Atopic Dermatitis
Conditions
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.
Interventions
BIOLOGICALS. hominis A 9 Product
Commensal staph species, phosphate buffered saline, and glycerol.
DRUGPlacebo
Phosphate buffered saline and glycerol
Sponsors
Atopic Dermatitis Research Network
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study, as all participants will receive active and placebo treatment. Participants will receive active treatment on one of their ventral arms and placebo on their contralateral ventral arm. Investigators, all investigational site staff, including those responsible for preparing/administering the investigational product, and all participants in this study will be blinded as to which arm received which treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Duration of ShA9 Survival on the Lesional Ventral Arm Skin of Atopic Dermatitis (AD) Participants Positive for S. Aureus (AD SA+). | Day 0 to Day 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Duration of ShA9 Survival on the Non-lesional Ventral Arm Skin of Atopic Dermatitis (AD) Participants Positive for S. Aureus (AD SA+). | Day 0 to Day 24 | 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. |
| The Count of Serious Treatment-emergent Adverse Events Per Participant. | Day 0 to Day 31 | 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. |
| The Count of Non-serious Treatment-emergent Adverse Events Per Participant. | Day 0 to Day 31 | 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. |
Countries
United States
Participant flow
Recruitment details
Enrollment was open JUL 2022-OCT 2023. Participants were recruited in person or via phone. Those who met recruitment criteria were invited to an in-clinic Screening Visit where informed consent was given and full eligibility assessed. Those meeting eligibility requirements began a pre-treatment phase for \ 7 days before the Day 0 clinic visit.
Pre-assignment details
21 participants were enrolled during the recruitment period. Enrolled participants were those who signed informed consent and met all eligibility criteria. 17 of the enrolled participants were randomized and received study therapy. 4 of the enrolled participants discontinued prior to randomization and did not receive study therapy.
Participants by arm
| Arm | Count |
|---|---|
| Safety Population The safety population includes all participants who were enrolled and received any amount of Staphylococcus hominis A9 (ShA9)/placebo. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 24.9 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 5 Participants |
| Staphylococcus aureus (SA) Status SA Negative | 7 Participants |
| Staphylococcus aureus (SA) Status SA Positive | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 2 / 17 | 2 / 17 | 3 / 21 | 3 / 21 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 21 | 0 / 21 |
Outcome results
Primary
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.
Time frame: Day 0 to Day 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| mITT, SA+ Participants | The Duration of ShA9 Survival on the Lesional Ventral Arm Skin of Atopic Dermatitis (AD) Participants Positive for S. Aureus (AD SA+). | 37.0 Hours |
Secondary
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.
Time frame: Day 0 to Day 31
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| mITT, SA+ Participants | The Count of Non-serious Treatment-emergent Adverse Events Per Participant. | 0.24 Non-serious TEAEs per participant | Standard Deviation 0.752 |
Secondary
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.
Time frame: Day 0 to Day 31
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| mITT, SA+ Participants | The Count of Serious Treatment-emergent Adverse Events Per Participant. | 0 Serious TEAEs per participant | Standard Deviation 0 |
Secondary
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.
Time frame: Day 0 to Day 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| mITT, SA+ Participants | The Duration of ShA9 Survival on the Non-lesional Ventral Arm Skin of Atopic Dermatitis (AD) Participants Positive for S. Aureus (AD SA+). | 6.0 Hours |