Targeted Investigation of Microbiome Elimination

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine the pharmacokinetics or survival of new product containing commensal infection fighting bacteria, on the skin of patients with Atopic Dermatitis (AD), after a single application.

Detailed Description
-----------------
This study will enroll a minimum of 20 participants, 18-80 years of age, with moderate-to-severe atopic dermatitis (AD) on their ventral arms. A minimum of 13 participants will have a positive Staphylococcus aureus (S. aureus) colonized lesion on both upper extremities. A minimum of 7 participants will have a negative S. aureus colonized lesion on both upper extremities. The participant's colonization status will be determined from cultures taken during a pre-treatment phase, approximately 7 days prior to receiving study treatment on Day 0. On Day 0, skin swabs will be collected from lesional and non-lesional sites (at least 21cm^2) on the participant's right and left ventral arms and one non-lesional site on the participant's face. After the skin swab collections, the participant will have ShA9 applied to their right or left ventral arm and placebo applied to their contralateral ventral arm. The assignment of ShA9 and placebo to the dominant and non-dominant arms will be randomized. Additional swabs will be collected 15 minutes, and 1, 2, 4, and 6 hours after the ShA9 and placebo applications on Day 0. Participants will be asked to return to the clinic 24 hours after receiving their single application and again on Days 3, 10, 17, and 24 for the assessment of adverse events (AEs) and the collection of skin swabs from the identified lesional and non-lesional sites, as needed. After the Day 3 visit, a participant will not be required to complete the Day 10, 17, and 24 visits if their lesional swabs are negative for Coagulase Negative Staphylococcal Species (CoNS). All randomized participants will complete a final End of Study Phone visit on Day 31 to assess for adverse events and status of their AD.

Official Title
-----------------
A Pilot Study to Evaluate the Survival of Transplanted Staphylococcus Hominis A9 on the Skin of Adults With Moderate-to-Severe Atopic Dermatitis (ADRN-UCSD-001)

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Biological: S. hominis A 9 Product
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must be able to understand and provide informed consent Meet Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria for active atopic dermatitis (AD) At least 21 cm^2 of lesional and 21 cm^2 of non-lesional skin on both the right and left ventral arms. The required area (lesional or non-lesional) may be one contiguous area or may encompass multiple areas with a total cumulative area of 21 cm^2 An Investigator Global Assessment (IGA) score, on the ventral arms of at least moderate severity Body surface area (BSA), as measured by Mostellar BSA Calculator, between 1.26 m^2 and 2.25 m^2 If female of child bearing potential, must agree to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraception (e.g. oral contraceptives, intrauterine device [IUD], barrier method with spermicide, or surgically sterilized partner, Depo- Provera, Norplant, NuvaRing, or hormonal implants) for the duration of study participation Exclusion Criteria: Inability or unwillingness of a participant to give written informed consent or comply with study protocol Pregnant or lactating females Active bacterial, viral, or fungal skin infections Any noticeable breaks or cracks in the skin on the target areas of investigational product application, including severely excoriated skin or skin with open or weeping wounds suggestive of an active infection or increased susceptibility to infection Sensitivity to or difficulty tolerating Dove fragrance-free bar soap, Cetaphil® Lotion, alcohol-based cleaners, glycerol, or soy products Participants with Netherton's syndrome or other genodermatoses that result in a defective epidermal barrier Any participant who is immunocompromised (e.g. history of lymphoma, Human Immunodeficiency Virus [HIV]/Acquired Immunodeficiency Syndrome [AIDS], Wiskott-Aldrich Syndrome), has an immune system disorder (e.g. autoimmune disease), or is using a systemic immunosuppressant (e.g. systemic corticosteroids, cyclosporine, methotrexate) Any participant with current malignant disease (with the exception of non-melanoma skin cancer in an area not affected by treatment) Participants with a history of psychiatric disease or history of alcohol or drug abuse that would interfere with the ability to comply with the study protocol Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. Ongoing participation in another investigational trial or use of investigational drugs within 8 weeks, or 5 half-lives (if known), whichever is longer, of the Screening Visit Treatment with non-steroid systemic immunosuppressant within 6 months of the Screening Visit Treatment with Dupilumab within 16 weeks of the Screening Visit Treatment with oral or injectable therapy for AD (excluding oral steroids) within 5 half-lives (if known) or 16 weeks before the Screening Visit, whichever is longer Participants with close contacts (e.g. spouse, children, or members in the same household) that have severe barrier defects or are immunocompromised Use of topical (including steroids and calcineurin inhibitors) AD treatments on the ventral arms or face within 7 days of the Treatment Visit; Use of topical steroids on areas outside of where investigational product is to be applied or swabbing is to be performed may be permitted, per investigator discretion Treatment with prescription moisturizers classified as medical device (e.g., Atopiclair(R), MimyX(R), Epiceram(R), etc.) on the ventral arms or face within 7 days of the Treatment Visit; Use on areas outside of where investigational product is to be applied or swabbing is to be performed is permitted Use of any oral or topical antibiotic within 7 days of the Treatment Visit Participants who have taken a bleach bath within 7 days of the Treatment Visit Use of any oral steroid therapies within 28 days of the Treatment Visit Any phototherapy for skin disease (such as narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + UVA [PUVA]) or regular use (more than 2 visits per week) of a tanning bed within 28 days of the Treatment Visit

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ShA9 dominant and placebo non-dominant<br>The ShA9 product and placebo will be provided in single dose dispensers. Dispensers will be stored at -80°Celsius (= -112 degrees Fahrenheit) and thawed to 4°Celsius (=39.2 degrees Fahrenheit) prior to administration. Participants will have a single application of ShA9 applied by clinic staff to their dominant arm (i.e. right arm for a right handed participant) and a single application of placebo applied to their contralateral arm (i.e. left arm for a right handed participant). | Biological: S. hominis A 9 Product<br>* Commensal staph species, phosphate buffered saline, and glycerol.<br>* Other names: ShA9;Drug: Placebo<br>* Phosphate buffered saline and glycerol<br>* Other names: Placebo for S. hominis A 9 Product;|
| Experimental: ShA9 non-dominant and placebo dominant<br>The ShA9 product and placebo will be provided in single dose dispensers. Dispensers will be stored at -80°Celsius (= -112 degrees Fahrenheit) and thawed to 4°Celsius (=39.2 degrees Fahrenheit) prior to administration. Participants will have a single application of placebo applied by clinic staff to their dominant arm (i.e. right arm for a right handed participant) and a single application of ShA9 applied to their contralateral arm (i.e. left arm for a right handed participant). | Biological: S. hominis A 9 Product<br>* Commensal staph species, phosphate buffered saline, and glycerol.<br>* Other names: ShA9;Drug: Placebo<br>* Phosphate buffered saline and glycerol<br>* Other names: Placebo for S. hominis A 9 Product;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The duration of ShA9 survival on the lesional ventral arm skin of atopic dermatitis (AD) participants positive for S. aureus (AD SA+) | Measured as the time needed for of commensal coagulase negative staphylococcus species Colony-Forming Unit (CoNS CFU) to drop below baseline density measured before application of ShA9 + 100 CFU/cm^2 | Day 0 to Day 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The duration of ShA9 survival on the non-lesional ventral arm skin of atopic dermatitis (AD) participants positive for S. aureus (AD SA+) | Measured as the time needed for the of commensal coagulase negative staphylococcus species Colony-Forming Unit (CoNS CFU) to drop below baseline density measured before application of ShA9 + 100 CFU/cm^2 | Day 0 to Day 24 | 
| The count of serious treatment-emergent adverse events | For this study, an adverse event will include any untoward or unfavorable medical occurrence associated with the study's treatment regimen or study mandated procedure, blood draw. An adverse event is considered 'serious' if, in the view of the investigator or Sponsor, it results in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. This endpoint is measured per participant. | Day 0 to Day 31 | 
| The count of non-serious treatment-emergent adverse events | For this study, an adverse event will include any untoward or unfavorable medical occurrence associated with the study's treatment regimen or study mandated procedure, blood draw. An adverse event is considered 'non-serious' if it does not result in any of the serious defined outcomes. This endpoint is measured per participant. | Day 0 to Day 31 |