Atopic Dermatitis
Conditions
Keywords
eczema, pediatric, tapinarof, phase 2, topical
Brief summary
This is an open-label, multicenter study to evaluate the systemic exposure and safety of topical tapinarof cream, 1% under conditions of maximal use in pediatric subjects with atopic dermatitis
Detailed description
This is a 4-week open-label study in which subjects will be assigned to receive tapinarof cream, 1% once daily for 4 weeks. At the end of the 4-week study treatment, qualified subjects will have the option to enroll in an open-label, long-term extension study for an additional 48 weeks of treatment. Subjects who do not participate in the open-label, long-term extension study will complete a follow-up visit approximately one week after the end of treatment in this study.
Interventions
Tapinarof cream, 1% applied topically once daily
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 17 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects age 2 to 17 with a confirmed clinical diagnosis of atopic dermatitis and present for at least 6 months for ages 6-17 years old, 3 months for ages 2-5 years old * BSA involvement ≥ 25% for subjects ages 12-17 years old, or ≥ 35% for subjects ages 2-11 years old, suitable for topical therapy. * vIGA-AD score of ≥ 3 at screening and baseline (pre-dose) * Female subjects of child bearing potential who are engaging in sexual activity that could lead to pregnancy agree to follow the specified contraceptive guidance throughout the study * Capable of giving written informed consent * Negative pregnancy test at Baseline (Day 1)
Exclusion criteria
* 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 |
|---|---|---|
| Change From Baseline in Vital Signs (C) | Baseline to Day 28 | Change in Temperature vital signs was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (10^9 Cells/L) | Baseline to Day 28 | Change in laboratory values was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (%) | Baseline to Day 28 | Change in laboratory values was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (pg) | Baseline to Day 28 | Change in Ery. mean corpuscular hemoglobin laboratory values was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (fL) | Baseline to Day 28 | Change in Ery. mean corpuscular volume laboratory values was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (10^12 Cells/L) | Baseline to Day 28 | Change in Erythrocytes laboratory values was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (L/L) | Baseline to Day 28 | Change in Hematocrit laboratory values was assessed for clinical relevance |
| Mean Change in Local Tolerability Scale (LTS) | Baseline to Day 28 | Local Tolerability Scale (LTS) is a clinical tool for assessing the presence and overall degree of irritation at the application sites, according to a 5-point scale. 0 indicates no irritation and 4 indicates Very Severe irritation. |
| Tapinarof Plasma PK Parameters on Day 1: AUC0-τ | Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose) | The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug. |
| Tapinarof Plasma PK Parameters on Day 1: Cmax | Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose) | The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing. |
| Tapinarof Plasma PK Parameters on Day 1: Tmax | Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose) | The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing. |
| Tapinarof Plasma Concentration: Cτ | Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose) | The Cτ is a pharmacokinetic parameter that is the last quantifiable concentration determined directly from individual concentration-time data |
| Change From Baseline in Vital Signs (Beats/Min) | Baseline to Day 28 | Change in pulse vital signs was assessed for clinical relevance |
| Change From Baseline in Vital Signs (mmHg) | Baseline to Day 28 | Change in Blood Pressure vital signs was assessed for clinical relevance |
| Number of Participants That Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline to Day 28 for subjects enrolling in Long-Term Extension (LTE), otherwise to Day 35 | Number of Participants that Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs). |
| Change From Baseline in Laboratory Values (U/L) | Baseline to Day 28 | Change in laboratory values was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (g/L) | Baseline to Day 28 | Change in laboratory values was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (mmol/L) | Baseline to Day 28 | Change in laboratory values was assessed for clinical relevance |
| Change From Baseline in Laboratory Values (Umol/L) | Baseline to Day 28 | Change in laboratory values was assessed for clinical relevance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Have a Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Score of Almost Clear (0 or 1) and at Least a 2-grade Reduction From Baseline | Baseline to Day 28 | The vIGA-AD is a global assessment of the current state of the disease. It is a static 5-point scale used to grade overall disease severity (scalp excluded), as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. The vIGA-AD ranges from 0 to 4 and is calculated as Clear (0), Almost clear (1), Mild (2), Moderate (3), and Severe (4). Higher vIGA-AD scores represent more severe disease. |
| Number of Subjects With ≥50%, Improvement in Eczema Area and Severity Index (EASI) Score | Baseline to Day 28 | The Eczema Area and Severity Index (EASI) is a scoring system that takes into account the overall severity of disease based on lesion severity and the extent of percent body surface area affected with atopic dermatitis. The EASI is a composite score ranging from 0 -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 percent body surface area involved for each body region relative to the whole body. A higher EASI score represents more severe disease. |
| Number of Subjects With ≥75%, Improvement in Eczema Area and Severity Index (EASI) Score | Baseline to Day 28 | 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. |
| Number of Subjects With ≥90%, Improvement in Eczema Area and Severity Index (EASI) Score | Baseline to Day 28 | 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. |
| Mean Change in Eczema Area and Severity Index EASI From Baseline to Day 28 | Baseline to Day 28 | 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 Change in Eczema Area and Severity Index EASI From Baseline to Day 28 | Baseline to Day 28 | 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. |
| Mean Change in Percent of Total Body Surface Area (%BSA) Affected | Baseline to Day 28 | The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores. |
| Percent Change in Percent of Total Body Surface Area (%BSA) Affected | Baseline to Day 28 | The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores. |
| Mean Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values | Baseline to Day 28 | 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 morphological assessment of overall disease severity using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting (0 indicates no inflammatory signs of atopic dermatitis and 4 indicates disease is widespread). The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. %BSA is a static assessment made without reference to previous scores and will be evaluated 0-100%. The computation is referenced below, and no unit is applicable for this outcome measure. A negative change indicates improvement in disease. \[Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)\] |
| Percent Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values | Baseline to Day 28 | 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 morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. Score of 0 indicates no inflammatory signs of atopic dermatitis and a 4 indicates disease is widespread in extent. The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores. Computation: Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) |
| Mean Change in Average Weekly Peak Pruritus Numerical Rating Scale (PP-NRS) Score | Baseline to Day 28 | The PP-NRS is a scale from 0-10 used to assess itch/pruritus severity over a 24-hour period which will be used daily to assess peak pruritus. Higher PP-NRS ratings represent more itch reported. |
| Proportion of Subjects With a Baseline Peak Pruritus Numerical Rating Scale (PP-NRS) Score ≥4 Who Achieved ≥4-point Reduction in PP-NRS Score | Baseline to Day 28 | The PP-NRS is a scale from 0-10 used to assess itch/pruritus severity over a 24-hour period which will be used daily to assess peak pruritus. Higher PP-NRS ratings represent more itch reported. |
| Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | Baseline to Day 28 | The vIGA-AD is a global assessment of the current state of the disease. It is a static 5-point scale used to grade overall disease severity (scalp excluded), as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. The vIGA-AD ranges from 0 to 4 and is calculated as Clear (0), Almost clear (1), Mild (2), Moderate (3), and Severe (4). Higher vIGA-AD scores represent more severe disease. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants from the DMVT-505-2104 study had the option to participate in the open label extension study (DMVT-505-3103, NCT05142774).
Participants by arm
| Arm | Count |
|---|---|
| Tapinarof Cream Tapinarof (DMVT-505) cream, 1% applied topically once daily
Tapinarof cream, 1%: Tapinarof cream, 1% applied topically once daily | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Tapinarof Cream |
|---|---|
| Age, Categorical <=18 years | 36 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 8.9 years STANDARD_DEVIATION 4.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 24 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 0 - Clear | 0 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 1 - Almost Clear | 0 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 2 - Mild | 0 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 3 - Moderate | 28 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 4 - Severe | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 36 |
| other Total, other adverse events | 8 / 36 |
| serious Total, serious adverse events | 0 / 36 |
Outcome results
Primary
Change From Baseline in Laboratory Values (%)
Change in laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (%) | Basophils/Total cells (%) | 0.05 % of cells | Standard Deviation 0.343 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (%) | Eosinophils/Total cells (%) | -0.13 % of cells | Standard Deviation 4.606 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (%) | Lymphocytes/Total cells (%) | 0.81 % of cells | Standard Deviation 11.023 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (%) | Monocytes/Total cells (%) | -0.81 % of cells | Standard Deviation 2.662 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (%) | Neutrophils/Total cells (%) | 0.08 % of cells | Standard Deviation 12.693 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (%) | Reticulocytes/Erythrocytes (%) | 0.06 % of cells | Standard Deviation 0.377 |
Primary
Change From Baseline in Laboratory Values (10^12 Cells/L)
Change in Erythrocytes laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (10^12 Cells/L) | -0.055 10^12 cells/L | Standard Deviation 0.2481 |
Primary
Change From Baseline in Laboratory Values (10^9 Cells/L)
Change in laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (10^9 Cells/L) | Basophils (10^9/L) | 0.01 10^9 cells/L | Standard Deviation 0.048 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (10^9 Cells/L) | Eosinophils (10^9/L) | 0.00 10^9 cells/L | Standard Deviation 0.419 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (10^9 Cells/L) | Leukocytes (10^9/L) | 0.71 10^9 cells/L | Standard Deviation 2.451 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (10^9 Cells/L) | Lymphocytes (10^9/L) | 0.38 10^9 cells/L | Standard Deviation 1.095 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (10^9 Cells/L) | Monocytes (10^9/L) | -0.06 10^9 cells/L | Standard Deviation 0.175 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (10^9 Cells/L) | Neutrophils (10^9/L) | 0.36 10^9 cells/L | Standard Deviation 2.124 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (10^9 Cells/L) | Platelets (10^9/L) | -34.8 10^9 cells/L | Standard Deviation 95.27 |
Primary
Change From Baseline in Laboratory Values (fL)
Change in Ery. mean corpuscular volume laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (fL) | 1.26 fL | Standard Deviation 1.973 |
Primary
Change From Baseline in Laboratory Values (g/L)
Change in laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (g/L) | Albumin (g/L) | -0.7 g/L | Standard Deviation 2.72 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (g/L) | Protein (g/L) | -0.5 g/L | Standard Deviation 4.2 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (g/L) | Ery. mean corpuscular HGB Concentration (g/L) | -1.7 g/L | Standard Deviation 7.68 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (g/L) | Hemoglobin (g/L) | 0.0 g/L | Standard Deviation 7.61 |
Primary
Change From Baseline in Laboratory Values (L/L)
Change in Hematocrit laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (L/L) | 0.002 L/L | Standard Deviation 0.0228 |
Primary
Change From Baseline in Laboratory Values (mmol/L)
Change in laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (mmol/L) | Bicarbonate (mmol/L) | -0.3 mmol/L | Standard Deviation 2.16 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (mmol/L) | Calcium (mmol/L) | -0.006 mmol/L | Standard Deviation 0.0846 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (mmol/L) | Chloride (mmol/L) | 0.0 mmol/L | Standard Deviation 2.99 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (mmol/L) | Glucose (mmol/L) | 0.20 mmol/L | Standard Deviation 0.819 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (mmol/L) | Potassium (mmol/L) | 0.08 mmol/L | Standard Deviation 0.532 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (mmol/L) | Sodium (mmol/L) | 0.1 mmol/L | Standard Deviation 1.98 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (mmol/L) | Blood urea nitrogen (mmol/L) | -0.06 mmol/L | Standard Deviation 0.989 |
Primary
Change From Baseline in Laboratory Values (pg)
Change in Ery. mean corpuscular hemoglobin laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (pg) | 0.26 pg | Standard Deviation 0.787 |
Primary
Change From Baseline in Laboratory Values (U/L)
Change in laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (U/L) | Alanine aminotransferase (U/L) | 1.9 U/L | Standard Deviation 10.8 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (U/L) | Alkaline phosphatase (U/L) | 0.7 U/L | Standard Deviation 52.95 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (U/L) | Aspartate aminotransferase (U/L) | 0.6 U/L | Standard Deviation 6.44 |
Primary
Change From Baseline in Laboratory Values (Umol/L)
Change in laboratory values was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Laboratory Values (Umol/L) | Bilirubin (umol/L) | -0.34 Umol/L | Standard Deviation 3.7 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (Umol/L) | Enzymatic Creatinine (umol/L) | -0.9 Umol/L | Standard Deviation 7.66 |
| Tapinarof Cream | Change From Baseline in Laboratory Values (Umol/L) | Urate (umol/L) | -6.0 Umol/L | Standard Deviation 52.16 |
Primary
Change From Baseline in Vital Signs (Beats/Min)
Change in pulse vital signs was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Vital Signs (Beats/Min) | 0.9 Beats/Min | Standard Deviation 14.4 |
Primary
Change From Baseline in Vital Signs (C)
Change in Temperature vital signs was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Vital Signs (C) | -0.08 degrees C | Standard Deviation 0.402 |
Primary
Change From Baseline in Vital Signs (mmHg)
Change in Blood Pressure vital signs was assessed for clinical relevance
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Vital Signs (mmHg) | Systolic Blood Pressure (mmHg) | 1.1 mmHg | Standard Deviation 8.78 |
| Tapinarof Cream | Change From Baseline in Vital Signs (mmHg) | Diastolic Blood Pressure (mmHg) | -0.9 mmHg | Standard Deviation 6.63 |
Primary
Mean Change in Local Tolerability Scale (LTS)
Local Tolerability Scale (LTS) is a clinical tool for assessing the presence and overall degree of irritation at the application sites, according to a 5-point scale. 0 indicates no irritation and 4 indicates Very Severe irritation.
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tapinarof Cream | Mean Change in Local Tolerability Scale (LTS) | Baseline | 0.2 Units on a scale | Standard Deviation 0.68 |
| Tapinarof Cream | Mean Change in Local Tolerability Scale (LTS) | Day 28 | 0.1 Units on a scale | Standard Deviation 0.4 |
Primary
Number of Participants That Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of Participants that Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs).
Time frame: Baseline to Day 28 for subjects enrolling in Long-Term Extension (LTE), otherwise to Day 35
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tapinarof Cream | Number of Participants That Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) | Experienced an AE | 8 Participants |
| Tapinarof Cream | Number of Participants That Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) | Experienced an SAE | 0 Participants |
Primary
Tapinarof Plasma Concentration: Cτ
The Cτ is a pharmacokinetic parameter that is the last quantifiable concentration determined directly from individual concentration-time data
Time frame: Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)
Population: PK Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Tapinarof Plasma Concentration: Cτ | 1330 pg/mL | Standard Deviation 3780 |
Primary
Tapinarof Plasma PK Parameters on Day 1: AUC0-τ
The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug.
Time frame: Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Tapinarof Plasma PK Parameters on Day 1: AUC0-τ | 4690 pg*h/mL | Standard Deviation 5600 |
Primary
Tapinarof Plasma PK Parameters on Day 1: Cmax
The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing.
Time frame: Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Tapinarof Plasma PK Parameters on Day 1: Cmax | 2440 pg/mL | Standard Deviation 3900 |
Primary
Tapinarof Plasma PK Parameters on Day 1: Tmax
The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing.
Time frame: Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)
Population: PK population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Tapinarof Plasma PK Parameters on Day 1: Tmax | 2.37 hour | Standard Deviation 1.19 |
Secondary
Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)
The vIGA-AD is a global assessment of the current state of the disease. It is a static 5-point scale used to grade overall disease severity (scalp excluded), as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. The vIGA-AD ranges from 0 to 4 and is calculated as Clear (0), Almost clear (1), Mild (2), Moderate (3), and Severe (4). Higher vIGA-AD scores represent more severe disease.
Time frame: Baseline to Day 28
Population: Safety population, Observed Cases
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | +4 = worsened by 4 | 0 Participants |
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | +3 = worsened by 3 | 0 Participants |
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | +2 = worsened by 2 | 0 Participants |
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | +1 = worsened by 1 | 0 Participants |
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | 0 - no change | 8 Participants |
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | -1 = improved by 1 | 14 Participants |
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | -2 = improved by 2 | 8 Participants |
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | -3 = improved by 3 | 2 Participants |
| Tapinarof Cream | Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) | -4 = improved by 4 | 0 Participants |
Secondary
Mean Change in Average Weekly Peak Pruritus Numerical Rating Scale (PP-NRS) Score
The PP-NRS is a scale from 0-10 used to assess itch/pruritus severity over a 24-hour period which will be used daily to assess peak pruritus. Higher PP-NRS ratings represent more itch reported.
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Mean Change in Average Weekly Peak Pruritus Numerical Rating Scale (PP-NRS) Score | -4.155 Units on a scale | Standard Deviation 2.4558 |
Secondary
Mean Change in Eczema Area and Severity Index EASI From Baseline to Day 28
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 Day 28
Population: Safety Population, Observed cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Mean Change in Eczema Area and Severity Index EASI From Baseline to Day 28 | -12.16 scores on a scale | Standard Deviation 9.742 |
Secondary
Mean Change in Percent of Total Body Surface Area (%BSA) Affected
The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores.
Time frame: Baseline to Day 28
Population: Safety Population, Observed cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Mean Change in Percent of Total Body Surface Area (%BSA) Affected | -21.06 percentage of BSA | Standard Deviation 18.789 |
Secondary
Mean Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values
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 morphological assessment of overall disease severity using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting (0 indicates no inflammatory signs of atopic dermatitis and 4 indicates disease is widespread). The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. %BSA is a static assessment made without reference to previous scores and will be evaluated 0-100%. The computation is referenced below, and no unit is applicable for this outcome measure. A negative change indicates improvement in disease. \[Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)\]
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Mean Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values | -85.15 unitless | Standard Deviation 65.848 |
Secondary
Number of Subjects Who Have a Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Score of Almost Clear (0 or 1) and at Least a 2-grade Reduction From Baseline
The vIGA-AD is a global assessment of the current state of the disease. It is a static 5-point scale used to grade overall disease severity (scalp excluded), as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. The vIGA-AD ranges from 0 to 4 and is calculated as Clear (0), Almost clear (1), Mild (2), Moderate (3), and Severe (4). Higher vIGA-AD scores represent more severe disease.
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | Number of Subjects Who Have a Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Score of Almost Clear (0 or 1) and at Least a 2-grade Reduction From Baseline | 8 Participants |
Secondary
Number of Subjects With ≥50%, Improvement in Eczema Area and Severity Index (EASI) Score
The Eczema Area and Severity Index (EASI) is a scoring system that takes into account the overall severity of disease based on lesion severity and the extent of percent body surface area affected with atopic dermatitis. The EASI is a composite score ranging from 0 -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 percent body surface area involved for each body region relative to the whole body. A higher EASI score represents more severe disease.
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | Number of Subjects With ≥50%, Improvement in Eczema Area and Severity Index (EASI) Score | 20 Participants |
Secondary
Number of Subjects With ≥75%, Improvement in Eczema Area and Severity Index (EASI) Score
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 Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | Number of Subjects With ≥75%, Improvement in Eczema Area and Severity Index (EASI) Score | 7 Participants |
Secondary
Number of Subjects With ≥90%, Improvement in Eczema Area and Severity Index (EASI) Score
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 Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tapinarof Cream | Number of Subjects With ≥90%, Improvement in Eczema Area and Severity Index (EASI) Score | 4 Participants |
Secondary
Percent Change in Eczema Area and Severity Index EASI From Baseline to Day 28
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 Day 28
Population: Safety Population, Observed cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Percent Change in Eczema Area and Severity Index EASI From Baseline to Day 28 | -53.38 % change from baseline | Standard Deviation 38.337 |
Secondary
Percent Change in Percent of Total Body Surface Area (%BSA) Affected
The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores.
Time frame: Baseline to Day 28
Population: Safety Population, Observed cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Percent Change in Percent of Total Body Surface Area (%BSA) Affected | -49.40 % change from baseline | Standard Deviation 41.3 |
Secondary
Percent Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values
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 morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. Score of 0 indicates no inflammatory signs of atopic dermatitis and a 4 indicates disease is widespread in extent. The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores. Computation: Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)
Time frame: Baseline to Day 28
Population: Safety Population, Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Percent Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values | -62.77 % change from baseline | Standard Deviation 35.29 |
Secondary
Proportion of Subjects With a Baseline Peak Pruritus Numerical Rating Scale (PP-NRS) Score ≥4 Who Achieved ≥4-point Reduction in PP-NRS Score
The PP-NRS is a scale from 0-10 used to assess itch/pruritus severity over a 24-hour period which will be used daily to assess peak pruritus. Higher PP-NRS ratings represent more itch reported.
Time frame: Baseline to Day 28
Population: Safety Population, Observed cases, subjects with baseline PP-NRS score ≥4
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tapinarof Cream | Proportion of Subjects With a Baseline Peak Pruritus Numerical Rating Scale (PP-NRS) Score ≥4 Who Achieved ≥4-point Reduction in PP-NRS Score | Achieved ≥ 4-Point Reduction from Baseline in the Average Weekly PP-NRS Score | 14 Participants |
| Tapinarof Cream | Proportion of Subjects With a Baseline Peak Pruritus Numerical Rating Scale (PP-NRS) Score ≥4 Who Achieved ≥4-point Reduction in PP-NRS Score | Failure to Achieve a ≥ 4-point Reduction from Baseline in the Average Weekly PP-NRS Score | 18 Participants |