Clinical trial NCT04490109: B244 Topical Spray for the Treatment of Pruritus in Adults With a History of Atopic Dermatitis
Official title: A Phase II, Randomized, Double-Blind, Vehicle Controlled Study of the Efficacy, Safety, and Tolerability of B244 Topical Spray for the Treatment of Pruritus in Adults With a History of Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Pruritus
Lead sponsor: AOBiome LLC
Sponsor class: INDUSTRY
Collaborators: name: bioRASI, LLC
First posted: 2020-07-28
Enrollment: 547
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male and female subjects 18 to 65 years of age.
2. 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.
3. Worst Itch Numeric Rating Scale (WI-NRS) score ≥ 7 in the 24-hour period prior to the initial Screening as well as Baseline visits.
4. Average weekly WI-NRS score ≥6 for each week of the washout period, as recorded in the eDiary.
5. 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.
6. 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.
7. An Investigator Global Assessment (IGA) score of 2-3 at Screening and Baseline.
8. 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.
9. Judged to be in good health in the investigator's opinion.,

Exclusion Criteria:

1. 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.
2. 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.
3. Treatment with systemic corticosteroids within 4 weeks prior to randomization.
4. 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.
5. 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.
6. 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.
7. 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).
8. Treatment with biologic therapies within 12 weeks or 5 half-lives prior to randomization, whichever is longer.
9. Use of an indoor tanning facility within 4 weeks prior to randomization.
10. Treatment with any investigational therapy within 4 weeks prior to randomization.
11. Allergen immunotherapy within 6 months prior to randomization.
12. Prior use of AO+ Mist.
13. 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.
14. History of a major psychiatric condition (including major depressive disorder, bipolar disorder, or schizophrenia), suicidal ideation, or suicide attempt.
15. Known active hepatitis infection.
16. Known history of human immunodeficiency virus (HIV) infection.
17. 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.
18. Currently pregnant or breastfeeding, or male subject with a pregnant or breastfeeding partner.
19. 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.

Primary outcomes:
measure: Mean Change in Worst Itch Numeric Rating Scale (WI-NRS)
timeFrame: Baseline to Day 28
Secondary outcomes:
measure: Proportion of Patients With ≥4 Point Improvement in Worst Itch Numeric Rating Scale (WI-NRS)
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With Any Improvement in Worst Itch Numeric Rating Scale (WI-NRS)
timeFrame: Baseline to Day 28
measure: Mean Change in Average Itch Numeric Rating Scale (AI-NRS)
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With ≥4 Point Improvement in Average Itch Numeric Rating Scale (AI-NRS)
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With Any Improvement in Average Itch Numeric Rating Scale (AI-NRS)
timeFrame: Baseline to Day 28
measure: Mean Change in Worst Itch Numeric Rating Scale (WI-NRS)
timeFrame: Baseline to Day 14
measure: Proportion of Subjects With ≥4 Point Improvement in Worst Itch Numeric Rating Scale (WI-NRS)
timeFrame: Baseline to Day 14
measure: Mean Change in Patient Oriented Eczema Measure (POEM)
timeFrame: Baseline to Day 28
measure: Mean Change in 5-D Pruritus Scale
timeFrame: Baseline to Day 28
Other outcomes:
measure: Mean Change in Investigator's Global Assessment (IGA)
timeFrame: Baseline to Day 28
measure: Mean Change in Eczema Area Severity Index (EASI)
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With Investigator's Global Assessment (IGA) of Clear or Almost Clear and ≥2 Point Improvement
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With Investigator's Global Assessment (IGA) of Clear or Almost Clear at Week 4
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With Any Improvement in Investigator's Global Assessment (IGA) From Baseline to Week 4
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With ≥50% Improvement in Eczema Area Severity Index (EASI-50)
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With ≥75% Improvement in Eczema Area Severity Index (EASI-75)
timeFrame: Baseline to Day 28
measure: Proportion of Subjects With ≥90% Improvement in Eczema Area Severity Index (EASI-90)
timeFrame: Baseline to Day 28
Locations:
city: Birmingham
country: United States
facility: Cahaba Dermatology
state: Alabama
city: Phoenix
country: United States
facility: Elite Clinical Studies, LLC
state: Arizona
city: Scottsdale
country: United States
facility: Cognitive Clinical Trials
state: Arizona
city: Bryant
country: United States
facility: Dermatology Trial Associates
state: Arkansas
city: Little Rock
country: United States
facility: Applied Research Center of Arkansas, Inc
state: Arkansas
city: Cerritos
country: United States
facility: Core Healthcare Group
state: California
city: Encino
country: United States
facility: Encino Research Center
state: California
city: Fremont
country: United States
facility: Center for Dermatology, INC
state: California
city: Lancaster
country: United States
facility: Antelope Valley Clinical Trials
state: California
city: Long Beach
country: United States
facility: Long Beach Clinical Trials Services
state: California
city: Los Angeles
country: United States
facility: L.A. Universal Research Center Inc
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
city: Clearwater
country: United States
facility: Tampa Bay Medical Research
state: Florida
city: Delray Beach
country: United States
facility: Palm Beach Dermatology Group
state: Florida
city: Miami Gardens
country: United States
facility: Meridian International Research
state: Florida
city: Miami
country: United States
facility: South Coast Research Center, Inc
state: Florida
city: Miami
country: United States
facility: D&H National Research Center
state: Florida
city: Pompano Beach
country: United States
facility: NAPA Research
state: Florida
city: Tampa
country: United States
facility: Clinical Research Trials of Florida, Inc
state: Florida
city: Tampa
country: United States
facility: Moore Clinical Research
state: Florida
city: Chicago
country: United States
facility: Medical Dermatology Associates of Chicago
state: Illinois
city: Libertyville
country: United States
facility: Clinical Investigation Specialists
state: Illinois
city: Normal
country: United States
facility: Sneeze Wheeze & Itch Associates, LLC
state: Illinois
city: Overland Park
country: United States
facility: Epiphany Dermatology
state: Kansas
city: Baton Rouge
country: United States
facility: Meridian Clinical Research
state: Louisiana
city: Towson
country: United States
facility: Continental Clinical Solutions
state: Maryland
city: Auburn Hills
country: United States
facility: Oakland Hills Dermatology
state: Michigan
city: Clarkston
country: United States
facility: Clarkston Dermatology
state: Michigan
city: Flint
country: United States
facility: Onyx Clinical Reserach
state: Michigan
city: Saint Joseph
country: United States
facility: mediSearch Clinical Trials
state: Missouri
city: Henderson
country: United States
facility: Thomas Dermatology
state: Nevada
city: Las Vegas
country: United States
facility: JDR Dermatology Research, LLC
state: Nevada
city: Portsmouth
country: United States
facility: ActivMed Practices & Research
state: New Hampshire
city: Verona
country: United States
facility: The Dermatology Group, P. C.
state: New Jersey
city: Brooklyn
country: United States
facility: Drug Trials Brooklyn
state: New York
city: Hartsdale
country: United States
facility: Drug Trials America
state: New York
city: New York
country: United States
facility: Saddick Research Group
state: New York
city: High Point
country: United States
facility: Dermatology Consulting Services, LLC
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research
state: North Carolina
city: Cleveland
country: United States
facility: Clinical Research Solutions
state: Ohio
city: Oklahoma City
country: United States
facility: Unity Clinical Research
state: Oklahoma
city: Medford
country: United States
facility: Velocity Clinical Research
state: Oregon
city: Sugarloaf
country: United States
facility: Dermdox Centers for Dematology
state: Pennsylvania
city: Upper Saint Clair
country: United States
facility: Peak Research LLC
state: Pennsylvania
city: Cranston
country: United States
facility: Greater Providence Clinical Research
state: Rhode Island
city: Warwick
country: United States
facility: AAPRI Research
state: Rhode Island
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Charleston
country: United States
facility: Dermatology & Laser Center of Charleston
state: South Carolina
city: Fort Mill
country: United States
facility: Peak Research LLC
state: South Carolina
city: Milan
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Plano
country: United States
facility: ACRC Trials
state: Texas
city: Orem
country: United States
facility: Aspen Dermatology
state: Utah
city: Salt Lake City
country: United States
facility: Advance Clinical Research
state: Utah
city: Richmond
country: United States
facility: Dominion Medical Associates
state: Virginia
Study officials:
affiliation: AOBiome LLC
name: Hyun Kim, PhD
role: STUDY_DIRECTOR
References: