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出境医 / 临床实验 / Tapinarof for the Treatment of Plaque Psoriasis in Adults (3001)

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

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Plaque Psoriasis Drug: Tapinarof (DMVT-505) Drug: Vehicle Cream Phase 3

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 510 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Following a 34-day screening period, eligible subjects will be randomized at a 2:1 ratio to receive once daily treatment with tapinarof cream, 1% or vehicle cream.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The Investigator, study center staff, subject, and Sponsor will be blinded to treatment assignment.
Primary Purpose: Treatment
Official Title: A Phase 3 Efficacy and Safety Study of Tapinarof for the Treatment of Plaque Psoriasis in Adults
Actual Study Start Date : May 21, 2019
Actual Primary Completion Date : May 26, 2020
Actual Study Completion Date : May 26, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: Tapinarof (DMVT-505)
Tapinarof (DMVT-505) Cream Group
 Drug: Tapinarof (DMVT-505)
Tapinarof cream, 1%, applied once daily
Placebo Comparator: Vehicle Cream
Vehicle Cream Group
 Drug: Vehicle Cream
Vehicle cream applied once daily
Outcome Measures
Primary Outcome Measures :
  1. Proportion 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 [ Time Frame: Baseline to Week 12 ]
    The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis at a given timepoint. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, scaling, and plaque thickness/elevation as guidelines. Higher PGA scores represent more severe disease.


Secondary Outcome Measures :
  1. Proportion of subjects with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI) from Baseline at Week 12 [ Time Frame: Baseline to Week 12 ]
    The PASI scoring system is a widely-used standard clinical tool for assessing the severity of psoriasis that takes into account the overall severity of erythema (redness), induration (plaque thickness), and scale, and the extent of %Body Surface Area (BSA) affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0 to 4) and the %BSA affected is scored on a 7-point scale (0 to 6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). 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.

  2. Proportion of subjects with a PGA score of 0 or 1 at Week 12 [ Time Frame: Baseline to Week 12 ]
    The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis at a given timepoint. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, scaling, and plaque thickness/elevation as guidelines. Higher PGA scores represent more severe disease.

  3. Mean change in percent of total body surface area (%BSA) affected from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores.

  4. Proportion of subjects with ≥90% improvement in PASI score from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The PASI scoring system is a widely-used standard clinical tool for assessing the severity of psoriasis that takes into account the overall severity of erythema (redness), induration (plaque thickness), and scale, and the extent of %BSA affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0 to 4) and the %BSA affected is scored on a 7-point scale (0 to 6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). 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.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Locations
Show Show 50 study locations
Sponsors and Collaborators
Dermavant Sciences GmbH
IQVIA Biotech
Investigators
Layout table for investigator information
Study Director: Victoria Butners Dermavant Sciences GmbH
Tracking Information
First Submitted Date  ICMJE May 16, 2019
First Posted Date  ICMJE May 20, 2019
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE May 21, 2019
Actual Primary Completion Date May 26, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2019) 		Proportion 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 [ Time Frame: Baseline to Week 12 ]
The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis at a given timepoint. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, scaling, and plaque thickness/elevation as guidelines. Higher PGA scores represent more severe disease.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2019)
  • Proportion of subjects with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI) from Baseline at Week 12 [ Time Frame: Baseline to Week 12 ]
    The PASI scoring system is a widely-used standard clinical tool for assessing the severity of psoriasis that takes into account the overall severity of erythema (redness), induration (plaque thickness), and scale, and the extent of %Body Surface Area (BSA) affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0 to 4) and the %BSA affected is scored on a 7-point scale (0 to 6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). 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.
  • Proportion of subjects with a PGA score of 0 or 1 at Week 12 [ Time Frame: Baseline to Week 12 ]
    The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis at a given timepoint. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, scaling, and plaque thickness/elevation as guidelines. Higher PGA scores represent more severe disease.
  • Mean change in percent of total body surface area (%BSA) affected from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores.
  • Proportion of subjects with ≥90% improvement in PASI score from Baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
    The PASI scoring system is a widely-used standard clinical tool for assessing the severity of psoriasis that takes into account the overall severity of erythema (redness), induration (plaque thickness), and scale, and the extent of %BSA affected with psoriasis. The 3 clinical signs are each graded on a 5-point scale (0 to 4) and the %BSA affected is scored on a 7-point scale (0 to 6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower extremities). 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tapinarof for the Treatment of Plaque Psoriasis in Adults (3001)
Official Title  ICMJE A Phase 3 Efficacy and Safety Study of Tapinarof for the Treatment of Plaque Psoriasis in Adults
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Following a 34-day screening period, eligible subjects will be randomized at a 2:1 ratio to receive once daily treatment with tapinarof cream, 1% or vehicle cream.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
The Investigator, study center staff, subject, and Sponsor will be blinded to treatment assignment.
Primary Purpose: Treatment
Condition  ICMJE Plaque Psoriasis
Intervention  ICMJE
  • Drug: Tapinarof (DMVT-505)
    Tapinarof cream, 1%, applied once daily
  • Drug: Vehicle Cream
    Vehicle cream applied once daily
Study Arms  ICMJE
  • Experimental: Tapinarof (DMVT-505)
    Tapinarof (DMVT-505) Cream Group
    Intervention: Drug: Tapinarof (DMVT-505)
  • Placebo Comparator: Vehicle Cream
    Vehicle Cream Group
    Intervention: Drug: Vehicle Cream
Publications *
  • Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology. 2015;230(1):27-33. doi: 10.1159/000365390. Epub 2015 Jan 20.
  • Lebwohl M, Swensen AR, Nyirady J, Kim E, Gwaltney CJ, Strober BE. The Psoriasis Symptom Diary: development and content validity of a novel patient-reported outcome instrument. Int J Dermatol. 2014 Jun;53(6):714-22. doi: 10.1111/j.1365-4632.2012.05798.x. Epub 2013 Apr 4.
  • Mason AR, Mason J, Cork M, Dooley G, Hancock H. Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev. 2013 Mar 28;(3):CD005028. doi: 10.1002/14651858.CD005028.pub3. Review.
  • Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013 Feb;133(2):377-85. doi: 10.1038/jid.2012.339. Epub 2012 Sep 27. Review.
  • Strober BE, Nyirady J, Mallya UG, Guettner A, Papavassilis C, Gottlieb AB, Elewski BE, Turner-Bowker DM, Shields AL, Gwaltney CJ, Lebwohl M. Item-level psychometric properties for a new patient-reported psoriasis symptom diary. Value Health. 2013 Sep-Oct;16(6):1014-22. doi: 10.1016/j.jval.2013.07.002.
  • Strober B, Zhao Y, Tran MH, Gnanasakthy A, Nyirady J, Papavassilis C, Nelson LM, McLeod LD, Mordin M, Gottlieb AB, Elewski BE, Lebwohl M. Psychometric validation of the Psoriasis Symptom Diary using Phase III study data from patients with chronic plaque psoriasis. Int J Dermatol. 2016 Mar;55(3):e147-55. doi: 10.1111/ijd.13117. Epub 2015 Oct 30.
  • Zoetis T, Hurtt ME. Species comparison of anatomical and functional renal development. Birth Defects Res B Dev Reprod Toxicol. 2003 Apr;68(2):111-20. Review.
  • Cappon GD and Hurtt ME. Developmental toxicity of the kidney. In: Kapp RW and Yyl L, editors. Reproductive Toxicology, Target Organ Series, 3rd edition. New York:Informa Healthcare, 2010:193-204.
  • Frazier KS and Seely JC. Urinary system. In: Sahota PS, Popp JA, Hardisty JF and Gopinath C, editors. Toxicologic Pathology: Nonclinical Safety Assessment. CRC Press, 2013:421-84.
  • Maruish, ME, editor. User's manual for the SF-36v2 health survey. Edition 3. Quality Metric Inc. 2011.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2020) 		510
Original Estimated Enrollment  ICMJE
 (submitted: May 17, 2019) 		500
Actual Study Completion Date  ICMJE May 26, 2020
Actual Primary Completion Date May 26, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03956355
Other Study ID Numbers  ICMJE DMVT-505-3001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dermavant Sciences GmbH
Study Sponsor  ICMJE Dermavant Sciences GmbH
Collaborators  ICMJE IQVIA Biotech
Investigators  ICMJE
Study Director: Victoria Butners Dermavant Sciences GmbH
PRS Account Dermavant Sciences GmbH
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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