A Phase 3 Trial of the VLP-Based Chikungunya Vaccine PXVX0317
- Conditions
- Chikungunya Virus
- Interventions
- Biological: CHIKV VLP/adjuvantBiological: Placebo
- Registration Number
- NCT05072080
- Lead Sponsor
- Bavarian Nordic
- Brief Summary
The goal of this multi-center, randomized, double blind, placebo controlled study is to evaluate the safety and immunogenicity of PXVX0317 in healthy adult and adolescent subjects.
- Detailed Description
Coprimary Objectives:
1. To evaluate the safety of PXVX0317 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 and placebo at Day 22, as measured by geometric mean titer (GMT) and clinically relevant difference in seroresponse rate.
3. To demonstrate the consistency of the anti-CHIKV SNA response across three lots of PXVX0317 at Day 22.
Secondary Objectives:
1. To compare the anti-CHIKV SNA response to PXVX0317 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3258
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 3 CHIKV VLP/adjuvant Group 3 - PXVX0317 lot C (Lot 106) Group 4 Placebo Group 4 - Placebo Group 1 CHIKV VLP/adjuvant Group 1 - PXVX0317 lot A (Lot 104) Group 2 CHIKV VLP/adjuvant Group 2 - PXVX0317 lot B (Lot 105)
- Primary Outcome Measures
Name Time Method Incidence of Solicited Adverse Events (AE) 7 days post-vaccination Incidence of solicited AEs through Day 8 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Incidence of Adverse Events of Special Interest (AESI) 182 days post-vaccination Incidence of AESIs, through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Incidence of Serious Adverse Event (SAE) 182 days post-vaccination Incidence of SAEs through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (Data Reported Per Arm - Adults 18 to <46) 21 days post-vaccination Anti-CHIKV SNA GMTs and associated 95% CIs for PXVX0317 (CHIKV VLP vaccine) and placebo in adults 18 to \<46 years of age in the IEP at Day 22.
Incidence of Unsolicited AEs 28 days post-vaccination Incidence of unsolicited AEs through Day 29 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Incidence of Medically Attended Adverse Event (MAAE) 182 days post-vaccination Incidence of MAAEs through Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for all age strata combined (safety population).
Anti-CHIKV Serum Neutralizing Antibody (SNA) Seroresponse Rates at Day 22 21 days post-vaccination Anti-CHIKV SNA seroresponse rates for PXVX0317 (CHIKV VLP vaccine) and placebo, difference (PXVX0317 minus placebo), and associated 95% confidence interval (CI) at Day 22 for the immunogenicity evaluable population (IEP), all age strata combined.
Anti-CHIKV Serum Neutralizing Antibody (SNA) Seroresponse Rates at Day 22 (Data Reported Per Arm) 21 days post-vaccination Anti-CHIKV SNA seroresponse rates and associated 95% confidence interval for PXVX0317 (CHIKV VLP vaccine) and placebo at Day 22 for the immunogenicity evaluable population (IEP), all age strata combined.
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 21 days post-vaccination Anti-CHIKV SNA GMTs and associated 95% CIs at Day 22 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined.
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (Data Reported Per Arm - All Age Strata) 21 days post-vaccination Anti-CHIKV SNA GMTs and associated 95% CIs at Day 22 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined.
Anti-CHIKV SNA Geometric Mean Titers (GMT) at Day 22 (for Lot Comparison) 21 days post-vaccination Anti-CHIKV SNA GMTs and associated 95% CIs between all three pairs of PXVX0317 (CHIKV VLP vaccine) lots (104:105, 104:106, 105:106) in adults 18 to \<46 years of age in the IEP at Day 22. Placebo group 4 is not relevant for this lot-to-lot consistency analysis.
Reported GMT estimates and 95% CIs are derived from an ANOVA model that includes site and product lot as fixed effects assuming normality of log titers.
- Secondary Outcome Measures
Name Time Method Anti-CHIKV SNA Seroresponse Rates at Days 15, 183, and 8 Day 15, 183, and 8 (14, 182, and 7 days post-vaccination, respectively) Anti-CHIKV SNA seroresponse rates for PXVX0317 (CHIKV VLP vaccine) and placebo, difference (PXVX0317 minus placebo), and associated 95% CIs at Day 15, Day 183, and Day 8, in that order, for the IEP, all age strata combined.
Number analyzed is number of participants with a sample result available at the indicated visit.Anti-CHIKV SNA Seroresponse Rates at Days 15, 183, and 8 (Data Reported Per Arm) Day 15, 183, and 8 (14, 182, and 7 days post-vaccination, respectively) Anti-CHIKV SNA seroresponse rates and associated 95% CIs for PXVX0317 (CHIKV VLP vaccine) and placebo at Day 15, Day 183, and Day 8, in that order, for the IEP, all age strata combined.
Number analyzed is number of participants with a sample result available at the indicated visit.Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183 Day 8, 15, and 183 (7, 14, and 182 days post-vaccination, respectively) Anti-CHIKV SNA GMTs with associated 95% CIs at Day 8, Day 15, and Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined.
Number analyzed is number of participants with a sample result available at the indicated visit.Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183 (Data Reported Per Arm) Day 8, 15, and 183 (7, 14, and 182 days post-vaccination, respectively) Anti-CHIKV SNA GMTs with associated 95% CIs at Day 8, Day 15, and Day 183 for PXVX0317 (CHIKV VLP vaccine) and placebo for the IEP, all age strata combined.
Number analyzed is number of participants with a sample result available at the indicated visitGeometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titers From Day 1 to Days 8, 15, 22, and 183 Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively) Geometric mean fold increase (GMFI) in anti-CHIKV SNA titers from Day 1 to Day 8, Day 15, Day 22, and Day 183 for the IEP for all age strata combined.
Fold rise in geometric mean titer is the ratio of the post-baseline value to the baseline value (e.g. number of 2 represents a post-baseline doubling of geometric mean titer).
Number analyzed is number of participants with a sample result available at both Day 1 and the indicated visit.Geometric Mean Fold Increase (GMFI) in Anti-CHIKV SNA Titers From Day 1 to Days 8, 15, 22, and 183 (Data Reported Per Arm) Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively) Geometric mean fold increase (GMFI) in anti-CHIKV SNA titers from Day 1 to Day 8, Day 15, Day 22, and Day 183 for the IEP for all age strata combined.
Fold rise in geometric mean titer is the ratio of the post-baseline value to the baseline value (e.g. number of 2 represents a post-baseline doubling of geometric mean titer).
Number analyzed is number of participants with a sample result available at both Day 1 and the indicated visit.Number and Percentage of Participants With Anti-CHIKV SNA Titer ≥15 and 4-fold Rise Over Baseline at Days 8, 15, 22, and 183 Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively) Number and percentage of participants with anti-CHIKV SNA titers ≥15 and 4-fold rise over baseline at Day 8, Day 15, Day 22, and Day 183 for the IEP for all age strata combined.
Number analyzed is number of participants with a sample result available at the indicated visit.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) Day 8, 15, 22, and 183 (7,14, 21, and 182 days post-vaccination, respectively) Number and percentage of participants with anti-CHIKV SNA titers ≥15 and 4-fold rise over baseline at Day 8, Day 15, Day 22, and Day 183 for the IEP for all age strata combined.
Number analyzed is number of participants with a sample result available at the indicated visit.
Trial Locations
- Locations (36)
Texas Center for Drug Development, Inc.
🇺🇸Houston, Texas, United States
Alliance for Multispecialty Research - Wichita East
🇺🇸Wichita, Kansas, United States
Johnson County ClinTrials
🇺🇸Lenexa, Kansas, United States
Synexus Clinical Research US, Inc.
🇺🇸Anderson, South Carolina, United States
Wr-Crcn, Llc
🇺🇸Las Vegas, Nevada, United States
Alliance for Multispecialty Research, LLC.
🇺🇸Las Vegas, Nevada, United States
Alliance for Multispecialty Research, LLC
🇺🇸Norfolk, Virginia, United States
Velocity Clinical Research, Banning
🇺🇸Banning, California, United States
Accel Research Sites-DeLand Clinical Research Unit
🇺🇸Lake Mary, Florida, United States
Velocity Clinical Research, Boise
🇺🇸Meridian, Idaho, United States
Lynn Institute of the Rockies
🇺🇸Colorado Springs, Colorado, United States
Alliance for Multispecialty Research - Kansas City
🇺🇸Kansas City, Missouri, United States
Jacksonville Center for Clinical Research
🇺🇸Jacksonville, Florida, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Optimal Research LLC
🇺🇸Peoria, Illinois, United States
Palm Beach Research Center
🇺🇸West Palm Beach, Florida, United States
Trial Management Associates, LLC
🇺🇸Wilmington, North Carolina, United States
Research Your Health
🇺🇸Plano, Texas, United States
Velocity Clinical Research, Medford
🇺🇸Medford, Oregon, United States
Lynn Institute of Norman
🇺🇸Norman, Oklahoma, United States
Velocity Clinical Research, Austin
🇺🇸Cedar Park, Texas, United States
Velocity Clinical Rsearch, Inc.
🇺🇸Cleveland, Ohio, United States
Coastal Carolina Research Center
🇺🇸North Charleston, South Carolina, United States
M3 Wake Research, Inc
🇺🇸Raleigh, North Carolina, United States
Velocity Clinical Research-Providence
🇺🇸East Greenwich, Rhode Island, United States
DM Clinical Research
🇺🇸Tomball, Texas, United States
Advanced Clinical Research
🇺🇸West Jordan, Utah, United States
BFHC Research
🇺🇸San Antonio, Texas, United States
Optimal Research, LLC
🇺🇸Rockville, Maryland, United States
Suncoast Research Associates, LLC
🇺🇸Miami, Florida, United States
Alliance for Multispecialty Research - Mobile
🇺🇸Mobile, Alabama, United States
Rochester Clinical Research, Inc.
🇺🇸Rochester, New York, United States
Cincinnati Children's Hospital Medical Center - The Gamble Vaccine Research Center
🇺🇸Cincinnati, Ohio, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
Aventiv Research Inc.
🇺🇸Columbus, Ohio, United States