Official Title: “Phase 2/3 Multi-Center, Double-Blind, Controlled Trial Comparing Topical ARYS-01 (Sorivudine) Cream 3%, Oral Valaciclovir, and Combination Topical ARYS-01 Cream /Oral Valaciclovir for Treatment of Herpes Zoster in Immunocompetent Patients 18 Years of Age or Older”

A multi-center, randomized, 4-arm, placebo-controlled, double-blind efficacy study of ARYS-01 (sorivudine) cream 3%.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: June 2009

More than 95% of people are infected with varicella Zoster virus (VZV) at one time of life or another. Primary VZV infection manifests as varicella (chicken pox). The virus then establishes a latent infection of the sensory ganglia from which it may reactivate years later to produce the clinical syndrome of Herpes Zoster (shingles). The initial cutaneous VZV lesions are pruritic, erythematous macules; and the lesions progress through maculopapular stage to vesicular, ulceration and crusting phases. The crusting phase signals the beginning of the healing process, and begins with clouding of the vesicular fluid, within about 24 to 48 h after the appearance of each lesion. This is a Phase 2 study to assess: 1) the overall benefit of ARYS-01 (sorivudine) cream 3% vs. Placebo cream (with immediate or delayed use of Valaciclovir therapy) on Herpes Zoster rash healing rates and postherpetic neuralgia (PHN), 2) the efficacy of ARYS-01 cream 3% vs. Placebo cream, prior to initiation of Valaciclovir, to build evidence for monotherapy treatment benefit of ARYS-01 cream on the initial onset of Herpes Zoster symptoms, 3) the efficacy of ARYS-01 cream 3% vs. Placebo cream, with immediate or delayed initiation of Valaciclovir, for synergetic effects on the initial onset of Herpes Zoster symptoms.

The primary efficacy endpoint is the effect of ARYS-01 cream (with or without Valaciclovir) on the reduction of the crusting stage of VZV rash present at Day 8. Secondary endpoints include time to cessation of new lesion formation, and time to cessation of Zoster-associated pains, pain intensity, rash healing and size reduction, and lesion dissemination.

Intervention(s) in this Clinical Trial

• Drug: ARYS-01 (sorivudine) cream 3% or placebo cream
  • sorivudine cream 3% or placebo cream twice daily for 10 days
• Drug: placebo
  • placebo cream and placebo valaciclovir
• Drug: valaciclovir
  • active valaciclovir

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
  • Placebo cream BID for 10 days and placebo valaciclovir caplets TID from days 1-3 and active valaciclovir caplets 1 gram TID from days 4-10
• Active Comparator: 2
  • Placebo cream BID for 10 days and active valaciclovir caplets TID from days 1-10
• Experimental: 3
  • Active cream BID for 10 days and placebo valaciclovir caplets TID from days 1-3 and active valaciclovir caplets 1 gram TID from days 4-10
• Other: 4
  • Active cream BID for 10 days and active valaciclovir caplets TID from days 1-10

Primary Measures

• The effect of ARYS-01 (sorivudine) cream (with or without Valaciclovir) on the reduction of the crusting stage of VZV rash present at Day 8.
  • Time Frame: Day 8
    Safety Issue?: No

Secondary Measures

• The time to cessation of new lesion formation, and time to cessation of Zoster-associated pains, pain intensity, rash healing and size reduction, and lesion dissemination.
  • Time Frame: Day 4
    Safety Issue?: No

Inclusion Criteria:

• at least 18 years of age
• diagnosed with herpes zoster
• confirmed for VZV with lesion swab at screening and subsequent PCR test.
• contraception for women of child-bearing potential
• be able to communicate with investigator and compliant

Exclusion Criteria:

• cytotoxic or immunosuppressive drugs within 3 mos, 5-FU or its pro-drugs, tricyclic antidepressants, probenecid, topical or systemic antiviral drugs or immunomodulatory agents for viral infection
• herpes zoster ophthalmicus
• female patients who are pregnant and/or nursing or planning a pregnancy
• congenital, acquired or corticosteroid-induced immunodeficiency, including malignancy
• renal insufficiency or creatinine level >2mg/dL
• clinical significant liver enzyme abnormalities and any other laboratory abnormalities determined by the screening lab
• history of intolerance or hypersensitivity to the cream components
• current significant skin disease within affected dermatome
• history of positive result for hepatitis B surface antigen, hepatitis C virus, or HIV
• current participation in another clinical drug research study

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: aRigen Pharmaceuticals, Inc.

Overall Clinical Trial Officials and Contacts

Overall Contact: Karen Cha, MA, MBA 626-568-8645 kcha@catalystpharm.com

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00652184

Study ID Number: ARYS-0701

ClinicalTrials.gov Identifier: NCT00652184

Health Authority: United States: Food and Drug Administration