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

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

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

The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of the 0.2% BID and 0.5% concentrations of RVT-501 in patients with atopic dermatitis.

Inclusion Criteria:

A subject will be eligible for inclusion in this study only if all of the following criteria apply:

1. 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.

2. 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.

3. Minimum EASI score of 7 at baseline.

4. 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.

   Non-child-bearing potential is defined as pre-menopausal females with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy; hysteroscopic sterilization; or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40mlU is confirmatory. Documented verbal history from the subject is acceptable.

5. Atopic Dermatitis present for at least 12 months according to the patient/care giver and stable disease for at least 1 month according to the patient/care giver.

6. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

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A subject will not be eligible for inclusion in this study if any of the following criteria apply:

1. A positive Hepatitis B surface antigen or positive Hepatitis C antibody result at screening.

2. A positive test for human immunodeficiency virus (HIV) antibody at screening.

3. Screening alanine aminotransferase (ALT) ≥ 3x the upper limit of normal (ULN).

4. 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%.

5. Corrected QT (QTc) interval >475 msec or >525 msec in the presence of bundle branch block.

6. 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.

7. 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

   From 7 days prior to the first application of the study drugs to the completion of the Treatment Phase or discontinuation:

   • Topical corticosteroids that were classified as low, medium, or high potency (fluocinonide, triamcinolone acetonide, desonide, hydrocortisone). Eye drop and nasal preparation are allowed.
   • Tacrolimus and pimecrolimus cream and/or ointment
   • Antihistamines/anti-allergics (oral, topical and injections): diphenhydramine, chlorpheniramine maleate, hydroxyzine).

   NOTE: The following antihistamines are allowed:

   • Loratadine, fexofenadine hydrochloride, cetirizine hydrochloride

   From baseline throughout the treatment period

8. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.

9. Pregnant females as determined by positive serum (screening) or urine (baseline) human chorionic gonadotropin test at screening or prior to dosing.

10. Lactating females.

11. 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.

12. The subject 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).

13. Current or a history of cancer within 5 years with the exception of fully excised skin basal cell carcinoma, squamous cell carcinoma or carcinoma in situ of the cervix.

14. Subjects with active infection that required oral or intravenous administration of antibiotics, antifungal or antiviral agents within 7 days of Baseline/Day 0.

15. Concurrent skin lesions in the treatment area or 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 subject.

16. Subjects with advanced disease or abnormal laboratory test values that could affect the safety of the subject or the implementation of this study.

17. Evidence of significant hepatic, renal, respiratory, endocrine, hematologic, neurologic, psychiatric, or cardiovascular system abnormalities or laboratory abnormality that will affect the health of the subject or interfere with interpretation of the results.

18. The subject has excessive sun exposure, is planning a trip to a sunny climate which 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.