B244 Topical Spray for the Treatment of Pruritus in Adults With a History of Atopic Dermatitis

Phase 2

Completed

Conditions: Atopic Dermatitis
Pruritus

Interventions: Biological: Vehicle
Biological: B244

Registration Number: NCT04490109

Lead Sponsor: AOBiome LLC

Brief Summary: This is a double-blind, randomized, vehicle-controlled study to assess the efficacy, safety, and tolerability of 2 doses of B244 for the treatment of pruritus in adults with a history of atopic dermatitis. Subjects who meet the study entry criteria will be randomized in a 1:1:1 ratio to receive twice daily topical doses of B244 O.D. 5.0, B244 O.D. 20.0, or vehicle (placebo) for 4 weeks.

Detailed Description: This is a Prospective, Vehicle Controlled, Double-Blind, Multicenter, Randomized Phase II Trial, comparing the effect of twice daily B244 applications for 4 weeks vs vehicle applications on treatment of mild to moderate pruritus associated with atopic dermatitis.

* Approximately 576 subjects may be enrolled.

* The total duration of the study will be approximately 11 weeks. Participants will report for a Screening visit and if all inclusion/exclusion criteria are met, subjects will go through a two-week washout phase before reporting for a Baseline visit.

* After screening and baseline, participants will be randomized to one of two doses of B244 or vehicle application for 4 weeks.

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

* All B244 randomized subjects will be treated at the dose of O.D. 5.0 or O.D. 20.0

* Subjects must be willing and able to complete diary within a consistent time frame on a daily basis and to comply with restrictions on allowable therapies for the duration of the study.

* All subjects will attend a screening visit not more than 21 days prior to Baseline (Day 0).

* Subjects will be required to return to the clinic at Baseline, Day 14 (Week 2) and Day 28 (Week 4) visits. All subjects will be asked to attend a Week 8 follow-up visit 4 weeks (28 (±3) days) after the last dose of study medication.

* Subjects will apply a total of 10 pumps of IP per application across all affected areas twice-a-day (i.e. 10 pumps in the morning and 10 pumps again at night) for 4 weeks.

* Safety evaluations will consist of review of participant's medical history at screening and on-going assessment of adverse events reported throughout the study duration.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 547

Inclusion Criteria

Male and female subjects 18 to 65 years of age.
Pruritus of at least 4 weeks duration prior to the initial Screening visit and during the 2 week washout period.

a. Subjects using stable doses of oral H1 antihistamines at the initial Screening visit must be willing to continue these at the same doses and frequencies throughout the study inclusive of the follow-up period.
Worst Itch Numeric Rating Scale (WI-NRS) score ≥ 7 in the 24-hour period prior to the initial Screening as well as Baseline visits.
Average weekly WI-NRS score ≥6 for each week of the washout period, as recorded in the eDiary.
A history of atopic dermatitis for greater than 12 months consistent with a diagnosis of atopic dermatitis, as defined by the 2014 American Academy of Dermatology (AAD) Guidelines of Care for the Management of Atopic Dermatitis.
1. Subjects using bland emollients at the initial Screening visit will be allowed to continue to use their emollient of choice at the same dose and frequency throughout the study.
2. Subjects using low- to mid-potency topical corticosteroids at the initial Screening visit will be allowed to use their topical corticosteroid of choice at the same dose and frequency no more than 7 days per month throughout the study as rescue medication.
A minimum of 10% and not more than 40% 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) at Screening and Baseline.

a. Subjects' BSA can include face and body OR body alone BUT NOT face alone.
An Investigator Global Assessment (IGA) score of 2-3 at Screening and Baseline.
Willing and able to complete once-daily eDiary entries within a consistent timeframe for the duration of the study and have ≥80% eDiary compliance rate during the washout period.
Judged to be in good health in the investigator's opinion.,

Exclusion Criteria

Clearly defined etiology for pruritus other than atopic dermatitis. These include but are not limited to urticaria, psoriasis or other non-atopic dermatologic conditions, hepatic or renal disease, psychogenic pruritus, drug reaction, untreated hyperthyroidism, parasite presence and presence of acute infection either systemically or in the AD lesions.
Presence of any acute condition which may risk inducing an atopic dermatitis flare during the course of the study, such as impetigo or active herpes simplex infection.
Treatment with systemic corticosteroids within 4 weeks prior to randomization.
Treatment with Class III or higher potency topical corticosteroids or any topical anti-pruritic therapies (other than stable doses of low- or mid-potency topical corticosteroids or bland emollients) within 4 weeks prior to randomization.
Treatment with systemic therapies with recognized anti-pruritic (e.g. tricyclic antidepressants, sedatives, tranquilizers, gabapentin, marijuana or other cannabinoids, opioid receptor agonists/antagonists) or pruritic (e.g. opioids, angiotensin-converting enzyme inhibitors, cocaine,,antimalarials) properties within 4 weeks prior to randomization.

a. Stable doses of H1 antihistamines will be permitted. Subjects must be willing to continue these at the same doses and frequencies throughout the study inclusive of the follow-up period.
Any clinically significant changes in type, dose, or frequency of bland emollients, low- or mid-potency corticosteroids, and/or oral H1 antihistamines throughout the study from screening to follow-up.
Treatment with systemic immunosuppressive/ immunomodulatory therapies within 4 weeks prior to randomization (including but not limited to phosphodiesterase-4 inhibitors, cyclosporine, mycophenolate-mofetil, methotrexate, azathioprine, interferon-gamma, or phototherapy).
Treatment with biologic therapies within 12 weeks or 5 half-lives prior to randomization, whichever is longer.
Use of an indoor tanning facility within 4 weeks prior to randomization.
Treatment with any investigational therapy within 4 weeks prior to randomization.
Allergen immunotherapy within 6 months prior to randomization.
Prior use of AO+ Mist.
History of malignancy within 5 years prior to randomization, with the exception of completely treated and non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin.
History of a major psychiatric condition (including major depressive disorder, bipolar disorder, or schizophrenia), suicidal ideation, or suicide attempt.
Known active hepatitis infection.
Known history of human immunodeficiency virus (HIV) infection.
Presence of any medical condition or disability that, in the investigator's opinion, could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject.
Currently pregnant or breastfeeding, or male subject with a pregnant or breastfeeding partner.
Females of childbearing potential who are unable or unwilling to practice highly effective contraception (pregnancy prevention); fertile males who are unable or unwilling to use condoms with female partners of childbearing potential.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Vehicle	Third arm of 192 subjects will receive a vehicle dosing.
B244 Suspension O.D. 5.0	B244	One arm of 192 Subjects will be receiving a dose of B244 O.D. 5.0 suspension
B244 Suspension O.D. 20.0	B244	Second arm of 192 subjects will receive a dose of B244 O.D. 20.0 suspension

Primary Outcome Measures

Name	Time	Method
Mean Change in Worst Itch Numeric Rating Scale (WI-NRS)	Baseline to Day 28	The Itch Numeric Rating Scale (I-NRS) is a validated, self-reported instrument for measurement of itch intensity. It uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. Worst itch intensity (WI-NRS) during a 24-hour recall period will be captured. The question for WI-NRS would be, "Please rate the itching severity due to your atopic dermatitis by circling the number that best describes your worst level of itching in the past 24 hours."

Secondary Outcome Measures

Name	Time	Method
Proportion of Patients With ≥4 Point Improvement in Worst Itch Numeric Rating Scale (WI-NRS)	Baseline to Day 28	The Itch Numeric Rating Scale (I-NRS) is a validated, self-reported instrument for measurement of itch intensity. It uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. Worst itch intensity (WI-NRS) during a 24-hour recall period will be captured. The question for WI-NRS would be, "Please rate the itching severity due to your atopic dermatitis by circling the number that best describes your worst level of itching in the past 24 hours."
Proportion of Subjects With Any Improvement in Worst Itch Numeric Rating Scale (WI-NRS)	Baseline to Day 28	The Itch Numeric Rating Scale (I-NRS) is a validated, self-reported instrument for measurement of itch intensity. It uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. Worst itch intensity (WI-NRS) during a 24-hour recall period will be captured. The question for WI-NRS would be, "Please rate the itching severity due to your atopic dermatitis by circling the number that best describes your worst level of itching in the past 24 hours."
Mean Change in Average Itch Numeric Rating Scale (AI-NRS)	Baseline to Day 28	The Itch Numeric Rating Scale (I-NRS) is a validated, self-reported instrument for measurement of itch intensity. It uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. Average itch intensity (AI-NRS) during a 24-hour recall period will be captured. The question for AI-NRS would be, "Please rate the itching severity due to your atopic dermatitis by circling the number that best describes your average level of itching in the past 24 hours."
Proportion of Subjects With ≥4 Point Improvement in Average Itch Numeric Rating Scale (AI-NRS)	Baseline to Day 28	The Itch Numeric Rating Scale (I-NRS) is a validated, self-reported instrument for measurement of itch intensity. It uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. Average itch intensity (AI-NRS) during a 24-hour recall period will be captured. The question for AI-NRS would be, "Please rate the itching severity due to your atopic dermatitis by circling the number that best describes your average level of itching in the past 24 hours."
Proportion of Subjects With Any Improvement in Average Itch Numeric Rating Scale (AI-NRS)	Baseline to Day 28	The Itch Numeric Rating Scale (I-NRS) is a validated, self-reported instrument for measurement of itch intensity. It uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. Average itch intensity (AI-NRS) during a 24-hour recall period will be captured. The question for AI-NRS would be, "Please rate the itching severity due to your atopic dermatitis by circling the number that best describes your average level of itching in the past 24 hours."
Mean Change in Worst Itch Numeric Rating Scale (WI-NRS)	Baseline to Day 14	The Itch Numeric Rating Scale (I-NRS) is a validated, self-reported instrument for measurement of itch intensity. It uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. Worst itch intensity (WI-NRS) during a 24-hour recall period will be captured. The question for WI-NRS would be, "Please rate the itching severity due to your atopic dermatitis by circling the number that best describes your worst level of itching in the past 24 hours."
Proportion of Subjects With ≥4 Point Improvement in Worst Itch Numeric Rating Scale (WI-NRS)	Baseline to Day 14	The Itch Numeric Rating Scale (I-NRS) is a validated, self-reported instrument for measurement of itch intensity. It uses a 24-hour recall period and asks subjects to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicate greater itch intensity. Worst itch intensity (WI-NRS) during a 24-hour recall period will be captured. The question for WI-NRS would be, "Please rate the itching severity due to your atopic dermatitis by circling the number that best describes your worst level of itching in the past 24 hours."
Mean Change in Patient Oriented Eczema Measure (POEM)	Baseline to Day 28	The Patient Oriented Eczema Measure (POEM) is a tool developed by the University of Nottingham, United Kingdom, for monitoring atopic dermatitis severity. The subject will complete the questionnaire at each of the assessment timepoints as outlined. Each of the 7 questions in the POEM questionnaire carries equal weight and is scored from 0 to 4: No days = 0. 1 to 2 days = 1. 3 to 4 days = 2. 5 to 6 days = 3. Every day = 4. Scores are then added to yield a total score of 0 to 28; higher scores mean the greater the severity of atopic dermatitis.
Mean Change in 5-D Pruritus Scale	Baseline to Day 28	The 5-D Pruritus Scale is a validated, multi-dimensional measure of itching that assesses the five domains of degree (score 1-5: 1=not present, 2=mild, 3=moderate, 4=severe, 5=unbearable), duration (score 1-5: 1=less than 6hrs/day, 2=6-12hrs/day, 3=12-18hrs/day, 4=18-23hrs/day, 5=all day), direction (score 1-5: 1=completely resolved, 2=much better/still present, 3=little bit better/still present, 4=unchanged, 5=getting worse), disability (score 1-5: 1=never affects activity, 2=rarely affects activity, 3=occasionally affects activity, 4=frequently affects activity, 5=always affects activity; highest activity score is taken), and distribution (check boxes of affected body parts; 0-2 body parts=score of 1, 3-5=score of 2, 6-10=score of 3, 11-13=score of 4, 14-16=score of 5). The domains are scored separately and then summed together to obtain a total 5-D score, ranging from 5 (no pruritus) to 25 (most severe pruritus). Subjects rate their symptoms over the preceding 2-week period.

Trial Locations

Locations (54): Sneeze Wheeze & Itch Associates, LLC
🇺🇸
Normal, Illinois, United States
Epiphany Dermatology
🇺🇸
Overland Park, Kansas, United States
Meridian Clinical Research
🇺🇸
Baton Rouge, Louisiana, United States
Continental Clinical Solutions
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Towson, Maryland, United States
Oakland Hills Dermatology
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Auburn Hills, Michigan, United States
Clarkston Dermatology
🇺🇸
Clarkston, Michigan, United States
Onyx Clinical Reserach
🇺🇸
Flint, Michigan, United States
mediSearch Clinical Trials
🇺🇸
Saint Joseph, Missouri, United States
JDR Dermatology Research, LLC
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Las Vegas, Nevada, United States
ActivMed Practices & Research
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Portsmouth, New Hampshire, United States
The Dermatology Group, P. C.
🇺🇸
Verona, New Jersey, United States
Drug Trials Brooklyn
🇺🇸
Brooklyn, New York, United States
Clinical Research Trials of Florida, Inc
🇺🇸
Tampa, Florida, United States
Moore Clinical Research
🇺🇸
Tampa, Florida, United States
Thomas Dermatology
🇺🇸
Henderson, Nevada, United States
Velocity Clinical Research
🇺🇸
Medford, Oregon, United States
Palm Beach Dermatology Group
🇺🇸
Delray Beach, Florida, United States
Medical Dermatology Associates of Chicago
🇺🇸
Chicago, Illinois, United States
Clinical Investigation Specialists
🇺🇸
Libertyville, Illinois, United States
Cahaba Dermatology
🇺🇸
Birmingham, Alabama, United States
Elite Clinical Studies, LLC
🇺🇸
Phoenix, Arizona, United States
Cognitive Clinical Trials
🇺🇸
Scottsdale, Arizona, United States
Dermatology Trial Associates
🇺🇸
Bryant, Arkansas, United States
Applied Research Center of Arkansas, Inc
🇺🇸
Little Rock, Arkansas, United States
Core Healthcare Group
🇺🇸
Cerritos, California, United States
Encino Research Center
🇺🇸
Encino, California, United States
Center for Dermatology, INC
🇺🇸
Fremont, California, United States
Antelope Valley Clinical Trials
🇺🇸
Lancaster, California, United States
Long Beach Clinical Trials Services
🇺🇸
Long Beach, California, United States
L.A. Universal Research Center Inc
🇺🇸
Los Angeles, California, United States
Providence Clinical Research
🇺🇸
North Hollywood, California, United States
Syrentis Clinical Research
🇺🇸
Santa Ana, California, United States
IMMUNOe Research Centers
🇺🇸
Centennial, Colorado, United States
Tampa Bay Medical Research
🇺🇸
Clearwater, Florida, United States
Meridian International Research
🇺🇸
Miami Gardens, Florida, United States
South Coast Research Center, Inc
🇺🇸
Miami, Florida, United States
D&H National Research Center
🇺🇸
Miami, Florida, United States
NAPA Research
🇺🇸
Pompano Beach, Florida, United States
Drug Trials America
🇺🇸
Hartsdale, New York, United States
Saddick Research Group
🇺🇸
New York, New York, United States
Dermatology Consulting Services, LLC
🇺🇸
High Point, North Carolina, United States
Wake Research
🇺🇸
Raleigh, North Carolina, United States
Clinical Research Solutions
🇺🇸
Milan, Tennessee, United States
Unity Clinical Research
🇺🇸
Oklahoma City, Oklahoma, United States
Dermdox Centers for Dematology
🇺🇸
Sugarloaf, Pennsylvania, United States
Peak Research LLC
🇺🇸
Fort Mill, South Carolina, United States
Greater Providence Clinical Research
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Cranston, Rhode Island, United States
AAPRI Research
🇺🇸
Warwick, Rhode Island, United States
Omega Medical Research
🇺🇸
Warwick, Rhode Island, United States
Dermatology & Laser Center of Charleston
🇺🇸
Charleston, South Carolina, United States
ACRC Trials
🇺🇸
Plano, Texas, United States
Aspen Dermatology
🇺🇸
Orem, Utah, United States
Advance Clinical Research
🇺🇸
Salt Lake City, Utah, United States
Dominion Medical Associates
🇺🇸
Richmond, Virginia, United States