Clinical trial NCT05072080: A Phase 3 Trial of the VLP-Based Chikungunya Vaccine PXVX0317 (CHIKV VLP Vaccine)
Official title: A Phase 3 Safety, Immunogenicity, and Lot-Consistency Trial of the VLP-Based Chikungunya Vaccine PXVX0317 in Healthy Adults and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chikungunya Virus
Keywords: Chikungunya
VLP
PXVX0317
vaccine
immunogenicity
CHIKV
Lead sponsor: Bavarian Nordic
Sponsor class: INDUSTRY
Collaborators: name: Emergent BioSolutions
First posted: 2021-10-08
Enrollment: 3258
Sex: ALL
Minimum age (years): 12
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in a 2:2:2:1 ratio within each age stratum (12 to \<18, 18 to \<46, and 46 to \<65). This study will be conducted in the US, using up to 50 sites.
Primary purpose: PREVENTION

Brief summary: The goal of this multi-center, randomized, double blind, placebo controlled study is to evaluate the safety and immunogenicity of PXVX0317 (CHIKV VLP vaccine) in healthy adult and adolescent subjects.

Detailed description: Coprimary Objectives:

1. To evaluate the safety of PXVX0317 (CHIKV VLP vaccine) in healthy adult and adolescent participants 12 to \<65 years of age.
2. To compare the anti-CHIKV serum neutralizing antibody (SNA) response to PXVX0317 (CHIKV VLP vaccine) and placebo at Day 22, as measured by geometric mean titer (GMT) and clinically relevant difference in seroresponse rate (PXVX0317 minus placebo).
3. To demonstrate the consistency of the anti-CHIKV SNA response across three consecutively manufactured lots of PXVX0317 (CHIKV VLP vaccine) at Day 22 as measured by GMT.

Secondary Objectives:

1. To compare the anti-CHIKV SNA response to PXVX0317 (CHIKV VLP vaccine) and placebo at Day 15, Day 183, and Day 8 as measured by GMT and seroresponse rate.
2. To compare the GMT fold increase in anti-CHIKV SNA response and number and percentage of participants with an anti-CHIKV SNA titer ≥15 and 4-fold rise over baseline, both at Day 8, 15, 22, and 183.

Eligibility criteria: Inclusion Criteria:

* Able and willing to provide informed consent (and assent, as applicable) voluntarily signed by participant (and guardian, as applicable).
* Males or females, 12 to \<65 years of age.
* Generally healthy, in the opinion of the investigator, based on medical history, physical examination, and screening laboratory assessments.
* Women who are either: (i) Not of childbearing potential (CBP): pre-menarche, surgically sterile (at least six weeks post bilateral tubal ligation, 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) or (ii) Meeting all the below criteria: Negative serum pregnancy test at screening visit, Negative urine pregnancy test immediately prior to dosing at Day 1, Using an acceptable method of contraception (if women of CBP) for the duration of participation, such as hormonal contraceptives (eg, implants, pills, patches) initiated ≥30 days prior to dosing, intrauterine device (IUD) inserted ≥30 days prior to dosing, double barrier type of birth control (male condom with female diaphragm, male condom with cervical cap), Abstinence is acceptable only for adolescents (12 to \<18 years old) who are not sexually active.

Exclusion Criteria:

* Currently pregnant, breastfeeding, or planning to become pregnant during the study.
* Body Mass Index (BMI) ≥35 kg/m2.
* Positive laboratory evidence of current infection with human immunodeficiency virus (HIV-1, HIV-2), hepatitis C virus (HCV) or hepatitis B virus (HBV).
* History of severe allergic reaction or anaphylaxis to any component of the vaccine.
* 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).
* Prior receipt or anticipated use of systemic immunomodulatory or immunosuppressive medications from six months prior to screening through Day 22. 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 screening through Day 22 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 screening through Day 22.
* Acute disease within the last 14 days (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).
* Clinically significant cardiac, pulmonary, rheumatologic, or other chronic disease, in the opinion of the investigator. This may include chronic illness requiring hospitalization in the last 30 days prior to screening.
* Enrollment in an interventional study and/or receipt of another investigational product from 30 days prior to screening through the duration of study participation.
* Receipt or anticipated receipt of any vaccine from 30 days prior to Day 1 through Day 22.
* Evidence of substance abuse that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study.
* Prior receipt of an investigational CHIKV vaccine/product.
* Any other medical condition that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study.

Primary outcomes:
measure: Incidence of Solicited Adverse Events (AE)
timeFrame: 7 days post-vaccination
measure: Incidence of Unsolicited AEs
timeFrame: 28 days post-vaccination
measure: Incidence of Adverse Events of Special Interest (AESI)
timeFrame: 182 days post-vaccination
measure: Incidence of Medically Attended Adverse Event (MAAE)
timeFrame: 182 days post-vaccination
measure: Incidence of Serious Adverse Event (SAE)
timeFrame: 182 days post-vaccination
measure: Anti-CHIKV Serum Neutralizing Antibody (SNA) Seroresponse Rates at Day 22
timeFrame: 21 days post-vaccination
measure: Anti-CHIKV Serum Neutralizing Antibody (SNA) Seroresponse Rates at Day 22 (Data Reported Per Arm)
timeFrame: 21 days post-vaccination
measure: Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22
timeFrame: 21 days post-vaccination
measure: Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (Data Reported Per Arm - All Age Strata)
timeFrame: 21 days post-vaccination
measure: Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (for Lot Comparison)
timeFrame: 21 days post-vaccination
measure: Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (Data Reported Per Arm - Adults 18 to <46)
timeFrame: 21 days post-vaccination
Secondary outcomes:
measure: Anti-CHIKV SNA Seroresponse Rates at Days 15, 183, and 8
timeFrame: Day 15, 183, and 8 (14, 182, and 7 days post-vaccination, respectively)
measure: Anti-CHIKV SNA Seroresponse Rates at Days 15, 183, and 8 (Data Reported Per Arm)
timeFrame: Day 15, 183, and 8 (14, 182, and 7 days post-vaccination, respectively)
measure: Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183
timeFrame: Day 8, 15, and 183 (7, 14, and 182 days post-vaccination, respectively)
measure: Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183 (Data Reported Per Arm)
timeFrame: Day 8, 15, and 183 (7, 14, and 182 days post-vaccination, respectively)
measure: Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titers From Day 1 to Days 8, 15, 22, and 183
timeFrame: Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively)
measure: Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titers From Day 1 to Days 8, 15, 22, and 183 (Data Reported Per Arm)
timeFrame: Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively)
measure: Number and Percentage of Participants With Anti-CHIKV SNA Titer ≥15 and 4-fold Rise Over Baseline at Days 8, 15, 22, and 183
timeFrame: Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively)
measure: Number and Percentage of Participants With Anti-CHIKV SNA Titer ≥15 and 4-fold Rise Over Baseline at Days 8, 15, 22, and 183 (Data Reported Per Arm)
timeFrame: Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively)
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Optimal Research, LLC
state: Alabama
city: Mobile
country: United States
facility: Alliance for Multispecialty Research - Mobile
state: Alabama
city: Tempe
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Arizona
city: Banning
country: United States
facility: Velocity Clinical Research, Banning
state: California
city: San Diego
country: United States
facility: Optimal Research, LLC
state: California
city: Colorado Springs
country: United States
facility: Lynn Institute of the Rockies
state: Colorado
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Lake Mary
country: United States
facility: Accel Research Sites-DeLand Clinical Research Unit
state: Florida
city: Melbourne
country: United States
facility: Optimal Research, LLC
state: Florida
city: Miami
country: United States
facility: Suncoast Research Associates, LLC
state: Florida
city: Pinellas Park
country: United States
facility: Synexus Clinical Research US, Inc.
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Meridian
country: United States
facility: Velocity Clinical Research, Boise
state: Idaho
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: Lenexa
country: United States
facility: Johnson County ClinTrials
state: Kansas
city: Newton
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Wichita
country: United States
facility: Alliance for Multispecialty Research - Wichita East
state: Kansas
city: Lexington
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kentucky
city: New Orleans
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Louisiana
city: Rockville
country: United States
facility: Optimal Research, LLC
state: Maryland
city: Kansas City
country: United States
facility: Alliance for Multispecialty Research - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Synexus Clinical Research US, Inc.
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, Inc.
state: New York
city: Raleigh
country: United States
facility: M3 Wake Research, Inc
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center - The Gamble Vaccine Research Center
state: Ohio
city: Cleveland
country: United States
facility: Velocity Clinical Rsearch, Inc.
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Norman
country: United States
facility: Lynn Institute of Norman
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
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: Anderson
country: United States
facility: Synexus Clinical Research US, Inc.
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Tennessee
city: Cedar Park
country: United States
facility: Velocity Clinical Research, Austin
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: Plano
country: United States
facility: Research Your Health
state: Texas
city: San Antonio
country: United States
facility: BFHC Research
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
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:
citation: Bennett SR, McCarty JM, Ramanathan R, Mendy J, Richardson JS, Smith J, Alexander J, Ledgerwood JE, de Lame PA, Royalty Tredo S, Warfield KL, Bedell L. Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial. Lancet Infect Dis. 2022 Sep;22(9):1343-1355. doi: 10.1016/S1473-3099(22)00226-2. Epub 2022 Jun 13.