Long Beach,
California
90806
Purpose:
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.
Study summary:
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.
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.