Clinical trial NCT06007183: Long-term Follow-up Study to Evaluate Safety and Immunogenicity of PXVX0317 Single or Booster Vaccination
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chikungunya Virus Infection
Keywords: Chikungunya
PXVX0317
Vaccine
Immunogenicity
CHIKV VLP
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
First posted: 2023-08-23
Enrollment: 800
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All eligible participants in the youngest (12 to \<18 years) and oldest 2 (≥65 years) age groups will be assigned to a booster at Year 3 (Group 1). All other participants will be randomized 1:1:1 to a booster at Year 3 (Group 1), 4 (Group 2), or 5 (Group 3). Prior to booster dose administration participants will be randomized 1:1 to CHIKV VLP vaccine booster or placebo booster.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants maintaining a preboost anti-CHIKV SNA titer ≥100 at yearly intervals up to 5 years post-initial vaccination
timeFrame: 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV317-005 until booster
measure: Proportion of vaccine boosted participants with composite booster response at 21 days after booster vaccination
timeFrame: 21 days after booster vaccination
Secondary outcomes:
measure: Anti-CHIKV SNA Geometric Mean Titers (GMTs) at yearly intervals
timeFrame: 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005 until booster
measure: Anti-CHIKV SNA GMTs at 21 days postboost
timeFrame: 21 days postboost for Groups 1a, 2a, and 3a
measure: Anti-CHIKV SNA Geometric Mean Fold Increase (GMFI) Prebooster to Postbooster
timeFrame: 21 days after booster vaccination and 5 years post-initial vaccination in feeder study EBSI-CV-317-004 or EBSI-CV-317-005
measure: Booster Response at 21 Days Relative to 21-day Response in Feeder Study EBSI-CV-317-004 or EBSI-CV-317-005
timeFrame: 21 days after booster vaccination
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Alabama
city: Tempe
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Arizona
city: Melbourne
country: United States
facility: Optimal Research, LLC
state: Florida
city: Miami
country: United States
facility: Suncoast Research Associates, LLC
state: Florida
city: Chicago
country: United States
facility: Synexus Clinical Research US, Inc.
state: Illinois
city: Peoria
country: United States
facility: Optimal Research, LLC
state: Illinois
city: Newton
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Wichita
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Lexington
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kentucky
city: Kansas City
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Missouri
city: Las Vegas
country: United States
facility: Wr-Crcn, Llc
state: Nevada
city: Las Vegas
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Nevada
city: Rochester
country: United States
facility: Rochester Clinical Research, LLC
state: New York
city: Raleigh
country: United States
facility: M3 Wake Research Inc.
state: North Carolina
city: Cleveland
country: United States
facility: Velocity Clinical Research, Cleveland
state: Ohio
city: Norman
country: United States
facility: Lynn Institute of Norman
state: Oklahoma
city: Medford
country: United States
facility: Velocity Clinical Research, Medford
state: Oregon
city: East Greenwich
country: United States
facility: Velocity Clinical Research, Providence
state: Rhode Island
city: Cedar Park
country: United States
facility: Velocity Clinical Research, Austin
state: Texas
city: Houston
country: United States
facility: DM Clinical Research
state: Texas
city: San Antonio
country: United States
facility: BFHC Research, LLC
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: West Jordan
country: United States
facility: Velocity Clinical Research, Salt Lake City
state: Utah
city: Norfolk
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Virginia
Study officials:
affiliation: Bavarian Nordic
name: Patrick Ajiboye, MD
role: STUDY_DIRECTOR
References: