Trial of a Chikungunya Vaccine, PXVX0317 CHIKV-VLP, in Healthy Adults

Study Overview
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Brief Summary
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The goal of this Phase 2 trial is to evaluate the immune response to and safety profile of various doses/formulations/and schedules of administration of PXVX0317 in healthy adults. Primary Objective: To assess the immune response to the vaccine Secondary Objectives: To assess the kinetics of the immune response to different doses/formulations/schedules To assess the persistence of immune responses to different doses/formulations/schedules To assess the effect of a booster dose of the vaccine Safety Objective: To assess local and systemic reactions to the vaccine and to describe the safety profile of the vaccine

Detailed Description
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The trial will explore 8 formulation/schedule combinations of CHIKV VLP vaccine with or without Alhydrogel adjuvant, and will also explore different dose schedules of Day 1 and 15 or Day 1 and 29 or Day 29 only.

Official Title
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A Phase 2 Parallel-Group, Randomized, Double-Blind Study to Assess the Safety and Immunogenicity of PXVX0317 (Chikungunya Virus Virus-Like Particle Vaccine [CHIKV-VLP], Unadjuvanted or Alum-adjuvanted)

Conditions
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Chikungunya Virus Infection

Intervention / Treatment
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* Biological: CHIKV VLP/unadjuvanted
* Biological: CHIKV VLP/adjuvanted
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Age 18 to 45 years old (inclusive) Using an acceptable method of contraception (if female of childbearing potential). Able and willing to provide informed consent for study participation. Exclusion Criteria: Current acute febrile illness. Clinically significant cardiac, respiratory, or rheumatologic disease, in the opinion of the Investigator. Pregnant or breast-feeding. Laboratory evidence of infection with Hepatitis B/C or HIV. History of chikungunya virus infection. Travel to a World Health Organization-designated chikungunya-endemic region within 30 days prior to Day 1. History of allergic reaction to any component of CHIKV-VLP vaccine, Diluent, or Alhydrogel®. Inability to discontinue systemic immunomodulatory or immunosuppressive medications 30 days prior to Day 1. Received or plans to receive any licensed vaccine from 30 days prior to Day 1 through Day 57. Received or plans to receive an investigational agent from 30 days prior to Day 1 through the duration of study participation. Any other condition that, in the opinion of the Investigator, creates an unacceptable risk to the subject. Any other condition that, in the opinion of the Investigator, may interfere with the conduct of the study or the validity of the data. Any other condition that, in the opinion of the Investigator, creates an unacceptable safety risk for apheresis (Group 9 & 10 only). Restricted venous access that would prevent the collection of PBMCs, plasma, and lymphocytes necessary for participation (Group 9 & 10 only). Weight < 110 pounds (Group 9 & 10 only)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: 20 mcg/unadjuvanted (Day 1 & 29)<br>20 mcg CHIKV VLP/unadjuvanted (Day 1) // Placebo (Day 15) // 20 mcg CHIKV VLP/unadjuvanted (Day 29) | Biological: CHIKV VLP/unadjuvanted<br>* Vaccine consists of virus-like particles of chikungunya virus antigens<br>Biological: Placebo<br>* Placebo is vaccine diluent alone<br>|
| Experimental: Group 2: 6 mcg/adjuvanted (Day 1 & 29)<br>6 mcg CHIKV VLP/adjuvanted (Day 1) // Placebo (Day 15) // 6 mcg CHIKV VLP/adjuvanted (Day 29) | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>Biological: Placebo<br>* Placebo is vaccine diluent alone<br>|
| Experimental: Group 3: 10 mcg/adjuvanted (Day 1 & 29)<br>10 mcg CHIKV VLP/adjuvanted (Day 1) // Placebo (Day 15) // 10 mcg CHIKV VLP/adjuvanted (Day 29) | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>Biological: Placebo<br>* Placebo is vaccine diluent alone<br>|
| Experimental: Group 4: 20mcg/adjuvanted (Day 1 & 29);40mcg/adjuvant (Day 547)<br>20 mcg CHIKV VLP/adjuvanted (Day 1) // Placebo (Day 15) // 20 mcg CHIKV VLP/adjuvanted (Day 29) // 40 mcg CHIKV (Day 547) | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>Biological: Placebo<br>* Placebo is vaccine diluent alone<br>|
| Experimental: Group 5: 6 mcg/adjuvanted (Day 15 & 29)<br>Placebo (Day 1) // 6 mcg CHIKV VLP/adjuvanted (Day 15) // 6 mcg CHIKV VLP/adjuvanted (Day 29) | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>Biological: Placebo<br>* Placebo is vaccine diluent alone<br>|
| Experimental: Group 6: 10 mcg/adjuvanted (Day 15 & 29)<br>Placebo (Day 1) // 10 mcg CHIKV VLP/adjuvanted (Day 15) // 10 mcg CHIKV VLP/adjuvanted (Day 29) | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>Biological: Placebo<br>* Placebo is vaccine diluent alone<br>|
| Experimental: Group 7: 20 mcg/adjuvanted (Day 15 & 29)<br>Placebo (Day 1) // 20 mcg CHIKV VLP/adjuvanted (Day 15) // 20 mcg CHIKV VLP/adjuvanted (Day 29) | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>Biological: Placebo<br>* Placebo is vaccine diluent alone<br>|
| Experimental: Group 8: 40 mcg/adjuvanted (Day 29)<br>Placebo (Day 1) // Placebo (Day 15) // 40 mcg CHIKV VLP/adjuvanted (Day 29) | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>Biological: Placebo<br>* Placebo is vaccine diluent alone<br>|
| Experimental: Group 9: 20 mcg/adjuvanted (Day 1 & 29)<br>20 mcg CHIKV VLP/adjuvanted (Day 1) // 20 mcg CHIKV VLP/adjuvanted (Day 29). This group will also have plasmapheresis performed on Day 57 and Leukapheresis on Day 182 | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>|
| Experimental: Group 10: 40 mcg/adjuvanted (Day 1)<br>40 mcg CHIKV VLP/adjuvanted (Day 1). This group will also have plasmapheresis performed on Day 22. | Biological: CHIKV VLP/adjuvanted<br>* Adjuvanted formulation includes Alhydrogel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-CHIKV Neutralizing Antibody Geometric Mean Titer 28 Days After the Last Injection for Groups 2-8. | To assess the induction of anti-chikungunya virus (CHIKV) neutralizing antibody geometric mean titers by different formulations and schedules, as measured at 28 days after the last injection (Day 57) for Groups 2-8. | Day 57 (from Day 1 vaccination), 28 days after the last injection. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics of Anti-chikungunya Virus (CHIKV) Neutralizing Antibody Geometric Mean Titer for Groups 2-8. | To describe the kinetics of induction of anti-CHIKV neutralizing antibody geometric mean titers by different formulations and schedules for Groups 2-8. | At Days 8, 15, 22, 29, 36, and 57. | 
| Differences in Persistence of Neutralizing Antibody Geometric Mean Titer for Groups 2-8. | To assess differences in persistence of neutralizing antibody geometric mean titers induced by different formulations and schedules, as measured up to 731 days after the last injection (Day 760) relative to earlier time points for Groups 2-8. | At Days 182, 365, 547, and 760. | 
| Boosting of Vaccine-induced Neutralizing Antibody Geometric Mean Titer by a Booster Dose of PXVX0317 for Group 4 Only. | To assess the effect of a booster dose of PXVX0317 on neutralizing antibody geometric mean titers when given at Day 547 for Group 4 only. Antibody levels will be measured at Day 547 prior to the booster dose and again 28 days later on Day 575 and then at Day 760. | Antibody levels will be measured at Day 547 prior to the booster dose and again 28 days later on Day 575 and then at Day 760. | 
| Percentage of Participants With an Anti-CHIKV Neutralizing Antibody Titer Exceeding the Following Cutoff Values: ≥15, 40, 160, 640, and 4-fold Rise Over Baseline. | Percentage of participants with an anti-CHIKV neutralizing antibody titer exceeding the following cutoff values: ≥15, 40, 160, 640, and 4-fold rise over baseline. | Day 57 (from Day 1 vaccination), 28 days after the last injection. |