Targeted Microbiome Transplant in Atopic Dermatitis

Study Overview
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Brief Summary
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The purpose of this study is to examine the safety and effectiveness of a new therapy, commensal lotion containing infection fighting bacteria, on decreasing or eliminating the infection causing bacteria found on the skin of Atopic Dermatitis (AD) patients.

Detailed Description
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This study will enroll adult participants, 18-60 years of age, with moderate-to-severe atopic dermatitis (AD) and a positive Staphylococcus aureus (S. aureus) colonized lesion (at least 15 cm^2 in size) on the upper extremities. Participants who are eligible based on their positive Staph culture results will be randomized to one of two treatments: Targeted Microbiome Transplant Lotion (TMT) or Placebo (2:1 randomization). One lesional site measuring at least 15 cm^2 and one non-lesional site of equal size will be identified on the participant's ventral upper extremities as the target swabbing areas. These sites will be photographed and marked for swabbing for reference at the participant's future visits. Participants will be instructed to apply investigational product with gloved hands to their ventral upper extremities bilaterally from the wrist to the upper humerus, which will include the identified lesional and non-lesional swabbing sites twice a day for 1 week starting on Day 0. Participants will return to clinic on Day 4 for the assessment of adverse events, the collection of skin swabs from the identified target sites, and to obtain additional investigational product and gloves. Participants will complete an additional clinic visit on Day 7 to correspond with the end of their 1 week treatment. During this visit, participants will be assessed for AEs and provide skin swab samples. All unused product and empty packets will be returned during the Day 4 and Day 7 visits. Three additional clinic visits on Days 8, 9, and 11 will be scheduled for additional skin swabs to assess the safety and the stability of the microbiome transplant and time to recurrence of Staph colonization. Participants will be followed through Day 38 to assess for safety and disease status.

Official Title
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A First in Man Evaluation of the Safety and Efficacy of an Allogeneic Targeted Microbiome Transplant in Adults With Moderate-to-Severe Atopic Dermatitis (ADRN-08)

Conditions
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Atopic Dermatitis (AD)

Intervention / Treatment
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* Biological: TMT Lotion
* Drug: Placebo Lotion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who meet all of the following criteria are eligible for enrollment as study participants: Participant must be able to understand and provide informed consent; Fulfills the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria (Appendix A) for active Atopic Dermatitis (AD); A Staphylococcus aureus (S. aureus) positive culture colonized lesion, at least 15 cm^2 in size, located on a ventral upper extremity (e.g., arm); An Investigator Global Assessment (IGA) score, on the ventral arms, of at least moderate severity; A body surface area (BSA), as measured by Mosteller BSA Calculator, between 1.26 m^2 (e.g., 4 feet, 10 inches and 85 pounds [38.6 Kg] and 2.25 m^2 (e.g., 6 feet, 3 inches and 210 pounds [95.5 Kg]; and Females of childbearing potential who are willing to use adequate contraception 30 days prior to the Screening Visit and until participation in the study is complete. --Females of childbearing potential must agree to use an acceptable method of birth control (e.g. total abstinence, oral contraceptives, intrauterine device [IUD], barrier method with spermicide, surgical sterilization or surgically sterilized partner, Depo-Provera, Norplant, NuvaRing, or hormonal implants) for the duration of study participation. Male participants who are willing to use an acceptable method of contraception (e.g. barrier methods with spermicide, surgical sterilization or surgically sterilized partner) or practice abstinence until participation in the study is complete. Exclusion Criteria: Inability or unwillingness of participant to give written informed consent or comply with study protocol; Pregnant or lactating females, or females who desire to become pregnant and/or breast feed within the duration of study participation; Active bacterial, viral, or fungal skin infections; Any noticeable breaks or cracks in the skin on the upper extremities, 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(R) Lotion, alcohol-based cleaners, macadamia nuts, soy, Vegetable glycerin, or palm kernels; Participants with prosthetic heart valves, pacemakers, intravascular catheters, or other foreign or prosthetic devices; 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 Immune Deficiency Syndrome (AIDS), Wiskott-Aldrich Syndrome) or has a history of malignant disease (with the exception of non-melanoma skin cancer); 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 biologics within 16 weeks of Screening Visit; Participants with close contacts (e.g. spouses, children, or members in the same household) that have severe barrier defects or are immunocompromised; Use of topical (including steroids and calcineurin inhibitors) Atopic Dermatitis (AD) treatments within 7 days of the Treatment Visit; Use of topical steroids on areas outside of where investigational product is to be applied may be permitted, per investigator discretion; Treatment of AD with prescription moisturizers classified as medical device (e.g., Atopiclair®, MimyX®, Epicerum®, Cerave®, etc.) within 7 days of the Treatment Visit; Use of any oral or topical antibiotics 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 AD therapies (antihistamines, steroids, immunosuppressive therapies) within 28 days of the Treatment Visit; or 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
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMT Lotion<br>The targeted microbiome transplant (TMT) lotion will be provided in single-dose sealed packets. The lotion should be stored at 4°Celsius (=39.2 degrees Fahrenheit). Participants randomized to active TMT will apply 2 grams of TMT to each ventral aspect of their arm (wrist to upper humerus). Frequency of lotion application: topical application administered twice daily for one week. | Biological: TMT Lotion<br>* TMT product and Vegetable glycerin-Cetaphil®<br>* Other names: Targeted Microbiome Transplant (TMT) Lotion;|
| Placebo Comparator: Placebo Lotion<br>Placebo lotion will be provided in single-dose sealed packets. The lotion should be stored at 4°Celsius (=39.2 degrees Fahrenheit). Participants randomized to placebo will apply 2 grams of placebo to each ventral aspect of their arm (wrist to upper humerus). Frequency of lotion application: topical application administered twice daily for one week. | Drug: Placebo Lotion<br>* Cetaphil® moisturizing lotion and vegetable glycerin<br>* Other names: Placebo for Targeted Microbiome Transplant (TMT) Lotion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per-Participant Daily Event Rate: Serious and Non-Serious Treatment Emergent Adverse Events (TEAEs) | Per-participant daily event rate of TEAEs was calculated as the number of events per-participant-days at risk. Statistical method employed: Poisson generalized linear model with a log link function and including the natural log of the number of days active in the study during Day 0 to Day 8. | Day 0 to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Occurrence of at Least One Serious or Non-Serious Treatment Emergent Adverse Event (TEAE) | The number of participants for which at least one treatment emergent adverse event (AE), defined as an increase in grade from baseline or from the last post-baseline value that does not meet grading criteria, was reported during the measure time frame. | Day 0 (after initiation of study treatment) through Day 8 (last day of study treatment) | 
| Per-Participant Daily Event Rate of Serious and Non-Serious Adverse Events (AEs) | Per-participant daily event rate of serious and non-serious AEs was calculated by the number of events per-participant days active in the study during Screening to Day 38. | Screening (up to 38 days before initiation of treatment) to Day 38 (last day of study participation) | 
| The Occurrence of at Least One Serious or Non-Serious Adverse Event (AE) | The number of participants for which at least one adverse event (AE) was reported | Screening (up to 38 days before initiation of treatment) to Day 38 (last day of study participation) | 
| The Eczema Area and Severity Index (EASI) Score of the Ventral Arms at Specific Days During the Measure Time Frame | The eczema area and severity index (EASI) for the ventral arms is a composite score measuring physical signs of atopic dermatitis. The scale ranges from 0-18. The components measuring severity are four signs/symptoms of atopic dermatitis: erythema, papulation, excoriation, and lichenification each scored on a scale of 0 (absent) to 3 (severe) for the ventral arms. The component measuring area is the percent area of the ventral arms with atopic dermatitis lesions scored on a scale of 0 (0%) to 6 (90-100%). | Days 0, 4, 7, 8 and 11 | 
| The Scoring Atopic Dermatitis (SCORAD) Score at Specific Days During the Measure Time Frame | SCORAD (Severity scoring of Atopic Dermatitis) is a composite severity index comprising A) the amount/extent of body surface area affected; A= 0-100%, B) disease intensity assessed as sum of scores for 6 parameters (erythema, edema/papulation, oozing/crusting, excoriation, lichenification, and dryness), each graded from 0 (none) to 3 (severe); B= 0-18, and C) subjective symptom visual analog assessments for pruritus [0 (no itch) to 10 (worst imaginable itch)] and sleep loss [0 (no sleep loss) to 10 (worst imaginable sleep loss)] summed for a total symptom score; C=0-20. The SCORAD = A/5 + 7B/2 + C and ranges from 0 (no AD present) to 103 (severe). | Days 0, 4, 7, 8 and 11 | 
| The Rajka-Langeland (RL) Score at Specific Days During the Measure Time Frame | The Rajka & Langeland (RL) eczema severity score is a simple assessment of AD severity as well as the classification of AD into mild, moderate, or severe. The score is based on the grading of: (i) eczema extent based on % body area affected, (ii) eczema course based on the number of months with remission during the previous year, and (iii) eczema intensity expressed in terms of nocturnal sleep disturbance due to itch. Each parameter is scored on a scale from 1-3, and the scores are summed. The RL score ranges from 3 to 9 (mild, 3-4; moderate, 4.5-7.5; severe, 8-9) | Days 0 and 7 | 
| The Pruritus Visual Analog Scale (VAS) Score of the Ventral Arms at Specific Days During the Measure Time Frame | The pruritus visual analog scale (VAS) asks participants to rate the status of their Pruritus based on the severity of their itch. Scores range from 0 to 10 (0 = no itch, 10 = worst imaginable itch) | Days 0, 4, 7, 8 and 11 | 
| The Abundance of Coagulase Negative Staphylococcal (CoNS) Species, as Measured by Culture, on Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of CoNS present on lesional and non-lesional skin measured by Colony Forming Units per centimeter squared (CFU/cm^2) | Days 0, 4, 7, 8 and 11 | 
| The Abundance of Coagulase Negative Staphylococcal (CoNS) Species, as Measured by qPCR (Quantitative Polymerase Chain Reaction), on Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of CoNS on lesional and non-lesional skin measured by qPCR relative colony forming units per centimeter squared [rCFU/cm^2] | At days 0, 4, 7, 8 and 11 | 
| The Change From Baseline Levels of Coagulase Negative Staphylococcal (CoNS) Bacteria Abundance, as Measured by Culture, on Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of CoNS present on lesional and non-lesional skin measured by Colony Forming Units per centimeter squared (CFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Change From Baseline Levels of Coagulase-Negative Staphylococcus (CoNS) Bacteria Abundance, as Measured by qPCR (Quantitative Polymerase Chain Reaction), on Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of CoNS present on lesional and non-lesional skin measured by qPCR (relative colony forming units per centimeter squared [rCFU/cm^2]) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Change From Baseline Levels of S. Hominis A9 Bacteria Abundance, as Measured by Quantitative Polymerase Chain Reaction (qPCR), on Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of S. hominis A9 present on lesional and non-lesional skin measured by qPCR (relative colony forming units per centimeter squared [rCFU/cm^2]) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Abundance of S. Aureus, as Measured by Culture, Between Treatment Groups on Lesional and Non-Lesional Skin Separately | Amount of S. aureus present on lesional and non-lesional skin measured by Colony Forming Units per centimeter squared (CFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Abundance of S. Aureus, as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Treatment Groups on Lesional and Non-Lesional Skin Separately | Amount of S. aureus present on lesional and non-lesional skin measured by relative Colony Forming Units per centimeter squared (rCFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Abundance of S. Aureus, as Measured by Culture, Between Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of S. aureus present on lesional and non-lesional skin measured by Colony Forming Units per centimeter squared (CFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Abundance of S. Aureus, as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of S.aureus present on lesional and non-lesional skin measured by relative Colony Forming Units per centimeter squared (rCFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Change From Baseline Levels of S. Aureus Abundance, as Measured by Culture, Between Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of S. aureus present on lesional and non-lesional skin measured by Colony Forming Units per centimeter squared (CFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Change From Baseline Levels of S. Aureus Abundance, as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Lesional and Non-Lesional Skin Within Each Treatment Group | Amount of S. aureus present on lesional and non-lesional skin measured by relative Colony Forming Units per centimeter squared (rCFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Abundance of Bacterial Deoxyribonucleic Acid (DNA) of Combined S. Hominis, as Measured by Quantitative Polymerase Chain Reaction (qPCR), Between Treatment Groups on Lesional and Non-Lesional Skin Separately | Amount of combined S. hominis present on lesional and non-lesional skin measured by relative Colony Forming Units per centimeter squared (rCFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Abundance of Bacterial Deoxyribonucleic Acid (DNA) of Combined Staphylococci, as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Treatment Groups on Lesional and Non-Lesional Skin Separately | Amount of combined Staphylococci present on lesional and non-lesional skin measured by relative Colony Forming Units per centimeter squared (rCFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 
| The Abundance of Combined Bacterial Deoxyribonucleic Acid (DNA), as Measured by qPCR (Quantitative Polymerase Chain Reaction), Between Treatment Groups on Lesional and Non-Lesional Skin Separately | Amount of combined bacteria present on lesional and non-lesional skin measured by relative Colony Forming Units per centimeter squared (rCFU/cm^2) | Days 0 (1 hour post treatment), 4, 7, 8 and 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allogeneic targeted microbiome transplant (TMT), dysbiosis in AD, Staphylococcus aureus colonized skin, antimicrobial peptides (AMPs), randomized trial