Efficacy and Safety of Roflumilast Foam 0.3% in Trial Participants With Seborrheic Dermatitis

Official title

A Phase 3 Multicenter, Randomized, Parallel Group, Double Blind, Vehicle-controlled Study of the Efficacy and Safety of Roflumilast Foam 0.3% (ZORYVE®) in Trial Participants With Seborrheic Dermatitis

Overview

This study will assess the safety and efficacy of Roflumilast foam 0.3% (ZORYVE®) versus vehicle applied once a day for 8 weeks by trial participants with seborrheic dermatitis.

Detailed description

This is a phase 3, randomized, parallel group, double blind, vehicle-controlled study in which Roflumilast foam 0.3% (ZORYVE®) or vehicle foam is applied QD for 8 weeks to trial participants 9 years of age and older with seborrheic dermatitis affecting the scalp and/or rest of body.

Interventions

• Drug Roflumilast Foam 0.3%
  Roflumilast foam 0.3% is applied once daily for 8 weeks.
• Drug Vehicle foam
  Vehicle foam is applied once daily for 8 weeks.

Primary outcome measures

• Percentage of trial participants with IGA success at Week 8 [Time frame: Baseline, Week 8]

Secondary outcome measures (8)

• Percentage of trial participants with WI-NRS success in subjects with a Baseline WI-NRS pruritus score of ≥4 [Time frame: Baseline, Week 2, Week 4, Week 8]
• Percentage of trial participants with IGA success at Week 2 and Week 4 [Time frame: Baseline, Week 2, Week 4]
• Achievement of an Overall Assessment of Scaling (0-3 scale) score of 0 at Week 8 [Time frame: Baseline, Week 8]
• Achievement of an Overall Assessment of Erythema (0-3 scale) score of 0 at Week 8 [Time frame: Baseline, Week 8]
• Achievement of an IGA score of 0 at Week 8 [Time frame: Baseline, Week 8]
• Safety: TEAE [Time frame: Throughout the study, up to 9 weeks]
• Safety: Other Safety Endpoint [Time frame: Up to 8 weeks.]
• Pharmacokinetic (PK) endpoint [Time frame: Up to 8 weeks.]

Eligibility criteria

Inclusion criteria

• Males and females ages 9 years and older (inclusive) at the time of consent.
• Clinical diagnosis of seborrheic dermatitis of at least 3 months duration at screening as determined by the Investigator. Stable disease for the past 4 weeks.
• Seborrheic dermatitis up to 20% BSA involvement. Involvement may be of the scalp and/or face and/or trunk and/or intertriginous areas.
• An Investigator Global Assessment (IGA) disease severity of at least moderate ('3') at baseline.
• Overall Assessment of Erythema and Overall Assessment of Scaling scores of at least Moderate ('2') at Baseline.
• Trial participants in good health as judged by the Investigator, based on medical history, physical examination, vital signs, serum chemistry labs, hematology values, and urinalysis.
• Women of Childbearing Potential (WOCBP) must have a negative serum pregnancy test at Screening (Visit 1) and negative urine pregnancy test at Baseline (Visit 2). WOCBP must have used highly effective contraception for at least 4 weeks prior to the first study drug administration, and agree to continue using highly effective contraception for 2 months after the last dose. If hormonal contraceptives are used, the dosage must have been stable for a minimum of 4 weeks before the first administration. Alternatively, WOCBP shall use barrier contraception from the time of signing the ICF through 2 months after the last dose. All WOCBP shall have no plan to conceive or donate oocytes throughout the study period.
• Trial participants are considered reliable and capable of adhering to the protocol and visit schedule according to the Investigator judgment.
• Participants legally competent to sign and give informed consent or (for children/adolescents) assent with consent of a parent(s) or legal guardian.

Exclusion criteria

• Trial participants with any serious medical condition or clinically significant laboratory abnormality that would prevent study participation or place the subject at significant risk, as determined by the Investigator.
• Any conditions in the treatment area judged by the investigator at screening or baseline that may interfere with efficacy assessment (e.g., confirmed cutaneous bacterial, viral or parasitic infections, psoriasis, atopic dermatitis, acne, as well as pigmentation, extensive scars, pigmentary lesions, sunburn, etc.).
• Trial participants with active pityriasis/tinea amiantacea.
• Current or history of cancer within 5 years from Screening with the exception of fully treated skin basal cell carcinoma, cutaneous squamous cell carcinoma, or carcinoma in situ of the cervix.
• A clinically relevant history of abuse of alcohol or other drugs within 6 months prior to screening.
• Known or suspected severe renal insufficiency as evidenced by calculated creatinine clearance <30 mL/min, or moderate to severe hepatic disorders (Child-Pugh B or C).
• History of severe depression, suicidal ideation or behavior, Baseline/Screening C-SSRS (for adolescents and adults 12 years old and older) indicative of suicidal behavior, whether lifetime or recent/recurrent.
• Trial participants with PHQ-8 (≥18 years old, inclusive) score ≥10 at Screening or Baseline visits, or children aged 9 to 11 years (inclusive), following discussion with their legal representatives, the investigator assesses the presence of depressive symptoms or suicide/depression risk.
• Systemic administration of antifungals, glucocorticoids, immunosuppressants, retinoids, roflumilast tablets, apremilast tablets, or systemic traditional Chinese medicine known or suspected to affect seborrheic dermatitis within 4 weeks prior to the first study drug administration.
• Receipt of phototherapy, sunbeds or any other light-emitting devices within 4 weeks prior to the first study drug administration, or planned excessive exposure of the treatment area to natural or artificial light.
• Use of topical medications or treatments within 2 weeks prior to the first study drug administration, including but not limited to topical antifungals, topical glucocorticoids, topical calcineurin inhibitors, topical phosphodiesterase 4 (PDE-4) inhibitors, sulfur-containing preparations, azelaic acid, metronidazole, medical devices, or topical traditional Chinese medicine known or suspected to affect seborrheic dermatitis.
• Use of medicinal shampoos or medical devices containing antifungals, glucocorticoids, zinc pyrithione, selenium sulfide, coal tar, or keratolytic agents (e.g., salicylic acid) within 2 weeks prior to the first study drug administration.
• Receipt of topical treatments on the scalp for indications other than seborrheic dermatitis within 2 weeks prior to the first study drug administration, if such treatments may alter scalp skin conditions (e.g., topical minoxidil for androgenetic alopecia, retinoids or tar preparations for scalp psoriasis, topical anti-allergic agents for allergic dermatitis, and certain oil-control or anti-dandruff shampoos).
• Use of potent cytochrome P450 (CYP) 3A4 inhibitors systemically within 2 weeks prior to the first study drug administration.
• Intravenous administration of antibiotics or antiviral agents within 1 week prior to the first study drug administration.
• Use of etanercept within 4 weeks prior to the first study drug administration, or use of any other biologics within 12 weeks or 5 half-lives (whichever is longer) prior to the first study drug administration.
• Participation in any clinical trial of biologics within 12 weeks or 5 half-lives (whichever is longer), any clinical trial of oral formulations within 5 half-lives, or any clinical trial of topical formulations within 2 weeks prior to the first study drug administration (excluding participants who only signed the ICF and did not receive any study drug or device).
• Participants who have undergone major surgery within 4 weeks prior to the first study drug administration or are scheduled to receive major surgery during the study period .
• Prior use of roflumilast cream or roflumilast foam.
• Known allergies or hypersensitivity to component(s) of the investigational product which includes roflumilast, petrolatum, isopropyl palmitate, methylparaben, propylparaben, diethylene glycol monoethyl ether, hexylene glycol, cetearyl alcohol, dicetyl phosphate and ceteth-10 phosphate.
• Liver function test results excursions that exceed: AST or ALT > 2x ULN; Total bilirubin: 1.5x ULN or >ULN and ≤1.5x ULN and direct bilirubin is >35% of total bilirubin; ALP ≥ 2x ULN.
• History of human immunodeficiency virus (HIV) infection or suspected HIV infection, or positive HIV antibody at screening; positive hepatitis B surface antigen (HBsAg), or negative HBsAg with positive hepatitis B core antibody and HBV-DNA level above the upper limit of normal reference range; positive hepatitis C virus (HCV) antibody with HCV-RNA level above the upper limit of normal reference range; positive treponemal-specific antibody for syphilis (Participants with negative non-specific syphilis antibody and clinically diagnosed as inactive infection may be enrolled). Participants with indeterminate screening results are not recommended for enrollment.
• Trial participants/caregivers unable to apply product to the scalp due to physical limitations if the trial participants has current or history of seborrheic dermatitis involving the scalp.
• Females who are pregnant, or are breast-feeding.
• Trial participants who are family members of the clinical study site, or clinical study staff, or sponsor, or family members residing in the same household of enrolled trial participants.
• Trial participants, parent(s)/legal guardian(s) of children/adolescent trial participants who are unable to communicate, read, or understand the study.
• Any condition that in the Investigator's assessment would preclude the trial participants from participating in the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 44 centers

• The First Affiliated Hospital of Wannan Medical Hospital — Wuhu
• The Second Affiliated Hospital of Wannan Medical Hospital — Wuhu
• The first affilated hospital of Fujian Medical university — Fuzhou
• The Second Affiliated Hospital of Xiamen Medical College — Xiamen
• Dermatology Hospital of Southern Medical University — Guangzhou
• Shenzhen Children's Hospital — Shenzhen
• Hainan Fifth People's Hospital — Haikou
• Beijing Children's Hospital, Capital Medical University Baoding Hospital — Baoding
• … and 36 more centers

Identifiers

NCT: NCT07683806 · HDM3014-3-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗