Targeted Investigation of Microbiome Elimination (TIME-1)

A Pilot Study to Evaluate the Survival of Transplanted Staphylococcus Hominis A9 on the Skin of Adults With Moderate-to-Severe Atopic Dermatitis (ADRN-13)

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.

Study Overview

• Status: Terminated
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Biological: S. hominis A 9 Product; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego: Dermatology Clinical Trials Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant must be able to understand and provide informed consent
2. Meet Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria for active atopic dermatitis (AD)
3. 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
4. An Investigator Global Assessment (IGA) score, on the ventral arms of at least moderate severity
5. Body surface area (BSA), as measured by Mostellar BSA Calculator, between 1.26 m^2 and 2.25 m^2
6. 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:

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol
2. Pregnant or lactating females
3. Active bacterial, viral, or fungal skin infections
4. 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
5. Sensitivity to or difficulty tolerating Dove fragrance-free bar soap, Cetaphil® Lotion, alcohol-based cleaners, glycerol, or soy products
6. Participants with Netherton's syndrome or other genodermatoses that result in a defective epidermal barrier
7. 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)
8. Any participant with current malignant disease (with the exception of non-melanoma skin cancer in an area not affected by treatment)
9. 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
10. 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.
11. 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
12. Treatment with non-steroid systemic immunosuppressant within 6 months of the Screening Visit
13. Treatment with Dupilumab within 16 weeks of the Screening Visit
14. 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
15. Participants with close contacts (e.g. spouse, children, or members in the same household) that have severe barrier defects or are immunocompromised
16. 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
17. 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
18. Use of any oral or topical antibiotic within 7 days of the Treatment Visit
19. Participants who have taken a bleach bath within 7 days of the Treatment Visit
20. Use of any oral steroid therapies within 28 days of the Treatment Visit
21. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ShA9; All participants will receive ShA9 active treatment on one of their ventral arms and placebo on their contralateral arm. The assignment of ShA9 and placebo to the dominant and non-dominant arms will be randomized.	Biological: S. hominis A 9 Product; Commensal staph species, phosphate buffered saline, and glycerol.; Other Names: ShA9; Drug: Placebo; Phosphate buffered saline and glycerol; 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 coagulase negative staphylococcus species (CoNS) colony-forming unit (CFU) to drop below baseline density measured before application of ShA9 + 100 CFU/cm2 (time to CoNS elimination). Baseline CoNS density was defined as the CoNS (CFU/cm2) result from the sample taken prior to treatment application during the Treatment Visit (Day 0). The primary endpoint was assessed based on samples from lesional skin from the arm (left or right) that received active treatment (ShA9) among SA+ participants. The event is CoNS elimination. Participants who did not experience CoNS elimination were right-censored. The median survival time (hours) was estimated using Kaplan Meier techniques. The 95% confidence interval for median survival time was estimated based on a log-log transformation of the survivor function.	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 coagulase negative staphylococcus species (CoNS) colony-forming unit (CFU) to drop below baseline density measured before application of ShA9 + 100 CFU/cm2 (time to CoNS elimination). Baseline CoNS density was defined as the CoNS (CFU/cm2) result from the sample taken prior to treatment application during the Treatment Visit (Day 0). This secondary endpoint was assessed based on samples from non-lesional skin from the arm (left or right) that received active treatment (ShA9) among SA+ participants. The event is CoNS elimination. Participants who did not experience CoNS elimination were right-censored. The median survival time (hours) was estimated using Kaplan Meier techniques. The 95% confidence interval for median survival time was estimated based on a log-log transformation of the survivor function.	Day 0 to Day 24
The Count of Serious Treatment-emergent Adverse Events Per Participant.	For this study, an adverse event included any untoward or unfavorable medical occurrence associated with the study treatment regimen or study mandated procedures. An adverse event was considered 'serious' if, in the view of the investigator or Sponsor, it resulted 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.	Day 0 to Day 31
The Count of Non-serious Treatment-emergent Adverse Events Per Participant.	For this study, an adverse event included any untoward or unfavorable medical occurrence associated with the study treatment regimen or study mandated procedures. An adverse event was considered 'non-serious' if it did not result in any of the serious defined outcomes.	Day 0 to Day 31

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Atopic Dermatitis Research Network
• Investigators: Study Chair: Tissa Hata, M.D., University of California, San Diego: Dermatology Clinical Trials Unit; Study Chair: Richard Gallo, M.D., Ph.D., University of California, San Diego: Dermatology Clinical Trials Unit

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2022
• Primary Completion (Actual): August 27, 2023
• Study Completion (Actual): October 13, 2023

Study Registration Dates

• First Submitted: December 15, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Estimated): November 12, 2024
• Last Update Submitted That Met QC Criteria: October 17, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis, Atopic; Dermatitis; Eczema
• Other Study ID Numbers: DAIT ADRN-13

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No