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

Chikungunya Virus Infection Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06007183
• Other study ID #: EBSI-CV-317-008
• Status: Recruiting
• Phase: Phase 3
• Start date: August 30, 2023
• Est. completion date: August 2028

Study information

• Verified date: March 2024
• Source: Bavarian Nordic
• Contact: Sufia Muhammad, MD
• Phone: 240-631-3573
• Email: SUMU[@]bavarian-nordic.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: August 2028
• Est. primary completion date: April 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 67 Years

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.

Related Conditions & MeSH terms

• Chikungunya Fever
• Chikungunya Virus Infection

Intervention

Biological:
• PXVX0317 vaccine booster
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.
• 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.

Locations

Country	Name	City	State
United States	Velocity Clinical Research, Austin	Cedar Park	Texas
United States	Synexus Clinical Research US, Inc.	Chicago	Illinois
United States	Velocity Clinical Research, Cleveland	Cleveland	Ohio
United States	Velocity Clinical Research, Providence	East Greenwich	Rhode Island
United States	DM Clinical Research	Houston	Texas
United States	Alliance for Multispecialty Research, LLC	Kansas City	Missouri
United States	Alliance for Multispecialty Research, LLC	Las Vegas	Nevada
United States	Wr-Crcn, Llc	Las Vegas	Nevada
United States	Alliance for Multispecialty Research, LLC	Lexington	Kentucky
United States	Velocity Clinical Research, Medford	Medford	Oregon
United States	Optimal Research, LLC	Melbourne	Florida
United States	Suncoast Research Associates, LLC	Miami	Florida
United States	Alliance for Multispecialty Research, LLC	Mobile	Alabama
United States	Alliance for Multispecialty Research, LLC	Newton	Kansas
United States	Alliance for Multispecialty Research, LLC	Norfolk	Virginia
United States	Lynn Institute of Norman	Norman	Oklahoma
United States	Optimal Research, LLC	Peoria	Illinois
United States	M3 Wake Research Inc.	Raleigh	North Carolina
United States	Rochester Clinical Research, LLC	Rochester	New York
United States	BFHC Research, LLC	San Antonio	Texas
United States	Alliance for Multispecialty Research, LLC	Tempe	Arizona
United States	DM Clinical Research	Tomball	Texas
United States	Velocity Clinical Research, Salt Lake City	West Jordan	Utah
United States	Alliance for Multispecialty Research, LLC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Bavarian Nordic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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