Atopic Dermatitis
Conditions
Keywords
eczema, pediatric, tapinarof, phase 3, topical
Brief summary
This is a double-blind, randomized, vehicle controlled Phase 3 study to evaluate the efficacy and safety of topical tapinarof cream, 1% compared to vehicle control cream in pediatric and adult subjects with atopic dermatitis.
Detailed description
This study is a 8-week double-blind, vehicle-controlled treatment study in which subjects will be randomized to receive tapinarof cream, 1% or vehicle cream once daily for 8 weeks. At the end of the 8-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
applied topically once daily
DRUGvehicle cream
applied topically once daily
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The investigator, study center staff, subject, and sponsor will be blinded to treatment assignment.
Intervention model description
Following a 30-day screening period, eligible subjects will be randomized at a 2:1 ratio to receive once daily treatment with tapinarof cream, 1% or vehicle cream.
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects ages 2 and above with clinical diagnosis of AD * Subject with atopic dermatitis covering ≥5% and ≤ 35% of the BSA * A vIGA-AD score of ≥3 at screening and baseline * An EASI score of ≥6 at screening and baseline * Atopic dermatitis present for at least 6 months for ages 6 years old and above or 3 months for ages 2 to 5 years old * Female subjects of childbearing potential who are engaging in sexual activity that could lead to pregnancy should use acceptable birth control methods * Must not be pregnant * Subject, subject's parent, or legal representative must be capable of giving written informed consent/assent
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 |
|---|---|---|
| Percent of Subjects Who Have a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of Clear or Almost Clear (0 or 1) With a Minimum 2-grade Improvement From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | Baseline to Week 8 | 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. Statistics are based on 100 imputed datasets. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | Baseline to Week 8 | 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. Statistics are based on 100 imputed datasets. |
| Mean Change in in Percent of Total Body Surface Area (%BSA) Affected From Baseline to Week 8. | Baseline to Week 8 | Assessment of percent body surface area (%BSA) is an estimate of the percentage of total involved skin with atopic dermatitis. Estimates were made using the handprint method, where the full palmar hand of the participant (fully extended palm, fingers and thumbs together) represented approximately 1% of the total BSA. Body regions are assigned a specific number of handprints with associated percentages (Head and neck = 10% \[10 handprints\], upper extremities = 20% \[20 handprints\], trunk (including axillae and groin) = 30% \[30 handprints\], lower extremities, including buttocks, = 40% \[40 handprints\]). Estimates of the percent involvement of each body region will be multiplied by the fraction of total body area to obtain the total %BSA involved by region and overall. |
| Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | Baseline to Week 8 | 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. Statistics are based on 100 imputed datasets. |
| Percent of Subjects ≥ 12 Years Old With a Baseline Peak Pruritis-Numeric Rating Scale (PP-NRS) Score ≥ 4 Who Achieve ≥ 4-point Reduction in the Average Weekly PP-NRS From Baseline to Week 8. | Baseline to Week 8 | 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 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. Statistics are based on 100 imputed datasets. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants from the main study (DMVT-505-3102) had the option to participate in the open label extension study (DMVT-505-3103, NCT05142774).
Participants by arm
| Arm | Count |
|---|---|
| Tapinarof Cream tapinarof cream, 1%, applied topically once daily | 271 |
| Vehicle Cream vehicle cream, applied topically once daily | 135 |
| Total | 406 |
Baseline characteristics
| Characteristic | Tapinarof Cream | Vehicle Cream | Total |
|---|---|---|---|
| Age, Continuous | 16.4 years STANDARD_DEVIATION 16.24 | 16.7 years STANDARD_DEVIATION 16.05 | 16.5 years STANDARD_DEVIATION 16.16 |
| Age, Customized 12-17 Years | 89 Participants | 44 Participants | 133 Participants |
| Age, Customized ≥18 Years | 53 Participants | 27 Participants | 80 Participants |
| Age, Customized 2-6 Years | 65 Participants | 32 Participants | 97 Participants |
| Age, Customized 7-11 Years | 64 Participants | 32 Participants | 96 Participants |
| Eczema Area and Severity Index (EASI) | 13.45 units on a scale STANDARD_DEVIATION 5.615 | 13.09 units on a scale STANDARD_DEVIATION 4.689 | 13.33 units on a scale STANDARD_DEVIATION 5.322 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 49 Participants | 27 Participants | 76 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 221 Participants | 107 Participants | 328 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Percent Body Surface Area (BSA) | 17.13 Percentage of Affected BSA STANDARD_DEVIATION 8.743 | 15.84 Percentage of Affected BSA STANDARD_DEVIATION 7.888 | 16.70 Percentage of Affected BSA STANDARD_DEVIATION 8.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 39 Participants | 23 Participants | 62 Participants |
| Race (NIH/OMB) Black or African American | 95 Participants | 47 Participants | 142 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) White | 124 Participants | 58 Participants | 182 Participants |
| Region of Enrollment Canada | 41 Count of participants | 22 Count of participants | 63 Count of participants |
| Region of Enrollment United States | 230 Count of participants | 113 Count of participants | 343 Count of participants |
| Sex: Female, Male Female | 154 Participants | 77 Participants | 231 Participants |
| Sex: Female, Male Male | 117 Participants | 58 Participants | 175 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 0 - Clear | 0 Participants | 0 Participants | 0 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 1 - Almost Clear | 0 Participants | 0 Participants | 0 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 2 - Mild | 0 Participants | 0 Participants | 0 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 3 - Moderate | 228 Participants | 113 Participants | 341 Participants |
| Validated Investigator Global Assessment for Atopic Dermatitis 4 - Severe | 43 Participants | 22 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 271 | 0 / 133 |
| other Total, other adverse events | 55 / 271 | 13 / 133 |
| serious Total, serious adverse events | 2 / 271 | 0 / 133 |
Outcome results
Primary
Percent of Subjects Who Have a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of Clear or Almost Clear (0 or 1) With a Minimum 2-grade Improvement From Baseline to Week 8. Analyses Were Done Using Multiple Imputation.
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. Statistics are based on 100 imputed datasets.
Time frame: Baseline to Week 8
Population: ITT Population (MI Estimand)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapinarof Cream | Percent of Subjects Who Have a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of Clear or Almost Clear (0 or 1) With a Minimum 2-grade Improvement From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | 46.4 Percentage of participants |
| Vehicle Cream | Percent of Subjects Who Have a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of Clear or Almost Clear (0 or 1) With a Minimum 2-grade Improvement From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | 18.0 Percentage of participants |
Comparison: H0: The proportion of subjects who achieve a vIGA-AD score of clear (0) or almost clear (1) and at least a 2-grade reduction from Baseline at Week 8 is equal between tapinarof cream, 1% and vehicle cream; H1: The proportion of subjects who achieve a vIGA-AD score of clear (0) or almost clear (1) and at least a 2-grade reduction from Baseline at Week 8 is different between the tapinarof cream, 1% and vehicle cream.p-value: <0.000195% CI: [1.54, 3.32]Cochran-Mantel-Haenszel
Secondary
Mean Change in in Percent of Total Body Surface Area (%BSA) Affected From Baseline to Week 8.
Assessment of percent body surface area (%BSA) is an estimate of the percentage of total involved skin with atopic dermatitis. Estimates were made using the handprint method, where the full palmar hand of the participant (fully extended palm, fingers and thumbs together) represented approximately 1% of the total BSA. Body regions are assigned a specific number of handprints with associated percentages (Head and neck = 10% \[10 handprints\], upper extremities = 20% \[20 handprints\], trunk (including axillae and groin) = 30% \[30 handprints\], lower extremities, including buttocks, = 40% \[40 handprints\]). Estimates of the percent involvement of 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 8
Population: ITT Population (MI Estimand)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tapinarof Cream | Mean Change in in Percent of Total Body Surface Area (%BSA) Affected From Baseline to Week 8. | -10.36 Change in affected BSA percentage | Standard Error 0.54 |
| Vehicle Cream | Mean Change in in Percent of Total Body Surface Area (%BSA) Affected From Baseline to Week 8. | -3.14 Change in affected BSA percentage | Standard Error 0.676 |
p-value: <0.000195% CI: [-8.17, -5.02]ANCOVA
Secondary
Percent of Subjects ≥ 12 Years Old With a Baseline Peak Pruritis-Numeric Rating Scale (PP-NRS) Score ≥ 4 Who Achieve ≥ 4-point Reduction in the Average Weekly PP-NRS From Baseline to Week 8.
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 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. Statistics are based on 100 imputed datasets.
Time frame: Baseline to Week 8
Population: ITT Population (MI Estimand)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapinarof Cream | Percent of Subjects ≥ 12 Years Old With a Baseline Peak Pruritis-Numeric Rating Scale (PP-NRS) Score ≥ 4 Who Achieve ≥ 4-point Reduction in the Average Weekly PP-NRS From Baseline to Week 8. | 52.8 Percentage of participants |
| Vehicle Cream | Percent of Subjects ≥ 12 Years Old With a Baseline Peak Pruritis-Numeric Rating Scale (PP-NRS) Score ≥ 4 Who Achieve ≥ 4-point Reduction in the Average Weekly PP-NRS From Baseline to Week 8. | 24.1 Percentage of participants |
p-value: 0.001595% CI: [1.34, 3.5]Cochran-Mantel-Haenszel
Secondary
Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation.
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. Statistics are based on 100 imputed datasets.
Time frame: Baseline to Week 8
Population: ITT Population (MI Estimand)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapinarof Cream | Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | 59.1 Percentage of participants |
| Vehicle Cream | Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | 21.2 Percentage of participants |
p-value: <0.000195% CI: [1.53, 3]Cochran-Mantel-Haenszel
Secondary
Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation.
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. Statistics are based on 100 imputed datasets.
Time frame: Baseline to Week 8
Population: ITT Population (MI Estimand)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tapinarof Cream | Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | 30.1 Percentage of participants |
| Vehicle Cream | Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation. | 10.0 Percentage of participants |
p-value: 0.001395% CI: [1.39, 3.94]Cochran-Mantel-Haenszel