A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial of Cardamom and Topical Roseomonas in Atopic Dermatitis

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial of Cardamom and Topical Roseomonas in Atopic Dermatitis

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial of Cardamom and Topical Roseomonas in Atopic Dermatitis

Study Description: This is a double-blind, randomized, phase 3 clinical trial for a topical formulation of a live biotherapeutic containing Roseomonas mucosa combined with ground cardamom seeds in a sucrose solution for patients with atopic dermatitis (AD). Participants will reconstitute the dried product in water and apply topically 2 or 3 times per week for 14 weeks. After 14 weeks, all interventions will cease, and participants will be followed for an additional 14 weeks to assess how long treatment effects last. During the course of study, we will assess disease severity (eg, itch, rash, and quality of life [QOL]) using a variety of AD assessments, ease of compliance with treatment, and changes in the microbiome profile of the skin. We hypothesize that topical treatment with Roseomonas mucosa, combined with ground cardamom seeds, will provide significantly more alleviation in AD symptoms than placebo, and that these effects will last beyond active treatment (due to the ability of the bacteria to colonize the patients' skin). Primary Objective: To determine if R mucosa combined with ground cardamom seeds can improve symptoms of AD in patients aged 2 and older, 14 weeks after treatment discontinuation. Secondary Objective: To determine if R mucosa combined with ground cardamom seeds can improve the Investigator s Global Assessment (IGA) in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation, and at study completion. To determine if R mucosa combined with ground cardamom seeds can improve the Numerical Rating Scale (NRS) in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation, and at study completion. To determine if R mucosa combined with ground cardamom seeds can improve the SCORing Atopic Dermatitis (SCORAD) in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation, and at study completion. To determine if R mucosa combined with ground cardamom seeds can improve the Patient-Oriented Eczema Measure (POEM) in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation, and at study completion. To determine if effects of R mucosa combined with ground cardamom seeds on the symptoms of AD differ by levels of pollution near home of residence. To determine if use of R mucosa permits less use of topical steroid treatments. To determine the safety of R mucosa use. Exploratory Objectives: To determine if patients and caregivers using topical R mucosa understand the instructions and precautions for use. To determine if topical R mucosa with cardamom seeds alters the skin microbiome profile during and after treatment. To determine if topical R mucosa colonizes the skin of patients during use. Primary Endpoint: Proportion of participants achieving a 90% improvement in Eczema Areav and Severity Index (EASI90; a measure of eczema rash) from baseline(week 0) to study completion (week 28). Secondary Endpoints: Proportion of adverse events (AEs). Mean number of average weekly topical steroid use over the study follow up. Change and percent change in IGA (a measure of eczema rash) from baseline (week 0) to: treatment completion (week 14), mid-follow-up (week 21), and study completion (week 28). Change and percent change in NRS (subjective measure of itch) from baseline (week 0) to: treatment completion (week 14), mid-follow-up (week 21), and study completion (week 28). Change and percent change in SCORAD (a combined metric of eczema itch, rash, QOL) from baseline (week 0) to: treatment completion (week 14), mid-follow-up (week 21), and study completion (week 28). Change and percent change in QOL measures, POEM, from baseline (week 0) to: treatment completion (week 14), mid-follow-up (week 21), and study completion (week 28). Proportion of participants achieving a 90% improvement in EASI90 (a measure of eczema rash) from baseline (week 0) to study completion (week 28) in the high-pollution areas and low-pollution areas. Exploratory Endpoints: Accuracy of identifying correct answers to questions about product applications and precautions. Qualitative input regarding ease of use of product. Presence of treatment strain of R mucosa as assessed by genetic detection (using polymerase chain reaction [PCR] primer). Change in skin microbiome profile during and after treatment.

Study Description: This is a double-blind, randomized, phase 3 clinical trial for a topical formulation of a live biotherapeutic containing Roseomonas mucosa combined with ground cardamom seeds in a sucrose solution for patients with atopic dermatitis (AD). Participants will reconstitute the dried product in water and apply topically 2 or 3 times per week for 14 weeks. After 14 weeks, all interventions will cease, and participants will be followed for an additional 14 weeks to assess how long treatment effects last. During the course of study, we will assess disease severity (eg, itch, rash, and quality of life [QOL]) using a variety of AD assessments, ease of compliance with treatment, and changes in the microbiome profile of the skin. We hypothesize that topical treatment with Roseomonas mucosa, combined with ground cardamom seeds, will provide significantly more alleviation in AD symptoms than placebo, and that these effects will last beyond active treatment (due to the ability of the bacteria to colonize the patients' skin). Primary Objective: To determine if R mucosa combined with ground cardamom seeds can improve symptoms of AD in patients aged 2 and older, 14 weeks after treatment discontinuation. Secondary Objective: To determine if R mucosa combined with ground cardamom seeds can improve the Investigator s Global Assessment (IGA) in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation, and at study completion. To determine if R mucosa combined with ground cardamom seeds can improve the Numerical Rating Scale (NRS) in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation, and at study completion. To determine if R mucosa combined with ground cardamom seeds can improve the SCORing Atopic Dermatitis (SCORAD) in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation, and at study completion. To determine if R mucosa combined with ground cardamom seeds can improve the Patient-Oriented Eczema Measure (POEM) in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation, and at study completion. To determine if effects of R mucosa combined with ground cardamom seeds on the symptoms of AD differ by levels of pollution near home of residence. To determine if use of R mucosa permits less use of topical steroid treatments. To determine the safety of R mucosa use. Exploratory Objectives: To determine if patients and caregivers using topical R mucosa understand the instructions and precautions for use. To determine if topical R mucosa with cardamom seeds alters the skin microbiome profile during and after treatment. To determine if topical R mucosa colonizes the skin of patients during use. Primary Endpoint: Proportion of participants achieving a 90% improvement in Eczema Areav and Severity Index (EASI90; a measure of eczema rash) from baseline(week 0) to study completion (week 28). Secondary Endpoints: Proportion of adverse events (AEs). Mean number of average weekly topical steroid use over the study follow up. Change and percent change in IGA (a measure of eczema rash) from baseline (week 0) to: treatment completion (week 14), mid-follow-up (week 21), and study completion (week 28). Change and percent change in NRS (subjective measure of itch) from baseline (week 0) to: treatment completion (week 14), mid-follow-up (week 21), and study completion (week 28). Change and percent change in SCORAD (a combined metric of eczema itch, rash, QOL) from baseline (week 0) to: treatment completion (week 14), mid-follow-up (week 21), and study completion (week 28). Change and percent change in QOL measures, POEM, from baseline (week 0) to: treatment completion (week 14), mid-follow-up (week 21), and study completion (week 28). Proportion of participants achieving a 90% improvement in EASI90 (a measure of eczema rash) from baseline (week 0) to study completion (week 28) in the high-pollution areas and low-pollution areas. Exploratory Endpoints: Accuracy of identifying correct answers to questions about product applications and precautions. Qualitative input regarding ease of use of product. Presence of treatment strain of R mucosa as assessed by genetic detection (using polymerase chain reaction [PCR] primer). Change in skin microbiome profile during and after treatment.

To determine if R mucosa combined with ground cardamom seeds can improve symptoms of AD in patients aged 2 and older, 14 weeks after treatment discontinuation.

Proportion of participants achieving a 90% improvement in EASI90 (a measure of eczema rash) from baseline (week 0) to study completion (week 28).

To determine if R mucosa combined with ground cardamom seeds can improve symptoms of AD in patients aged 2 and older, during active treatment as well as 7 weeks after treatment discontinuation.

1.<TAB>Proportion of AEs. 2.<TAB>Proportion of participants using topical steroids over the course of the study.3.<TAB>Change and percent change in IGA (a measure of eczema rash) from baseline (week 0) to: treatment completion (week 14), mid-washout (week 21) and study completion (week 28).4.<TAB>Change and percent change in NRS (subjective measure of itch) from baseline (week 0) to: treatment completion (week 14), mid-washout (week 21), and study completion (week 28).5.<TAB>Change and percent change in SCORAD (a combined metric of eczema itch, rash, QoL) from baseline (week 0) to: treatment completion (week 14), mid-washout (week 21), and study completion (week 28).6.<TAB>Change and percent change in QOL measures, POEM, from baseline (week 0) to: treatment completion (week 14), mid-washout (week 21), and study completion (week 28).

INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all of the following criteria: Aged >=2 years Have a documented primary care provider near residence Fluency in English (applicable to participant or caregiver who will be answering questionnaires) Clinical diagnosis of AD, as defined by Hanifin and Rajka criteria, that has been present for >=3 months before the screening visit Major Criteria: Must have >=3 basic features: Pruritus Typical morphology and distribution (flexural lichenification in adults, facial and extensor eruptions in infants and children) Chronic or chronically relapsing dermatitis Personal or family history of atopy (asthma, allergic rhinitis, AD) Minor Criteria: Must have >=3 minor features: Xerosis Ichthyosis/palmar hyperlinearity, keratosis pilaris Immediate (type 1) skin-test reactivity Raised serum IgE Early age of onset Tendency toward cutaneous infections (especially Staphylococcus aureus and herpes simplex), impaired cell-mediated immunity Tendency toward non-specific hand or foot dermatitis Nipple eczema Cheilitis Recurrent conjunctivitis Dennie-Morgan infraorbital fold Keratoconus Anterior subcapsular cataracts Orbital darkening Facial pallor, facial erythema Pityriasis alba Anterior neck folds Itch when sweating Intolerance to wool and lipid solvents Perifollicular accentuation Food intolerance Course influenced by environmental or emotional factors White dermographism, delayed blanch Sexually active participants of childbearing potential must agree to use adequate methods of contraception from the screening visit continuously until 30 days after stopping treatment with the investigational product. Childbearing potential is defined for children as participants who have begun menstruating and for adults as participants who are not surgically sterile (hysterectomy and/or tubal ligation) or menopausal (age >=45 years plus no menses for 12 consecutive months without an alternative medical cause). Adequate contraception methods include: a barrier method (eg, condom use), oral contraceptive pill, hormonal patch or ring, hormonal injection, parenteral hormonal implant, or an intrauterine device. Participants and parents/legal guardians (for minor participants) are willing and able to comply with all study visits and/or study-related procedures. Participants/parents/guardians must have the ability to provide informed consent/assent as applicable. Willingness to perform visits virtually. EXCLUSION CRITERIA: <TAB>Previous treatment of AD: Within 4 weeks prior to the baseline visit with any of the following: Immunosuppressive or immunomodulating systemic drugs such as systemic corticosteroids, azathioprine, methotrexate, cyclosporine Phototherapy or photochemotherapy for AD Within 12 weeks prior to the baseline visit with any of the following having been newly initiated: Topical steroids or topical calcineurin inhibitors Janus kinase (JAK) inhibitors (oral or topical) Dupilumab or any other biologic agent Topical PDE4 inhibitor Emollients containing ceramides, hyaluronic acid, urea or filaggrin degradation products. Bleach baths Active infection (chronic or acute) requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the baseline visit. Superficial skin infection requiring topical treatment within 1 week of baseline visit. Known or suspected history of immunosuppression or immunodeficiency. Existence of indwelling central line. Co-habitation with someone that has a known or suspected history of immunosuppression or immunodeficiency or has a central line. Any clinically significant laboratory, history, or exam findings that, in the investigator s opinion, would suggest an increased risk to the participant. Self-reported pregnancy or breastfeeding. Menstruating females who have not menstruated within 6 weeks prior to screening. Participants who have an intrauterine device or implanted long-term contraceptive agent that prevents them from menstruating regularly will not be excluded.

.All clinical data will be striped of PII and included in the publication. All microbiome data will be deposited in the appropriate databases.

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