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
Overview
- Phase
- Phase 2
- Intervention
- B244
- Conditions
- Atopic Dermatitis
- Sponsor
- AOBiome LLC
- Enrollment
- 547
- Locations
- 54
- Primary Endpoint
- Mean Change in Worst Itch Numeric Rating Scale (WI-NRS)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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.
- •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.
- •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.
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.
Arms & Interventions
B244 Suspension O.D. 5.0
One arm of 192 Subjects will be receiving a dose of B244 O.D. 5.0 suspension
Intervention: B244
B244 Suspension O.D. 20.0
Second arm of 192 subjects will receive a dose of B244 O.D. 20.0 suspension
Intervention: B244
Placebo
Third arm of 192 subjects will receive a vehicle dosing.
Intervention: Vehicle
Outcomes
Primary Outcomes
Mean Change in Worst Itch Numeric Rating Scale (WI-NRS)
Time Frame: 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 Outcomes
- Proportion of Patients With ≥4 Point Improvement in Worst Itch Numeric Rating Scale (WI-NRS)(Baseline to Day 28)
- Proportion of Subjects With Any Improvement in Worst Itch Numeric Rating Scale (WI-NRS)(Baseline to Day 28)
- Mean Change in Average Itch Numeric Rating Scale (AI-NRS)(Baseline to Day 28)
- Proportion of Subjects With ≥4 Point Improvement in Average Itch Numeric Rating Scale (AI-NRS)(Baseline to Day 28)
- Proportion of Subjects With Any Improvement in Average Itch Numeric Rating Scale (AI-NRS)(Baseline to Day 28)
- Mean Change in Worst Itch Numeric Rating Scale (WI-NRS)(Baseline to Day 14)
- Proportion of Subjects With ≥4 Point Improvement in Worst Itch Numeric Rating Scale (WI-NRS)(Baseline to Day 14)
- Mean Change in Patient Oriented Eczema Measure (POEM)(Baseline to Day 28)
- Mean Change in 5-D Pruritus Scale(Baseline to Day 28)