A Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047

Study Overview
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Brief Summary
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PXVX0047 (Adenovirus Type 4 and Type 7 Vaccine [A549 Cells], Live, Oral) is an investigational vaccine in development for the indication of active immunization against adenovirus infection. The primary goals of this Phase 1 study are to evaluate safety, pharmacodynamics (viral shedding), and immunogenicity of PXVX0047.

Official Title
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A Phase 1 Two-Arm, Randomized, Double-blind, Active-controlled Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047 (Adenovirus Type 4 and Type 7 Vaccine [A549 Cells], Live, Oral)

Conditions
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Adenoviral Infection

Intervention / Treatment
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* Biological: PXVX0047 Vaccine
* Biological: Teva Ad4/Ad7 Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Age 18 to 35 Seronegative for Ad4 and Ad7 by CPE-based assay (if female of childbearing potential) Using an acceptable method of contraception If male, subject agrees to use a highly effective method of contraception with female sexual partners of childbearing potential Able and willing to provide informed consent for study participation Exclusion Criteria: Current acute febrile illness Current acute gastrointestinal illness Clinically significant cardiac, respiratory, or gastrointestinal disease (if female of childbearing potential) Pregnant or nursing, or who plan to become pregnant or nurse during the study Persons with occupations which may create an increased risk of transmission of vaccine virus (including but not limited to health care workers, child or elderly care providers, food handlers or preparers) who also have expected occupational contact with children less than 7 years of age, pregnant or nursing women, women of childbearing potential not using an acceptable method of contraception, or chronically ill or immunosuppressed individuals through Day 29. Expected household contact with children less than 7 years of age, pregnant or nursing women, women of childbearing potential not using an acceptable method of contraception, or chronically ill or immunosuppressed individuals through Day 29. Laboratory evidence of infection with Hepatitis B/C or HIV. History of severe allergic reaction (e.g. anaphylaxis) to any component of the vaccine. Inability to swallow capsules or tablets whole without chewing or crushing. Immunosuppressed individuals, including those treated or planned to be treated with systemic immunosuppressive medications within the 30 days prior to enrollment through 30 days after study treatment. Concomitant or planned use of other vaccines, investigational agents, cidofovir, ribavirin, or medications expected by the Investigator to have antiviral activity against adenovirus within 30 days prior to enrollment through Day 29. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PXVX0047 treatment group<br>Subjects will receive PXVX0047 vaccine and Teva Placebo-to-Match | Biological: PXVX0047 Vaccine<br>* PXVX0047 is a live Adenovirus Type 4 (Ad4) / Adenovirus Type 7 (Ad7) vaccine for single-dose oral administration. The Ad4 and Ad7 strains in PXVX 0047 are unattenuated strains propagated in A549 human adenocarcinomic alveolar basal epithelial cells.<br>|
| Active Comparator: Teva Ad4/Ad7 treatment group<br>Subjects will receive Teva Ad4/Ad7 vaccine and PXVX0047 Placebo-to-Match | Biological: Teva Ad4/Ad7 Vaccine<br>* Teva Ad4/Ad7 is a live Adenovirus Type 4 (Ad4) / Adenovirus Type 7 (Ad7) vaccine for single-dose oral administration. The Ad4 and Ad7 strains in Teva Ad4/Ad7 are unattenuated strains propagated in WI-38 human diploid fibroblast cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety and tolerability of PXVX0047 by documenting the incidence of severity of solicited adverse events | Incidence of severity of solicited adverse events include abdominal pain, nausea, vomiting, diarrhea, cough, nasal congestion, dyspnea, sore throat, headache, fever fatigue chills myalgia, arthralgia | From Day 1 through Day 15 | 
| Evaluate the safety and tolerability of PXVX0047 by documenting the incidence and severity of adverse events that are not solicited. | Unsolicited adverse events include clinical significant laboratory abnormalities | From Day 1 through Day 29 | 
| Evaluate the induction of anti-Ad4 neutralizing activity by measuring the Ad4 and Ad7 seroconversion rate | The Ad4 seroconversion rate is defined as the percent of subjects seroconverted (i.e. with a 4-fold or greater rise over baseline in neutralizing antibody titer) to Ad4 as determined by cytopathic-effect (CPE)-based assay | From Day 1 to Day 29 | 
| Evaluate the induction of anti-Ad7 neutralizing activity by measuring the Ad7 seroconversion rate | The Ad7 seroconversion rate is defined as the percent of subjects seroconverted (i.e. with a 4-fold or greater rise over baseline in neutralizing antibody titer) to Ad7 as determined by cytopathic-effect (CPE)-based assay | From Day 1 to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the pharmacodynamics of PXVX0047 by measuring the shedding of Ad4 viruses via the GI tract | Shedding of Ad4 via the GI tract, as assessed by rectal swabs | Days 4, 8, 15, 22, and 29 | 
| Evaluate the pharmacodynamics of PXVX0047 by measuring the shedding of Ad7 viruses via the GI tract | Shedding of Ad7 via the GI tract, as assessed by rectal swabs | Days 4, 8, 15, 22, and 29 | 
| Evaluate the pharmacodynamics of PXVX0047 by measuring the shedding of Ad4 viruses via the respiratory tract | Shedding of Ad4 via the respiratory tract, as assessed by throat swabs. | Days 4, 8, 15, 22, and 29 | 
| Evaluate the pharmacodynamics of PXVX0047 by measuring the shedding of Ad7 viruses via the respiratory tract | Shedding of Ad7 via the respiratory tract, as assessed by throat swabs. | Days 4, 8, 15, 22, and 29 | 
| Evaluate the pharmacodynamics of PXVX0047 by measuring the presence of Ad4 viremia | Presence of Ad4 viremia in the blood | Days 4, 8, 15, 22, and 29 | 
| Evaluate the pharmacodynamics of PXVX0047 by measuring the presence of Ad7 viremia | Presence of Ad7 viremia in the blood | Days 4, 8, 15, 22, and 29 | 
| Evaluate the immunogenicity of PXVX0047 by measuring Ad4 seroconversion rates | The Ad4 seroconversion rates, measured independently, determined by luciferase and CPE-based assays | Through Day 57 | 
| Evaluate the immunogenicity of PXVX0047 by measuring Ad7 seroconversion rates | The Ad7 seroconversion rates, measured independently, determined by luciferase and CPE-based assays | Through Day 57 | 
| Evaluate the immunogenicity of PXVX0047 by measuring cumulative Ad4 seroconversion rates | The cumulative Ad4 seroconversion rates, measured independently, where cumulative seroconversion through a particular visit is defined as having seroconverted at or prior to that visit. | Through Day 57 | 
| Evaluate the immunogenicity of PXVX0047 by measuring cumulative Ad7 seroconversion rates | The cumulative Ad7 seroconversion rates, measured independently, where cumulative seroconversion through a particular visit is defined as having seroconverted at or prior to that visit. | Through Day 57 | 
| Evaluate the immunogenicity of PXVX0047 by measuring geometric mean titer | The geometric mean titer (GMT) of neutralizing antibodies to Ad4, measured independently | Through Day 57 | 
| Evaluate the immunogenicity of PXVX0047 by measuring geometric mean titer | The geometric mean titer (GMT) of neutralizing antibodies to Ad7, measured independently | Through Day 57 | 
| Evaluate the immunogenicity of PXVX0047 by measuring the fold-rise over baseline of neutralizing antibodies to Ad4 viruses | The fold-rise over baseline in neutralizing antibodies to Ad4, measured independently | Through Day 57 | 
| Evaluate the immunogenicity of PXVX0047 by measuring the fold-rise over baseline of neutralizing antibodies to Ad7 viruses | The fold-rise over baseline in neutralizing antibodies to Ad7, measured independently | Through Day 57 | 
| Evaluate the immunogenicity of PXVX0047 by measuring the cellular immune responses to Ad4 viruses | The cellular immune responses to Ad4, measured independently | At Days 29 and 57. | 
| Evaluate the immunogenicity of PXVX0047 by measuring the cellular immune responses to Ad7 viruses | The cellular immune responses to Ad7, measured independently | At Days 29 and 57. |