Overview
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.
Description
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.
Eligibility
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.