NasoShield in Healthy Adults to Study Safety and Immunogenicity

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety for up to two doses of NasoShield, to determine if antibodies that protect against anthrax are formed after treatment with NasoShield, and to determine whether the formation of these antibodies are affected by different positions of administration.

Detailed Description
-----------------
After being informed about the study and potential risks, all healthy volunteers that have given written informed consent will undergo screening to determine eligibility for study entry. If the healthy volunteer qualifies for the study, they will be randomly assigned to 1 of 3 treatment groups. Within the treatment group, the participant will be randomized in a double-blind manner in a 5:2 ratio to NasoShield or placebo. The investigational drug (either NasoShield or placebo) will be administered on Days 1 and 29 after qualifying into the study. The position of administration and the amount of time the subject will need to stay in the specified position will depend on the group to which the subject is assigned. Participants will return to the investigational site for multiple visits through Day 210 (approximately 6 months after the second dose). At each visit, the participant will be asked about interim medical history and use of any medications, and safety and immunogenicity assessments will be performed.

Official Title
-----------------
A Double-blind, Randomized, Placebo-controlled, Study of the Safety and Immunogenicity of NasoShield Administered as One or Two Doses in Different Dosing Positions

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Biological: NasoShield
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women 18 to 49 years of age, inclusive Good general health status Adequate venous access for repeated phlebotomies Screening laboratory results within institutional normal range or Grade 1 abnormality if the Investigator documents clinical insignificance. Creatine kinase or bilirubin may be Grade 2 if associated with normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the Investigator considers the result not to be clinically significant due to vigorous exercise or Gilbert's syndrome Negative drug and alcohol screen at Screening and predose on Day 1 For women who have not been surgically sterilized or who do not have laboratory confirmation of postmenopausal status, negative pregnancy test Willingness to practice a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with a postmenopausal partner, monogamous relationship with vasectomized partner, vasectomy, surgical sterilization (hysterectomy, bilateral tubal ligation, salpingectomy, or oophorectomy), licensed hormonal methods, intrauterine device (IUD), or consistent use of a barrier method (eg, condom, diaphragm) with spermicide for 28 days after the last IP dose Willingness to participate and comply with all aspects of the study through the entire study period, including nasopharyngeal swabs and blood and urine samples Provision of written informed consent Exclusion Criteria: Pregnant, possibly pregnant, or lactating women Body mass index > 35.0 kg/m2 Positive result for HIV, hepatitis B virus, or hepatitis C virus at Screening Asthma or other chronic lung disease that is greater than mild in severity. Specifically excluded are participants with any of the following events in the past year: Daily symptoms Daily use of short acting beta 2 agonists Use of inhaled steroids or theophylline Use of pulse systemic steroids Emergency care or hospitalization related to asthma or other chronic lung disease Systemic steroids for asthma exacerbation History of diabetes mellitus (gestational diabetes is allowed if treatment was not required postpartum and serum glucose is currently in the normal range) History of coronary artery disease, arrhythmia, or congestive heart failure Clinically significant ECG abnormality Poorly controlled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 95 mmHg) at Screening or predose on Day 1 History of anaphylaxis or angioedema Known allergy to any of the ingredients in the vaccine formulation Known allergy or sensitivity to latex History of chronic rhinitis, nasal septal defect, cleft palate, nasal polyps, or other nasal abnormality that might affect vaccine administration Previous nasal surgery or nasal cauterization Any symptoms of upper respiratory infection or temperature > 38°C within 3 days before Day 1 Any symptoms within 24 hours before Day 1 of upper respiratory illness or allergy flare-up that, in the opinion of the Investigator, presents as nasal congestion or rhinorrhea that could inhibit the proper administration of the IP Known or suspected malignancy, excluding non-melanoma skin cancers and other early stage surgically excised malignancies that the Investigator considers to be exceedingly unlikely to recur Immunocompromised individuals, including those who have used corticosteroids(including intranasal steroids), alkylating drugs, antimetabolites, radiation, immune-modulating biologics, or other immunomodulating therapies within 90 days before Day 1 or those who plan use during the study period History of autoimmune or demyelinating disease Use of statin medication within 30 days before Day 1 (see list in Section 6.7.1) Receipt of intranasal medications (including over-the-counter medications) within 30 days before Day 1 Receipt of any IP within 30 days before Day 1 Receipt of any vaccine within 30 days before Day 1 Receipt of intranasal vaccine within 90 days before Day 1 Receipt of any licensed or investigational anthrax vaccine in civilian or military life Any change in medication for a chronic medical condition within 30 days before Day 1 Past regular use or current use of intranasal illicit drugs Any medical, psychiatric, or social condition or occupational or other responsibility that in the judgment of the Investigator would interfere with or serve as a contraindication to protocol adherence, assessment of safety (including reactogenicity), or a subject's ability to give informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3 parallel groups defined by dosing position and number of doses
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NasoShield One Dose in Position 1<br>NasoShield on Day 1 and saline placebo on Day 29 in position 1 (Group 1) | Biological: NasoShield<br>* NasoShield is an adenovirus-vectored anthrax vaccine<br>Other: Placebo<br>* Normal saline<br>|
| Placebo Comparator: Placebo in Position 1<br>Saline placebo on Day 1 and saline placebo on Day 29 in position 1 (Group 1) | Other: Placebo<br>* Normal saline<br>|
| Experimental: NasoShield Two Doses in Position 2<br>NasoShield on Day 1 and Day 29 in position 2 (Group 2) | Biological: NasoShield<br>* NasoShield is an adenovirus-vectored anthrax vaccine<br>|
| Placebo Comparator: Placebo in Position 2<br>Saline placebo on Day 1 and Day 29 in position 2 (Group 2) | Other: Placebo<br>* Normal saline<br>|
| Experimental: NasoShield Two Doses in Position 3<br>NasoShield on Day 1 and Day 29 in position 3 (Group 3) | Biological: NasoShield<br>* NasoShield is an adenovirus-vectored anthrax vaccine<br>|
| Placebo Comparator: Placebo in Position 3<br>Saline placebo on Day 1 and Day 29 in position 3 (Group 3) | Other: Placebo<br>* Normal saline<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactogenicity to evaluate the safety of NasoShield | Subjects will record solicited local and systemic events for 7 days after each dose | For 7 days after vaccination | 
| Adverse Events (AEs) to evaluate the safety of NasoShield | All adverse events from Day 1 to Day 57; serious adverse events (SAE), medically attended adverse events (MAAE), and new-onset chronic illnesses (NCI) from Day 1 to Day 210 | From Day 1 to Day 210 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-protective antigen (PA) immunoglobulin G (IgG) to evaluate humoral immunogenicity | Titer measured by enzyme-linked immunosorbent assay (ELISA) in serum | From Day 1 to Day 210 | 
| Toxin neutralization antibody 50% neutralization factor (TNA-NF50) titer measured in serum by cytotoxic assay to evaluate humoral immunogenicity |  | From Day 1 to Day 210 | 
| Anti-protective antigen (PA) immunoglobulin A (IgA) to evaluate mucosal immune response | Titer measured by enzyme-linked immunosorbent assay (ELISA) in serum | From Day 1 to Day 57 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anthrax