Study to Determine Safety and Efficacy of B244 in Subjects With Mild to Moderate Atopic Dermatitis

• ClinicalTrials.gov Identifier: NCT03235024
• Recruitment Status: Completed
• First Posted: August 1, 2017
• Results First Posted: October 10, 2022
• Last Update Posted: October 10, 2022
• Sponsor: AOBiome LLC
• Collaborator: Veristat, Inc.
• Information provided by (Responsible Party): AOBiome LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis Eczema
• Interventions: Biological: B244; Biological: Vehicle
• Enrollment: 122

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	B244	Vehicle
Arm/Group Description	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	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
Period Title: Overall Study
Started	61	61
Completed	55	51
Not Completed	6	10
Reason Not Completed
Adverse Event	2	2
Death	1	0
Lost to Follow-up	2	5
Protocol Violation	1	0
Withdrawal by Subject	0	3

Baseline Characteristics

Arm/Group Title		B244	Vehicle	Total
Arm/Group Description		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	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	Total of all reporting groups
Overall Number of Baseline Participants		61	61	122
Baseline Analysis Population Description		Intent to Treat (ITT) population included all randomized subjects.
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	61 participants	61 participants	122 participants
< 30 years		12 19.7%	12 19.7%	24 19.7%
≥ 30 years		49 80.3%	49 80.3%	98 80.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	61 participants	122 participants
	Female	36 59.0%	44 72.1%	80 65.6%
	Male	25 41.0%	17 27.9%	42 34.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	61 participants	122 participants
	Hispanic or Latino	15 24.6%	10 16.4%	25 20.5%
	Not Hispanic or Latino	46 75.4%	50 82.0%	96 78.7%
	Unknown or Not Reported	0 0.0%	1 1.6%	1 0.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	61 participants	122 participants
	American Indian or Alaska Native	1 1.6%	0 0.0%	1 0.8%
	Asian	5 8.2%	4 6.6%	9 7.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 1.6%	1 0.8%
	Black or African American	25 41.0%	28 45.9%	53 43.4%
	White	27 44.3%	27 44.3%	54 44.3%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	3 4.9%	1 1.6%	4 3.3%
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	61 participants	61 participants	122 participants
		85.420 (24.9020)	85.542 (22.8794)	85.481 (23.8132)
BMI; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	61 participants	61 participants	122 participants
		30.027 (9.2237)	30.551 (7.0286)	30.289 (8.1702)
BMI Category; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	61 participants	122 participants
	<20 kg/m^2	5 8.2%	2 3.3%	7 5.7%
	20 to <25 kg/m^2	15 24.6%	12 19.7%	27 22.1%
	25 to <30 kg/m^2	12 19.7%	22 36.1%	34 27.9%
	≥30 kg/m^2	29 47.5%	25 41.0%	54 44.3%
Smoking History; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	61 participants	122 participants
	Never	32 52.5%	39 63.9%	71 58.2%
	Former	10 16.4%	3 4.9%	13 10.7%
	Current	19 31.1%	19 31.1%	38 31.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Description	Safety and tolerability endpoints will consist of all adverse events reporting during the study duration.
Time Frame	Baseline to Day 42

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population included all randomized subjects.

Arm/Group Title	B244	Vehicle
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	61	61
Measure Type: Count of Participants; Unit of Measure: Participants
At Least 1 Treatment-Related TEAE	2 3.3%	4 6.6%
At Least 1 Treatment-Related Grade 3 or 4 TEAE	0 0.0%	0 0.0%
At Least 1 Treatment-Related Serious TEAE	0 0.0%	0 0.0%

2. Secondary Outcome

Title	Change in Eczema Area Severity Index (EASI) Score Between the Active and Vehicle Groups
Description	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

Outcome Measure Data

Analysis Population Description

Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28.

Arm/Group Title	B244	Vehicle
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	56	51
Mean (Standard Deviation); Unit of Measure: score on a scale
	-5.7 (4.46)	-5.9 (5.90)

3. Other Pre-specified Outcome

Title	Change in Visual Analog Scale (VAS) Score for Pruritus Between the Active and Vehicle Group
Description	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

Outcome Measure Data

Analysis Population Description

Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28.

Arm/Group Title	B244	Vehicle
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	56	51
Mean (Standard Deviation); Unit of Measure: score on a scale
Week 2 Change from Baseline	-1.5 (2.23)	-0.6 (1.92)
Week 4 Change from Baseline	-1.8 (2.81)	-1.4 (2.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	B244, Vehicle
	Comments	[Not Specified]
	Type of Statistical Test	Equivalence
	Comments	A sample size of 52 per group would achieve >80% power to reject the null hypothesis of equal means when the population mean difference is μ1 - μ2 = (-1.4) - (-5.3) = 3.9 with a standard deviation for both groups of 7.0 and with a significance level (alpha) of 0.025 using a 1-sided 2-sample equal variance t-test.
Statistical Test of Hypothesis	P-Value	0.0228
	Comments	At Week 2
	Method	t-test, 1 sided
	Comments	[Not Specified]

4. Other Pre-specified Outcome

Title	Change in the Skindex 16 Score Between the Active and Vehicle Group
Description	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

Outcome Measure Data

Analysis Population Description

Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28.

Arm/Group Title	B244	Vehicle
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	56	51
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.2 (5.74)	-0.8 (1.28)

5. Other Pre-specified Outcome

Title	Change in the IGA Score Between the Active and Vehicle Groups
Description	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

Outcome Measure Data

Analysis Population Description

Subjects from the Intent to Treat (ITT) population (all randomized subjects) that remained in the study at Day 28.

Arm/Group Title	B244	Vehicle
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	56	51
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.6 (0.82)	-0.7 (0.94)

6. Other Pre-specified Outcome

Title	Difference in Actigraphy Scratching Event Count Per Hour During the Night Between the Active and Vehicle Group
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	B244	Vehicle
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	7	4
Mean (Standard Deviation); Unit of Measure: average scratching events per hour
	-3.4 (8.26)	3 (7.92)

7. Other Pre-specified Outcome

Title	Difference in Biomarkers Between Active and Vehicle Groups.
Description	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

Outcome Measure Data

Analysis Population Description

Data was not collected for this exploratory endpoint.

Arm/Group Title	B244	Vehicle
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Other Pre-specified Outcome

Title	Microbial Content
Description	Evaluate if B244 administration on skin twice daily will affect the microbial content on collected skin swab samples.
Time Frame	Baseline and Day 28

Outcome Measure Data

Analysis Population Description

Data was not collected for this exploratory endpoint.

Arm/Group Title	B244	Vehicle
Arm/Group Description:	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	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
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Baseline to Week 6.
Adverse Event Reporting Description	All AEs occurring after signing of the ICF through study completion/early termination were to be reported. All AEs were to be recorded irrespective of whether they were considered drug related. AEs were to be evaluated by the Investigator at each visit for duration, intensity, and whether the event could have been associated with the IP or other causes. Adverse events believed to be possibly related to IP must have been followed until their resolution.
Arm/Group Title	B244		Vehicle
Arm/Group Description	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		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
All-Cause Mortality
	B244		Vehicle
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/61 (1.64%)		0/61 (0.00%)
Serious Adverse Events
	B244		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/61 (1.64%)		0/61 (0.00%)
Vascular disorders
Arteriosclerosis †	1/61 (1.64%)	1	0/61 (0.00%)	0
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	B244		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/61 (26.23%)		14/61 (22.95%)
Ear and labyrinth disorders
Ear swelling †	1/61 (1.64%)		0/61 (0.00%)
Gastrointestinal disorders
Abdominal Discomfort †	1/61 (1.64%)		0/61 (0.00%)
Diarrhoea †	1/61 (1.64%)		0/61 (0.00%)
Lip Swelling †	1/61 (1.64%)		0/61 (0.00%)
Toothache †	0/61 (0.00%)		1/61 (1.64%)
General disorders
Application site pain †	1/61 (1.64%)		1/61 (1.64%)
Application site pruritus †	1/61 (1.64%)		0/61 (0.00%)
Immune system disorders
Seasonal allergy †	0/61 (0.00%)		1/61 (1.64%)
Infections and infestations
Bronchitis †	2/61 (3.28%)		0/61 (0.00%)
Superinfection †	1/61 (1.64%)		0/61 (0.00%)
Upper respiratory infection †	2/61 (3.28%)		1/61 (1.64%)
Urinary tract infection †	0/61 (0.00%)		1/61 (1.64%)
Viral upper respiratory tract infection †	1/61 (1.64%)		1/61 (1.64%)
Injury, poisoning and procedural complications
Concussion †	1/61 (1.64%)		0/61 (0.00%)
Facial bones fracture †	1/61 (1.64%)		0/61 (0.00%)
Foot fracture †	1/61 (1.64%)		0/61 (0.00%)
Contusion †	1/61 (1.64%)		0/61 (0.00%)
Investigations
Haemeoglobin decreased †	1/61 (1.64%)		0/61 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain †	1/61 (1.64%)		1/61 (1.64%)
Pain in extremity †	0/61 (0.00%)		1/61 (1.64%)
Nervous system disorders
Burning Sensation †	0/61 (0.00%)		1/61 (1.64%)
Headache †	3/61 (4.92%)		3/61 (4.92%)
Reproductive system and breast disorders
Uterine cyst †	1/61 (1.64%)		0/61 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis †	1/61 (1.64%)		0/61 (0.00%)
Dermatitis atopic †	0/61 (0.00%)		2/61 (3.28%)
Dermatitis contact †	2/61 (3.28%)		1/61 (1.64%)
Pruritus †	0/61 (0.00%)		2/61 (3.28%)
Rosacea †	0/61 (0.00%)		1/61 (1.64%)
Urticaria †	1/61 (1.64%)		0/61 (0.00%)
Vascular disorders
Arteriosclerosis †	1/61 (1.64%)		0/61 (0.00%)
Hypertension †	0/61 (0.00%)		1/61 (1.64%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Sponsor shall have 45 days to review the papers. Sponsor shall have the right to require Institution/Principal Investigator, as applicable, to remove specifically identified confidential information and/or delay the proposed publication or presentation for an additional one hundred twenty (120) days to enable Sponsor to seek patent protections.

Results Point of Contact

• Name/Title: Hyun Kim, Vice President Clinical Operations
• Organization: AOBiome Therapeutics
• Phone: 617-639-9980
• EMail: hkim@aobiome.com

• Responsible Party: AOBiome LLC
• ClinicalTrials.gov Identifier: NCT03235024
• Other Study ID Numbers: ADB244-001
• First Submitted: July 20, 2017
• First Posted: August 1, 2017
• Results First Submitted: July 19, 2022
• Results First Posted: October 10, 2022
• Last Update Posted: October 10, 2022