Trial Outcomes & Findings for Long Term Extension Study of Tapinarof Cream, 1% for Subjects With Atopic Dermatitis (NCT NCT05142774)

NCT ID: NCT05142774

Last Updated: 2025-08-13

Results Overview

The hematology parameter, Erythrocytes, was assessed for changes and trends over the course of the study.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 728 participants
• Primary outcome timeframe: Baseline to Week 48
• Results posted on: 2025-08-13

Participant Flow

Eligible study participants from DMVT-505-3101 (NCT05014568), DMVT-505-3102 (NCT05032859), and DMVT-505-2104 (NCT05186805) were offered the option of participating in the DMVT-505-3103 open label extension study.

Participant milestones

Measure	Tapinarof Cream Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects were advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation. Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 received treatment with study drug until they achieved vIGA-AD=0, at which time treatment was discontinued and subjects were monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment was re-initiated and continued until vIGA-AD =0 was achieved. Subjects entering with a vIGA-AD=0 discontinued treatment and were monitored for duration of remittive response. If/when disease worsening occured (vIGA-AD ≥2), treatment was re-initiated and continued until vIGA-AD =0 was achieved. This treatment and re-treatment pattern of use continued until the end of the study.
Overall Study STARTED	728
Overall Study COMPLETED	497
Overall Study NOT COMPLETED	231

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Long Term Extension Study of Tapinarof Cream, 1% for Subjects With Atopic Dermatitis

Baseline characteristics by cohort

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Age, Continuous	15.0 years STANDARD_DEVIATION 15.32 • n=5 Participants
Age, Customized 2-6 years	194 Participants n=5 Participants
Age, Customized 7-11 years	197 Participants n=5 Participants
Age, Customized 12-17 years	213 Participants n=5 Participants
Age, Customized ≥18 years	124 Participants n=5 Participants
Sex: Female, Male Female	389 Participants n=5 Participants
Sex: Female, Male Male	339 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	163 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	562 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants
Race (NIH/OMB) Asian	81 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	219 Participants n=5 Participants
Race (NIH/OMB) White	383 Participants n=5 Participants
Race (NIH/OMB) More than one race	27 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants
Region of Enrollment Canada	112 Count of participants n=5 Participants
Region of Enrollment United States	616 Count of participants n=5 Participants
Validated Investigator Global Assessment for Atopic Dermatitis 0 - clear	58 Participants n=5 Participants
Validated Investigator Global Assessment for Atopic Dermatitis 1 - almost clear	189 Participants n=5 Participants
Validated Investigator Global Assessment for Atopic Dermatitis 2 - mild	268 Participants n=5 Participants
Validated Investigator Global Assessment for Atopic Dermatitis 3 - moderate	182 Participants n=5 Participants
Validated Investigator Global Assessment for Atopic Dermatitis 4 - severe	31 Participants n=5 Participants
Percent Body Surface Area (BSA)	10.62 Affected Body Surface Area percentage STANDARD_DEVIATION 14.259 • n=5 Participants
Eczema Area and Severity Index (EASI)	6.31 units on a scale STANDARD_DEVIATION 8.247 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49

Population: ITT Population

For rollover subjects, all AEs reported in this extension study were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug will be considered a TEAE.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Number of Subjects With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events Any treatment-emergent AE	451 Participants
Number of Subjects With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events Serious treatment-emergent AE	34 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49

Population: ITT Population

All AEs reported in this extension study were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. Subjects could have reported more than one TEAE.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Frequency of Adverse Events and Serious Adverse Events Treatment-emergent AE	1226 Events
Frequency of Adverse Events and Serious Adverse Events Serious treatment-emergent AE	45 Events

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean chemistry and hematology parameters were assessed for changes and trends over the course of the study.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Change From Baseline in Clinical Laboratory Values (g/L) Albumin (g/L)	-0.5 g/L Standard Deviation 2.43
Change From Baseline in Clinical Laboratory Values (g/L) Protein (g/L)	0.0 g/L Standard Deviation 3.95
Change From Baseline in Clinical Laboratory Values (g/L) Hemoglobin (g/L)	1.7 g/L Standard Deviation 8.45
Change From Baseline in Clinical Laboratory Values (g/L) Ery. Mean Corpuscular HGB Concentration (g/L)	0.0 g/L Standard Deviation 7.61

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean chemistry parameters were assessed for changes and trends over the course of the study.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Change From Baseline in Clinical Laboratory Values (U/L) Alkaline Phosphatase (U/L)	-14.9 U/L Standard Deviation 69.45
Change From Baseline in Clinical Laboratory Values (U/L) Alanine Aminotransferase (U/L)	-1.5 U/L Standard Deviation 11.96
Change From Baseline in Clinical Laboratory Values (U/L) Aspartate Aminotransferase (U/L)	-2.6 U/L Standard Deviation 16.13

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean chemistry parameters were assessed for changes and trends over the course of the study.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Change From Baseline in Clinical Laboratory Values (mmol/L) Bicarbonate (mmol/L)	-0.2 mmol/L Standard Deviation 2.31
Change From Baseline in Clinical Laboratory Values (mmol/L) Blood Urea Nitrogen (mmol/L)	0.04 mmol/L Standard Deviation 1.428
Change From Baseline in Clinical Laboratory Values (mmol/L) Calcium (mmol/L)	-0.019 mmol/L Standard Deviation 0.0926
Change From Baseline in Clinical Laboratory Values (mmol/L) Chloride (mmol/L)	-0.3 mmol/L Standard Deviation 2.43
Change From Baseline in Clinical Laboratory Values (mmol/L) Glucose (mmol/L)	0.13 mmol/L Standard Deviation 1.462
Change From Baseline in Clinical Laboratory Values (mmol/L) Potassium (mmol/L)	-0.03 mmol/L Standard Deviation 0.493
Change From Baseline in Clinical Laboratory Values (mmol/L) Sodium (mmol/L)	-0.1 mmol/L Standard Deviation 2.14

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean chemistry parameters were assessed for changes and trends over the course of the study.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Change From Baseline in Clinical Laboratory Values (Umol/L) Bilirubin (umol/L)	0.40 umol/L Standard Deviation 3.434
Change From Baseline in Clinical Laboratory Values (Umol/L) Enzymatic Creatinine (umol/L)	2.1 umol/L Standard Deviation 7.92
Change From Baseline in Clinical Laboratory Values (Umol/L) Creatinine (Jaffe) (umol/L)	2.7 umol/L Standard Deviation 12.06
Change From Baseline in Clinical Laboratory Values (Umol/L) Urate (umol/L)	0.9 umol/L Standard Deviation 52.32

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean hematology parameters were assessed for changes and trends over the course of the study.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) Eosinophils (10^9/L)	-.03 10^9 cells/L Standard Deviation 0.308
Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) Basophils (10^9/L)	0.01 10^9 cells/L Standard Deviation 0.051
Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) Lymphocytes (10^9/L)	-0.02 10^9 cells/L Standard Deviation 0.909
Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) Monocytes (10^9/L)	0.00 10^9 cells/L Standard Deviation 0.192
Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) Neutrophils (10^9/L)	0.22 10^9 cells/L Standard Deviation 2.079
Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) Platelets (10^9/L)	-4.0 10^9 cells/L Standard Deviation 59.57
Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) Leukocytes (10^9/L)	0.18 10^9 cells/L Standard Deviation 2.474

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean hematology parameters were assessed for changes and trends over the course of the study.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Change From Baseline in Clinical Laboratory Values (%) Basophils/Total Cells (%)	0.03 % of cells Standard Deviation 0.272
Change From Baseline in Clinical Laboratory Values (%) Eosinophils/Total Cells (%)	-0.39 % of cells Standard Deviation 3.427
Change From Baseline in Clinical Laboratory Values (%) Lymphocytes/Total Cells (%)	-0.73 % of cells Standard Deviation 10.440
Change From Baseline in Clinical Laboratory Values (%) Monocytes/Total Cells (%)	-0.09 % of cells Standard Deviation 2.592
Change From Baseline in Clinical Laboratory Values (%) Neutrophils/Total Cells (%)	1.18 % of cells Standard Deviation 11.436
Change From Baseline in Clinical Laboratory Values (%) Reticulocytes/Erythrocytes (%)	-0.06 % of cells Standard Deviation 0.402

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The hematology parameter, Hematocrit, was assessed for changes and trends over the course of the study.

Outcome measures

Measure

Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Change From Baseline in Clinical Laboratory Values (L/L)

0.005 L/L Standard Deviation 0.0263

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The hematology parameter, Ery. Mean Corpuscular Hemoglobin was assessed for changes and trends over the course of the study.

Outcome measures

Measure

Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Change From Baseline in Clinical Laboratory Values (pg)

0.13 pg Standard Deviation 0.823

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The hematology parameter, Ery. Mean Corpuscular Volume, was assessed for changes and trends over the course of the study.

Outcome measures

Measure

Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Change From Baseline in Clinical Laboratory Values (fl)

0.37 fl Standard Deviation 2.364

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The hematology parameter, Erythrocytes, was assessed for changes and trends over the course of the study.

Outcome measures

Measure

Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Change From Baseline in Clinical Laboratory Values (10^12 Cells/L)

0.038 10^12 cells/L Standard Deviation 0.2905

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Subjects Entering the Study with vIGA-AD Score ≥1, Observed Cases

The vIGA-AD is a clinical tool for assessing the current state/severity of a subject's atopic dermatitis at a given timepoint. It is a static 5-point (0-4) morphological assessment of overall disease severity (scalp excluded), as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. Higher vIGA-AD scores represents more severe disease.

Outcome measures

Measure

Tapinarof Cream n=670 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Complete Disease Clearance During LTE: Number of Subjects Achieving Disease Clearance vIGA-AD =0 (Clear) While on Therapy for Subjects Entered LTE vIGA-AD ≥ 1 (Almost Clear )

320 Participants

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Subjects Entering the Study with vIGA-AD Score ≥2, Observed Cases

The vIGA-AD is a clinical tool for assessing the current state/severity of a subject's atopic dermatitis at a given timepoint. It is a static 5-point (0-4) morphological assessment of overall disease severity (scalp excluded), as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. Higher vIGA-AD scores represents more severe disease.

Outcome measures

Measure

Tapinarof Cream n=481 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Response During LTE: Number of Subjects Achieving vIGA-AD =0 or 1 (Clear or Almost Clear) While on Therapy for Subjects Who Entered LTE With vIGA-AD ≥ 2 (Mild)

347 Participants

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

Subjects received treatment with tapinarof intermittently guided by disease severity. This outcome measure assesses the change from baseline in %BSA affected in all subjects, including those on and those off therapy.

Assessment of BSA with Atopic Dermatitis was estimated by means of the handprint method, where the full palmar hand of the participant (fully extended palm, fingers and thumb together) represented approximately 1% of the total BSA. Body regions are assigned specific number of handprints with percentage [Head and neck = 10% (10 handprints), upper extremities = 20% (20 handprints), Trunk (including axillae and groin) = 30% (30 handprints), lower extremities (including buttocks) = 40% (40 handprints)]. Lesions on the scalp will not be included in the calculation of %BSA affected. Estimates of the % involvement in each body region will be multiplied by the fraction of total body area to obtain the total %BSA involved by region and overall.

Outcome measures

Measure

Tapinarof Cream n=506 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Absolute Change From Baseline in %BSA Affected

-7.14 percentage of BSA Standard Deviation 12.881

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases; Participants with %BSA=0 at baseline were excluded

Subjects received treatment with tapinarof intermittently guided by disease severity. This outcome measure assesses the % change from baseline in %BSA affected in all subjects, including those on and those off therapy.

Assessment of BSA with Atopic Dermatitis was estimated by means of the handprint method, where the full palmar hand of the participant (fully extended palm, fingers and thumb together) represented approximately 1% of the total BSA. Body regions are assigned specific number of handprints with percentage [Head and neck = 10% (10 handprints), upper extremities = 20% (20 handprints), Trunk (including axillae and groin) = 30% (30 handprints), lower extremities (including buttocks) = 40% (40 handprints)]. Lesions on the scalp will not be included in the calculation of %BSA affected. Estimates of the % involvement in each body region will be multiplied by the fraction of total body area to obtain the total %BSA involved by region and overall.

Outcome measures

Measure

Tapinarof Cream n=462 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Percent Change From Baseline in %BSA Affected

-37.45 percent change from baseline in % total Standard Deviation 189.905

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

Subjects received treatment with tapinarof intermittently guided by disease severity. This outcome measure assesses the change from baseline in EASI score in all subjects, including those on and those off therapy.

The EASI scoring system is a clinical tool that quantifies the severity of a subject's AD based on both lesion severity and %BSA affected. The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. The subject's scalp is excluded from this assessment. Higher EASI scores indicate more severe disease.

Outcome measures

Measure

Tapinarof Cream n=506 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score

-4.19 Units on a scale Standard Deviation 7.248

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases; Participants with EASI=0 at baseline were excluded

Subjects received treatment with tapinarof intermittently guided by disease severity. This outcome measure assesses the % change from baseline in EASI score in all subjects, including those on and those off therapy.

The EASI scoring system is a clinical tool that quantifies the severity of a subject's AD based on both lesion severity and %BSA affected. The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. The subject's scalp is excluded from this assessment. Higher EASI scores indicate more severe disease.

Outcome measures

Measure

Tapinarof Cream n=462 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score

-33.70 Units on a scale Standard Deviation 139.557

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases; Participants with EASI=0 at baseline were excluded

The EASI scoring system is a clinical tool that quantifies the severity of a subject's AD based on both lesion severity and %BSA affected. The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.

Outcome measures

Measure

Tapinarof Cream n=462 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Percent of Subjects With ≥ 50% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48.

325 Participants

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases; Participants with EASI=0 at baseline were excluded

The EASI scoring system is a clinical tool that quantifies the severity of a subject's AD based on both lesion severity and %BSA affected. The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. The subject's scalp is excluded from this assessment. Higher EASI scores indicate more severe disease.

Outcome measures

Measure

Tapinarof Cream n=462 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48.

256 Participants

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases; Participants with EASI=0 at baseline were excluded

The EASI scoring system is a clinical tool that quantifies the severity of a subject's AD based on both lesion severity and %BSA affected. The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. The subject's scalp is excluded from this assessment. Higher EASI scores indicate more severe disease.

Outcome measures

Measure

Tapinarof Cream n=462 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48.

178 Participants

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The Peak Pruritus Numeric Rating Scale (PP-NRS) is used to quickly assess itch/pruritus severity over a 24-hour period. The PP-NRS is scored on a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable". The subject or caregiver will utilize the scale to assess peak pruritis once per day and record the results in their diaries. The daily ratings are averaged to generate a score for the week.

Outcome measures

Measure

Tapinarof Cream n=483 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Mean Change in Peak Pruritis-Numeric Rating Scale (PP-NRS) From Baseline

-1.618 Units on a scale Standard Deviation 2.7756

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Subjects with a Baseline PP-NRS Score ≥4, Observed Cases

The Peak Pruritus Numeric Rating Scale (PP-NRS) is used to quickly assess itch/pruritus severity over a 24-hour period. The PP-NRS is scored on a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable". The subject or caregiver will utilize the scale to assess peak pruritis once per day and record the results in their diaries. The daily ratings are averaged to generate a score for the week.

Outcome measures

Measure

Tapinarof Cream n=182 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Number of Subjects With a Baseline Peak Pruritis-Numeric Rating Scale (PP-NRS) Score ≥ 4 Who Achieve ≥ 4-point Reduction in the PP-NRS From Baseline

94 Participants

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean vital sign parameters were assessed for changes and trends over the course of the study. Shifts from Baseline in vital sign parameters were assessed for clinical relevance.

Outcome measures

Measure

Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Change From Baseline in Vital Signs - Pulse

-0.9 beats per minute (bpm) Standard Deviation 12.61

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean vital sign parameters were assessed for changes and trends over the course of the study. Shifts from Baseline in vital sign parameters were assessed for clinical relevance.

Outcome measures

Measure	Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Change From Baseline in Vital Signs - Blood Pressure (Systolic and Diastolic) Systolic Blood Pressure (mmHg)	1.0 mmHg Standard Deviation 10.72
Change From Baseline in Vital Signs - Blood Pressure (Systolic and Diastolic) Diastolic Blood Pressure (mmHg)	0.7 mmHg Standard Deviation 9.78

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: ITT Population, Observed Cases

The mean vital sign parameters were assessed for changes and trends over the course of the study. Shifts from Baseline in vital sign parameters were assessed for clinical relevance.

Outcome measures

Measure

Tapinarof Cream n=728 Participants Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.

Change From Baseline in Vital Signs - Temperature

0.02 degrees C Standard Deviation 0.437

Adverse Events

Continuous or Intermittent Use of Tapinarof Cream (DMVT-505) Cream According to vIGA-AD Score

Serious events: 34 serious events

Other events: 451 other events

Deaths: 0 deaths

Serious adverse events

Measure	Continuous or Intermittent Use of Tapinarof Cream (DMVT-505) Cream According to vIGA-AD Score n=728 participants at risk Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Endocrine disorders Hypothyroidism	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Immune system disorders Anaphylactic reaction	0.27% 2/728 • Number of events 2 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Pneumonia	0.69% 5/728 • Number of events 6 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Appendicitis	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Pneumonia respiratory syncytial viral	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Postoperative abscess	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Respiratory syncytial virus infection	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Injury, poisoning and procedural complications Humerus fracture	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Metabolism and nutrition disorders Diabetes mellitus	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Metabolism and nutrition disorders Hyperglycaemia	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Psychiatric disorders Alcohol withdrawal syndome	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Respiratory, thoracic and mediastinal disorders Asthma	2.6% 19/728 • Number of events 20 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.41% 3/728 • Number of events 3 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Respiratory, thoracic and mediastinal disorders Cough	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Skin and subcutaneous tissue disorders Dermatitis exfoliative generalised	0.14% 1/728 • Number of events 1 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.

Other adverse events

Measure	Continuous or Intermittent Use of Tapinarof Cream (DMVT-505) Cream According to vIGA-AD Score n=728 participants at risk Subjects entering with vIGA-AD (Validated Investigator Global Assessment of Atopic Dermatitis) ≥1 receive treatment with study drug until they achieve vIGA-AD=0, at which time treatment is discontinued and subjects are monitored for durability of response (remittive response). If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. Subjects entering with a vIGA-AD=0 discontinue treatment and are monitored for duration of remittive response. If/when disease worsening occurs (vIGA-AD ≥2), treatment is re-initiated and continued until vIGA-AD =0 is achieved. This treatment and re-treatment pattern of use continue until the end of the study. Tapinarof cream, 1%: Tapinarof cream, 1%, applied daily to affected areas by subjects or their caregivers based on vIGA-AD. Subjects are advised to choose the application time they prefer and apply the study drug at that approximate time each day of study participation.
Gastrointestinal disorders Vomiting	2.3% 17/728 • Number of events 21 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
General disorders Pyrexia	2.2% 16/728 • Number of events 19 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Immune system disorders Seasonal allergy	2.3% 17/728 • Number of events 17 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Folliculitis	12.1% 88/728 • Number of events 101 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Nasopharyngitis	6.9% 50/728 • Number of events 64 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Upper respiratory tract infection	6.9% 50/728 • Number of events 73 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations COVID-19	5.8% 42/728 • Number of events 43 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Influenza	3.7% 27/728 • Number of events 28 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Impetigo	3.0% 22/728 • Number of events 26 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Pharyngitis streptococcal	2.9% 21/728 • Number of events 23 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Ear infection	2.3% 17/728 • Number of events 24 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Gastroenteritis viral	2.3% 17/728 • Number of events 18 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Infections and infestations Otitis media	2.2% 16/728 • Number of events 19 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Nervous system disorders Headache	3.4% 25/728 • Number of events 28 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Respiratory, thoracic and mediastinal disorders Asthma	6.0% 44/728 • Number of events 59 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.
Respiratory, thoracic and mediastinal disorders Cough	3.3% 24/728 • Number of events 27 • For rollover subjects, all AEs reported in this extension study, through study completion, up to 48 weeks, were considered as TEAEs except for those AEs ongoing at the end of previous studies but resolved prior to the Visit 1 date for this extension study. For direct-enrolling subjects, all AEs that start after the first dose of study drug and through study completion, up to 48 weeks, will be considered a TEAE.

Additional Information

Clinical Lead, Late-Stage Clinical Development

Organon and Co

Phone: 551-430-6000

Email: pdrl@organon.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place