Clinical trial NCT01979406: A Phase 1 Ascending Dose Study to Assess the Safety and Immunogenicity of Adenovirus Anthrax Vector Candidate Vaccines
Official title: A Phase 1 Randomized Double-Blind Positive-Controlled Ascending Dose Study to Evaluate the Safety and Immunogenicity of a Replication-Competent Adenovirus Serotype 4 Anthrax Vector Candidate Vaccines - Ad4-PA (Protective Antigen)and Ad4-PA-GPI (Glycosylphosphatidylinositol)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anthrax Infection
Keywords: Anthrax vaccine
Lead sponsor: Emergent BioSolutions
Sponsor class: INDUSTRY
First posted: 2013-11-08
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate 2 vaccine candidates against anthrax compared to the positive (vaccine) control as studied in normal healthy volunteers.

Detailed description: A Phase 1, randomized, double-blind, positive controlled, increasing dose clinical trial in healthy adult subjects at multiple sites. The study will assess safety and immunogenicity of two adenovirus vaccine candidates against anthrax compared to the positive control, Anthrax Vaccine Adsorbed (AVA). The trial will enroll 108 subjects in the anthrax vector vaccine arms and 12 subjects in the AVA positive control subjects. The study will look at three different dose of oral dosages of Ad4-PA (protective antigen) and Ad4-PA-GPI (10\^9, 10\^10, 10\^11 vp/dose)as well as 3 vaccine administration schedules (1 and 15 days; 1 and 29 days; 1, 15, and 29 days); 2 of 3 schedules will include an intramuscular (IM) AVA booster immunization, 1 schedule will include 3 vaccine administrations of Ad4-PA or Ad4-PA-GPI (glycosylphosphatidylinositol) alone, and 1 schedule will include 3 vaccine administrations of AVA alone.

Eligibility criteria: Inclusion Criteria:

* Able to understand the study and give written informed consent.
* Healthy men or women aged 18-40 years old,
* BMI between 18 to 36 kg/m2
* Women of child bearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to vaccination on all vaccination days; they must also be willing to use adequate birth control for the duration of the study and have additional pregnancy tests if indicated.
* Intact upper arms with sufficient muscular tissue in the deltoid region for IM vaccine administration.
* Subject must be available for the study duration
* Subject must avoid strenuous exercise for at least 72 hours prior to each study vaccine administration.

Exclusion Criteria:

* Subject is a healthcare worker who has direct contact with patients or has an household contact (HHC) who is immunodeficient or HIV-positive, pregnant, has an unstable medical condition, or is under the age of 18.
* Subject is a childcare worker or a parent who has direct contact with children 5 years old and younger.
* Subject directly prepares food in the food industry.
* Pregnant or breastfeeding throughout the duration of the study until the final visit
* Military service between 1971 and 1999, or after 2012 when Ad4 vaccine was/is routinely given
* Employment in an industry involved in contact with ruminant animals, veterinary sciences, or other potential exposure to B. anthracis
* Received previous Ad4 vaccination or experimental Ad4 vector vaccines
* Received previous anthrax vaccine
* Received or plans to receive any other approved or investigational vaccines from 30 days prior to the first study vaccination until 30 days after the final study vaccination for live attenuated vaccines and from 15 days prior to the first study vaccination until 15 days after the final study vaccination for inactivated vaccines
* HIV or Hepatitis B or C positive
* Immunodeficient or has an unstable medical condition including psychiatric conditions
* Active or past history of acute or chronic gastrointestinal conditions
* Active or past history of cancer except basal cell carcinoma
* Recipient of bone marrow or solid organ transplant
* Received or plans to receive systemic antiviral medication, within 30 days prior to the first study vaccination
* Known allergy to any component of the study vaccine
* Known allergy to, or known medical condition that precludes use of any systemic antiviral medication
* Received or plans to receive medications indicated for decreasing acidity of stomach including:
* Proton pump inhibitors or antacids or histamine 2-receptor antagonists
* Received or plans to receive immunoglobulin or other blood products within 60 days prior to the first study vaccination
* Received or plans to receive other investigational drugs within 30 days prior to the first study vaccination
* Received or plans to receive systemic immunosuppressive therapy, radiation therapy, or inhaled steroids within 30 days prior to the first study vaccination
* Asthmatic or requires asthmatic medications on a daily basis
* Use of systemic chemotherapy within 5 years prior to study
* Body temperature \>38.1°C or acute illness within 3 days prior to vaccination
* History of excessive alcohol consumption, drug abuse, or significant psychiatric illness
* History of Guillain-Barré Syndrome
* Blood donation within 2 months prior to first study vaccination
* Expected to be noncompliant with study visits or plans to move away or be living with different HHCs during the next 8 months
* Drinks more than 1200 mL of tea/coffee/cocoa/cola or other caffeinated beverage per day.
* Any condition or finding that in the view of the primary investigator would impede full study participation

Primary outcomes:
measure: The safety, tolerability and immunogenicity of the Ad4 PA and Ad4 PA GPI vaccines across a range of dosages and schedules.
timeFrame: Day 1 through Day 211
Secondary outcomes:
measure: Antibody response of the Ad4-PA formulation to Ad4 PA GPI
timeFrame: Day 1 through Day 85 (Day 211 if Day 85 is positive)
measure: Antibody response of the Ad4-PA and Ad4-PA-GPI vaccination regimens to the anticipated AVA PEP regimen.
timeFrame: Days 1 through 85 (Day 211 if Day 85 is positive)
measure: Antibody response induced by 3 different dosages of Ad4 PA and Ad4 PA GPI.
timeFrame: Days 1 through 85 (Day 211 if Day 85 is positive)
measure: TNA and antibody response induced by Ad4 PA and Ad4 PA GPI on 3 different vaccination schedules.
timeFrame: Days 1 through 85 (Day 211 if Day 85 is positive)
measure: Pre-existing Ad4 immunity on TNA and PA-ELISA response induced by Ad4 PA and Ad4 PA GPI.
timeFrame: Days 1 through 85 (Day 211 if Day 85 is positive)
measure: Evaluate the kinetics of the TNA and PA-ELISA antibody response induced by 3 different doses of Ad4 PA and Ad4 PA GPI on 3 different administration schedules.
timeFrame: Days 1 through 85 (Day 211 if Day 85 is positive)
measure: In vivo replication/excretion of the Ad4 PA and Ad4 PA GPI vaccines
timeFrame: Days 1 through 211
Other outcomes:
measure: Systemic PA-specific cellular immune response induced by Ad4-PA and Ad4-PA-GPI
timeFrame: Days 1 through 43
measure: Mucosal PA-ELISA antibody responses induced by Ad4-PA and Ad4 PA-GPI
timeFrame: Days 1 through 29
Locations:
city: Kansas City
country: United States
facility: The Center for Pharmaceutical Research
state: Kansas
city: Silver Spring
country: United States
facility: Walter Reed Army Institute for Research
state: Maryland
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
Study officials:
affiliation: Emergent BioSolutions
name: Marc Gurwith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emergent BioSolutions
name: Jakub Simon, MD
role: STUDY_DIRECTOR
affiliation: National Institutes of Health (NIH)
name: Mo Elsafy, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: