Study to Compare Efficacy of Topical ARYS-01 (Sorivudine) Cream 3%, Oral Valaciclovir and Combination ARYS-01 Cream 3%/Oral Valaciclovir for Treatment of Herpes Zoster (Shingles)

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

Detailed Description
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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.

Official Title
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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

Conditions
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Herpes Zoster, Postherpetic Neuralgia

Intervention / Treatment
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* Drug: ARYS-01 (sorivudine) cream 3% or placebo cream
* Drug: placebo
* Drug: valaciclovir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>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 | Drug: placebo<br>* placebo cream and placebo valaciclovir<br>Drug: valaciclovir<br>* active valaciclovir<br>|
| Active Comparator: 2<br>Placebo cream BID for 10 days and active valaciclovir caplets TID from days 1-10 | Drug: ARYS-01 (sorivudine) cream 3% or placebo cream<br>* sorivudine cream 3% or placebo cream twice daily for 10 days<br>* Other names: topical sorivudine 3%;Drug: placebo<br>* placebo cream and placebo valaciclovir<br>Drug: valaciclovir<br>* active valaciclovir<br>|
| Experimental: 3<br>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 | Drug: ARYS-01 (sorivudine) cream 3% or placebo cream<br>* sorivudine cream 3% or placebo cream twice daily for 10 days<br>* Other names: topical sorivudine 3%;Drug: placebo<br>* placebo cream and placebo valaciclovir<br>Drug: valaciclovir<br>* active valaciclovir<br>|
| Other: 4<br>Active cream BID for 10 days and active valaciclovir caplets TID from days 1-10 | Drug: ARYS-01 (sorivudine) cream 3% or placebo cream<br>* sorivudine cream 3% or placebo cream twice daily for 10 days<br>* Other names: topical sorivudine 3%;Drug: valaciclovir<br>* active valaciclovir<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | Day 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antiviral, herpes zoster, postherpetic neuralgia, varicella zoster virus, shingles