Long Term Extension Study of Tapinarof for Plaque Psoriasis in Adults (3003)

Plaque Psoriasis Clinical Trial

Official title:

A Long-Term, Open-Label, Extension Study to Evaluate the Safety and Efficacy of Tapinarof Cream, 1% for the Treatment of Plaque Psoriasis in Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04053387
• Other study ID #: DMVT-505-3003
• Status: Completed
• Phase: Phase 3
• Start date: August 13, 2019
• Est. completion date: April 6, 2021

Study information

• Verified date: August 2022
• Source: Dermavant Sciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a long-term, open-label, multicenter, study to evaluate the safety and efficacy of topical tapinarof cream, 1% in adults with plaque psoriasis. Subjects in this study completed treatment in 1 of 2 Phase 3 pivotal efficacy and safety studies (Study DMVT-505-3001 or Study DMVT-505-3002). This study will consist of up to 40 weeks of treatment and a 4-week safety follow-up period.

Description:

At the completion of the Week-12 visit of the pivotal study (Baseline [Day 1] in this study), all eligible subjects will be offered enrollment in the long-term extension 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 44 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 763
• Est. completion date: April 6, 2021
• Est. primary completion date: April 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Completed the 12-week treatment period in 1 of the 2 parent studies (Study DMVT-505-3001 or Study DMVT-505-3002);

2. Male and female subjects

3. Females of child bearing potential and male subjects who are engaging in sexual activity that could lead to pregnancy agree to follow the specified contraceptive guidance while on the study, and for at least 4 weeks after the last exposure to study treatment

4. Capable of giving written informed consent

Exclusion Criteria:

1. Used a prohibited concomitant product or procedure to treat psoriasis during parent study

2. Had a serious adverse event (SAE) that was potentially related to treatment or experienced an adverse event (AE) that led to permanent discontinuation of treatment in the parent study

3. 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 completion of the study

4. Known hypersensitivity to tapinarof

Related Conditions & MeSH terms

• Plaque Psoriasis
• Psoriasis

Intervention

Drug:
• tapinarof cream, 1%
Intermittent use of Tapinarof cream, 1%, applied once daily according to PGA score

Locations

Country	Name	City	State
Canada	Dermavant Investigative Site	Ajax	Ontario
Canada	Dermavant Clinical Site	Burlington	Ontario
Canada	Dermavant Investigative Site	Cobourg	Ontario
Canada	Dermavant Investigative Site	Edmonton	Alberta
Canada	Dermavant Investigative Site	Etobicoke	Ontario
Canada	Dermavant Clinical Site	Hamilton	Ontario
Canada	Dermavant Investigative Site	Hamilton	Ontario
Canada	Dermavant Clinical Site	Markham	Ontario
Canada	Dermavant Investigative Site	Markham	Ontario
Canada	Dermavant Investigative Site	Montréal	Quebec
Canada	Dermavant Investigative Site	North Bay	Ontario
Canada	Dermavant Investigative Site	Oakville	Ontario
Canada	Dermavant Investigative Site	Ottawa	Ontario
Canada	Dermavant Investigative Site	Richmond Hill	Ontario
Canada	Dermavant Investigative Site	Surrey	Bristish Columbia
Canada	Dermavant Investigative Site	Surrey	British Columbia
Canada	Dermavant Investigative Site	Toronto	Ontario
Canada	Dermavant Investigative Site	Waterloo	Ontario
Canada	Dermavant Investigative Site	Windsor	Ontario
United States	Dermavant Investigative Site	Arlington	Texas
United States	Dermavant Investigative Site	Baton Rouge	Louisiana
United States	Dermavant Investigative Site	Bay City	Michigan
United States	Dermavant Investigative Site	Beachwood	Ohio
United States	Dermavant Clinical 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	Boise	Idaho
United States	Dermavant Investigative Site	Boston	Massachusetts
United States	Dermavant Investigative Site	Boynton Beach	Florida
United States	Dermavant Clinical Site	Brooklyn	New York
United States	Dermavant Investigative Site	Bryant	Arkansas
United States	Dermavant Investigative Site	Cary	North Carolina
United States	Dermavant Investigative Site	Charleston	South Carolina
United States	Dermavant Investigative Site	Clarkston	Michigan
United States	Dermavant Investigative Site	College Station	Texas
United States	Dermavant Investigative Site	Cromwell	Connecticut
United States	Dermavant Investigative Site	Denver	Colorado
United States	Dermavant Clinical Site	Detroit	Michigan
United States	Dermavant Investigational Site	Detroit	Michigan
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 Gratiot	Michigan
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	Fresno	California
United States	Dermavant Investigative Site	Fridley	Minnesota
United States	Dermavant Clinical Site	Gresham	Oregon
United States	Dermavant Investigative Site	Hackensack	New Jersey
United States	Dermavant Investigative Site	Hialeah	Florida
United States	Dermavant Investigative Site	High Point	North Carolina
United States	Dermavant Clinical Site	Houston	Texas
United States	Dermavant Investigative Site	Houston	Texas
United States	Dermavant Investigative Site	Indianapolis	Indiana
United States	Dermavant Investigative Site	Johnston	Rhode Island
United States	Dermavant Investigative Site	Kew Gardens	New York
United States	Dermavant Clinical Site	Las Vegas	Nevada
United States	Dermavant Investigative Site	Las Vegas	Nevada
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	Margate	Florida
United States	Dermavant Investigative Site	Miami	Florida
United States	Dermavant Investigative Site	Miramar	Florida
United States	Dermavant Investigative Site	Nashville	Tennessee
United States	Dermavant Investigative Site	New Albany	Indiana
United States	Dermavant Investigative Site	New Orleans	Louisiana
United States	Dermavant Investigative Site	New York	New York
United States	Dermavant Investigative Site	Norfolk	Virginia
United States	Dermavant Investigate Site	Norman	Oklahoma
United States	Dermavant Investigative Site	Norman	Oklahoma
United States	Dermavant Investigative Site	Norman	Oklahoma
United States	Dermavant Investigative Site	Northridge	California
United States	Dermavant Investigative Site	Oceanside	California
United States	Dermavant Investigative Site	Omaha	Nebraska
United States	Dermavant Investigative Site	Overland Park	Kansas
United States	Dermavant Investigative Site	Owensboro	Kentucky
United States	Dermavant Investigative Site	Pflugerville	Texas
United States	Dermavant Investigative Site	Phoenix	Arizona
United States	Dermavant Investigative Site	Pittsburgh	Pennsylvania
United States	Dermavant Investigative Site	Plainfield	Indiana
United States	Dermavant Investigative Site	Plano	Texas
United States	Dermavant Investigative Site	Portland	Oregon
United States	Dermavant Investigative Site	Portland	Oregon
United States	Dermavant Investigative Site	Rochester	New York
United States	Dermavant Investigative Site	Rockville	Maryland
United States	Dermavant Investigative Site	Rolling Meadows	Illinois
United States	Dermavant Investigative Site	Saint Joseph	Missouri
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	Santa Ana	California
United States	Dermavant Investigative Site	Santa Monica	California
United States	Dermavant Investigative Site	Spokane	Washington
United States	Dermavant Investigative Site	Stony Brook	New York
United States	Dermavant Investigative Site	Verona	New Jersey
United States	Dermavant Investigative Site	Warren	Michigan
United States	Dermavant Clinical Site	Watertown	New York
United States	Dermavant Investigative Site	Webster	Texas
United States	Dermavant Investigative Site	West Jordan	Utah
United States	Dermavant Investigative Site	Wilmington	North Carolina
United States	Dermavant Investigative Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Dermavant Sciences GmbH	IQVIA Biotech

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With 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 the pivotal Phase 3 studies but resolved prior to the Visit 1 date for this extension study.; All SAEs were deemed unrelated to treatment with tapinarof cream, 1%.	Baseline to 44 weeks
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 the pivotal Phase 3 studies but resolved prior to the Visit 1 date for this extension study. Subjects could have reported more than one TEAE.; All SAEs were deemed unrelated to treatment with tapinarof cream, 1%.	Baseline to 44 weeks
Primary	Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs	The mean chemistry and hematology parameters were assessed for changes and trends over the course of the study. Shifts from Baseline in chemistry and hematology parameters for individual subjects were assessed for clinical relevance. The number of subjects with clinically significant changes from baseline in laboratory values was assessed for clinical relevance.	Baseline to 40 weeks
Primary	Remittive Effect of Treatment Success in Pivotal: Median Time to First Worsening (PGA = 2) While Off Therapy for Subjects Who Entered LTE PGA = 0 (Clear)	Subjects who completed 1 of the phase 3 studies evaluating the safety and efficacy of tapinarof had the option to enter this extension study. Subjects entering with a PGA = 0 had treatment discontinued and were monitored for duration of remittive response. If/when disease worsening occurred, as evidenced by a PGA = 2, treatment was re-initiated and continued until a PGA = 0 was achieved. This outcome measure assesses the median time for subjects entering with a PGA = 0 to first worsening (PGA = 2) while off therapy during this extension study.; The PGA is an assessment of a subject's psoriasis using a static 5-point scale to grade lesions on the clinical characteristics of erythema, scaling, and plaque thickness/elevation. The PGA ranges from 0 to 4, where 0 = clear, 1= almost clear, 2 = mild, 3 = moderate, and 4 = severe.	Baseline to 44 weeks
Primary	Complete Disease Clearance During LTE: Number of Subjects Achieving Disease Clearance PGA =0 (Clear) While on Therapy for Subjects Entered LTE PGA = 1 (Almost Clear)	Subjects who completed 1 of the phase 3 studies evaluating the safety and efficacy of tapinarof had the option to enter this extension study. Subjects entering with a PGA = 1 continued treatment with tapinarof until they achieved a PGA = 0, at which time treatment was discontinued and subjects were monitored for remittive response. If/when disease worsening occurred, as evidenced by a PGA = 2, treatment was re-initiated and continued until a PGA = 0 was achieved. This outcome measure assesses the number of subjects who entered the extension study with a PGA = 1 and achieved complete disease clearance (PGA=0) while on therapy during this extension study.; The PGA is an assessment of a subject's psoriasis using a static 5-point scale to grade lesions on the clinical characteristics of erythema, scaling, and plaque thickness/elevation. The PGA ranges from 0 to 4, where 0 = clear, 1= almost clear, 2 = mild, 3 = moderate, and 4 = severe. Higher PGA scores represent more severe disease.	Baseline to 44 weeks
Primary	Response During LTE: Number of Subjects Achieving PGA =0 or 1 (Clear or Almost Clear) While on Therapy for Subjects Who Entered LTE With PGA = 2 (Mild)	Subjects who completed 1 of the phase 3 studies evaluating the safety and efficacy of tapinarof had the option to enter this extension study. Subjects entering with a PGA = 1 continued treatment with tapinarof until they achieved a PGA = 0, at which time treatment was discontinued and subjects were monitored for remittive response. If/when disease worsening occurred, as evidenced by a PGA = 2, treatment was re-initiated and continued until a PGA = 0 was achieved.; This outcome measure assesses the number of these subjects who entered the study with a PGA= 2 and achieved a PGA of 0 or 1 (clear or almost clear) while on therapy during this extension study.; The PGA is an assessment of a subject's psoriasis using a static 5-point scale to grade lesions on the clinical characteristics of erythema, scaling, and plaque thickness/elevation. The PGA ranges from 0 to 4, where 0 = clear, 1= almost clear, 2 = mild, 3 = moderate, and 4 = severe. Higher PGA scores represent more severe disease.	Baseline to 44 weeks
Primary	Remittive Effect of Treatment Success: Number of Subjects Experiencing Worsening (PGA = 2) While Off Therapy for Subjects Who Entered LTE With a PGA = 0 (Clear)	Subjects who completed 1 of the phase 3 studies evaluating the safety and efficacy of tapinarof had the option to enter this extension study. Subjects entering with a PGA = 0 had treatment discontinued and were monitored for duration of remittive response. If/when disease worsening occurred, as evidenced by a PGA = 2, treatment was re-initiated and continued until a PGA = 0 was achieved. This treatment and re-treatment pattern of use was continued until the end of the study. This outcome measure assesses the number of these subjects entering the study with a PGA= 0 who experienced worsening (PGA = 2) while off therapy at least once during this extension study.; The PGA is an assessment of a subject's psoriasis using a static 5-point scale to grade lesions on the clinical characteristics of erythema, scaling, and plaque thickness/elevation. The PGA ranges from 0 to 4, where 0 = clear, 1= almost clear, 2 = mild, 3 = moderate, and 4 = severe.	Baseline to 44 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.; BSA affected was estimated by the handprint method, where the full palmar hand of the subject represented approximately 1% of the total BSA. Body regions are assigned specific number of handprints (hp) with percentage [Head and neck = 10% (10 hp), upper extremities = 20% (20 hp), Trunk (including axillae and groin) = 30% (30 hp), lower extremities (including buttocks) = 40% (40 hp)]. The total %BSA involved was estimated = % involvement	Baseline to 40 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.; BSA affected was estimated by the handprint method, where the full palmar hand of the subject represented approximately 1% of the total BSA. Body regions are assigned specific number of handprints (hp) with percentage [Head and neck = 10% (10 hp), upper extremities = 20% (20 hp), Trunk (including axillae and groin) = 30% (30 hp), lower extremities (including buttocks) = 40% (40 hp)]. The total %BSA involved was estimated = % involvement	Baseline to 40 weeks
Primary	Mean Duration (Days) of Treatment Course	Subjects who completed 1 of the phase 3 studies evaluating the safety and efficacy of tapinarof had the option to enter this extension study. Subjects entering with a PGA = 1 continued tapinarof until they achieved a PGA = 0, at which time treatment was discontinued. If/when disease worsening occurred, as evidenced by a PGA = 2, treatment was re-initiated and continued until a PGA = 0 was achieved.; Mean duration (days) of treatment episode = time (days) from date of each PGA = 2 (or PGA = 1 for the first episode) to 1 day before each subsequent PGA = 0.; The PGA is an assessment of a subject's psoriasis using a static 5-point scale to grade lesions on the clinical characteristics of erythema, scaling, and plaque thickness/elevation. The PGA ranges from 0 to 4, where 0 = clear, 1= almost clear, 2 = mild, 3 = moderate, and 4 = severe. Higher PGA scores represent more severe disease.	Baseline to 40 weeks
Primary	Change From Baseline in Psoriasis Area and Severity Index (PASI) Score	Subjects received treatment with tapinarof intermittently guided by disease severity. This outcome measure assesses the change from baseline in PASI score in all subjects, including those on and those off therapy.; The PASI scoring system combines the assessment of lesion severity and extent of affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, and legs). Each area is assessed for 3 signs: erythema (redness), induration (plaque thickness), and scale. The severity of each sign in each body area is assessed and scored independently using a 5-point scale, where 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. Each area is also assessed for percent of skin involved: 0 = (0%), 1 = (1-<10%), 2 = (10-<30%), 3 = (30-<50%), 4 = (50 -<70%), 5 = (70-<90%), 6 = (90-100%). Overall PASI = the sum of (individual scores x by a weighted factor for each body region).	Baseline to 40 weeks
Primary	Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score	Subjects received treatment with tapinarof intermittently guided by disease severity. This outcome measure assesses the % change from baseline in PASI score in all subjects, including those on and those off therapy.; The PASI scoring system combines the assessment of lesion severity and extent of affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, and legs). Each area is assessed for 3 signs: erythema (redness), induration (plaque thickness), and scale. The severity of each sign in each body area is assessed and scored independently using a 5-point scale, where 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. Each area is also assessed for percent of skin involved: 0 = (0%), 1 = (1-<10%), 2 = (10-<30%), 3 = (30-<50%), 4 = (50 -<70%), 5 = (70-<90%), 6 = (90-100%). Overall PASI = the sum of (individual scores x by a weighted factor for each body region).	Baseline to 40 weeks
Primary	Change From Baseline in Disease Impact on Daily Activities, as Measured by the Dermatology Life Quality Index (DLQI)	Subjects received treatment with tapinarof intermittently guided by disease severity. This outcome measure assesses change from baseline in disease impact on daily activities, as measured by the DLQI, in all subjects including those on and those off therapy.; The DLQI is a 10-item PRO measure that assesses the extent to which the skin condition has affected the subject's quality of life over the past week, including 6 domains (daily activities, personal relationships, symptoms and feelings, leisure, work/school, and treatment). The total score (0-30) is the sum of 10 questions with each ranging from 0 to 3. The scoring of each question is as follows: Very much= 3, A lot=2, A little = 1, Not at all = 0, Not relevant = 0, Question unanswered = 0.; DLQI scores range from 0 to 30, with a higher score indicating a more impaired quality of life.	Baseline to 40 weeks
Primary	Percent Change From Baseline in Disease Impact on Daily Activities, as Measured by the Dermatology Life Quality Index (DLQI)	Subjects received treatment with tapinarof intermittently guided by disease severity. This outcome measure assesses % change from baseline in disease impact on daily activities, as measured by the DLQI, in all subjects including those on and those off therapy.; The DLQI is a 10-item PRO measure that assesses the extent to which the skin condition has affected the subject's quality of life over the past week, including 6 domains (daily activities, personal relationships, symptoms and feelings, leisure, work/school, and treatment). The total score (0-30) is the sum of 10 questions with each ranging from 0 to 3. The scoring of each question is as follows: Very much= 3, A lot=2, A little = 1, Not at all = 0, Not relevant = 0, Question unanswered = 0.	Baseline to 40 weeks