Atopic Dermatitis Eczema
Conditions
Brief summary
This is a Prospective, Vehicle Controlled, Double Blind, Multicenter, Randomized Phase II trial, comparing the effect of twice daily B244 application for 28 days vs vehicle application on treatment of mild to moderate AD
Detailed description
This is a Prospective, Vehicle Controlled, Double Blind, Multicenter, Randomized Phase II trial, comparing the effect of twice daily B244 application for 28 days vs vehicle application on treatment of mild to moderate AD At Screening and Baseline, all subjects must have atopic dermatitis, as defined by the Hanifin and Rajka criteria, which involves a minimum of 10% and a maximum of 30% body surface area, EASI score of 10 to 21 and pruritus visual analogue scale scores of ≥ 5 points on the VAS scale (at least moderate). The total duration of the study will be approximately 9 weeks. Participants will report for a Screening visit and if all inclusion criteria are met, subjects will go through a two week washout phase before reporting for a Baseline visit. Subjects will come in for visits at Day 14 (Week 2), Day 28 (Week 4). A final visit will be conducted at Day 42 (Week 6). Efficacy will be assessed using Atopic Dermatitis Area and Severity Index (EASI) and Visual Analog Scale (VAS). Blood and urine samples will be collected for standard safety laboratory tests and effect of the drug on inflammatory biomarkers. Participant's safety will be monitored throughout the study. Investigators plan to enroll approximately 130 total patients. Randomization will be 1:1 so that equal number of patients will be treated in each Arm of the study.
Interventions
BIOLOGICALB244
B244 suspension
BIOLOGICALVehicle
Vehicle suspension
Sponsors
Veristat, Inc.
AOBiome LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double blind study. Participants will be assigned to study treatment in accordance with the randomization schedule generated for the allocation of vehicle or B244 prior to the initiation of the trial. Randomization will be centrally-based and performed using an appropriate IWRS (an automated randomization system). Each participant scheduled to receive investigational product (IP) will receive a randomization number at the time of randomization. The randomization number will be used to identify the study medication kit assigned to the participant and indicate the treatment to be administered to that participant.
Intervention model description
Randomization will be 1:1 so that equal number of patients will be treated in each Arm of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects ≥18 years of age * In good general health as determined by a thorough medical history and physical examination, and vital signs * Clinical diagnosis of mild to moderate atopic dermatitis according to the criteria of Hanifin and Rajka * Mild to moderate Atopic Dermatitis area and severity index \[EASI\] 10-21 * A score of at least ≥ 5 points (moderate pruritus) on the VAS for pruritus * A minimum of 10% and not more than 30% 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) * An IGA score of 2-3 * Patient has a history of AD for ≥12 months * Ability to read and understand English and to provide written informed consent and authorization for protected health information disclosure
Exclusion criteria
* Pregnant and lactating women by urine pregnancy testing * Subjects with any significant clinical abnormalities which may interfere with study participation * Any skin condition which may interfere with evaluation of AD * Atopic dermatitis only on the head or scalp * Subjects with Atopic dermatitis on the face * Unstable or actively infected atopic dermatitis * Patients suffering from pruritus from conditions other than AD * Patients with chronic pruritus due to systemic disease * Patients with conditions requiring inhaled steroids * Have concurrent skin disease of such severity in the study area that it could interfere with the study evaluation * Have active skin infections on the treatment area * Have received or planning to receive topical corticosteroids, topical coal tar, topical sulfur, topical PDE-4 inhibitors, topical antihistamines, topical antiseptics or antibiotics, topical antifungals, bleach baths, UVA or UVB phototherapy, oral/IV/inhaled steroids, antibiotics/antiviral/antifungal agents, oral probiotics, glucocorticoids treatment, calcineurin inhibitors, immunomodulating biologic agents, systemic glucocorticoids, systemic immunosuppressive or immunomodulatory agents within 2 weeks of Baseline visit. * Current or recent history (≤3 months of systemic use of Otrexup™, Rasuvo®, Rheumatrex® and Trexall™ or its generic versions such as Methotrexate * History of being seropositive for human immunodeficiency virus (HIV) at screening by laboratory testing at Screening * History of being positive for Hepatitis B virus surface antigen (HBsAg) or positive Hepatitis C virus antibody (HCV Ab) at screening by laboratory testing at Screening * History of renal disease * Use of any investigational drugs within the previous 30 days prior to dosing or within a period of less than five times the drug's half-life, whichever is longer * Use of any biologic within a period of 5 times its half-life * Use of vinegar or bleach baths within 2 weeks of starting the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Baseline to Day 42 | Safety and tolerability endpoints will consist of all adverse events reporting during the study duration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Eczema Area Severity Index (EASI) Score Between the Active and Vehicle Groups | Baseline to Day 28 | EASI is a validated tool used to measure the severity and extent of atopic dermatitis where clinical investigators assess the presence and severity of erythema, edema/papulation, excoriation, and lichenification (score 0-3: none=0, mild=1, moderate=2, severe=3, half-points allowed) and area of involvement (score 0-6: 0=0% involvement, 1=1-9% involvement, 2=10-29% involvement, 3=30-49% involvement, 4=50-69% involvement, 5=70-89% involvement, 6=90-100% involvement) across head and neck, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks). The EASI score can range from 0.0to 72.0 with increments of 0.1 and higher scores representing a greater severity of atopic dermatitis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in the IGA Score Between the Active and Vehicle Groups | Baseline to Day 28 | 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). |
| Difference in Actigraphy Scratching Event Count Per Hour During the Night Between the Active and Vehicle Group | Baseline to Day 28 | Subjects were provided two Actigraphy watches (one on each wrist) to accurately monitor subject's sleep, activity, and itching patterns. |
| Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group | Baseline to Day 28 | VAS (Visual Analog Scale) was performed as a measure of pruritus. The VAS is composed of a 10-cm line divided into a scale from 0 to 10, and subjects were to indicate the score that best represented the intensity of their itching over the 24-hour period before each visit where a higher score indicated greater severity in pruritus. |
| Microbial Content | Baseline and Day 28 | Evaluate if B244 administration on skin twice daily will affect the microbial content on collected skin swab samples. |
| Difference in Biomarkers Between Active and Vehicle Groups. | Baseline and Day 28 | To evaluate if B244 administration on the skin twice daily for 28 days will affect the levels of immune biomarkers. |
| Change in the Skindex 16 Score Between the Active and Vehicle Group | Baseline to Day 28 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| B244 B244 suspension (4x10E9 cells/ml) in 30ml/bottle
Subjects will apply a total of 8 pumps of IP per application to all affected areas twice-a-day
B244: B244 suspension | 61 |
| Vehicle Vehicle, 30ml/bottle
Subjects will apply a total of 8 pumps of IP per application to all affected areas twice-a-day
Vehicle: Vehicle suspension | 61 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 5 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Total | B244 | Vehicle |
|---|---|---|---|
| Age, Customized < 30 years | 24 Participants | 12 Participants | 12 Participants |
| Age, Customized ≥ 30 years | 98 Participants | 49 Participants | 49 Participants |
| BMI | 30.289 kg/m^2 STANDARD_DEVIATION 8.1702 | 30.027 kg/m^2 STANDARD_DEVIATION 9.2237 | 30.551 kg/m^2 STANDARD_DEVIATION 7.0286 |
| BMI Category <20 kg/m^2 | 7 Participants | 5 Participants | 2 Participants |
| BMI Category 20 to <25 kg/m^2 | 27 Participants | 15 Participants | 12 Participants |
| BMI Category 25 to <30 kg/m^2 | 34 Participants | 12 Participants | 22 Participants |
| BMI Category ≥30 kg/m^2 | 54 Participants | 29 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 15 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 46 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 53 Participants | 25 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 54 Participants | 27 Participants | 27 Participants |
| Sex: Female, Male Female | 80 Participants | 36 Participants | 44 Participants |
| Sex: Female, Male Male | 42 Participants | 25 Participants | 17 Participants |
| Smoking History Current | 38 Participants | 19 Participants | 19 Participants |
| Smoking History Former | 13 Participants | 10 Participants | 3 Participants |
| Smoking History Never | 71 Participants | 32 Participants | 39 Participants |
| Weight | 85.481 kg STANDARD_DEVIATION 23.8132 | 85.420 kg STANDARD_DEVIATION 24.902 | 85.542 kg STANDARD_DEVIATION 22.8794 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 61 | 0 / 61 |
| other Total, other adverse events | 16 / 61 | 14 / 61 |
| serious Total, serious adverse events | 1 / 61 | 0 / 61 |
Outcome results
Primary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Safety and tolerability endpoints will consist of all adverse events reporting during the study duration.
Time frame: Baseline to Day 42
Population: Intent to Treat (ITT) population included all randomized subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| B244 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment-Related TEAE | 2 Participants |
| B244 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment-Related Grade 3 or 4 TEAE | 0 Participants |
| B244 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment-Related Serious TEAE | 0 Participants |
| Vehicle | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment-Related TEAE | 4 Participants |
| Vehicle | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment-Related Grade 3 or 4 TEAE | 0 Participants |
| Vehicle | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | At Least 1 Treatment-Related Serious TEAE | 0 Participants |
Secondary
Change in Eczema Area Severity Index (EASI) Score Between the Active and Vehicle Groups
EASI is a validated tool used to measure the severity and extent of atopic dermatitis where clinical investigators assess the presence and severity of erythema, edema/papulation, excoriation, and lichenification (score 0-3: none=0, mild=1, moderate=2, severe=3, half-points allowed) and area of involvement (score 0-6: 0=0% involvement, 1=1-9% involvement, 2=10-29% involvement, 3=30-49% involvement, 4=50-69% involvement, 5=70-89% involvement, 6=90-100% involvement) across head and neck, trunk (including the genital area), upper extremities, and lower extremities (including the buttocks). The EASI score can range from 0.0to 72.0 with increments of 0.1 and higher scores representing a greater severity of atopic dermatitis.
Time frame: Baseline to Day 28
Population: Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B244 | Change in Eczema Area Severity Index (EASI) Score Between the Active and Vehicle Groups | -5.7 score on a scale | Standard Deviation 4.46 |
| Vehicle | Change in Eczema Area Severity Index (EASI) Score Between the Active and Vehicle Groups | -5.9 score on a scale | Standard Deviation 5.9 |
Other Pre-specified
Change in the IGA Score Between the Active and Vehicle Groups
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).
Time frame: Baseline to Day 28
Population: Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B244 | Change in the IGA Score Between the Active and Vehicle Groups | -0.6 score on a scale | Standard Deviation 0.82 |
| Vehicle | Change in the IGA Score Between the Active and Vehicle Groups | -0.7 score on a scale | Standard Deviation 0.94 |
Other Pre-specified
Change in the Skindex 16 Score Between the Active and Vehicle Group
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.
Time frame: Baseline to Day 28
Population: Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B244 | Change in the Skindex 16 Score Between the Active and Vehicle Group | -0.2 score on a scale | Standard Deviation 5.74 |
| Vehicle | Change in the Skindex 16 Score Between the Active and Vehicle Group | -0.8 score on a scale | Standard Deviation 1.28 |
Other Pre-specified
Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group
VAS (Visual Analog Scale) was performed as a measure of pruritus. The VAS is composed of a 10-cm line divided into a scale from 0 to 10, and subjects were to indicate the score that best represented the intensity of their itching over the 24-hour period before each visit where a higher score indicated greater severity in pruritus.
Time frame: Baseline to Day 28
Population: Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B244 | Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group | Week 2 Change from Baseline | -1.5 score on a scale | Standard Deviation 2.23 |
| B244 | Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group | Week 4 Change from Baseline | -1.8 score on a scale | Standard Deviation 2.81 |
| Vehicle | Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group | Week 2 Change from Baseline | -0.6 score on a scale | Standard Deviation 1.92 |
| Vehicle | Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group | Week 4 Change from Baseline | -1.4 score on a scale | Standard Deviation 2.32 |
p-value: 0.0228t-test, 1 sided
Other Pre-specified
Difference in Actigraphy Scratching Event Count Per Hour During the Night Between the Active and Vehicle Group
Subjects were provided two Actigraphy watches (one on each wrist) to accurately monitor subject's sleep, activity, and itching patterns.
Time frame: Baseline to Day 28
Population: Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28 with data collected from Actigraphy watches (subjects with missing data were excluded from analysis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B244 | Difference in Actigraphy Scratching Event Count Per Hour During the Night Between the Active and Vehicle Group | -3.4 average scratching events per hour | Standard Deviation 8.26 |
| Vehicle | Difference in Actigraphy Scratching Event Count Per Hour During the Night Between the Active and Vehicle Group | 3 average scratching events per hour | Standard Deviation 7.92 |
Other Pre-specified
Difference in Biomarkers Between Active and Vehicle Groups.
To evaluate if B244 administration on the skin twice daily for 28 days will affect the levels of immune biomarkers.
Time frame: Baseline and Day 28
Population: Data was not collected for this exploratory endpoint.
Other Pre-specified
Microbial Content
Evaluate if B244 administration on skin twice daily will affect the microbial content on collected skin swab samples.
Time frame: Baseline and Day 28
Population: Data was not collected for this exploratory endpoint.