Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of RVT-501 Topical Ointment in Pediatric Patients With Atopic Dermatitis
Overview
- Phase
- Phase 1
- Intervention
- RVT-501 0.5% topical ointment
- Conditions
- Atopic Dermatitis
- Sponsor
- Dermavant Sciences GmbH
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Frequency and severity of adverse events (local and systemic)
- Last Updated
- 7 years ago
Overview
Brief Summary
This is a multicenter, open-label Phase 1b study in pediatric patients age 2-11 years old with extensive atopic dermatitis.
Detailed Description
The purpose of this multicenter, open-label study is to evaluate the safety, tolerability, and pharmacokinetics of RVT-501 0.5% topical ointment administered twice daily (BID) for 4 weeks in pediatric patients age 2-11 years of age with extensive atopic dermatitis. The efficacy of RVT-501 will also be evaluated as a secondary objective in these patients. The study will consist of three phases: Screening (up to 30 days), Treatment Phase (28 days), and Follow-up (7-10 days).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female pediatric patients aged 2 to 11 with confirmed diagnosis of atopic dermatitis by Hanifin and Rajka criteria.
- •Patients with atopic dermatitis covering \> 25% of the body surface area and with an Investigator Global Assessment of disease severity of 2 or greater at baseline.
- •Minimum body weight of 10 kg.
- •Females of childbearing potential and male patients, 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
- •Oral Contraceptive, either combined or progestogen alone
Exclusion Criteria
- •A positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody result, or positive human immunodeficiency virus (HIV) antibody at Screening.
- •Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5x the upper limit of normal (ULN).
- •Screening total bilirubin \> 1.5x ULN; total bilirubin \> ULN and ≤ 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%.
- •Patients with a skin condition such as Kaposi's varicelliform eruption, scabies, molluscum contagiosum, impetigo, psoriasis, severe acne, connective tissue disorder, or Netherton's syndrome, or any other disease that could impact study evaluations.
- •Use of any prohibited medication. Prohibited concomitant medications, therapy, etc. during the defined period are as listed in the bullets below. If a patient 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 visit or discontinuation:
- •Biological products that might have significantly affected the evaluation of atopic dermatitis condition (e.g., tumor necrosis factor \[TNF\] inhibitors, anti-immunoglobulin \[Ig\]E antibodies, anti-CD20 antibodies, anti-interleukin \[IL\]-4 receptor).
- •From 28 days prior to the first application of study drug until the completion of the Follow-up visit or discontinuation:
- •Corticosteroid preparations (oral, injection, and suppository preparations) and topical corticosteroids that were classified as super-high potency (clobetasol propionate). Eye drops and nasal preparations are allowed. Inhaled preparations are allowed if used for a stable condition and at 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.);
Arms & Interventions
Open-label treatment arm
Open-label treatment arm - patients will receive RVT-501 0.5% twice daily (BID) for 4 weeks.
Intervention: RVT-501 0.5% topical ointment
Outcomes
Primary Outcomes
Frequency and severity of adverse events (local and systemic)
Time Frame: 28 days
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
Laboratory values
Time Frame: 28 days
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.
Vital signs
Time Frame: 28 days
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.
Plasma concentrations of RVT-501
Time Frame: 28 days
PK samples will be collected at week 1 pre-dose, 2-4 hours post-dose, and 6-8 hours post dose for all subjects. At week PK samples will be collected pre-dose. RVT-501 will be measured in plasma by validated assay in all subjects to confirm exposure. These plasma concentrations will be listed by metabolite, subject, treatment, and time; and will be summarized by analyte and time. If data permit, RVT-501 and M11 concentrations will be summarized descriptively at each collection time point.
Plasma concentrations of M11 metabolite
Time Frame: 28 days
PK samples will be collected at week 1 pre-dose, 2-4 hours post-dose, and 6-8 hours post dose for all subjects. At week 4 PK samples will be collected pre-dose. The M11 metabolite will be measured in plasma by validated assay in all subjects to confirm exposure. These plasma concentrations will be listed by metabolite, subject, treatment, and time; and will be summarized by metabolite, treatment and time. If data permit, RVT-501 and M11 concentrations will be summarized descriptively at each collection time point.
Secondary Outcomes
- Efficacy - Investigators Global Assessment (IGA)(28 days)
- Efficacy - 2-point improvement in IGA(28 days)
- Efficacy - IGA of 0 or 1 at study end(28 days)
- Efficacy - Eczema Area and Severity Index (EASI) score(28 days)
- Efficacy - EASI-50(28 days)
- Efficacy - Peak Pruritus Numeric Rating Scale (NRS)(28 days)
- Efficacy - Body Surface Area (BSA)(28 days)
- Efficacy - Patient/caregiver reported itch severity (local)(28 days)
- Efficacy - Patient/caregiver reported itch severity (global)(28 days)