This is a Phase 1b, randomized, placebo/vehicle-controlled, double-blinded, multi-center trial. It is designed to assess the safety and efficacy of S. hominis A9 (ShA9) topical application as a treatment for atopic dermatitis (AD). The trial will enroll adults and adolescents with atopic dermatitis who are culture positive for S. aureus colonization. The primary safety objective of this study is to compare the safety profile of ShA9 to placebo (vehicle) over 14 weeks of application, which includes an initial two-week period of co-treatment with topical corticosteroids (TCS). The primary efficacy objective of this study is to assess the ability of ShA9, compared to placebo (vehicle), to prolong the period of atopic dermatitis control over 12 weeks after conclusion of an initial two-week period of co-treatment with TCS.
Protocol ADRN-14 TIME-2 is a Phase 1b, randomized, placebo/vehicle-controlled, double-blinded, multi-center trial designed to assess the safety and efficacy of ShA9 topical application as a treatment for AD. This study will aim to enroll up to 86 participants; participants must be 12 years of age or older, have AD, and test culture positive for S. aureus (SA+) on their lesional skin. An individual participant's involvement in this study will take approximately 20 weeks to complete, including approximately 2 weeks of screening, 14 weeks of treatment, and 4 weeks of safety follow-up. An initial screening visit will be conducted to evaluate eligibility, including by assessing skin swabs collected from each participant for S. aureus positivity. SA+ participants will then begin an approximately 14-day period of standardized skin care by using over-the-counter products (e.g., Dove soap, Cetaphil moisturizer) which will be distributed from the study clinic. This is done to establish an informative baseline and allow for washout of any prohibited medications. Participants who continue to meet eligibility criteria will then be randomized 1:1 to use either ShA9 gel or placebo (vehicle) gel for treatment of AD. Following randomization, for two weeks, each participant will receive co-treatment using TCS together with their assigned study product (active or placebo). Participants will then continue using their assigned study product without TCS for 12 more weeks. Participants will be seen in clinic approximately every 4 weeks during this time for sample/data collection and safety monitoring. Participants may be seen in clinic for additional visits to address any skin exacerbations while enrolled. Participation concludes with a 4-week safety follow-up period during which use of ShA9 or placebo (vehicle) gel is halted. Participants will return to using over-the-counter products that will be distributed from the study clinic as needed, continuing to avoid prohibited medications and will be monitored for skin exacerbations or other adverse events.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
86
The ShA9 topical gel contains phosphate-buffered saline solution (PBS), Glycerol, and hydroxyethylcellulose containing lyophilized ShA9 bacteria. The ShA9 bacteria is derived from a healthy donor-derived (allogeneic) commensal Staph species. The gel is manufactured and packaged by University of California San Diego (UCSD). It is applied twice daily to all areas identified as actively lesional during the Baseline Visit, regardless of ongoing lesional status, until the Week 14 Visit. If new lesions arise during this time, these areas will also be treated, regardless of ongoing lesional status, until the Week 14 Visit.
All participants will apply hydrocortisone ointment 2.5% alongside the study product in sensitive body areas (e.g., face, neck, intertriginous regions) for the first two weeks of the trial. It is applied twice daily to all areas identified as actively lesional during the Baseline Visit, regardless of ongoing lesional status, until the Week 2 Visit. If new lesions arise during this time, these areas will also be treated, regardless of ongoing lesional status, until the Week 2 Visit.
All participants will apply clobetasol ointment 0.05% alongside the study product in non-sensitive body areas (e.g., arms, legs, torso) for the first two weeks of the trial. It will be applied twice daily to lesional skin and selected sampling areas from Baseline to Week 2. It is applied twice daily to all areas identified as actively lesional during the Baseline Visit, regardless of ongoing lesional status, until the Week 2 Visit. If new lesions arise during this time, these areas will also be treated, regardless of ongoing lesional status, until the Week 2 Visit.
Participants with a past intolerance to clobetasol or who become too sensitive to clobetasol in the initial two-week cotreatment period will apply fluocinonide ointment 0.05% as an alternative. In these cases, fluocinonide ointment 0.05% will be applied alongside the study product in non-sensitive body areas (e.g., arms, legs, torso) for the first two weeks of the trial. It is applied twice daily to all areas identified as actively lesional during the Baseline Visit, regardless of ongoing lesional status, until the Week 2 Visit. If new lesions arise during this time, these areas will also be treated, regardless of ongoing lesional status, until the Week 2 Visit.
The placebo (vehicle) topical gel contains phosphate-buffered saline solution (PBS), Glycerol, and hydroxyethylcellulose. The gel is manufactured and packaged by University of California San Diego (UCSD). It is applied twice daily to all areas identified as actively lesional during the Baseline Visit, regardless of ongoing lesional status, until the Week 14 Visit. If new lesions arise during this time, these areas will also be treated, regardless of ongoing lesional status, until the Week 14 Visit.
University of California, San Diego: Dermatology Clinical Trials Unit
San Diego, California, United States
RECRUITINGNational Jewish Health: Division of Pediatric Allergy and Clinical Immunology
Denver, Colorado, United States
RECRUITINGNorthwestern University Feinberg School of Medicine: Department of Dermatology
Chicago, Illinois, United States
RECRUITINGNew York University Langone Health: Department of Pediatric Allergy and Immunology
New York, New York, United States
RECRUITINGIcahn School of Medicine at Mount Sinai: Department of Pediatrics Allergy & Immunology
New York, New York, United States
RECRUITINGUniversity of Rochester Medical Center: Department of Dermatology
Rochester, New York, United States
RECRUITINGCincinnati Children's Hospital Medical Center: Asthma Center
Cincinnati, Ohio, United States
RECRUITINGUniversity of Wisconsin School of Medicine and Public Health: Division of Pediatric Allergy, Immunology and Rheumatology
Madison, Wisconsin, United States
RECRUITINGTime to the first Atopic Dermatitis (AD) flare.
Time (in days) to the first Atopic Dermatitis (AD) flare, indicated by having an Investigator Global Assessment (IGA) score that is greater than or equal to 2 and greater than the IGA score determined at Week 2. The IGA score is used to describe the overall appearance of AD lesions on a scale of 0 (clear) to 4 (severe).
Time frame: Week 2 (exclusive) through Week 14 (inclusive)
Serious and non-serious treatment-emergent adverse events (TEAEs) related or possibly related to study treatment.
The number of serious and non-serious treatment-emergent adverse events (TEAEs) related or possibly related to study treatment. If a participant experiences the same TEAE on multiple occasions, the event will be counted once for each occurrence when reporting the number of TEAEs.
Time frame: Baseline through Week 14
Serious and non-serious TEAEs related or possibly related to study treatment.
The number of serious and non-serious TEAEs related or possibly related to study treatment. If a participant experiences the same TEAE on multiple occasions, the event will be counted once for each occurrence when reporting the number of TEAEs.
Time frame: Week 14 (exclusive) through Week 18
Antibiotic sensitivity of S. aureus and S. epidermidis on the skin.
The proportion of the skin bacteria, S. aureus and S. epidermidis, which can be isolated from skin swabs, that are sensitive to each of the following antibiotics: penicillin G, tetracycline, and erythromycin at Week 14 (post-ShA9 treatment) adjusted for the proportion of bacteria sensitive to antibiotic at Baseline.
Time frame: Baseline, Week 14
Change in total Eczema Area and Severity Index (EASI) score.
The change in total Eczema Area and Severity Index (EASI) score, which measures physical signs of atopic dermatitis, including area of involvement and severity (range: 0-72). Severity components include erythema, papulation, excoriation, and lichenification (0=absent, 1=mild, 2=moderate, 3=severe) for each body region (head/neck, trunk, arms, legs). Area of involvement (%) is assessed for each body region. Area and severity of each body region is weighted based on size of region, and region scores are added for a total EASI score (≤7=mild, \>7 and ≤21.1=moderate, \>21.1=severe). Descriptive note regarding time frame: if a participant was rescued with TCS within 14 days prior to their Week 14 visit, then their total EASI score at this timepoint will not be considered. Instead, the most recent total EASI score before the use of rescue TCS will be carried forward to represent Week 14.
Time frame: Baseline, Week 14
EASI 50
The proportion of participants who achieve 50% or more reduction in their total EASI score. Descriptive note regarding time frame: if a participant was rescued with TCS within 14 days prior to their Week 14 visit, then their total EASI score at this timepoint will not be considered. Instead, the most recent total EASI score before the use of rescue TCS will be carried forward to represent Week 14.
Time frame: Baseline, Week 14
EASI 75
The proportion of participants who achieve 75% or more reduction in their total EASI score. Descriptive note regarding time frame: if a participant was rescued with TCS within 14 days prior to their Week 14 visit, then their total EASI score at this timepoint will not be considered. Instead, the most recent total EASI score before the use of rescue TCS will be carried forward to represent Week 14.
Time frame: Baseline, Week 14
Change in IGA score
The change in IGA score. The IGA score is used to describe the overall appearance of AD lesions on a scale of 0 (clear) to 4 (severe). Descriptive note regarding time frame: if a participant was rescued with TCS within 14 days prior to their Week 14 visit, then their IGA score at this timepoint will not be considered. Instead, the most recent IGA score before the use of rescue TCS will be carried forward to represent Week 14.
Time frame: Baseline, Week 14
Change in Pruritus Numeric Rating Scale (NRS) score.
The change in Pruritus Numeric Rating Scale (NRS) score, which measures the average intensity of a pruritus (itch) during a 24-hour recall period on a scale of 0 (none) to 10 (worst imaginable itch). Descriptive note regarding time frame: if a participant was rescued with TCS within 14 days prior to their Week 14 visit, then their NRS score at this timepoint will not be considered. Instead, the most recent NRS score before the use of rescue TCS will be carried forward to represent Week 14.
Time frame: Baseline, Week 14
Change in SCORing Atopic Dermatitis (SCORAD) score.
The change in SCORing Atopic Dermatitis (SCORAD) score, which ranges from 0 (no AD) to 103 (severe). SCORAD is a composite index comprising a) the amount/extent of body surface area affected, b) subjective symptom visual analog assessments of itch and sleep loss, each on a scale of 0 (none) to 10 (worst imaginable), and c) 6 disease intensity assessments: dryness, erythema, edema/papulation, excoriation, lichenification and oozing/crusting, each graded from 0 (none) to 3 (severe). Descriptive note regarding time frame: if a participant was rescued with TCS within 14 days prior to their Week 14 visit, then their SCORAD score at this timepoint will not be considered. Instead, the most recent SCORAD score before the use of rescue TCS will be carried forward to represent Week 14.
Time frame: Baseline, Week 14
Duration of rescue topical corticosteroid (TCS) use.
The total number of days that topical corticosteroid (TCS) was used as a rescue medication within the upper extremities, lower extremities, and trunk of the body region, overall and separated by the potency class of steroids. The decision to begin the rescue TCS regimen due to skin exacerbation is dependent on investigator assessment, self-reported participant need, and standard of care.
Time frame: Week 2 (exclusive) through Week 14 (inclusive)
Time to the first reported use of rescue TCS.
Time (in days) to the first reported use of rescue TCS. The decision to begin the rescue TCS regimen due to skin exacerbation is dependent on investigator assessment, self-reported participant need, and standard of care.
Time frame: Week 2 (exclusive) through Week 14 (inclusive)
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