A Study to Determine Safety and Efficacy of B244 in Subjects With Mild to Moderate Rosacea

Study Overview
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Brief Summary
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This is a Prospective, Vehicle Controlled, Double Blind, Multicenter, Randomized Phase II trial, comparing the effect of twice daily B244 application for 8 weeks vs. vehicle application on treatment of mild to moderate rosacea.

Detailed Description
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This is a Prospective, Vehicle Controlled, Double Blind, Multicenter, Randomized Phase II trial, comparing the effect of twice daily B244 application for 8 weeks vs. vehicle application on treatment of mild to moderate rosacea. At Screening and Baseline all subjects must have Type 1 erythematotelangiectatic rosacea (ETR). The total duration of the study will be approximately 12 weeks. Participants will report for a Screening visit and if all inclusion criteria are met will undergo a washout period, between 2 days and 4 weeks, depending on current treatment. Subjects will then report for the Baseline visit. Subjects will come in for visits at Day 7 (Week 1), Day 28 (Week 4), and Day 56 (Week 8). A final visit will be conducted at Day 84 (Week 12). Efficacy will be assessed using Clinician Erythema Assessment (CEA), Investigator Global Assessment (IGA), Skindex16, and Patient Self-Assessment (PSA). Blood and urine samples will be collected for standard safety laboratory tests. Participant's safety will be monitored throughout the study. Investigators plan to enroll approximately 130 subjects. Randomization will be 1:1 so that equal numbers of subjects will be treated in each arm of the study.

Official Title
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A Vehicle-Controlled, Double-Blind, Randomized Phase II Study of B244 Delivered as a Topical Spray to Determine Safety and Efficacy in Subjects With Mild to Moderate Rosacea

Conditions
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Rosacea

Intervention / Treatment
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* Biological: B244
* Biological: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects ≥18. A clinical diagnosis of mild to moderate facial rosacea. In good general health as determined by a thorough medical history, physical examination, clinical chemistry and hematology. Presence of 3 to 20 inflammatory lesions on the face (i.e. papules/pustules). A Clinician Erythema Assessment (CEA) score of 2-3 at Screening and at Baseline Visits (prior to the investigational product application). Mild to Moderate IGA score of 2-3 at Screening and at Baseline Visits (prior to the investigational product application). Willing to refrain from using any topical or systemic treatments for the treatment of rosacea, other than the investigational product. Females of childbearing potential with a negative urine pregnancy test (UPT) at Screening and Baseline/Day 1 (prior to the investigational product application). Ability to comprehend and comply with study procedures. Agree to commit to participate in the current protocol. Provide written informed consent prior to any study procedure being performed. Exclusion Criteria: Female subjects who are pregnant, lactating or who are trying to conceive will be excluded from participation in this study. Any uncontrolled chronic or serious disease or medical condition that would normally prevent participation in a clinical trial, or, in the judgment of the Investigator, would put the subject at undue risk, or might confound the study assessments (e.g., other dermatological diseases), or might interfere with the subject's participation in the study, (e.g., planned hospitalization during the study). Particular forms of rosacea (e.g., rosacea conglobata, rosacea fulminans, isolated rhinophyma, isolated pustulosis of the chin, Ocular rosacea Phymatous rosacea, Steroid-induced rosacea, severe rosacea including pyoderma faciale) or other concomitant facial dermatoses that are similar to rosacea such as peri-oral dermatitis, demodicidosis, facial keratosis pilaris, seborrheic dermatitis, acute lupus erythematosus, or actinic telangiectasia. Presence of more than two (2) nodulocystic lesions on the face. Presence of less than 3 and more than 20 inflammatory lesions on the face (i.e. papules/pustules). Severe papulopustular rosacea requiring systemic treatment. Participation at the time of eligibility assessment (Screening) in any other investigational drug or device study or may have participated within 30 days prior to Screening. Commencement of new hormonal therapy or dose change to hormonal therapy within 30 days prior to baseline. Dose and frequency of use of any hormonal therapy started more than 30 days prior to baseline must remain unchanged throughout the study. Hormonal therapies include, but are not limited to, oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (e.g. vaginal ring or transdermal hormone contraception) Presence of beard or excessive facial hair at Screening which would interfere with the study treatments or study assessments and refusal to remove for duration of study. Carcinoid, Pheochromocytoma or other systemic causes of flushing. Known sensitivity to B244 or its components. Refusal to submit to blood and urine sampling for laboratory analysis. Treatment with prohibited medications.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization will be 1:1 so that equal numbers of patients will be treated in each arm of the study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: B244<br>B244 suspension in 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. | Biological: B244<br>* B244 Suspension<br>|
| Placebo Comparator: Vehicle<br>Vehicle, 30ml/bottle Subjects will apply a total of 4 pumps of IP per application to the face twice-a-day. | Biological: Vehicle<br>* Vehicle suspension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Safety and tolerability endpoints will consist of all treatment-related adverse events reporting during the study duration. | Baseline to Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With IGA Improvement at Week 8 Relative to Baseline. | IGA (Investigator's Global Assessment) was used to assess the overall diseases severity on a scale of 0 to 4 (0=clear, 1=almost clear, 2=mild disease, 3=moderate disease, and 4=severe disease). Improvement is defined as at least 1-grade change. | Baseline to Day 56 | 
| Proportion of Subjects With CEA Improvement at Week 8 Relative to Baseline. | Clinical Erythema Assessment (CEA) was used to assess the extent of rosacea on a scale of 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). Improvement is defined as at least 1-grade change. | Baseline to Day 56 | 
| Change in IGA From Week 8 to Baseline. | IGA (Investigator's Global Assessment) was used to assess the overall diseases severity on a scale of 0 to 4 (0=clear, 1=almost clear, 2=mild disease, 3=moderate disease, and 4=severe disease). A higher grade change indicates greater improvement in disease. | Baseline to Day 56 | 
| Change in CEA From Week 8 to Baseline. | Clinical Erythema Assessment (CEA) was used to assess the extent of rosacea on a scale of 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). A higher grade change indicates greater improvement in disease. | Baseline to Day 56 | 
| Change in Skindex 16 and Skindex 16 Sub Scores at Week 1, Week 4, Week 8 and Week 12 From Baseline. | The Skindex 16 questionnaire was assigned to subjects to examine the relationship between the subject's skin health and quality of life. Subjects scored 16 questions from 0 to 6 (0=never bothered, 6=always bothered). Total scores could range between 0 to 96, where a higher score is associated with a worse quality of life. | Baseline to Day 84 | 
| Proportion of Subjects With Change in PSA at Week 1, Week 4, Week 8 and Week 12 From Baseline. | Subjects were asked to perform static (snap-shot) evaluations of their rosacea-associated facial erythema severity using the Patient Self Assessment scale (PSA) at each study visit, and report the one integer that best describes the overall severity of their facial redness as seen in a mirror at the time of the evaluation on a scale of 0 to 4 (0=no redness, 1=very mild redness, 2=mild redness, 3=moderate redness, 4=severe redness). A higher grade change indicates greater improvement. | Baseline to Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 erythematotelangiectatic rosacea