Study of RVT-501 in Adult and Adolescent Subjects With Atopic Dermatitis

NCT02950922 | Completed Phase 2

• 1 other identifier: RVT-501-2001
• Study Type: interventional
• Target: 157
• Locations: 2 countries
• Sites: 20

Brief Summary

This is a multi-center, randomized, vehicle-controlled, double-blind Phase 2 study in adults and adolescent subjects with mild to moderate atopic dermatitis.

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (6)

• Frequency and severity of adverse events (local and systemic)

  Adverse events will be coded using the most current release of MedDRA® (Medical Dictionary for Regulatory Activities). The number and proportion of subjects with adverse events will be summarized by treatment, system organ class, and preferred term for all adverse events, all adverse events considered by the investigator to be related to study drug, all serious adverse events, and all adverse events leading to study drug discontinuation

  28 days

• Laboratory values

  Selected laboratory data will be summarized by the observed data and by the change from baseline (as appropriate) across time. Incidence of treatment emergent laboratory values that are considered clinically significantly abnormal will be summarized by treatment group.

  28 days

• Vital signs

  Vital signs will be measured in supine or semi-supine position after a 5 minute rest and will include systolic and diastolic blood pressure and pulse rate. Vital sign data will be listed by subject and summarized by treatment.

  28 days

• ECGs

  Single 12-lead ECGs will be obtained at Screening, Day 0, Day 7, Day 28 and during follow up 7-10 days-post-dose using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. ECG data will be listed by subject and summarized by treatment.

  28 Days

• Plasma concentrations of RVT-501

  PK samples will be collected pre-dose at week 1 for all subjects. At week 4, PK samples will be collected pre-dose and within 2-4 hours post-dose. RVT-501 will be measured in plasma by validated assay in all subjects to confirm exposure. These plasma concentrations will be listed separately for adults and adolescents by metabolite, subject, treatment, and time; and will be summarized by metabolite, treatment and time. The number of percent of subjects with measurable concentration at each time point and any time during the study will be provided.

  28 Days

• Plasma concentrations of M11 metabolite

  PK samples will be collected pre-dose at week 1 for all subjects. At week 4, PK samples will be collected pre-dose and within 2-4 hours post-dose. The M11 metabolite will be measured in plasma by validated assay in all subjects to confirm exposure. These plasma concentrations will be listed separately for adults and adolescents by metabolite, subject, treatment, and time; and will be summarized by metabolite, treatment and time. The number of percent of subjects with measurable concentration at each time point and any time during the study will be provided.

  28 Days

Secondary Outcomes (3)

• Efficacy - Investigators Global Assessment (IGA)

  28 days

• Efficacy - Eczema Area and Severity Index (EASI)

  28 Days

• Efficacy - Numeric Rating Scale (NRS) for Pruritus

  28 Days

Other Outcomes (2)

• Patient Reported Symptoms

  28 days

• Patient Report Outcomes

  28 Days

Study Arms (3)

RVT-501 0.2% ointment

EXPERIMENTAL

RVT-501 0.2% ointment BID x 28 days (30 adults, 20 adolescents)

Drug: RVT-501 0.2% ointment

RVT-501 0.5% ointment

EXPERIMENTAL

RVT-501 0.5% ointment BID x 28 days (30 adults, 20 adolescents)

Drug: RVT-501 0.5% ointment

Vehicle ointment

PLACEBO COMPARATOR

Vehicle ointment BID x 28 days (30 adults, 20 adolescents)

Other: Vehicle ointment

Interventions

RVT-501 0.2% ointment DRUG

RVT-501 0.2% ointment

RVT-501 0.5% ointment DRUG

RVT-501 0.5% ointment

Vehicle ointment OTHER

Placebo comparator

Vehicle ointment

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females with confirmed diagnosis of atopic dermatitis by Hanifin and Rajka criteria (Appendix 4: Criteria for Atopic Dermatitis Diagnosis).
• For adult subjects, the age range is 18 to 70 years. For adolescent subjects, the age range is 12 to 17 years.
• Subjects with atopic dermatitis covering ≥ 3% and \< 40% of the body surface area and with an Investigator Global Assessment (IGA) of 2 or 3 (mild to moderate) at baseline. Scalp, palms and soles should be excluded from the BSA calculation to determine eligibility at baseline.
• NOTE: Subjects with mild disease (IGA =2) will be limited to approximately 25% of total enrollment.
• Minimum EASI score of 7 at baseline.
• Females of childbearing potential and male subjects and who are engaging in sexual activity that could lead to pregnancy must use the following adequate birth control methods while on study and for 2 weeks after stopping study drug. Acceptable contraception methods are:
• Male or Male partner with vasectomy OR
• Male condom, AND partner use of one of the contraceptive options below:
• Spermicide
• Contraceptive subdermal implant that meets effectiveness criteria including a \<1% rate of failure per year, as stated in the product label
• Intrauterine device or intrauterine system that meets effectiveness criteria including a \<1% rate of failure per year, as stated in the product label \[Hatcher, 2007a\]
• Oral Contraceptive, either combined or progestogen alone \[Hatcher, 2007a\] Injectable progestogen \[Hatcher, 2007a\]
• Contraceptive vaginal ring \[Hatcher, 2007a\]
• Percutaneous contraceptive patches \[Hatcher, 2007a\]
• These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.

You may not qualify if:

• A positive Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.
• A positive test for human immunodeficiency virus (HIV) antibody at screening.
• Screening alanine aminotransferase (ALT) ≥ 3x the upper limit of normal (ULN).
• Total bilirubin \> 1.5x the upper limit of normal (ULN); total bilirubin \> ULN and ≤ 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%.
• Corrected QT (QTc) interval \>475 msec or \>525 msec in the presence of bundle branch block.
• Subjects with a present illness of Kaposi's varicelliform eruption, scabies, molluscum contagiosum, impetigo, psoriasis, connective tissue disorder, or Netherton's syndrome, or any other disease which could have an effect on the pathological evaluation of atopic dermatitis.
• Use of any prohibited medication.
• Prohibited concomitant medications, therapy, etc. during the defined period are as follows. If a subject requires any of these medications throughout the study period, he/she may be excluded from or discontinued from the study, at the discretion of the investigator and medical monitor.
• From 6 months prior to the first application of study drugs to the completion of the follow-up examination or discontinuation:
• Biological products that might have significantly affected the evaluation of atopic dermatitis condition (e.g., TNF inhibitors, anti-IgE antibodies, anti-CD20 antibodies, anti-IL4 receptor)
• From 28 days prior to the first application of study drug until the completion of the Treatment Phase or discontinuation:
• Corticosteroid preparations (oral, injection, and suppository preparations) and topical corticosteroids that were classified as super high potency (clobetasol propionate). Eye drop and nasal preparations are allowed. Inhaled preparations are allowed if used for a stable condition and at a stable dose for \> 28 days before screening, and are continued at the same dose throughout the study.
• Oral preparations and injections of immunosuppressants (cyclosporine, methotrexate, azathioprine, tacrolimus, etc.)
• Over the counter or herbal medicines for atopic dermatitis (topical and oral preparations)
• Excessive sun exposure, tanning booth, other UV light source and phototherapy including PUVA therapy

Sponsors & Collaborators

• Dermavant Sciences GmbH: lead

Study Sites (20)

Dermavant Investigator Site

Fremont, California, 94538, United States

Location

Dermavant Investigator Site

Los Angeles, California, 90045, United States

Location

Dermavant Investigator Site

San Diego, California, 92123, United States

Location

Dermavant Investigator Site

San Luis Obispo, California, 93405, United States

Location

Dermavant Investigator Site

Louisville, Kentucky, 40202, United States

Location

Dermavant Investigator Site

Louisville, Kentucky, 40217, United States

Location

Dermavant Investigator Site

Berlin, New Jersey, 08009, United States

Location

Dermavant Investigator Site

Portland, Oregon, 97223, United States

Location

Dermavant Investigator Site

Portland, Oregon, 97239, United States

Location

Dermavant Investigator Site

Hershey, Pennsylvania, 17022, United States

Location

Dermavant Investigator Site

Johnston, Rhode Island, 02919, United States

Location

Dermavant Investigational Site

Dallas, Texas, 75230, United States

Location

Dermavant Investigator Site

Houston, Texas, 77004, United States

Location

Dermavant Investigator Site

Houston, Texas, 77030, United States

Location

Dermavant Investigator Site

San Antonio, Texas, 78213, United States

Location

Dermavant Investigator Site

Norfolk, Virginia, 23502, United States

Location

Unknown Facility

Surrey, British Columbia, Canada

Location

Dermavant Investigator Site

Richmond, Ontario, Canada

Location

Dermavant Investigator Site

Waterloo, Ontario, Canada

Location

Dermavant Investigational Site

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

methyl 4-(((3-(6,7-dimethoxy-2-(methylamino)quinazolin-4-yl)phenyl)amino)carbonyl)benzoate; Ointments

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• James Lee, MD, PhD

  Dermavant Sciences, Chief Medical Officer

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2016
• First Posted: November 1, 2016
• Study Start: November 1, 2016
• Primary Completion: July 3, 2017
• Study Completion: July 3, 2017
• Last Updated: August 6, 2018

Record last verified: 2018-02

Locations

US (16); CA (4)