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

Adenoviral Infection Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03160339
• Other study ID #: PXVX-AD-047-001
• Status: Terminated
• Phase: Phase 1
• Start date: May 1, 2017
• Est. completion date: November 27, 2017

Study information

• Verified date: March 2024
• Source: Emergent BioSolutions
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: November 27, 2017
• Est. primary completion date: November 27, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenoviral Infection
• Adenoviridae Infections

Intervention

Biological:
• PXVX0047 Vaccine
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.
• Teva Ad4/Ad7 Vaccine
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.

Locations

Country	Name	City	State
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Emergent BioSolutions	Walter Reed Army Institute of Research (WRAIR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.