Trial Outcomes & Findings for Safety and Efficacy of AN2728 Topical Ointment, 2% in Children, Adolescents, and Adults (Ages 2 Years and Older) With Atopic Dermatitis (NCT NCT02118766)

Last Updated: 2017-03-06

Results Overview

ISGA assessed the severity of AD (except scalp and venous access area) on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual hypo/hyper pigmentation, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Treatment success was defined as an ISGA score of Clear (0) or Almost Clear (1) with at least a 2-grade improvement from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

763 participants

Primary outcome timeframe

Day 29

Results posted on

2017-03-06

Participant Flow

Participant milestones

Participant milestones
Measure	AN2728 Topical Ointment, 2 Percent Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Overall Study STARTED	507	256
Overall Study Treated	503	256
Overall Study COMPLETED	477	225
Overall Study NOT COMPLETED	30	31

Reasons for withdrawal

Reasons for withdrawal
Measure	AN2728 Topical Ointment, 2 Percent Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Overall Study Adverse Event	7	2
Overall Study Withdrawal by Subject	3	6
Overall Study Lost to Follow-up	5	4
Overall Study Withdrawal by parent/guardian	12	18
Overall Study Other	3	1

Baseline Characteristics

Safety and Efficacy of AN2728 Topical Ointment, 2% in Children, Adolescents, and Adults (Ages 2 Years and Older) With Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AN2728 Topical Ointment, 2 Percent n=503 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=256 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	Total n=759 Participants Total of all reporting groups
Age, Customized 2-6 years	162 Participants n=5 Participants	78 Participants n=7 Participants	240 Participants n=5 Participants
Age, Customized 7-11 years	155 Participants n=5 Participants	73 Participants n=7 Participants	228 Participants n=5 Participants
Age, Customized 12-17 years	121 Participants n=5 Participants	67 Participants n=7 Participants	188 Participants n=5 Participants
Age, Customized greater than or equal to 18 years	65 Participants n=5 Participants	38 Participants n=7 Participants	103 Participants n=5 Participants
Gender Female	284 Participants n=5 Participants	143 Participants n=7 Participants	427 Participants n=5 Participants
Gender Male	219 Participants n=5 Participants	113 Participants n=7 Participants	332 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 29

Population: Intent to treat population included all randomized participants who received the study drug.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=503 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=256 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Percentage of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA) at Day 29	32.8 percentage of participants	25.4 percentage of participants

PRIMARY outcome

Timeframe: AEs: Baseline (Day 1) up to Day 29, SAEs: Baseline (Day 1) up to Day 36

Population: Safety population included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.

An AE was any untoward medical occurrence attributed to a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study that were absent before treatment or that worsened relative to pre-treatment state.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=502 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=252 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) AEs	147 participants	50 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) SAEs	5 participants	1 participants

PRIMARY outcome

Timeframe: Baseline, Day 29

Population: Safety population included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.

Following parameters were analyzed for examination of vital signs: systolic and diastolic blood pressure, respiratory rate and body temperature. Vital sign measurements were performed with the participant in the seated or supine position. Clinical significance of change from baseline value was determined by investigator.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=502 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=252 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Day 29	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline, Day 29

Population: Safety population included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.

Laboratory values included: Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Albumin, Blood Urea Nitrogen, Creatinine, Hematocrit, Hemoglobin, Lymphocytes, Monocytes, Neutrophils, Platelets, Basophils, Eosinophils, Red blood cell count, White blood cell count, Total bilirubin and Glucose (nonfasting), Potassium, Total Protein, and Sodium. Clinical significance of change from baseline value was determined by investigator.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=502 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=252 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Number of Participants With Clinically Significant Change From Baseline in Laboratory Values at Day 29	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 29

Population: Intent to treat population included all randomized participants who received the study drug.

ISGA assessed the severity of AD (except scalp and venous access area) on a 5-point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of AD. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Percentage of participants with an ISGA score of 0 or 1 were reported.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=503 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=256 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Percentage of Participants With an Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 29	51.7 percentage of participants	40.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Day 29

Population: Intent to treat population included all randomized participants who received the study drug.

Time to achieve treatment success based on ISGA was defined as the time interval between the administrations of first dose of study drug until first documentation of success in ISGA. Success in ISGA was defined as an ISGA score of clear (0) or almost clear (1) with at least 2-grade improvement from baseline. It was analyzed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=503 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=256 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Time to Achieve Treatment Success Based on Investigator's Static Global Assessment (ISGA)	NA days The median time to achieve success in ISGA and its 95% confidence interval (CI) were not estimable, as fewer participants (less than 50 percent) reached success in ISGA.	NA days The median time to achieve success in ISGA and its 95% CI were not estimable, as fewer participants (less than 50 percent) reached success in ISGA.

SECONDARY outcome

Timeframe: Baseline, Day 29

Population: Intent to treat population included all participants who were randomized and dispensed study drug. Here, Number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure and 'n' signifies those participants who were evaluable at specified time point for each arm, respectively.

Signs of AD included erythema, induration/papulation, exudation, excoriation and lichenification. Each sign was assessed on a 4- point scale ranges from 0 to 3, where 0= none, 1= mild, 2= moderate to 3= severe. Higher score indicates severe signs and symptoms of AD.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=503 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=256 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Erythema: Baseline (n= 503, 256)	1.7 units on a scale Standard Deviation 0.59	1.6 units on a scale Standard Deviation 0.57
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Erythema: Change at Day 29 (n=478,228)	-0.7 units on a scale Standard Deviation 0.79	-0.4 units on a scale Standard Deviation 0.77
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Induration/Papulation: Baseline (n= 503, 256)	1.8 units on a scale Standard Deviation 0.59	1.9 units on a scale Standard Deviation 0.56
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Induration/Papulation:Change at Day 29(n=478,228)	-0.7 units on a scale Standard Deviation 0.85	-0.7 units on a scale Standard Deviation 0.73
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Exudation: Baseline (n= 503, 256)	0.8 units on a scale Standard Deviation 0.82	0.8 units on a scale Standard Deviation 0.86
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Exudation: Change at Day 29 (n=478, 228)	-0.5 units on a scale Standard Deviation 0.78	-0.3 units on a scale Standard Deviation 0.80
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Excoriation: Baseline (n= 503, 256)	1.4 units on a scale Standard Deviation 0.70	1.5 units on a scale Standard Deviation 0.71
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Excoriation: Change at Day 29 (n=478, 228)	-0.8 units on a scale Standard Deviation 0.81	-0.7 units on a scale Standard Deviation 0.89
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Lichenification: Baseline (n= 503, 256)	1.5 units on a scale Standard Deviation 0.73	1.5 units on a scale Standard Deviation 0.67
Change From Baseline in Signs of Atopic Dermatitis (AD) at Day 29 Lichenification: Change at Day 29 (n=478, 228)	-0.7 units on a scale Standard Deviation 0.81	-0.5 units on a scale Standard Deviation 0.77

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 29

Population: Intent to treat population included all participants who were randomized and dispensed study drug. Here, 'N' signifies those participants who were evaluable for this measure.

Time to improvement in pruritus was defined as the time interval between the administration of first dose of study drug till the first documentation of improvement in pruritus. Improvement in pruritus was defined as achieving none (0) or mild (1) score with at least a 1- grade improvement from baseline. Severity of pruritus was assessed on 4-point numeric scale ranges from 0 to 3, where 0= none (no itching), 1= mild (occasional, slight itching/scratching), 2= moderate (constant or intermittent itching/scratching which is not disturbing sleep) and 3= severe (bothersome itching/scratching which is disturbing sleep). Higher scores indicated more severe condition. It was analyzed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=428 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=210 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Time to Improvement in Pruritus	1.32 days Interval 1.19 to 1.6	1.87 days Interval 1.45 to 2.64

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 29

Population: Intent to treat population included all participants who were randomized and dispensed study drug. Here, 'n' signifies those participants who were evaluable at specified time point for each arm, respectively.

The DLQI was a 10-item questionnaire that measures the impact of skin disease on participant's quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The DLQI total score ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the participant's life; 2-6 = small effect on the participant's life; 7-12 = moderate effect on the participant's life; 13-18 = very large effect on the participant's life; 19-30 = extremely large effect on the participant's life. Higher scores indicate more impact on quality of life of participants.

Outcome measures

Outcome measures
Measure	AN2728 Topical Ointment, 2 Percent n=503 Participants Participants with mild to moderate atopic dermatitis (AD) applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	AN2728 Topical Ointment, Vehicle n=256 Participants Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29 Baseline (n =95, 52)	9.6 units on a scale Standard Deviation 6.37	9.5 units on a scale Standard Deviation 6.52
Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Day 29 Change at Day 29 (n =87, 44)	-5.5 units on a scale Standard Deviation 5.45	-3.6 units on a scale Standard Deviation 4.60

Adverse Events

Crisaborole (AN2728) Ointment, 2 Percent

Serious events: 5 serious events

Other events: 147 other events

Deaths: 0 deaths

Crisaborole (AN2728) Ointment Vehicle

Serious events: 1 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Crisaborole (AN2728) Ointment, 2 Percent n=502 participants at risk Participants with mild to moderate AD applied AN2728 ointment, 2 percent to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.	Crisaborole (AN2728) Ointment Vehicle n=252 participants at risk Participants with mild to moderate AD applied AN2728 ointment matching vehicle to treatment-targeted lesions, twice daily from Day 1 to Day 28. Target lesions were identified at Baseline (Day 1) by investigator.
Infections and infestations Appendicitis	0.20% 1/502 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.	0.00% 0/252 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
Infections and infestations Cellulitis	0.00% 0/502 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.	0.40% 1/252 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
Infections and infestations Pneumonia	0.20% 1/502 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.	0.00% 0/252 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
Psychiatric disorders Suicide attempt	0.20% 1/502 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.	0.00% 0/252 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
Respiratory, thoracic and mediastinal disorders Asthma	0.20% 1/502 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.	0.00% 0/252 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.
Vascular disorders Kawasaki's disease	0.20% 1/502 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.	0.00% 0/252 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non serious in another participant, or one participant may have experienced both a serious and non serious event during the study. AEs and SAEs were analyzed for safety population which included all randomized participants who received at least 1 confirmed dose of study drug, and had at least 1 post-baseline assessment.

Other adverse events

Additional Information

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Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results
Publication restrictions are in place

Restriction type: OTHER