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

Organon and Co728 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

728

Conditions

Atopic Dermatitis

Interventions

Tapinarof cream, 1%DRUG

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.

Eligibility

Sex: ALLMin age: 2 Years

Medical Language ↔ Plain English

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)

Locations (112)

Outcomes

Primary Outcomes

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

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

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

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

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

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

Change From Baseline in Clinical Laboratory Values (10^9 Cells/L)

Data from ClinicalTrials.gov

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Dermavant Investigative Site

Birmingham, Alabama, United States

Dermavant Investigative Site

Phoenix, Arizona, United States

Dermavant Investigative Site

Scottsdale, Arizona, United States

Dermavant Investigative Site

Scottsdale, Arizona, United States

Dermavant Investigative Site

Bryant, Arkansas, United States

Dermavant Investigative Site

Fort Smith, Arkansas, United States

Dermavant Investigative Site

Cerritos, California, United States

Dermavant Investigative Site

Fountain Valley, California, United States

Dermavant Investigative Site

Fremont, California, United States

Dermavant Investigative Site

Huntington Beach, California, United States

...and 102 more locations

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

Time frame: Baseline to Week 48

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

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

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

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

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

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

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)

Time frame: Baseline to Week 48

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

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

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

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

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

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

Time frame: Baseline to Week 48

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

Time frame: Baseline to Week 48

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

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

Time frame: Baseline to Week 48

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

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

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