Zoster Eye Disease Study

NCT03134196 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 16-004631U10EY026869
• Study Type: interventional
• Target: 527
• Locations: 2 countries
• Sites: 78

Brief Summary

This is a multi-center, randomized, double-masked, placebo-controlled clinical trial of suppressive valacyclovir for one year in immunocompetent study participants with an episode of dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, and/or iritis due to Herpes Zoster Ophthalmicus (HZO) in the year prior to enrollment.

Conditions

Herpes Zoster Ophthalmicus

Keywords

Herpes Zoster Ophthalmicus; Zoster Eye Disease Study; Varicella Zoster Virus; Zoster; Shingles

Outcome Measures

Primary Outcomes (1)

• Number of Participants With the First Occurrence of New or Worsening Stromal Keratitis Without Ulceration (SK), Endothelial Keratitis (EK), Iritis (IR), Dendriform Epithelial Keratitis (DEK), or Stromal Keratitis With Ulceration (SKU)

  The number of participants with the first confirmed endpoint (new or worsening SK, EK, IR, DEK or SKU associated with pre-specified definitions of these disease manifestations and associated treatment requirements within 12 months in study participants assigned to valacyclovir compared to placebo. Diagnostic criteria were defined using the classification for SK, EK, SKU, and DEK caused by Herpes Simplex Virus (HSV) and standardization of uveitis nomenclature (SUN) for IR. A substantial increase in topical steroid treatment, defined as starting, shifting from a lower to higher potency steroid, or doubling frequency of steroid at one visit (new) or gradually within 3 months (worsening) was required for SK, EK, IR, and SKU.

  Month 12

Secondary Outcomes (5)

• Number of Participants With Persistent Treatment Benefit at 18 Months, 6 Months After Cessation of Treatment

  Month 18 (6 months post treatment)

• Number of Postherpetic Neuralgia (PHN) Episodes

  Month 12

• Number of Postherpetic Neuralgia (PHN) Episodes

  Month 18 (6 months post treatment)

• Average Duration of Postherpetic Neuralgia (PHN) Pain

  Month 24 (12 months post-treatment)

• Average Duration of Postherpetic Neuralgia (PHN) Pain

  Month 30 (18 months post treatment)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Encapsulated masked placebo

Drug: Masked Placebo

Masked Oral Valacyclovir 1000 mg daily

ACTIVE COMPARATOR

Valacyclovir, 500 mg, oral pill, two 500mg pills daily

Drug: Masked Oral Valacyclovir

Interventions

Masked Placebo DRUG

Oral Placebo

Placebo

Masked Oral Valacyclovir DRUG

Oral Valacyclovir 1000 mg/day

Also known as: Valtrex

Masked Oral Valacyclovir 1000 mg daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible for study participation, an individual must meet all of the following criteria:
• Ability to understand, and willingness and ability to read and sign, the informed consent form.
• Ability to understand and follow instructions and study procedures.
• Willingness to comply with all study procedures and be available for the duration of the study.
• Ability to take oral medication, and are willing to adhere to study medication regimen.
• Age 18 years or older.
• Diagnosed with HZO in one eye based on both of these criteria:
• History of characteristic unilateral, usually vesicular, HZO rash in the dermatomal distribution of cranial nerve V1 or V2.
• Medical record documentation of an episode of active dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, and/or iritis due to HZO within the preceding year. This episode of active anterior segment ocular disease may be due to HZO of recent onset (within the preceding 6 months); or chronic HZO (with onset six or more months ago); may be new, worsening, or recurrent disease after a period of inactivity; and may occur after medication was reduced.
• i. Study participants with chronic HZO must be on a stable treatment regimen and off antivirals for at least 30 days before enrollment. Study participants with chronic HZO who do not meet this criterion may be rescreened, if they are able to meet this criterion within 3 months after the study visit. This is not a requirement for study participants with recent onset HZO, who may be enrolled at any time, preferably after completing recommended acute antiviral treatment, if prescribed, is completed. They can be on variable dose of steroids, and only need to be off oral and topical antivirals by the enrollment visit.
• For females with reproductive potential, willingness to use highly effective contraception (e.g., hormonal contraception, barrier contraception, intrauterine device, or abstinence).

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• History of immunocompromised status as defined by current CDC contraindications for the vaccine against zoster (44).
• Study participants who are diagnosed with leukemia, lymphomas or other malignant neoplasms affecting bone marrow or lymphatic system, unless leukemia in remission and off chemotherapy for at least 3 months.
• Study participants who are diagnosed with Acquired Immune Deficiency Syndrome (AIDS) or presents with other clinical manifestations of Human Immunodeficiency virus (HIV) including CD4 count of ≤ 200 cells/ml.
• Study participants on immunosuppressive therapy including:
• i. High-dose corticosteroids (greater than equivalent of prednisone 20 mg/day within 1 month) ii. Chemotherapy, other than low dose used for treatment of immune-mediated diseases within 3 months iii. Study participants receiving recombinant human immune mediators and immune modulators, especially antitumor necrosis agents, within 1 month prior to enrollment d. Study participants with unspecified cellular immunodeficiency. e. Study participants with history of hematopoietic stem cell transplantation.
• Renal insufficiency:
• Requires dialysis or has history of renal transplant or
• eGFR less than 45, determined within 3 months days preceding enrollment.
• Allergy or adverse reaction to valacyclovir or acyclovir.
• Keratorefractive surgery, other than limbal relaxing incisions or astigmatic keratotomies at the time of cataract surgery, within 5 years of enrollment, or keratoplasty of the involved eye with zoster.
• On systemic antivirals with activity against herpes within the past 30 days, including acyclovir, valacyclovir, or famciclovir, for any reason except for treatment of recent onset HZO, including investigational drug trial.
• Sexually active women who are pregnant, nursing, or in their reproductive years who do not agree to use contraception during the 1-year treatment period.
• Incarceration
• Any condition or circumstance that in the opinion of the study investigator, would place the study participant in increased risk or affect his/her full compliance or completion of the study.

Sponsors & Collaborators

• NYU Langone Health: lead
• National Eye Institute (NEI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (78)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic - Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Scripps Clinic

La Jolla, California, 92037, United States

Location

Loma Linda University Eye Institute

Loma Linda, California, 92354, United States

Location

Jules Stein Eye Clinic - UCLA

Los Angeles, California, 90095, United States

Location

Byers Eye Institute at Stanford University

Palo Alto, California, 94303, United States

Location

UCSF- Francis I. Proctor Foundation

San Francisco, California, 94131, United States

Location

Pacific Eye Surgeons, Inc.

San Luis Obispo, California, 93401, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Colorado Cornea Consultants P.C.

Littleton, Colorado, 80120, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Delray Eye Associates, PA

Delray Beach, Florida, 33484, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Florida Eye Specialists

Jacksonville, Florida, 33204, United States

Location

University of Miami - Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Eye Consultants of Atlanta, PC

Atlanta, Georgia, 30339, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

NorthShore University Health System

Glenview, Illinois, 60026, United States

Location

Case Western Reserve University

Cleveland, Indiana, 44106, United States

Location

Indiana University - Glick Eye Institute

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Prairie Village, Kansas, 66208, United States

Location

University of Kentucky

Lexington, Kentucky, 40509, United States

Location

LSU Health Science Center

New Orleans, Louisiana, 70112, United States

Location

Shreveport Eye Clinic

Shreveport, Louisiana, 71106, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

The Krieger Eye Institute

Baltimore, Maryland, 21215, United States

Location

Wilmer Eye Institute John Hopkins

Bethesda, Maryland, 20817, United States

Location

Crossroads Eye Physician

Owings Mills, Maryland, 21117, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Lahey Medical Center

Peabody, Massachusetts, 01960, United States

Location

Eye Health Services

Weymouth, Massachusetts, 02189, United States

Location

University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Verdier Eye Center

Grand Rapids, Michigan, 49546, United States

Location

Northwest Eye Clinic

Golden Valley, Minnesota, 55427, United States

Location

Jennifer Burdick

Minnetonka, Minnesota, 55305, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University Opthalmology

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

EyeCare MD of NJ

Morristown, New Jersey, 07960, United States

Location

Albany Stratton VA Medical Center

Albany, New York, 12208, United States

Location

Finger Lakes Ophthalmology /The Eye Care Center

Canandaigua, New York, 14424, United States

Location

Stony Brook Ophthalmology

East Setauket, New York, 11733, United States

Location

Northwell Health

Great Neck, New York, 11021, United States

Location

New York Eye and Ear Infirmary

New York, New York, 10003, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Weill Cornell Ophthalmology

New York, New York, 10021, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Devers Eye Institute

Portland, Oregon, 97210, United States

Location

Casey Eye Institute - Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Vantage Eye Care Center, LLC

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Geisinger Eye Clinic

Danville, Pennsylvania, 17822, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Corneal Associates at Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Tennessee - Hamilton Eye Institute

Memphis, Tennessee, 38163, United States

Location

Cornea and Cataract Consultants of Nashville

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Eye Institute

Nashville, Tennessee, 37232, United States

Location

Cornea Associates of Texas

Dallas, Texas, 75231, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Cornea Consultants of Texas

Fort Worth, Texas, 76107, United States

Location

Alkek Eye Center - Baylor College of Medicine

Houston, Texas, 77030, United States

Location

R and R Eye Research, LLC

San Antonio, Texas, 78229, United States

Location

University of Utah - Moran Eye Center

Salt Lake City, Utah, 84132, United States

Location

Virginia Eye Institute

Richmond, Virginia, 23226, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

NY Eye Surgeons

Seattle, Washington, 98133, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53705, United States

Location

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

University of British Columbia/Vancouver General Hospital Eye Care Centre

Vancouver, British Columbia, V5Z 3N0, Canada

Location

Kingston Health Sciences Centre-HDH Site and Queen's University

Kingston, Ontario, K7L 5G2, Canada

Location

Prism Eye Institute

Oakville, Ontario, L6H 0J8, Canada

Location

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

Location

The Research Institute of the McGill University Health Centre/McGill Academic Eye Centre

Montreal, Quebec, H3A 4S5, Canada

Location

Clinique Axe Visuel

Sherbrooke, Quebec, J1H4C7, Canada

Location

Related Publications (4)

• Warner DB, Jeng BH, Kim J, Liu M, Troxel AB, Hochman JS, Baratz KH, Mian SI, Choulakian MY, Meyer JJ, Lu Y, Twi-Yeboah A, Lee TF, Lopez-Jimenez C, Laury SC, Cohen EJ; ZEDS Trial Research Group. Low-Dose Valacyclovir for Postherpetic Neuralgia in the Zoster Eye Disease Study: A Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):277-285. doi: 10.1001/jamaophthalmol.2024.6113.

  PMID: 40048191 DERIVED

• Cohen EJ, Troxel AB, Liu M, Hochman JS, Baratz KH, Mian SI, Choulakian MY, Warner DB, Lu Y, Twi-Yeboah A, Lee TF, Kim J, Lopez-Jimenez C, Laury SC, Jeng BH; ZEDS Trial Research Group. Low-Dose Valacyclovir in Herpes Zoster Ophthalmicus: The Zoster Eye Disease Randomized Clinical Trial. JAMA Ophthalmol. 2025 Apr 1;143(4):269-276. doi: 10.1001/jamaophthalmol.2024.6114.

  PMID: 40048183 DERIVED

• Prescott CR, Cohen EJ, Hochman JS, Troxel AB, Lu Y, Twi-Yeboah A, Jimenez CL, Mian SI, Mazen CY, Warner DB, Baratz KH, Jeng BH; ZEDS Trial Research Group. Baseline Participant Characteristics at Enrollment in the Zoster Eye Disease Study. Cornea. 2024 Dec 1;43(12):1473-1480. doi: 10.1097/ICO.0000000000003497.

  PMID: 38411973 DERIVED

• Cohen EJ, Hochman JS, Troxel AB, Colby KA, Jeng BH; ZEDS Trial Research Group. Zoster Eye Disease Study: Rationale and Design. Cornea. 2022 May 1;41(5):562-571. doi: 10.1097/ICO.0000000000002743.

  PMID: 35090154 DERIVED

Related Links

• Study website

MeSH Terms

Conditions

Herpes Zoster Ophthalmicus; Chickenpox; Herpes Zoster

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Eye Infections, Viral; Eye Infections; Infections; Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Elisabeth Cohen, MD
• Organization: NYU Langone Health

Elisabeth.Cohen@nyulangone.org

9294552412

Study Officials

• Elisabeth Cohen, MD

  NYU Langone Health

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: April 28, 2017
• Study Start: August 23, 2017
• Primary Completion: December 31, 2023
• Study Completion: July 22, 2024
• Last Updated: March 7, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (71); CA (7)