A Phase 3 Trial of the VLP-Based Chikungunya Vaccine PXVX0317

Study Overview
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Brief Summary
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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
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Coprimary Objectives: To evaluate the safety of PXVX0317 in healthy adult and adolescent participants 12 to <65 years of age. 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. To demonstrate the consistency of the anti-CHIKV SNA response across three lots of PXVX0317 at Day 22. Secondary Objectives: 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. 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.

Official Title
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A Phase 3 Safety, Immunogenicity, and Lot-Consistency Trial of the VLP-Based Chikungunya Vaccine PXVX0317 in Healthy Adults and Adolescents

Conditions
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Chikungunya Virus

Intervention / Treatment
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* Biological: CHIKV VLP/adjuvant
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Group 1 - PXVX0317 lot A (Lot 104) | Biological: CHIKV VLP/adjuvant<br>* PXVX0317 vaccine is comprised of chikungunya virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide (Alhydrogel®) adjuvant 2%<br>|
| Experimental: Group 2<br>Group 2 - PXVX0317 lot B (Lot 105) | Biological: CHIKV VLP/adjuvant<br>* PXVX0317 vaccine is comprised of chikungunya virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide (Alhydrogel®) adjuvant 2%<br>|
| Experimental: Group 3<br>Group 3 - PXVX0317 lot C (Lot 106) | Biological: CHIKV VLP/adjuvant<br>* PXVX0317 vaccine is comprised of chikungunya virus-like particles (CHIKV VLP), adsorbed on aluminum hydroxide (Alhydrogel®) adjuvant 2%<br>|
| Placebo Comparator: Group 4<br>Group 4 - Placebo | Biological: Placebo<br>* Placebo is comprised of formulation buffer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of solicited Adverse Events (AE) | Incidence of solicited AEs through Day 8 for PXVX0317 and placebo for all age strata combined (safety population). | 8 days | 
| Incidence of unsolicited AEs | Incidence of unsolicited AEs through Day 29 for PXVX0317 and placebo for all age strata combined (safety population). | 29 days | 
| Incidence of Adverse Events of Special Interest (AESI) | Incidence of AESIs, through Day 183 for PXVX0317 and placebo for all age strata combined (safety population). | 183 days | 
| Incidence of Medically Attended Adverse Event (MAAE) | Incidence of MAAEs through Day 183 for PXVX0317 and placebo for all age strata combined (safety population). | 183 days | 
| Incidence of Serious Adverse Event (SAE) | Incidence of SAEs through Day 183 for PXVX0317 and placebo for all age strata combined (safety population). | 183 days | 
| Anti-CHIKV serum neutralizing antibody (SNA) seroresponse rates at Day 22 | Anti-CHIKV SNA seroresponse rates for PXVX0317 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. | 22 days | 
| Anti-CHIKV SNA geometric mean titers (GMT) at Day 22 | Anti-CHIKV SNA GMTs and associated 95% CIs at Day 22 for PXVX0317 and placebo for the IEP, all age strata combined. | 22 days | 
| Anti-CHIKV SNA GMT ratios between pairs of PXVX0317 lots at Day 22 | Anti-CHIKV SNA GMT ratios and associated 95% CIs between all three pairs of PXVX0317 lots (A:B, A:C, B:C) in adults 18 to <46 years of age in the IEP at Day 22. | 22 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-CHIKV SNA seroresponse rates at Days 15, 183, and 8 | Anti-CHIKV SNA seroresponse rates for PXVX0317 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. | 183 days | 
| Anti-CHIKV SNA Geometric Mean Titers (GMTs) at Days 8, 15, and 183 | Anti-CHIKV SNA GMTs with associated 95% CIs at Day 8, Day 15, and Day 183 for PXVX0317 and placebo for the IEP, all age strata combined. | 183 days | 
| Geometric Mean Fold Increase (GMFI) in anti-CHIKV SNA titers from Day 1 to Days 8, 15, 22, and 183 | 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. | 183 days | 
| Number and percentage of participants with anti-CHIKV SNA titer >15 and 4-fold rise over baseline at Days 8, 15, 22, and 183 | 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. | 183 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, immunogenicity, Chikungunya, VLP, PXVX0317