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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: tapinarof cream, 1%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed the 12-week treatment period in 1 of the 2 parent studies (Study DMVT-505-3001 or Study DMVT-505-3002); Male and female subjects 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 Capable of giving written informed consent Exclusion Criteria: Used a prohibited concomitant product or procedure to treat psoriasis during parent study 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 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 Known hypersensitivity to tapinarof

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Subjects in this study completed treatment with tapinarof or vehicle in 1 of 2 parent Phase 3 pivotal efficacy and safety studies (Study DMVT-505-3001 or Study DMVT-505-3002). The study will consist of up to 40 weeks of tapinarof cream, 1%, and a 4-week safety follow-up period.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tapinarof (DMVT-505) Cream Group<br>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 received treatment with tapinarof cream, 1% until they achieve a PGA = 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 a PGA ≥ 2, treatment was re initiated and continued until a PGA = 0 was achieved. 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 | Drug: tapinarof cream, 1%<br>* Intermittent use of Tapinarof cream, 1%, applied once daily according to PGA score<br>* Other names: DMVT-505;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tapinarof, adult, plaque psoriasis,, phase 3, topical, open-label, efficacy, safety, psoriasis, long-term, therapeutic aryl hydrocarbon receptor modulating agent