A Double Blind, Placebo-Controlled, Randomized Study in Subjects With Acne Vulgaris

Study Overview
=================
Brief Summary
-----------------
This is a single center, randomized, double-blind, placebo-controlled study in subjects with acne vulgaris.

Detailed Description
-----------------
After a screening visit and a one-week washout (if applicable), three sequential ascending doses of the study drug will be applied twice-daily (BID) for 14 days in three groups of subjects. Each group of subjects will be randomized to receive the planned doses of B244 or placebo BID

Official Title
-----------------
A Double Blind, Placebo-Controlled, Single Center, Randomized, Sequential, Ascending 14-Day Multiple Dose Study in Subjects With Acne Vulgaris to Evaluate the Safety, Tolerability and Preliminary Efficacy of B244 Delivered as a Topical Spray

Conditions
-----------------
Acne Vulgaris

Intervention / Treatment
-----------------
* Drug: B244
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female subjects ≥18 and ≤45 years of age In good general health as determined by a thorough medical history and physical examination, electrocardiogram (ECG), vital signs, and clinical laboratory evaluation. Results of clinical laboratory tests must be without clinically significant abnormalities, including hematology, clinical chemistry and urinalysis. Clinical diagnosis of facial acne vulgaris defined as: ≥105 inflammatory lesions ≥10 non-inflammatory lesions IGA ≥2 Willing to refrain from using any treatments, other than the investigational product, including antibiotics, for acne present on the face. Topical acne treatments that do not have significant or measurable systemic absorption (e.g., benzoyl peroxide, salicylic acid) are allowed for treatment of acne of the back, shoulders and chest only. Ability to comprehend and comply with procedures Agree to commit to participate in the current protocol Provide written informed consent prior to any study procedure being performed (all subjects should be able to understand the informed consent form and any other documents that subjects are required to read) Exclusion Criteria: Female subjects who are pregnant or lactating or who are trying to conceive Female subjects with a positive urine β-human chorionic gonadotropin (β-hCG) test at screening or positive β-hCG urine at pre-dose Any clinically relevant abnormality identified on the screening history, physical or laboratory examinations, or any other medical condition or circumstance making the volunteer unsuitable for participation in the study Any skin condition which may interfere with the evaluation of safety or of acne vulgaris (e.g., rosacea; seborrheic dermatitis; perioral dermatitis; corticosteroid-induced acne or folliculitis) Use of tanning booths or excessive sun exposure, in the opinion of the investigator Active cystic acne or acne congoblata, acne fulminans, and secondary acne Two or more active nodular lesions Treatment with over-the-counter topical medications for the treatment of acne vulgaris including benzoyl peroxide, topical anti-inflammatory medications, corticosteroids, α-hydroxy/glycolic acid on the face within 2 weeks prior to baseline Treatment with systemic corticosteroids (including intranasal and inhaled corticosteroids) within 4 weeks prior to baseline Treatment with systemic antibiotics or systemic anti-acne drugs or systemic anti-inflammatory drugs within 4 weeks prior to baseline Prescription topical retinoid use on the face within 4 weeks of baseline (e.g., tretinoin, tazarotene, adapalene) Treatment with hormonal therapy or dose change to hormonal therapy within 12 weeks prior to baseline. Dose and frequency of use of any hormonal therapy started more than 12 weeks prior to baseline must remain unchanged throughout the study. Hormonal therapies include, but are not limited to, estrogenic and progestational agents such as birth control pills. Use of androgen receptor blockers (such as spironolactone or flutamide) Oral retinoid use (e.g., isotretinoin) within 12 months prior to baseline or vitamin A supplements greater than 10,000 units/day within 6 months of baseline Facial procedures (chemical or laser peel, microdermabrasion, etc.) within the 8 weeks of the first dose or during the study A positive urine drug screen for drugs of abuse, including alcohol or positive urine cotinine (≥300 ng/mL for cotinine) at the screening visit or at entry to the clinic (Note: urine cotinine required at screening visit only) Treatment with any investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the beginning of the screening period (this includes investigational formulations of marketed products, inhaled and topical drugs) Hypersensitivity to B244 or its components Blood collection of greater than 500 mL within 56 days prior to screening Seropositive for human immunodeficiency virus (HIV) at screening Positive for Hepatitis B virus surface antigen (HBsAg) or positive Hepatitis C virus antibody (HCV Ab) at screening Any other condition and/or situation that causes the Investigator to deem a subject unsuitable for the study (e.g., due to expected study medication non-compliance, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose I<br>B244 Dose 1 (dose level [cells/mL] 20,000,000,000) | Drug: B244<br>* 10 pumps (1.4 ml) of spray must be applied BID twice a day to the entire face for 14 days<br>Drug: Placebo<br>* 10 pumps (1.4 ml) of spray must be applied BID twice a day to the entire face for 14 days<br>|
| Experimental: Dose II<br>B244 Dose 2 (dose level [cells/mL] 40,000,000,000) | Drug: B244<br>* 10 pumps (1.4 ml) of spray must be applied BID twice a day to the entire face for 14 days<br>Drug: Placebo<br>* 10 pumps (1.4 ml) of spray must be applied BID twice a day to the entire face for 14 days<br>|
| Experimental: Dose III<br>B244 Dose 3 (dose level [cells/mL] 80,000,000,000) | Drug: B244<br>* 10 pumps (1.4 ml) of spray must be applied BID twice a day to the entire face for 14 days<br>Drug: Placebo<br>* 10 pumps (1.4 ml) of spray must be applied BID twice a day to the entire face for 14 days<br>|
| Placebo Comparator: Placebo<br>Placebo to Match B244 | Drug: B244<br>* 10 pumps (1.4 ml) of spray must be applied BID twice a day to the entire face for 14 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Number of Participants With Treatment Related Adverse Events) | Number of participants with treatment related adverse events as assessed by physical examination, vital signs, clinical laboratory values, local skin responses | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Absolute Change from Baseline in Total Number of Lesions | Baseline and 4 weeks |