Maximal Use Study of Tapinarof Cream, 1% in Pediatric Subjects With Extensive Atopic Dermatitis

Atopic Dermatitis Clinical Trial

Official title:

Open Label Maximal Use Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Tapinarof Cream, 1% in Pediatric Subjects With Extensive Atopic Dermatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05186805
• Other study ID #: DMVT-505-2104
• Status: Completed
• Phase: Phase 2
• Start date: November 15, 2021
• Est. completion date: August 24, 2022

Study information

• Verified date: July 2023
• Source: Dermavant Sciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter study to evaluate the systemic exposure and safety of topical tapinarof cream, 1% under conditions of maximal use in pediatric subjects with atopic dermatitis

Description:

This is a 4-week open-label study in which subjects will be assigned to receive tapinarof cream, 1% once daily for 4 weeks. At the end of the 4-week study treatment, qualified subjects will have the option to enroll in an open-label, long-term extension study for an additional 48 weeks of treatment. Subjects who do not participate in the open-label, long-term extension study will complete a follow-up visit approximately one week after the end of treatment in this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 24, 2022
• Est. primary completion date: August 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

Inclusion Criteria:

• Male and female subjects age 2 to 17 with a confirmed clinical diagnosis of atopic dermatitis and present for at least 6 months for ages 6-17 years old, 3 months for ages 2-5 years old

• BSA involvement = 25% for subjects ages 12-17 years old, or = 35% for subjects ages 2-11 years old, suitable for topical therapy.

• vIGA-AD score of = 3 at screening and baseline (pre-dose)

• Female subjects of child bearing potential who are engaging in sexual activity that could lead to pregnancy agree to follow the specified contraceptive guidance throughout the study

• Capable of giving written informed consent

• Negative pregnancy test at Baseline (Day 1)

Exclusion Criteria:

• Immunocompromised at screening

• Chronic or acute systemic or superficial infection requiring treatment with systemic antibacterials or antifungals within one week prior to baseline visit

• Significant dermatological or inflammatory condition other than AD 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) =2.0x the upper limit of normal (ULN).

• Screening total bilirubin > 1.5x ULN

• Current or chronic history of liver disease

• Current or history of cancer within 5 years except for adequately treated cutaneous basal cell carcinoma, squamous cell carcinoma or carcinoma in situ of the cervix

• Subjects who would not be considered suitable for topical therapy

• Use of any prohibited medication or procedure within the indicated period before the baseline visit including other investigational product within 30 days or 5 half-lives of the investigational product (whichever is longer)

• 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 participation in the study, interpretation of results, or ability to understand and give informed consent.

• Pregnant or lactating females

• History of sensitivity to the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the -Investigator or Medical Monitor, contraindicates their participation

• Previous known participation in a clinical study with tapinarof (previously known as GSK2894512 and WBI-1001)

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Tapinarof cream, 1%
Tapinarof cream, 1% applied topically once daily

Locations

Country	Name	City	State
Canada	Dermavant Investigative Site	Calgary	Alberta
United States	Dermavant Investigative Site	Centennial	Colorado
United States	Dermavant Investigative Site	Chicago	Illinois
United States	Dermavant Investigative Site	Coral Gables	Florida
United States	Dermavant Investigative Site	Hialeah	Florida
United States	Dermavant Investigative Site	Houston	Texas
United States	Dermavant Investigative Site	Miami Lakes	Florida
United States	Dermavant Investigative Site	San Antonio	Texas
United States	Dermavant Investigative Site	Summerville	South Carolina
United States	Dermavant Investigative Site	Thousand Oaks	California

Sponsors (1)

Lead Sponsor	Collaborator
Dermavant Sciences, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (14)

Bashaw ED, Tran DC, Shukla CG, Liu X. Maximal Usage Trial: An Overview of the Design of Systemic Bioavailability Trial for Topical Dermatological Products. Ther Innov Regul Sci. 2015 Jan;49(1):108-115. doi: 10.1177/2168479014539157. Epub 2014 Jun 27. — View Citation

Bieber T. Atopic dermatitis. N Engl J Med. 2008 Apr 3;358(14):1483-94. doi: 10.1056/NEJMra074081. No abstract available. — View Citation

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.

Carroll CL, Balkrishnan R, Feldman SR, Fleischer AB Jr, Manuel JC. The burden of atopic dermatitis: impact on the patient, family, and society. Pediatr Dermatol. 2005 May-Jun;22(3):192-9. doi: 10.1111/j.1525-1470.2005.22303.x. — View Citation

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.

Furue M, Hashimoto-Hachiya A, Tsuji G. Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis. Int J Mol Sci. 2019 Oct 31;20(21):5424. doi: 10.3390/ijms20215424. — View Citation

Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermato-Venereologica Supplementum. 1980;92:44-7.

Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001 Feb;10(1):11-8. doi: 10.1034/j.1600-0625.2001.100102.x. — View Citation

Kalia YN, Nonato LB, Lund CH, Guy RH. Development of skin barrier function in premature infants. J Invest Dermatol. 1998 Aug;111(2):320-6. doi: 10.1046/j.1523-1747.1998.00289.x. — View Citation

Lewis-Jones S. Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema. Int J Clin Pract. 2006 Aug;60(8):984-92. doi: 10.1111/j.1742-1241.2006.01047.x. — View Citation

Nikolovski J, Stamatas GN, Kollias N, Wiegand BC. Barrier function and water-holding and transport properties of infant stratum corneum are different from adult and continue to develop through the first year of life. J Invest Dermatol. 2008 Jul;128(7):1728-36. doi: 10.1038/sj.jid.5701239. Epub 2008 Jan 17. — View Citation

Peppers J, Paller AS, Maeda-Chubachi T, Wu S, Robbins K, Gallagher K, Kraus JE. A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J Am Acad Dermatol. 2019 Jan;80(1):89-98.e3. doi: 10.1016/j.jaad.2018.06.047. Epub 2018 Jul 3. — View Citation

Smith SH, Jayawickreme C, Rickard DJ, Nicodeme E, Bui T, Simmons C, Coquery CM, Neil J, Pryor WM, Mayhew D, Rajpal DK, Creech K, Furst S, Lee J, Wu D, Rastinejad F, Willson TM, Viviani F, Morris DC, Moore JT, Cote-Sierra J. Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans. J Invest Dermatol. 2017 Oct;137(10):2110-2119. doi: 10.1016/j.jid.2017.05.004. Epub 2017 Jun 6. — View Citation

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. doi: 10.1002/bdrb.10013. No abstract available. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants that Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs)	Frequency, Severity, and Duration AEs (local and systemic)	Baseline to Day 28
Primary	Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Values and Vital Signs	Change in laboratory values and vial signs were assessed for clinical relevance	Baseline to Day 28
Primary	Number of participants with irritation as assessed by the Local Tolerability Scale (LTS)	Local Tolerability Scale (LTS) is a clinical tool for assessing the presence and overall degree of irritation at the application sites, according to a 5-point scale. 0 indicates no irritation and 4 indicates Very Severe irritation.	Baseline to Day 28
Primary	Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1: AUC0-t	The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug.	Day 1 and Day 28 (PK samples collected at pre-dose and at 1, 3, and 5 hours after dosing)
Primary	Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1: Cmax	The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing.	Day 1 and Day 28 (PK samples collected at pre-dose and at 1, 3, and 5 hours after dosing)
Primary	Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1: tmax	The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing.	Day 1 and Day 28 (PK sample collected at pre-dose and at 1, 3, and 5 hours after dosing)
Primary	Tapinarof and Tapinarof Sulfate (Metabolite) Plasma concentration on Day 28: Ct	The Ct is a pharmacokinetic parameter that describes the time of last quantifiable concentration that is achieved after the last dose.	Day 28 (PK sample collected approximately 24 hours after the last dose)
Secondary	Change from Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)	The vIGA-AD is a clinical tool for assessing the current state/severity of a subject's atopic dermatitis 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, induration/papulation, lichenification, oozing/crusting. Score of 0 indicates no inflammatory signs of atopic dermatitis and a 4 indicates disease is widespread in extent.	Baseline to Day 28
Secondary	Number of subjects who have a Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) score of almost clear (0 or 1) from baseline to Day 28	The vIGA-AD is a clinical tool for assessing the current state/severity of a subject's atopic dermatitis 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, induration/papulation, lichenification, oozing/crusting. Score of 0 indicates no inflammatory signs of atopic dermatitis and a 4 indicates disease is widespread in extent.	Baseline to Day 28
Secondary	Number of subjects with =50%, improvement in Eczema Area and Severity Index (EASI) score from Baseline to each visit	The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.	Baseline to Day 28
Secondary	Number of subjects with =75%, improvement in Eczema Area and Severity Index (EASI) score from Baseline to each visit	The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.	Baseline to Day 28
Secondary	Number of subjects with =90%, improvement in Eczema Area and Severity Index (EASI) score from Baseline to each visit	The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.	Baseline to Day 28
Secondary	Mean change in Eczema Area and Severity Index EASI from baseline to Day 28	The EASI is a composite score ranging from 0 to 72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.	Baseline to Day 28
Secondary	Mean change in Percent of Total Body Surface Area (%BSA) affected from Baseline to Day 28	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.	Baseline to Day 28
Secondary	Mean change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) values form Baseline to Day 28	The vIGA-AD is a clinical tool for assessing the current state/severity of a subject's atopic dermatitis 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, induration/papulation, lichenification, oozing/crusting. Score of 0 indicates no inflammatory signs of atopic dermatitis and a 4 indicates disease is widespread in extent. 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.	Baseline to Day 28
Secondary	Mean change in average weekly Peak Pruritus Numerical Rating Scale (PP-NRS) score by age group from Baseline to Day 28	The PP-NRS is a scale from 0-10 used to assess itch/pruritus severity over a 24-hour period which will be used daily to assess peak pruritus. Higher PP-NRS ratings represent more itch reported.	Baseline to Day 28
Secondary	Proportion of subjects with a Baseline Peak Pruritus Numerical Rating Scale (PP-NRS) score =4-point reduction in PP-NRS score from Baseline to Day 28	The PP-NRS is a scale from 0-10 used to assess itch/pruritus severity over a 24-hour period which will be used daily to assess peak pruritus. Higher PP-NRS ratings represent more itch reported.	Baseline to Day 28