Back to resultsA Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047
Primary Purpose
Adenoviral Infection
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PXVX0047 Vaccine
Teva Ad4/Ad7 Vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Adenoviral Infection
Eligibility Criteria
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.
Sites / Locations
- Cincinnati Children's Hospital Medical Center
- University of Vermont Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
PXVX0047 treatment group
Teva Ad4/Ad7 treatment group
Arm Description
Subjects will receive PXVX0047 vaccine and Teva Placebo-to-Match
Subjects will receive Teva Ad4/Ad7 vaccine and PXVX0047 Placebo-to-Match
Outcomes
Primary Outcome Measures
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
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
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
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
Secondary Outcome Measures
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
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
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.
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.
Evaluate the pharmacodynamics of PXVX0047 by measuring the presence of Ad4 viremia
Presence of Ad4 viremia in the blood
Evaluate the pharmacodynamics of PXVX0047 by measuring the presence of Ad7 viremia
Presence of Ad7 viremia in the blood
Evaluate the immunogenicity of PXVX0047 by measuring Ad4 seroconversion rates
The Ad4 seroconversion rates, measured independently, determined by luciferase and CPE-based assays
Evaluate the immunogenicity of PXVX0047 by measuring Ad7 seroconversion rates
The Ad7 seroconversion rates, measured independently, determined by luciferase and CPE-based assays
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.
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.
Evaluate the immunogenicity of PXVX0047 by measuring geometric mean titer
The geometric mean titer (GMT) of neutralizing antibodies to Ad4, measured independently
Evaluate the immunogenicity of PXVX0047 by measuring geometric mean titer
The geometric mean titer (GMT) of neutralizing antibodies to Ad7, measured independently
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
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
Evaluate the immunogenicity of PXVX0047 by measuring the cellular immune responses to Ad4 viruses
The cellular immune responses to Ad4, measured independently
Evaluate the immunogenicity of PXVX0047 by measuring the cellular immune responses to Ad7 viruses
The cellular immune responses to Ad7, measured independently
Full Information
NCT ID
NCT03160339
First Posted
May 15, 2017
Last Updated
March 3, 2020
Sponsor
Emergent BioSolutions
Collaborators
Walter Reed Army Institute of Research (WRAIR)
1. Study Identification
Unique Protocol Identification Number
NCT03160339
Brief Title
A Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
Sponsor Decision
Study Start Date
May 1, 2017 (Actual)
Primary Completion Date
November 27, 2017 (Actual)
Study Completion Date
November 27, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Emergent BioSolutions
Collaborators
Walter Reed Army Institute of Research (WRAIR)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenoviral Infection
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PXVX0047 treatment group
Arm Type
Experimental
Arm Description
Subjects will receive PXVX0047 vaccine and Teva Placebo-to-Match
Arm Title
Teva Ad4/Ad7 treatment group
Arm Type
Active Comparator
Arm Description
Subjects will receive Teva Ad4/Ad7 vaccine and PXVX0047 Placebo-to-Match
Intervention Type
Biological
Intervention Name(s)
PXVX0047 Vaccine
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Teva Ad4/Ad7 Vaccine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Evaluate safety and tolerability of PXVX0047 by documenting the incidence of severity of solicited adverse events
Description
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
Time Frame
From Day 1 through Day 15
Title
Evaluate the safety and tolerability of PXVX0047 by documenting the incidence and severity of adverse events that are not solicited.
Description
Unsolicited adverse events include clinical significant laboratory abnormalities
Time Frame
From Day 1 through Day 29
Title
Evaluate the induction of anti-Ad4 neutralizing activity by measuring the Ad4 and Ad7 seroconversion rate
Description
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
Time Frame
From Day 1 to Day 29
Title
Evaluate the induction of anti-Ad7 neutralizing activity by measuring the Ad7 seroconversion rate
Description
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
Time Frame
From Day 1 to Day 29
Secondary Outcome Measure Information:
Title
Evaluate the pharmacodynamics of PXVX0047 by measuring the shedding of Ad4 viruses via the GI tract
Description
Shedding of Ad4 via the GI tract, as assessed by rectal swabs
Time Frame
Days 4, 8, 15, 22, and 29
Title
Evaluate the pharmacodynamics of PXVX0047 by measuring the shedding of Ad7 viruses via the GI tract
Description
Shedding of Ad7 via the GI tract, as assessed by rectal swabs
Time Frame
Days 4, 8, 15, 22, and 29
Title
Evaluate the pharmacodynamics of PXVX0047 by measuring the shedding of Ad4 viruses via the respiratory tract
Description
Shedding of Ad4 via the respiratory tract, as assessed by throat swabs.
Time Frame
Days 4, 8, 15, 22, and 29
Title
Evaluate the pharmacodynamics of PXVX0047 by measuring the shedding of Ad7 viruses via the respiratory tract
Description
Shedding of Ad7 via the respiratory tract, as assessed by throat swabs.
Time Frame
Days 4, 8, 15, 22, and 29
Title
Evaluate the pharmacodynamics of PXVX0047 by measuring the presence of Ad4 viremia
Description
Presence of Ad4 viremia in the blood
Time Frame
Days 4, 8, 15, 22, and 29
Title
Evaluate the pharmacodynamics of PXVX0047 by measuring the presence of Ad7 viremia
Description
Presence of Ad7 viremia in the blood
Time Frame
Days 4, 8, 15, 22, and 29
Title
Evaluate the immunogenicity of PXVX0047 by measuring Ad4 seroconversion rates
Description
The Ad4 seroconversion rates, measured independently, determined by luciferase and CPE-based assays
Time Frame
Through Day 57
Title
Evaluate the immunogenicity of PXVX0047 by measuring Ad7 seroconversion rates
Description
The Ad7 seroconversion rates, measured independently, determined by luciferase and CPE-based assays
Time Frame
Through Day 57
Title
Evaluate the immunogenicity of PXVX0047 by measuring cumulative Ad4 seroconversion rates
Description
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.
Time Frame
Through Day 57
Title
Evaluate the immunogenicity of PXVX0047 by measuring cumulative Ad7 seroconversion rates
Description
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.
Time Frame
Through Day 57
Title
Evaluate the immunogenicity of PXVX0047 by measuring geometric mean titer
Description
The geometric mean titer (GMT) of neutralizing antibodies to Ad4, measured independently
Time Frame
Through Day 57
Title
Evaluate the immunogenicity of PXVX0047 by measuring geometric mean titer
Description
The geometric mean titer (GMT) of neutralizing antibodies to Ad7, measured independently
Time Frame
Through Day 57
Title
Evaluate the immunogenicity of PXVX0047 by measuring the fold-rise over baseline of neutralizing antibodies to Ad4 viruses
Description
The fold-rise over baseline in neutralizing antibodies to Ad4, measured independently
Time Frame
Through Day 57
Title
Evaluate the immunogenicity of PXVX0047 by measuring the fold-rise over baseline of neutralizing antibodies to Ad7 viruses
Description
The fold-rise over baseline in neutralizing antibodies to Ad7, measured independently
Time Frame
Through Day 57
Title
Evaluate the immunogenicity of PXVX0047 by measuring the cellular immune responses to Ad4 viruses
Description
The cellular immune responses to Ad4, measured independently
Time Frame
At Days 29 and 57.
Title
Evaluate the immunogenicity of PXVX0047 by measuring the cellular immune responses to Ad7 viruses
Description
The cellular immune responses to Ad7, measured independently
Time Frame
At Days 29 and 57.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University of Vermont Medical Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Study to Assess the Safety, Pharmacodynamics, and Immunogenicity of PXVX0047
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