Plaque Psoriasis
Conditions
Keywords
Tapinarof, plaque psoriasis,, adult, phase 3, topical, open-label, efficacy, safety, psoriasis, long-term, therapeutic aryl hydrocarbon receptor modulating agent
Brief 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.
Detailed 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.
Interventions
Intermittent use of Tapinarof cream, 1%, applied once daily according to PGA score
Sponsors
IQVIA Biotech
Organon and Co
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events and Serious Adverse Events | Baseline to 44 weeks | 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%. |
| Frequency of Adverse Events and Serious Adverse Events | Baseline to 44 weeks | 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%. |
| Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs | Baseline to 40 weeks | 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. |
| 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) | Baseline to 44 weeks | 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. |
| 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) | Baseline to 44 weeks | 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. |
| 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) | Baseline to 44 weeks | 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. |
| Change From Baseline in Disease Impact on Daily Activities, as Measured by the Dermatology Life Quality Index (DLQI) | Baseline to 40 weeks | 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. |
| 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) | Baseline to 44 weeks | 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. |
| Change From Baseline in %BSA Affected | Baseline to 40 weeks | 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 |
| Percent Change From Baseline in %BSA Affected | Baseline to 40 weeks | 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 |
| Mean Duration (Days) of Treatment Course | Baseline to 40 weeks | 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. |
| Change From Baseline in Psoriasis Area and Severity Index (PASI) Score | Baseline to 40 weeks | 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). |
| Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score | Baseline to 40 weeks | 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). |
| Percent Change From Baseline in Disease Impact on Daily Activities, as Measured by the Dermatology Life Quality Index (DLQI) | Baseline to 40 weeks | 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score 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 achieved 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. | 763 |
| Total | 763 |
Baseline characteristics
| Characteristic | Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score |
|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 12.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 117 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 641 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 51 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants |
| Race (NIH/OMB) More than one race | 18 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 643 Participants |
| Sex: Female, Male Female | 315 Participants |
| Sex: Female, Male Male | 448 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 763 |
| other Total, other adverse events | 204 / 763 |
| serious Total, serious adverse events | 19 / 763 |
Outcome results
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
Time frame: Baseline to 40 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Change From Baseline in %BSA Affected | -2.03 percentage of BSA affected | Standard Deviation 4.848 |
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.
Time frame: Baseline to 40 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Change From Baseline in Disease Impact on Daily Activities, as Measured by the Dermatology Life Quality Index (DLQI) | -2.0 scores on a scale | Standard Deviation 4.31 |
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).
Time frame: Baseline to 40 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Change From Baseline in Psoriasis Area and Severity Index (PASI) Score | -1.80 scores on a scale | Standard Deviation 4.334 |
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.
Time frame: Baseline to 44 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | 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) | 233 Participants |
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%.
Time frame: Baseline to 44 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Frequency of Adverse Events and Serious Adverse Events | Adverse Events | 1190 events |
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Frequency of Adverse Events and Serious Adverse Events | Serious Adverse Events | 21 events |
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.
Time frame: Baseline to 40 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Mean Duration (Days) of Treatment Course | 172.9 days | Standard Deviation 102.17 |
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%.
Time frame: Baseline to 44 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Number of Subjects With Adverse Events and Serious Adverse Events | Adverse Events | 474 Participants |
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Number of Subjects With Adverse Events and Serious Adverse Events | Serious Adverse Events | 19 Participants |
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.
Time frame: Baseline to 40 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs | Clinically meaningful changes in diastolic blood pressure | 16 Participants |
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs | Clinically Meaningful changes in hematology | 0 Participants |
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs | Clinically meaningful changes in chemistry | 0 Participants |
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs | Clinically meaningful changes in urinalysis | 0 Participants |
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs | Clinically meaningful changes in pulse rate | 7 Participants |
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Number of Subjects With Clinically Meaningful Changes From Baseline in Clinical Laboratory Values and Vital Signs | Clinically meaningful changes in systolic blood pressure | 6 Participants |
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
Time frame: Baseline to 40 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Percent Change From Baseline in %BSA Affected | -18.48 percentage change | Standard Deviation 149.908 |
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.
Time frame: Baseline to 40 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Percent Change From Baseline in Disease Impact on Daily Activities, as Measured by the Dermatology Life Quality Index (DLQI) | -37.1 percentage change | Standard Deviation 121.35 |
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).
Time frame: Baseline to 40 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score | -11.90 percentage change | Standard Deviation 151.684 |
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.
Time frame: Baseline to 44 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | 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) | 115 days from baseline visit |
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.
Time frame: Baseline to 44 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | 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) | Number of subjects entering with PGA=0 who experienced PGA ≥ 2 at least 1 time during the study | 60 Participants |
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | 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) | Number of subjects entering with PGA=0 who never experienced PGA ≥ 2 throughout the study | 19 Participants |
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.
Time frame: Baseline to 44 weeks
Population: Subjects entering with a PGA = 0 had treatment discontinued. Subjects entering with a PGA ≥ 1 received tapinarof until they achieved a PGA = 0 and had treatment discontinued. If/when disease worsening (PGA ≥ 2) occurred 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. The ITT population includes all subjects who signed the informed consent and enrolled in this extension study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Continuous or Intermittent Use of Tapinarof (DMVT-505) Cream According to PGA Score | 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) | 302 Participants |