Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Open-Label Study of RVT-501 Topical Ointment in Pediatric Patients With Atopic Dermatitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03415282
Recruitment Status : Active, not recruiting
First Posted : January 30, 2018
Last Update Posted : May 11, 2018
Sponsor:
Information provided by (Responsible Party):
Dermavant Sciences GmbH

Brief Summary:
This is a multicenter, open-label Phase 1b study in pediatric patients age 2-11 years old with extensive atopic dermatitis.

Condition or disease Intervention/treatment Phase
Atopic Dermatitis Drug: RVT-501 0.5% topical ointment Phase 1

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of RVT-501 Topical Ointment in Pediatric Patients With Atopic Dermatitis
Actual Study Start Date : February 5, 2018
Estimated Primary Completion Date : July 24, 2018
Estimated Study Completion Date : August 7, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Experimental: Open-label treatment arm
Open-label treatment arm - patients will receive RVT-501 0.5% twice daily (BID) for 4 weeks.
Drug: RVT-501 0.5% topical ointment
RVT-501 0.5% topical ointment twice daily (BID) for 4 weeks.




Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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 Outcome Measures :
  1. Efficacy - Investigators Global Assessment (IGA) [ Time Frame: 28 days ]
    Efficacy will be evaluated as the change from Baseline in IGA score.

  2. Efficacy - 2-point improvement in IGA [ Time Frame: 28 days ]
    Efficacy will be evaluated by the proportion of patients who achieve an IGA of 0 or 1 with at least a 2-point improvement from Basline

  3. Efficacy - IGA of 0 or 1 at study end [ Time Frame: 28 days ]
    Efficacy will be evaluated by the proportion of patients who achieve an IGA of 0 or 1 at Week 4.

  4. Efficacy - Eczema Area and Severity Index (EASI) score [ Time Frame: 28 days ]
    Efficacy will be evaluated as the change from Baseline in EASI score.

  5. Efficacy - EASI-50 [ Time Frame: 28 days ]
    Efficacy will be evaluated by the proportion of patients who achieve at least a 50% reduction from Baseline EASI (EASI-50) at Week 4.

  6. Efficacy - Peak Pruritus Numeric Rating Scale (NRS) [ Time Frame: 28 days ]
    Efficacy will be evaluated as the change from Baseline in Peak Pruritus as measured with the NRS at Week 4.

  7. Efficacy - Body Surface Area (BSA) [ Time Frame: 28 days ]
    Efficacy will be evaluated as the change from Baseline in BSA affected by disease at Week 4.

  8. Efficacy - Patient/caregiver reported itch severity (local) [ Time Frame: 28 days ]
    The patient or their caregiver will assess itch severity at the application site and efficacy will be determined as a change from Baseline.

  9. Efficacy - Patient/caregiver reported itch severity (global) [ Time Frame: 28 days ]
    The patient or their caregiver will assess global itch severity and efficacy will be determined as change from Baseline.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female pediatric patients aged 2 to 11 with confirmed diagnosis of atopic dermatitis by Hanifin and Rajka criteria.
  2. 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.
  3. Minimum body weight of 10 kg.
  4. 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
      • Injectable progestogen
      • Contraceptive vaginal ring
      • Percutaneous contraceptive patches

    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 patients understand how to properly use these methods of contraception.

    Nonchildbearing potential is defined as premenarchal or premenopausal females with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy; or hysteroscopic sterilization. Documented verbal history from the patient is acceptable.

    Patients who are abstinent are eligible, but they must use one of the birth control methods listed above if they start engaging in sexual activity that could lead to pregnancy during the study.

    Female patients of childbearing potential must have a negative pregnancy test at screening and Baseline (Day 0).

  5. History of atopic dermatitis and stable disease for at least 1 month according to the patient or caregiver.
  6. Patient or patient's parent(s)/legal representative must be capable of giving written informed consent or verbal assent, as applicable, which includes compliance with the requirements and restrictions listed in the consent/assent form; written informed consent must be obtained prior to any study related procedures.

Exclusion Criteria:

  1. A positive Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody result, or positive human immunodeficiency virus (HIV) antibody at Screening.
  2. Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5x the upper limit of normal (ULN).
  3. Screening total bilirubin > 1.5x ULN; total bilirubin > ULN and ≤ 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%.
  4. 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.
  5. 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.);
      • Excessive sun exposure, tanning booth, other ultraviolet (UV) light source and phototherapy including psoralen and ultraviolet A (PUVA) therapy.
    • From 14 days prior to the first application of the study drug to the completion of the

    Follow-up visit or discontinuation:

    • Herbal medicines for atopic dermatitis (topical and oral preparations), unless specifically approved by the Sponsor;
    • Eucrisa™ (crisaborole) and any other topical phosphodiesterase 4 (PDE4) inhibitor;
    • Tacrolimus and pimecrolimus cream and/or ointment;
    • Topical corticosteroids that were classified as low, medium, or high potency (e.g., fluocinonide, triamcinolone acetonide, desonide, hydrocortisone). Eye drops and nasal preparations are allowed.

      • From 7 days prior to the first application of the study drug to the completion of the Follow- up visit or discontinuation:
    • Oral or intravenous antibiotics, antifungal or antivirus medications
    • Antihistamines/anti-allergics (oral, topical and injections): diphenhydramine, chlorpheniramine maleate, hydroxyzine).

    NOTE: The following antihistamines are allowed:

    • Loratadine, fexofenadine hydrochloride, cetirizine hydrochloride
  6. Pregnant or lactating females.
  7. 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.
  8. The patient has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
  9. Current or a history of cancer within 5 years.
  10. Patients with active infection in atopic dermatitis areas requiring antibiotics, antifungals, or antiviral agents within 7 days of Baseline (Day 0).
  11. Patients with pruritus due to conditions other than atopic dermatitis that, in the opinion of the Investigator, would either interfere with study evaluations or affect the safety of the patient.
  12. Patients with advanced disease or recent abnormal laboratory test values that could affect the safety of the patient or the implementation of this study.
  13. History of and/or concurrent condition of serious hypersensitivity (anaphylactic shock or anaphylactoid reaction) to PDE4 inhibitors.
  14. Prior exposure to RVT-501.
  15. Evidence of significant hepatic, renal, respiratory, endocrine, hematologic, neurologic, psychiatric, or cardiovascular system abnormalities or laboratory abnormalities that will affect the health of the patient or interfere with interpretation of the results.
  16. The patient has excessive sun exposure, is planning a trip to a sunny climate that would involve excessive sun exposure, or used tanning booths within 28 days prior to Baseline (Day 0) or is not willing to minimize natural and artificial sunlight exposure during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03415282


Locations
Layout table for location information
United States, Alabama
Dermavant Investigational Site
Anniston, Alabama, United States, 36207
United States, California
Dermavant Investigational Site
Irvine, California, United States, 92617
United States, Florida
Dermavant Investigational Site
Jacksonville, Florida, United States, 32256
Dermavant Investigational Site
Miami, Florida, United States, 33172
Dermavant Investigational Site
Miami, Florida, United States, 33174
United States, Georgia
Dermavant Investigational Site
Stockbridge, Georgia, United States, 30281
United States, Indiana
Dermavant Investigational Site
Indianapolis, Indiana, United States, 46256
United States, North Carolina
Dermavant Investigational Site
Raleigh, North Carolina, United States, 27612
United States, Texas
Dermavant Investigational Site
Arlington, Texas, United States, 76011
Dermavant Investigational Site
San Antonio, Texas, United States, 78213
Dermavant Investigational Site
San Antonio, Texas, United States, 78229
United States, Virginia
Dermavant Investigational Site
Richmond, Virginia, United States, 23220
Sponsors and Collaborators
Dermavant Sciences GmbH
Investigators
Layout table for investigator information
Study Chair: James Lee, MD, PhD Dermavant Sciences GmbH

Additional Information:
Layout table for additonal information
Responsible Party: Dermavant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03415282     History of Changes
Other Study ID Numbers: RVT-501-2007
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: May 11, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Dermatitis
Dermatitis, Atopic
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases