Study to Determine Safety and Efficacy of B244 in Subjects With Mild to Moderate Atopic Dermatitis

This is a Prospective, Vehicle Controlled, Double Blind, Multicenter, Randomized Phase II trial, comparing the effect of twice daily B244 application for 28 days vs vehicle application on treatment of mild to moderate AD

At Screening and Baseline, all subjects must have atopic dermatitis, as defined by the Hanifin and Rajka criteria, which involves a minimum of 10% and a maximum of 30% body surface area, EASI score of 10 to 21 and pruritus visual analogue scale scores of ≥ 5 points on the VAS scale (at least moderate).

The total duration of the study will be approximately 9 weeks. Participants will report for a Screening visit and if all inclusion criteria are met, subjects will go through a two week washout phase before reporting for a Baseline visit.

Subjects will come in for visits at Day 14 (Week 2), Day 28 (Week 4). A final visit will be conducted at Day 42 (Week 6).

Efficacy will be assessed using Atopic Dermatitis Area and Severity Index (EASI) and Visual Analog Scale (VAS).

Blood and urine samples will be collected for standard safety laboratory tests and effect of the drug on inflammatory biomarkers. Participant's safety will be monitored throughout the study.

Investigators plan to enroll approximately 130 total patients.

Randomization will be 1:1 so that equal number of patients will be treated in each Arm of the study.

• B244 (Biological): B244 suspension
• Vehicle (Biological): Vehicle suspension

Primary outcomes

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [Baseline to Day 42]: Safety and tolerability endpoints will consist of all adverse events reporting during the study duration.

Secondary outcomes

• Change in Eczema Area Severity Index (EASI) Score Between the Active and Vehicle Groups [Baseline to Day 28]: EASI is a validated tool used to measure the severity and extent of atopic dermatitis where clinical investigators assess the presence and severity of erythema, edema/papulation, excoriation, and lichenification (score 0-3: none=0, mild=1, moderate=2, severe=3, half-points allowed) and area of involvement (score 0-6: 0=0% involvement, 1=1-9% involvement, 2=10-29% involvement, 3=30-49% involvement, 4=50-69% involvement, 5=70-89% involvement, 6=90-100% involvement) across head and neck, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks). The EASI score can range from 0.0to 72.0 with increments of 0.1 and higher scores representing a greater severity of atopic dermatitis.

Other outcomes

• Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group [Baseline to Day 28]: VAS (Visual Analog Scale) was performed as a measure of pruritus. The VAS is composed of a 10-cm line divided into a scale from 0 to 10, and subjects were to indicate the score that best represented the intensity of their itching over the 24-hour period before each visit where a higher score indicated greater severity in pruritus.
• Change in the Skindex 16 Score Between the Active and Vehicle Group [Baseline to Day 28]: The Skindex 16 questionnaire was assigned to subjects to examine the relationship between the subject's skin health and quality of life. Subjects scored 16 questions from 0 to 6 (0=never bothered, 6=always bothered). Total scores could range between 0 to 96, where a higher score is associated with a worse quality of life.
• Change in the IGA Score Between the Active and Vehicle Groups [Baseline to Day 28]: IGA (Investigator's Global Assessment) was used to assess the overall diseases severity on a scale of 0 to 4 (0=clear, 1=almost clear, 2=mild disease, 3=moderate disease, and 4=severe disease).
• Difference in Actigraphy Scratching Event Count Per Hour During the Night Between the Active and Vehicle Group [Baseline to Day 28]: Subjects were provided two Actigraphy watches (one on each wrist) to accurately monitor subject's sleep, activity, and itching patterns.
• Difference in Biomarkers Between Active and Vehicle Groups. [Baseline and Day 28]: To evaluate if B244 administration on the skin twice daily for 28 days will affect the levels of immune biomarkers.
• Microbial Content [Baseline and Day 28]: Evaluate if B244 administration on skin twice daily will affect the microbial content on collected skin swab samples.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Male and female subjects ≥18 years of age
* In good general health as determined by a thorough medical history and physical examination, and vital signs
* Clinical diagnosis of mild to moderate atopic dermatitis according to the criteria of Hanifin and Rajka
* Mild to moderate Atopic Dermatitis area and severity index \[EASI\] 10-21
* A score of at least ≥ 5 points (moderate pruritus) on the VAS for pruritus
* A minimum of 10% and not more than 30% of the subjects' BSA affected by atopic dermatitis (affected is defined by physical examination findings: erythema, edema, scaling, lichenification, excoriation, with the excoriation serving as the physical examination correlate of pruritus)
* An IGA score of 2-3
* Patient has a history of AD for ≥12 months
* Ability to read and understand English and to provide written informed consent and authorization for protected health information disclosure

Exclusion Criteria:

* Pregnant and lactating women by urine pregnancy testing
* Subjects with any significant clinical abnormalities which may interfere with study participation
* Any skin condition which may interfere with evaluation of AD
* Atopic dermatitis only on the head or scalp
* Subjects with Atopic dermatitis on the face
* Unstable or actively infected atopic dermatitis
* Patients suffering from pruritus from conditions other than AD
* Patients with chronic pruritus due to systemic disease
* Patients with conditions requiring inhaled steroids
* Have concurrent skin disease of such severity in the study area that it could interfere with the study evaluation
* Have active skin infections on the treatment area
* Have received or planning to receive topical corticosteroids, topical coal tar, topical sulfur, topical PDE-4 inhibitors, topical antihistamines, topical antiseptics or antibiotics, topical antifungals, bleach baths, UVA or UVB phototherapy, oral/IV/inhaled steroids, antibiotics/antiviral/antifungal agents, oral probiotics, glucocorticoids treatment, calcineurin inhibitors, immunomodulating biologic agents, systemic glucocorticoids, systemic immunosuppressive or immunomodulatory agents within 2 weeks of Baseline visit.
* Current or recent history (≤3 months of systemic use of Otrexup™, Rasuvo®, Rheumatrex® and Trexall™ or its generic versions such as Methotrexate
* History of being seropositive for human immunodeficiency virus (HIV) at screening by laboratory testing at Screening
* History of being positive for Hepatitis B virus surface antigen (HBsAg) or positive Hepatitis C virus antibody (HCV Ab) at screening by laboratory testing at Screening
* History of renal disease
* Use of any investigational drugs within the previous 30 days prior to dosing or within a period of less than five times the drug's half-life, whichever is longer
* Use of any biologic within a period of 5 times its half-life
* Use of vinegar or bleach baths within 2 weeks of starting the study

Participant flow

Outcome results

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (Primary), Count of participants, Participants: B244 2; Vehicle 4
• Change in Eczema Area Severity Index (EASI) Score Between the Active and Vehicle Groups (Secondary), Mean, score on a scale: B244 -5.7 +/- 4.46; Vehicle -5.9 +/- 5.90
• Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group (Other pre specified), Mean, score on a scale: B244 -1.5 +/- 2.23; Vehicle -0.6 +/- 1.92 (p 0.0228)
• Change in the Skindex 16 Score Between the Active and Vehicle Group (Other pre specified), Mean, score on a scale: B244 -0.2 +/- 5.74; Vehicle -0.8 +/- 1.28
• Change in the IGA Score Between the Active and Vehicle Groups (Other pre specified), Mean, score on a scale: B244 -0.6 +/- 0.82; Vehicle -0.7 +/- 0.94
• Difference in Actigraphy Scratching Event Count Per Hour During the Night Between the Active and Vehicle Group (Other pre specified), Mean, average scratching events per hour: B244 -3.4 +/- 8.26; Vehicle 3 +/- 7.92
• Difference in Biomarkers Between Active and Vehicle Groups. (Other pre specified)
• Microbial Content (Other pre specified)

Adverse events

Time frame: Baseline to Week 6.

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2018-10-05)
• Statistical Analysis Plan (PDF, 2018-10-30)

• Judith Ng-Cashin, MD, Study director, Chief Medical Officer
• Spiros Jamas, ScD, Study director, AOBiome LLC