Atopic Dermatitis
Conditions
Keywords
eczema, pediatric, tapinarof, phase 3, topical
Brief summary
This is an open-label, long-term multicenter, study to evaluate the safety and efficacy of topical tapinarof cream, 1% in subjects with atopic dermatitis. Subjects in this study have completed treatment in one of two Phase 3 pivotal studies (DMVT-505-3101 or DMVT-505-3102) or completed treatment in the DMVT-505-2104 study, or directly enrolled into this study. This study will consist of up to 48 weeks of treatment and a 1 week safety follow-up period.
Detailed description
At the completion of the Week 8 visit of study DMVT-505-3101 (NCT05014568) or study DMVT-505-3102 (NCT05032859) or the Day 28 visit of study DMVT-505-2104 (NCT05186805) (Day 1 \[Baseline\] in this study), all eligible subjects will be offered enrollment in this open-label long-term extension (OL-LTE) study. Approximately 125 additional pediatric subjects ages 2 to \< 18 years who are not eligible for participation in the Phase 3 pivotal studies (DMVT-505-3101 or DMVT-505-3102) will be enrolled directly into this OL-LTE study. Study visits during the treatment period for all subjects will occur every 4 weeks (± 3 days). The total duration of study participation will be approximately 48 weeks for rollover subjects (Baseline to Final Visit) with a 1-week Safety Follow-up Period and approximately 52 weeks for direct-enrolling subjects (Screening to Final Visit) with a 1-week Safety Follow-up Period.
Interventions
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.
Sponsors
Organon and Co
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For Roll-over Subjects Only: * Met the criteria as a Study Completer in one of three studies (DMVT-505-3101 study, DMVT-505-3102 study, or DMVT-505-2104 study). * Must not be pregnant at Baseline For Direct-Enrolling Subjects Only: * Male and female subjects ages 2 years to \< 18 years at the time of consent with clinical diagnosis of AD * Subjects with a vIGA-AD™ score of ≥ 3 and AD covering ≥ 40% of the BSA at Screening and Baseline (pre-randomization), or subjects with a vIGA-AD™ score of 2 at Screening and Baseline (pre-randomization) regardless of BSA. Subjects must have screened for the DMVT-505-3101 or DMVT-505-3102 study and failed to meet BSA and/or vIGA-AD™ eligibility criteria. * AD present for at least 6 months for ages 6 years old and above or 3 months for ages 2 to 5 years old * Must not be pregnant at Screening or Baseline For All Subjects: * Female subjects of childbearing potential who are engaging in sexual activity that could lead to pregnancy should use acceptable birth control methods * Subject, subject's parent, or legal representative must be capable of giving written informed consent/assent
Exclusion criteria
For Rollover Subjects Only: 1. Subjects who were not receiving study drug at the time of the last visit in the pivotal study (DMVT-505-3101, DMVT-505-3102, or DMVT-505-2104) 2. Used a prohibited concomitant product or procedure to treat AD during the pivotal study. 3. Had an SAE that was related to treatment or experienced an AE that led to permanent discontinuation of treatment in the pivotal study. 4. Pregnant females For Direct-Enrolling Subjects: * Immunocompromised at screening * Chronic or acute systemic or superficial infection requiring treatment with systemic antibacterials or antifungals within one week prior to baseline visit * Significant dermatological or inflammatory condition other than AD that, in the Investigator's opinion, would make it difficult to interpret data or assessments during the study * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.0x the upper limit of normal (ULN). * Screening total bilirubin \> 1.5x ULN * Current or chronic history of liver disease * Current or history of cancer within 5 years except for adequately treated cutaneous basal cell carcinoma, squamous cell carcinoma or carcinoma in situ of the cervix * Subjects who would not be considered suitable for topical therapy * Use of any prohibited medication or procedure within the indicated period before the baseline visit including other investigational product within 30 days or 5 half-lives of the investigational product (whichever is longer) * History of or ongoing serious illness or medical, physical, or psychiatric condition(s) that, in the Investigator's opinion, may interfere with the subject's participation in the study, interpretation of results, or ability to understand and give informed consent. * Pregnant or lactating females * History of sensitivity to the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation * Previous known participation in a clinical study with tapinarof (previously known as GSK2894512 and WBI-1001)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events | Baseline to Week 49 | 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. |
| Frequency of Adverse Events and Serious Adverse Events | Baseline to Week 49 | 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. |
| Change From Baseline in Clinical Laboratory Values (g/L) | Baseline to Week 48 | The mean chemistry and hematology parameters were assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (U/L) | Baseline to Week 48 | The mean chemistry parameters were assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (mmol/L) | Baseline to Week 48 | The mean chemistry parameters were assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (Umol/L) | Baseline to Week 48 | The mean chemistry parameters were assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) | Baseline to Week 48 | The mean hematology parameters were assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (%) | Baseline to Week 48 | The mean hematology parameters were assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (L/L) | Baseline to Week 48 | The hematology parameter, Hematocrit, was assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (pg) | Baseline to Week 48 | The hematology parameter, Ery. Mean Corpuscular Hemoglobin was assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (fl) | Baseline to Week 48 | The hematology parameter, Ery. Mean Corpuscular Volume, was assessed for changes and trends over the course of the study. |
| Change From Baseline in Clinical Laboratory Values (10^12 Cells/L) | Baseline to Week 48 | The hematology parameter, Erythrocytes, was assessed for changes and trends over the course of the study. |
| 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 ) | Baseline to Week 48 | 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. |
| 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) | Baseline to Week 48 | 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. |
| Absolute Change From Baseline in %BSA Affected | Baseline to Week 48 | 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. |
| Percent Change From Baseline in %BSA Affected | Baseline to Week 48 | 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. |
| Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline to Week 48 | 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. |
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | Baseline to Week 48 | 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. |
| Percent of Subjects With ≥ 50% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48. | Baseline to Week 48 | 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. |
| Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48. | Baseline to Week 48 | 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. |
| Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48. | Baseline to Week 48 | 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. |
| Mean Change in Peak Pruritis-Numeric Rating Scale (PP-NRS) From Baseline | Baseline to Week 48 | 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. |
| 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 | Baseline to Week 48 | 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. |
| Change From Baseline in Vital Signs - Pulse | Baseline to Week 48 | 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. |
| Change From Baseline in Vital Signs - Blood Pressure (Systolic and Diastolic) | Baseline to Week 48 | 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. |
| Change From Baseline in Vital Signs - Temperature | Baseline to Week 48 | 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. |
Countries
Canada, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Tapinarof Cream 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. | 728 |
| Total | 728 |
Baseline characteristics
| Characteristic | Tapinarof Cream |
|---|---|
| Age, Continuous | 15.0 years STANDARD_DEVIATION 15.32 |
| Age, Customized 12-17 years | 213 Participants |
| Age, Customized ≥18 years | 124 Participants |
| Age, Customized 2-6 years | 194 Participants |
| Age, Customized 7-11 years | 197 Participants |
| Eczema Area and Severity Index (EASI) | 6.31 units on a scale STANDARD_DEVIATION 8.247 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 163 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 562 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Percent Body Surface Area (BSA) | 10.62 Affected Body Surface Area percentage STANDARD_DEVIATION 14.259 |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 81 Participants |
| Race (NIH/OMB) Black or African American | 219 Participants |
| Race (NIH/OMB) More than one race | 27 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 383 Participants |
| Region of Enrollment Canada | 112 Count of participants |
| Region of Enrollment United States | 616 Count of participants |
| Sex: Female, Male Female | 389 Participants |
| Sex: Female, Male Male | 339 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 0 - clear | 58 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 1 - almost clear | 189 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 2 - mild | 268 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 3 - moderate | 182 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 4 - severe | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 728 |
| other Total, other adverse events | 451 / 728 |
| serious Total, serious adverse events | 34 / 728 |
Outcome results
Primary
Absolute Change From Baseline in %BSA Affected
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Absolute Change From Baseline in %BSA Affected | -7.14 percentage of BSA | Standard Deviation 12.881 |
Primary
Change From Baseline in Clinical Laboratory Values (%)
The mean hematology parameters were assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (%) | Basophils/Total Cells (%) | 0.03 % of cells | Standard Deviation 0.272 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (%) | Eosinophils/Total Cells (%) | -0.39 % of cells | Standard Deviation 3.427 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (%) | Lymphocytes/Total Cells (%) | -0.73 % of cells | Standard Deviation 10.44 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (%) | Monocytes/Total Cells (%) | -0.09 % of cells | Standard Deviation 2.592 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (%) | Neutrophils/Total Cells (%) | 1.18 % of cells | Standard Deviation 11.436 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (%) | Reticulocytes/Erythrocytes (%) | -0.06 % of cells | Standard Deviation 0.402 |
Primary
Change From Baseline in Clinical Laboratory Values (10^12 Cells/L)
The hematology parameter, Erythrocytes, was assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (10^12 Cells/L) | 0.038 10^12 cells/L | Standard Deviation 0.2905 |
Primary
Change From Baseline in Clinical Laboratory Values (10^9 Cells/L)
The mean hematology parameters were assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | 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 |
| Tapinarof Cream | 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 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (10^9 Cells/L) | Eosinophils (10^9/L) | -.03 10^9 cells/L | Standard Deviation 0.308 |
| Tapinarof Cream | 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 |
| Tapinarof Cream | 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 |
| Tapinarof Cream | 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 |
| Tapinarof Cream | 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 |
Primary
Change From Baseline in Clinical Laboratory Values (fl)
The hematology parameter, Ery. Mean Corpuscular Volume, was assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (fl) | 0.37 fl | Standard Deviation 2.364 |
Primary
Change From Baseline in Clinical Laboratory Values (g/L)
The mean chemistry and hematology parameters were assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (g/L) | Albumin (g/L) | -0.5 g/L | Standard Deviation 2.43 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (g/L) | Protein (g/L) | 0.0 g/L | Standard Deviation 3.95 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (g/L) | Hemoglobin (g/L) | 1.7 g/L | Standard Deviation 8.45 |
| Tapinarof Cream | 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
Change From Baseline in Clinical Laboratory Values (L/L)
The hematology parameter, Hematocrit, was assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (L/L) | 0.005 L/L | Standard Deviation 0.0263 |
Primary
Change From Baseline in Clinical Laboratory Values (mmol/L)
The mean chemistry parameters were assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (mmol/L) | Bicarbonate (mmol/L) | -0.2 mmol/L | Standard Deviation 2.31 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (mmol/L) | Blood Urea Nitrogen (mmol/L) | 0.04 mmol/L | Standard Deviation 1.428 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (mmol/L) | Calcium (mmol/L) | -0.019 mmol/L | Standard Deviation 0.0926 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (mmol/L) | Chloride (mmol/L) | -0.3 mmol/L | Standard Deviation 2.43 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (mmol/L) | Glucose (mmol/L) | 0.13 mmol/L | Standard Deviation 1.462 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (mmol/L) | Potassium (mmol/L) | -0.03 mmol/L | Standard Deviation 0.493 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (mmol/L) | Sodium (mmol/L) | -0.1 mmol/L | Standard Deviation 2.14 |
Primary
Change From Baseline in Clinical Laboratory Values (pg)
The hematology parameter, Ery. Mean Corpuscular Hemoglobin was assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (pg) | 0.13 pg | Standard Deviation 0.823 |
Primary
Change From Baseline in Clinical Laboratory Values (U/L)
The mean chemistry parameters were assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (U/L) | Alkaline Phosphatase (U/L) | -14.9 U/L | Standard Deviation 69.45 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (U/L) | Alanine Aminotransferase (U/L) | -1.5 U/L | Standard Deviation 11.96 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (U/L) | Aspartate Aminotransferase (U/L) | -2.6 U/L | Standard Deviation 16.13 |
Primary
Change From Baseline in Clinical Laboratory Values (Umol/L)
The mean chemistry parameters were assessed for changes and trends over the course of the study.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (Umol/L) | Bilirubin (umol/L) | 0.40 umol/L | Standard Deviation 3.434 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (Umol/L) | Enzymatic Creatinine (umol/L) | 2.1 umol/L | Standard Deviation 7.92 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (Umol/L) | Creatinine (Jaffe) (umol/L) | 2.7 umol/L | Standard Deviation 12.06 |
| Tapinarof Cream | Change From Baseline in Clinical Laboratory Values (Umol/L) | Urate (umol/L) | 0.9 umol/L | Standard Deviation 52.32 |
Primary
Change From Baseline in Vital Signs - Blood Pressure (Systolic and Diastolic)
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Vital Signs - Blood Pressure (Systolic and Diastolic) | Systolic Blood Pressure (mmHg) | 1.0 mmHg | Standard Deviation 10.72 |
| Tapinarof Cream | Change From Baseline in Vital Signs - Blood Pressure (Systolic and Diastolic) | Diastolic Blood Pressure (mmHg) | 0.7 mmHg | Standard Deviation 9.78 |
Primary
Change From Baseline in Vital Signs - Pulse
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Vital Signs - Pulse | -0.9 beats per minute (bpm) | Standard Deviation 12.61 |
Primary
Change From Baseline in Vital Signs - Temperature
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Vital Signs - Temperature | 0.02 degrees C | Standard Deviation 0.437 |
Primary
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 )
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.
Time frame: Baseline to Week 48
Population: ITT Population, Subjects Entering the Study with vIGA-AD Score ≥1, Observed Cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | 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
Frequency of Adverse Events and Serious Adverse Events
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.
Time frame: Baseline to Week 49
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tapinarof Cream | Frequency of Adverse Events and Serious Adverse Events | Treatment-emergent AE | 1226 Events |
| Tapinarof Cream | Frequency of Adverse Events and Serious Adverse Events | Serious treatment-emergent AE | 45 Events |
Primary
Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Mean Change From Baseline in Eczema Area and Severity Index (EASI) Score | -4.19 Units on a scale | Standard Deviation 7.248 |
Primary
Mean Change in Peak Pruritis-Numeric Rating Scale (PP-NRS) From Baseline
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Mean Change in Peak Pruritis-Numeric Rating Scale (PP-NRS) From Baseline | -1.618 Units on a scale | Standard Deviation 2.7756 |
Primary
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
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.
Time frame: Baseline to Week 48
Population: ITT Population, Subjects with a Baseline PP-NRS Score ≥4, Observed Cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | 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
Number of Subjects With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events
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.
Time frame: Baseline to Week 49
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tapinarof Cream | Number of Subjects With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events | Any treatment-emergent AE | 451 Participants |
| Tapinarof Cream | Number of Subjects With Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events | Serious treatment-emergent AE | 34 Participants |
Primary
Percent Change From Baseline in %BSA Affected
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases; Participants with %BSA=0 at baseline were excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Percent Change From Baseline in %BSA Affected | -37.45 percent change from baseline in % total | Standard Deviation 189.905 |
Primary
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases; Participants with EASI=0 at baseline were excluded
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Score | -33.70 Units on a scale | Standard Deviation 139.557 |
Primary
Percent of Subjects With ≥ 50% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48.
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases; Participants with EASI=0 at baseline were excluded
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | Percent of Subjects With ≥ 50% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48. | 325 Participants |
Primary
Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48.
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases; Participants with EASI=0 at baseline were excluded
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48. | 256 Participants |
Primary
Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48.
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.
Time frame: Baseline to Week 48
Population: ITT Population, Observed Cases; Participants with EASI=0 at baseline were excluded
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline at Week 48. | 178 Participants |
Primary
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)
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.
Time frame: Baseline to Week 48
Population: ITT Population, Subjects Entering the Study with vIGA-AD Score ≥2, Observed Cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | 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 |