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

Atopic Dermatitis Clinical Trial

Official title:

An Open-Label, Long-Term Extension Study to Evaluate the Safety and Efficacy of Tapinarof Cream, 1% in Subjects With Atopic Dermatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05142774
• Other study ID #: DMVT-505-3103
• Status: Completed
• Phase: Phase 3
• Start date: October 28, 2021
• Est. completion date: March 7, 2024

Study information

• Verified date: April 2024
• Source: Dermavant Sciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

At the completion of the Week 8 visit of study DMVT-505-3101 or study DMVT-505-3102 or the Day 28 visit of study DMVT-505-2104 (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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 728
• Est. completion date: March 7, 2024
• Est. primary completion date: February 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Tapinarof cream, 1%
Tapinarof cream, 1%, applied daily Subjects entering with vIGA-AD =1 received treatment with tapinarof cream, 1% until they achieved vIGA-AD=0, at which time treatment was discontinued and subjects were monitored for durability of response (remittive response). If/when disease worsening occurred, as evidenced by vIGA-AD =2, treatment was re-initiated and continued until vIGA-AD =0 was achieved. Subjects entering with a vIGA-AD=0 had treatment discontinued and were monitored for duration of remittive response. If/when disease worsening occurred, as evidenced by vIGA-AD =2, treatment was re-initiated and continued until vIGA-AD =0 was achieved. This treatment and re-treatment pattern of use was continued until the end of the study.

Locations

Country	Name	City	State
Canada	Dermavant Investigative Site	Barrie	Ontario
Canada	Dermavant Investigative Site	Calgary	Alberta
Canada	Dermavant Investigative Site	Cobourg	Ontario
Canada	Dermavant Investigative Site	Montréal	Quebec
Canada	Dermavant Investigative Site	Oakville	Ontario
Canada	Dermavant Investigative Site	Ottawa	Ontario
Canada	Dermavant Investigative Site	Surrey	British Columbia
Canada	Dermavant Investigative Site	Waterloo	Ontario
Canada	Dermavant Investigative Site	Windsor	Ontario
Canada	Dermavant Investigative Site	Winnipeg	Manitoba
United States	Dermavant Investigative Site	Anderson	South Carolina
United States	Dermavant Investigative Site	Baton Rouge	Louisiana
United States	Dermavant Investigative Site	Baton Rouge	Louisiana
United States	Dermavant Investigative Site	Bay City	Michigan
United States	Dermavant Investigative Site	Bellaire	Texas
United States	Dermavant Investigative Site	Bexley	Ohio
United States	Dermavant Investigative Site	Birmingham	Alabama
United States	Dermavant Investigative Site	Boca Raton	Florida
United States	Dermavant Investigative Site	Boca Raton	Florida
United States	Dermavant Investigative Site	Brandon	Florida
United States	Dermavant Investigative Site	Bryant	Arkansas
United States	Dermavant Investigative Site	Cerritos	California
United States	Dermavant Investigative Site	Charlotte	North Carolina
United States	Dermavant Investigative Site	Chicago	Illinois
United States	Dermavant Investigative Site	Clarkston	Michigan
United States	Dermavant Investigative Site	Cleveland	Ohio
United States	Dermavant Investigative Site	Coral Gables	Florida
United States	Dermavant Investigative Site	Covington	Louisiana
United States	Dermavant Investigative Site	Cypress	Texas
United States	Dermavant Investigative Site	Dallas	Texas
United States	Dermavant Investigative Site	Dayton	Ohio
United States	Dermavant Investigative Site	Delray Beach	Florida
United States	Dermavant Investigative Site	Dripping Springs	Texas
United States	Dermavant Investigative Site	East Windsor	New Jersey
United States	Dermavant Investigative Site	Evansville	Indiana
United States	Dermavant Investigative Site	Fort Smith	Arkansas
United States	Dermavant Investigative Site	Fountain Valley	California
United States	Dermavant Investigative Site	Fremont	California
United States	Dermavant Investigative Site	Garden City	New York
United States	Dermavant Investigative Site	Grapevine	Texas
United States	Dermavant lnvestigative Site	Greenville	South Carolina
United States	Dermavant Investigative Site	Hialeah	Florida
United States	Dermavant Investigative Site	Houston	Texas
United States	Dermavant Investigative Site	Huntington Beach	California
United States	Dermavant Investigative Site	Inglewood	California
United States	Dermavant Investigative Site	Jacksonville	Florida
United States	Dermavant Investigative Site	Knoxville	Tennessee
United States	Dermavant Investigative Site	Lancaster	California
United States	Dermavant Investigative Site	Largo	Maryland
United States	Dermavant Investigative Site	Lexington	Kentucky
United States	Dermavant Investigative Site	Long Beach	California
United States	Dermavant Investigative Site	Los Angeles	California
United States	Dermavant Investigative Site	Los Angeles	California
United States	Dermavant Investigative Site	Los Angeles	California
United States	Dermavant Investigative Site	Louisville	Kentucky
United States	Dermavant Investigative Site	Louisville	Kentucky
United States	Dermavant Investigative Site	Margate	Florida
United States	Dermavant Investigative Site	Marietta	Georgia
United States	Dermavant Investigative Site	Mason	Ohio
United States	Dermavant Investigative Site	Mayfield Heights	Ohio
United States	Dermavant Investigative Site	Medford	Oregon
United States	Dermavant Investigative Site	Memphis	Tennessee
United States	Dermavant Investigative Site	Miami	Florida
United States	Dermavant Investigative Site	Miami	Florida
United States	Dermavant Investigative Site	Miami Lakes	Florida
United States	Dermavant Investigative Site	Mission Viejo	California
United States	Dermavant Investigative Site	Missoula	Montana
United States	Dermavant Investigative Site	Monroe	Louisiana
United States	Dermavant Investigative Site	Mount Pleasant	South Carolina
United States	Dermavant Investigative Site	New Brighton	Minnesota
United States	Dermavant Investigative Site	New Orleans	Louisiana
United States	Dermavant Investigative Site	New York	New York
United States	Dermavant Investigative Site	Norman	Oklahoma
United States	Dermavant Investigative Site	North Charleston	South Carolina
United States	Dermavant Investigative Site	Oklahoma City	Oklahoma
United States	Dermavant Investigative Site	Omaha	Nebraska
United States	Dermavant Investigative Site	Orlando	Florida
United States	Dermavant Investigative Site	Overland Park	Kansas
United States	Dermavant Investigative Site	Owensboro	Kentucky
United States	Dermavant Investigative Site	Phoenix	Arizona
United States	Dermavant Investigative Site	Pinellas Park	Florida
United States	Dermavant Investigative Site	Plainfield	Indiana
United States	Dermavant Investigative Site	Portland	Oregon
United States	Dermavant Investigative Site	Portland	Oregon
United States	Dermavant Investigative Site	Portland	Oregon
United States	Dermavant Investigative Site	Richmond	Virginia
United States	Dermavant Investigative Site	Rockville	Maryland
United States	Dermavant Investigative Site	Sacramento	California
United States	Dermavant Investigative Site	San Antonio	Texas
United States	Dermavant Investigative Site	San Antonio	Texas
United States	Dermavant Investigative Site	San Antonio	Texas
United States	Dermavant Investigative Site	San Diego	California
United States	Dermavant Investigative Site	San Francisco	California
United States	Dermavant Investigative Site	Sandy Springs	Georgia
United States	Dermavant Investigative Site	Santa Ana	California
United States	Dermavant Investigative Site	Santa Monica	California
United States	Dermavant Investigative Site	Savannah	Georgia
United States	Dermavant Investigative Site	Scottsdale	Arizona
United States	Dermavant Investigative Site	Scottsdale	Arizona
United States	Dermavant Investigative Site	Snellville	Georgia
United States	Dermavant Investigative Site	Spartanburg	South Carolina
United States	Dermavant Investigative Site	Spokane	Washington
United States	Dermavant Investigative Site	Sugar Land	Texas
United States	Dermavant Investigative Site	Sweetwater	Florida
United States	Dermavant Investigative Site	Tampa	Florida
United States	Dermavant Investigative Site	Thornton	Colorado
United States	Dermavant Investigative Site	Thousand Oaks	California
United States	Dermavant Investigative Site	Tulsa	Oklahoma
United States	Dermavant Investigative Site	Warren	Michigan
United States	Dermavant Investigative Site	Washington	District of Columbia
United States	Dermavant Investigative Site	Webster	Texas
United States	Dermavant Investigative Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Dermavant Sciences, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline to Week 49
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.	Baseline up to Week 49
Primary	Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs	The mean chemistry and hematology parameters and vital signs were assessed for changes and trends over the course of the study. Shifts from Baseline in chemistry and hematology parameters and vital signs for individual subjects were assessed for clinical relevance. The number of subjects with clinically significant changes from baseline in laboratory values or vital signs were assessed for clinical relevance.	Baseline up to Week 48
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.	Baseline to 49 weeks
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.	Baseline to 49 weeks
Primary	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.	Baseline to 48 weeks
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.	Baseline to 48 weeks
Primary	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 48 weeks
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.	Baseline to 48 weeks
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.	Baseline to Week 48
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.	Baseline to Week 48
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.	Baseline to Week 48
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.	Baseline to Week 48
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.	Baseline to Week 48