVX0317 vaccine booster, 4 years post initial vaccination | Biological: PXVX0317 vaccine booster<br>* PXVX0317 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.<br>* Other names: CHIKV VLP;|
| Placebo Comparator: Group 2b<br>Placebo booster, 4 years post initial vaccination | Biological: Placebo booster<br>* 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.<br>|
| Active Comparator: Group 3a<br>PXVX0317 vaccine booster, 5 years post initial vaccination | Biological: PXVX0317 vaccine booster<br>* PXVX0317 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.<br>* Other names: CHIKV VLP;|
| Placebo Comparator: Group 3b<br>Placebo booster, 5 years post initial vaccination | Biological: Placebo booster<br>* 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.<br>|
| No Intervention: Group 4<br>Unrandomized or unboosted participants, for any reason | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants maintaining an anti-CHIKV SNA titer ≥100 at yearly intervals up to 5 years post-initial vaccination | For all groups using the immunogenicity evaluable population (IEP) anti-CHIKV SNA titer ≥100 (seroresponse rate, also considered the presumptive seroprotection rate) preboost at yearly intervals up to 5 years post-initial vaccination in feeder study EBSI-CV-317-004; only prebooster data will be summarized. | 5 years post-initial vaccination in feeder study EBSI-CV-317-004 until booster | 
| Proportion of vaccine boosted participants with composite booster response at 21 days after booster vaccination | For IEP participants who receive a PXVX0317 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 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 PXVX0317 vaccination in feeder study EBSI-CV-317-004 and; only prebooster data will be summarized. | 5 years post-initial vaccination in feeder study EBSI-CV-317-004 until booster | 
| 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 Fold Increase (GMFI) Prebooster to Postbooster | For IEP participants who receive a PXVX0317 booster (Groups 1a, 2a, and 3a; PXVX0317 IEP booster population) 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. | 21 days after booster vaccination and 5 years post-initial vaccination in feeder study EBSI-CV-317-004 | 
| Booster Response at 21 Days Relative to 21-day Response in Feeder Study EBSI-CV-317-004 | For IEP participants who receive a PXVX0317 booster (Groups 1a, 2a, and 3a; PXVX0317 IEP booster population) and have a 21-day postboost SNA titer, GMFI from feeder study EBSI-CV-317-004 Day 22 SNA titer to 21-day postbooster SNA titer in the rollover study. | 21 days after booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chikungunya, PXVX0317, Vaccine, Immunogenicity, CHIKV VLP