Tapinarof for the Treatment of Plaque Psoriasis in Adults (3001)

A Phase 3 Efficacy and Safety Study of Tapinarof for the Treatment of Plaque Psoriasis in Adults

This is a randomized, double-blind, vehicle-controlled Phase 3 study to evaluate the efficacy and safety of topical tapinarof cream, 1% once daily for the treatment of plaque psoriasis in adults. Approximately 500 adult subjects with plaque psoriasis will be randomized 2:1 to receive either tapinarof cream, 1% or matching vehicle cream once daily for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: Tapinarof; Drug: Vehicle Cream

Detailed Description

This study is a 12-week double-blind, vehicle-controlled treatment study in which subjects will be randomized to receive tapinarof cream, 1% or vehicle cream once daily for 12 weeks. At the end of the 12-week study treatment, qualified subjects completing the study will have the option to enter a separate open-label, long-term safety and efficacy study for an additional 40 weeks of treatment with tapinarof cream, 1%. Subjects who do not enroll in the open-label long-term study will complete a follow-up visit approximately 4 weeks after end of treatment in this study (at Week 16).

• Study Type: Interventional
• Enrollment (Actual): 510
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • Saint Johns, Newfoundland and Labrador, Canada, A1C 2H5
      • Dermavant Investigative Site
  • Ontario
    • Ajax, Ontario, Canada, L1S 7K8
      • Dermavant Investigative Site
    • Coburg, Ontario, Canada, K9A 0Z4
      • Dermavant Investigative Site
    • North Bay, Ontario, Canada, P1B 3Z7
      • Dermavant Investigative Site
    • Richmond Hill, Ontario, Canada, L4C 9M7
      • Dermavant Investigative Site
    • Toronto, Ontario, Canada, M3H 5Y8
      • Dermavant Investigative Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Dermavant Investigative Site
    • Windsor, Ontario, Canada, N8W 5L7
      • Dermavant Investigative Site
  • Quebec
    • Montréal, Quebec, Canada, H2X 2V1
      • Dermavant Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Dermavant Investigative Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Dermavant Investigative Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Dermavant Investigative Site
    • Rogers, Arkansas, United States, 72758
      • Dermavant Investigative Site
  • California
    • Anaheim Hills, California, United States, 92807
      • Dermavant Investigative Site
    • Fresno, California, United States, 93720
      • Dermavant Investigative Site
    • Los Angeles, California, United States, 90033
      • Dermavant Investigative Site
    • Northridge, California, United States, 91324
      • Dermavant Investigative Site
    • San Diego, California, United States, 92123
      • Dermavant Investigative Site
    • Santa Ana, California, United States, 92701
      • Dermavant Investigative Site
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Dermavant Investigative Site
  • Florida
    • Boca Raton, Florida, United States, 33431
      • Dermavant Investigative Site
    • Brandon, Florida, United States, 33511
      • Dermavant Investigative Site
    • Hialeah, Florida, United States, 33016
      • Dermavant Investigative Site
    • Miramar, Florida, United States, 33027
      • Dermavant Investigative Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Dermavant Investigative Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Dermavant Investigative Site
    • Indianapolis, Indiana, United States, 46250
      • Dermavant Investigative Site
    • New Albany, Indiana, United States, 47150
      • Dermavant Investigative Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Dermavant Investigative Site
    • Owensboro, Kentucky, United States, 42301
      • Dermavant Investigative Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Dermavant Investigative Site
    • New Orleans, Louisiana, United States, 70115
      • Dermavant Investigative Site
    • New Orleans, Louisiana, United States, 70112
      • Dermavant Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dermavant Investigative Site
  • Michigan
    • Clarkston, Michigan, United States, 48346
      • Dermavant Investigative Site
    • Warren, Michigan, United States, 48088
      • Dermavant Investigative Site
  • Missouri
    • Saint Joseph, Missouri, United States, 64506
      • Dermavant Investigative Site
  • New Jersey
    • Verona, New Jersey, United States, 07044
      • Dermavant Investigative Site
  • New York
    • Kew Gardens, New York, United States, 11374
      • Dermavant Investigative Site
    • New York, New York, United States, 10029
      • Dermavant Investigative Site
    • Rochester, New York, United States, 14623
      • Dermavant Investigative Site
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Dermavant Investigative Site
    • High Point, North Carolina, United States, 27262
      • Dermavant Investigative Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Dermavant Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97210
      • Dermavant Investigative Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Dermavant Investigative Site
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Dermavant Investigative Site
  • Texas
    • Arlington, Texas, United States, 76011
      • Dermavant Investigative Site
    • College Station, Texas, United States, 77802
      • Dermavant Investigative Site
    • Dripping Springs, Texas, United States, 78620
      • Dermavant Investigative Site
    • Houston, Texas, United States, 77004
      • Dermavant Investigative Site
    • San Antonio, Texas, United States, 78213
      • Dermavant Investigative Site
  • Utah
    • West Jordan, Utah, United States, 84088
      • Dermavant Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects ages 18 to 75 years with clinical diagnosis of chronic plaque psoriasis and stable disease for at least 6 months prior to the study.
• BSA involvement ≥ 3% and ≤ 20%
• A PGA score of 2 (mild), 3 (moderate) or 4 (severe) at screening and baseline
• 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 throughout the study, including screening, during the treatment period, and for at least 4 weeks after the last exposure to study treatment
• Capable of giving written informed consent

Exclusion Criteria:

• Psoriasis other than plaque variant
• Any sign of infection of any of the psoriatic lesions
• Concurrent conditions or history of other diseases:
• Immunocompromised at Screening
• Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to the Baseline visit
• Acute active bacterial, fungal, or viral (herpes simplex, herpes zoster, chicken pox) skin infection within 1 week prior to the Baseline visit
• Significant dermatologic or inflammatory condition other than plaque psoriasis 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) ≥ 1.5x the upper limit of normal (ULN)
• Total bilirubin > 1.5 x ULN; total bilirubin > ULN and ≤ 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%
• Corrected QT interval > 475
• Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result, or a positive anti-hepatitis B core antigen (anti-HBc) result
• Ultraviolet (UV) light therapy or prolonged exposure to natural or artificial sources of UV radiation within 4 weeks prior to the Baseline visit and/or plans to have such exposures during the study which could potentially impact the subject's psoriasis
• Use of any prohibited medication within the indicated period before the first dose of study drug
• Within a minimum of 5 half-lives for biologic agents:
• Within 4 weeks for systemic immunosuppressive or immunomodulating agents, fumaric acid derivatives, vitamin D3 and analogs, retinoids, psoralens, corticosteroids, adrenocorticotropic hormone analogs, and tazarotene
• 2 weeks for immunizations with a live viral component; drugs known to possibly worsen psoriasis, unless on a stable dose for > 12 weeks
• With the exception of non-medicated emollients, 2 weeks for topical treatments including corticosteroids, immunomodulators, anthralin (dithranol), vitamin D derivatives or coal tar.
• Pregnant females or lactating females
• History of sensitivity to the study drugs, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates the subject's participation in the study
• The subject has received an investigational product within 30 days, 5 half-lives, or twice the duration of the biological effect of the study drug (whichever is longer) prior to first dose of study drug
• Current or a history of cancer within 5 years except for fully excised skin basal cell carcinoma, squamous cell carcinoma or carcinoma in situ of the cervix
• Subjects with active infection that required oral, intramuscular, or intravenous administration of antibiotics, antifungal or antiviral agents within 7 days of Baseline/Day 1
• Previous known participation in a clinical study with tapinarof
• Evidence of significant hepatic, renal, respiratory, endocrine, hematologic, neurologic, psychiatric, or cardiovascular (CV) system abnormalities or laboratory abnormality that will affect the health of the subject or interfere with interpretation of the results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tapinarof (DMVT-505); Tapinarof (DMVT-505) Cream Group	Drug: Tapinarof; Tapinarof cream, 1%, applied once daily; Other Names: DMVT-505
Placebo Comparator: Vehicle Cream; Vehicle Cream Group	Drug: Vehicle Cream; Vehicle cream applied once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects Who Achieve a Physician Global Assessment (PGA) Score of Clear (0) or Almost Clear (1) With a Minimum 2-grade Improvement From Baseline at Week 12. Analyses Were Done Using Multiple Imputation	The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis at a given timepoint. A static 5-point scale is used to grade lesions on the clinical characteristics of erythema, scaling, and plaque thickness/elevation. The PGA ranges from 0 to 4, and is calculated as Clear (0), Almost clear (1), Mild (2), Moderate (3), and Severe (4). Higher PGA scores represent more severe disease. Analyses were done using multiple imputation.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects With ≥ 75% Improvement in Psoriasis Area and Severity Index (PASI) From Baseline at Week 12. Analyses Were Done Using Multiple Imputation.	The Psoriasis Area and Severity Index (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%). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. Higher scores indicate more severe disease. PASI is a static assessment made without reference to previous scores. Analyses were done using multiple imputation.	Baseline to Week 12
Percent of Subjects With a PGA Score of 0 or 1 at Week 12. Analyses Were Done Using Multiple Imputation.	The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis at a given timepoint. A static 5-point scale is used to grade lesions on the clinical characteristics of erythema, scaling, and plaque thickness/elevation. The PGA ranges from 0 to 4, and is calculated as Clear (0), Almost clear (1), Mild (2), Moderate (3), and Severe (4). Higher PGA scores represent more severe disease. Analyses were done using multiple imputation.	Baseline to Week 12
Mean Change in Percent of Total Body Surface Area (%BSA) Affected From Baseline to Week 12	Assessment of BSA with psoriasis 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)]. 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 Week 12
Percent of Subjects With ≥90% Improvement in PASI Score From Baseline to Week 12. Analyses Were Done Using Multiple Imputation.	The Psoriasis Area and Severity Index (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%). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. Higher scores indicate more severe disease. PASI is a static assessment made without reference to previous scores. Analyses were done using multiple imputation.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Dermavant Sciences GmbH
• Collaborators: IQVIA Biotech
• Investigators: Study Director: Victoria Butners, Dermavant Sciences GmbH

Publications and helpful links

General Publications

• Lebwohl MG, Stein Gold L, Strober B, Papp KA, Armstrong AW, Bagel J, Kircik L, Ehst B, Hong HC, Soung J, Fromowitz J, Guenthner S, Piscitelli SC, Rubenstein DS, Brown PM, Tallman AM, Bissonnette R. Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. N Engl J Med. 2021 Dec 9;385(24):2219-2229. doi: 10.1056/NEJMoa2103629.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2019
• Primary Completion (Actual): May 26, 2020
• Study Completion (Actual): May 26, 2020

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: September 16, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: adult; safety; efficacy; topical; psoriasis; double-blind; plaque psoriasis; phase 3; Tapinarof
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: DMVT-505-3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No