Zoster Eye Disease Study

Herpes Zoster Ophthalmicus Clinical Trial

— ZEDS  

Official title:

Long-term Suppressive Valacyclovir Treatment for Herpes Zoster Ophthalmicus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03134196
• Other study ID #: 16-00463
• Secondary ID: 1U10EY026869
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: August 23, 2017
• Est. completion date: July 31, 2024

Study information

• Verified date: February 2024
• Source: NYU Langone Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The objective of the Zoster Eye Disease Study (ZEDS) is to determine whether prolonged suppressive oral antiviral treatment with valacyclovir reduces complications of Herpes Zoster Ophthalmicus (HZO), thereby improving clinical outcomes in this common and potentially vision- and life-threatening disease. There are 1,000,000 new cases of Herpes Zoster (HZ) per year in the USA, with 10-20% being HZO.

Specific AIMS

Primary Aim: The primary aim of this double-masked, placebo controlled multicenter randomized clinical trial will test the hypothesis that suppressive antiviral treatment for 12 months with oral valacyclovir 1000 mg daily reduces the rate of new or worsening dendriform epithelial keratitis, stromal keratitis, endothelial keratitis or iritis compared to placebo, at 12 months as the primary endpoint, and at 18 months including 6 months of follow-up after treatment, as a secondary endpoint, in patients with HZO who have had an episode of one of these disease manifestations during the year prior to enrollment.

Secondary AIM: The second aim is to test the hypothesis that suppressive treatment for 12 months with oral valacyclovir 1000 mg daily reduces the severity and duration of postherpetic neuralgia (PHN), compared to placebo, at 12 months and at 18 months as secondary endpoints, in similar patients with HZO. PHN is a debilitating chronic pain syndrome that negatively impacts quality of life, especially in elderly patients.

The study will enroll immunocompetent patients age 18 years and older who have HZO diagnosed at variable times in the past, with these types of active anterior segment ocular segment disease within the past year. Eligible patients will be randomized in a 1:1 ratio to long-term suppressive treatment with oral valacyclovir 1000 mg daily or placebo for 12 months, plus usual ophthalmic care, and followed every 3 months for a total of 18 months, to determine outcomes of new or worsening dendriform epithelial keratitis, stromal keratitis, endothelial keratitis or iritis and/or severity and duration of PHN during 12 months of treatment and for 6 months following treatment discontinuation. The results with regard to PHN may be applicable to HZ in other locations. If suppressive valacyclovir treatment is determined to be effective, the potentially devastating disease burden of HZO and HZ may be reduced for patients, as well as the annual costs to society, estimated in the USA to be one billion dollars.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 652
• Est. completion date: July 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

PARTICIPANT INCLUSION CRITERIA

To be eligible for study participation, an individual must meet all of the following criteria:

1. Ability to understand, and willingness and ability to read and sign, the informed consent form.

2. Ability to understand and follow instructions and study procedures.

3. Willingness to comply with all study procedures and be available for the duration of the study.

4. Ability to take oral medication, and are willing to adhere to study medication regimen.

5. Age 18 years or older.

6. Diagnosed with HZO in one eye based on both of these criteria:

1. History of characteristic unilateral, usually vesicular, HZO rash in the dermatomal distribution of cranial nerve V1 or V2.

2. 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.

7. For females with reproductive potential, willingness to use highly effective contraception (e.g., hormonal contraception, barrier contraception, intrauterine device, or abstinence).

PARTICIPANT EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

1. History of immunocompromised status as defined by current CDC contraindications for the vaccine against zoster (44).

1. 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.

2. 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.

3. 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.

2. Medical history of a systemic disease and thought likely to meet one of the exclusion criteria listed in exclusion criterion #1 during the 18-month study period.

3. Renal insufficiency:

1. Requires dialysis or has history of renal transplant or

2. eGFR less than 45, determined within 3 months days preceding enrollment.

4. Allergy or adverse reaction to valacyclovir or acyclovir.

5. History of vaccination against zoster within one month prior to enrollment. Study participants who meet this exclusion criterion may be may be screened and enrollment delayed until eligible within 3 months. If the study participant receives the Herpes Zoster Subunit vaccine (Recombinant Zoster Vaccine (RZV), Shingrix), rescreening should take place one month after the second required dose of the vaccine.

6. 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.

7. 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.

8. History of another condition that may require treatment with one of these three antivirals listed above in exclusion criterion #7, during the course of the study; study participants who require chronic suppressive antiviral treatment with these medications will be excluded.

9. 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.

10. Incarceration

11. 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.

12. Participation in a clinical study testing a drug, biologic, device or other intervention within the last 30 days from enrollment visit. Study participants who meet this criterion may be rescreened.

Related Conditions & MeSH terms

• Herpes Simplex
• Herpes Zoster
• Herpes Zoster Ophthalmicus

Intervention

Drug:
• Masked Placebo
Oral Placebo
• Masked Oral Valacyclovir
Oral Valacyclovir 1000 mg/day

Locations

Country	Name	City	State
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	Kingston Health Sciences Centre-HDH Site and Queen's University	Kingston	Ontario
Canada	Centre Hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec
Canada	The Research Institute of the McGill University Health Centre/McGill Academic Eye Centre	Montréal	Quebec
Canada	Prism Eye Institute	Oakville	Ontario
Canada	Clinique Axe Visuel	Sherbrooke	Quebec
Canada	University of British Columbia/Vancouver General Hospital Eye Care Centre	Vancouver	British Columbia
United States	Albany Stratton VA Medical Center	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Eye Consultants of Atlanta, PC	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Vantage Eye Care Center, LLC	Bala-Cynwyd	Pennsylvania
United States	The Krieger Eye Institute	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Wilmer Eye Institute John Hopkins	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Finger Lakes Ophthalmology /The Eye Care Center	Canandaigua	New York
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Eye Institute	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Case Western Reserve University	Cleveland	Indiana
United States	Cornea Associates of Texas	Dallas	Texas
United States	University of Texas Southwestern	Dallas	Texas
United States	Geisinger Eye Clinic	Danville	Pennsylvania
United States	Delray Eye Associates, PA	Delray Beach	Florida
United States	Duke University	Durham	North Carolina
United States	Stony Brook Ophthalmology	East Setauket	New York
United States	Cornea Consultants of Texas	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	NorthShore University Health System	Glenview	Illinois
United States	Northwest Eye Clinic	Golden Valley	Minnesota
United States	Verdier Eye Center	Grand Rapids	Michigan
United States	Northwell Health	Great Neck	New York
United States	Alkek Eye Center - Baylor College of Medicine	Houston	Texas
United States	Indiana University - Glick Eye Institute	Indianapolis	Indiana
United States	Florida Eye Specialists	Jacksonville	Florida
United States	Scripps Clinic	La Jolla	California
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Colorado Cornea Consultants P.C.	Littleton	Colorado
United States	Loma Linda University Eye Institute	Loma Linda	California
United States	Jules Stein Eye Clinic - UCLA	Los Angeles	California
United States	University of Wisconsin - Madison	Madison	Wisconsin
United States	University of Tennessee - Hamilton Eye Institute	Memphis	Tennessee
United States	University of Miami - Bascom Palmer Eye Institute	Miami	Florida
United States	Jennifer Burdick	Minnetonka	Minnesota
United States	EyeCare MD of NJ	Morristown	New Jersey
United States	Cornea and Cataract Consultants of Nashville	Nashville	Tennessee
United States	Vanderbilt Eye Institute	Nashville	Tennessee
United States	LSU Health Science Center	New Orleans	Louisiana
United States	New York Eye and Ear Infirmary	New York	New York
United States	NYU Langone Health	New York	New York
United States	Weill Cornell Ophthalmology	New York	New York
United States	Crossroads Eye Physician	Owings Mills	Maryland
United States	Byers Eye Institute at Stanford University	Palo Alto	California
United States	Lahey Medical Center	Peabody	Massachusetts
United States	Corneal Associates at Wills Eye Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Casey Eye Institute - Oregon Health and Science University	Portland	Oregon
United States	Devers Eye Institute	Portland	Oregon
United States	University of Kansas Medical Center	Prairie Village	Kansas
United States	Virginia Eye Institute	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University Opthalmology	Saint Louis	Missouri
United States	University of Utah - Moran Eye Center	Salt Lake City	Utah
United States	R and R Eye Research, LLC	San Antonio	Texas
United States	UCSF- Francis I. Proctor Foundation	San Francisco	California
United States	Pacific Eye Surgeons, Inc.	San Luis Obispo	California
United States	Mayo Clinic - Arizona	Scottsdale	Arizona
United States	NY Eye Surgeons	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Shreveport Eye Clinic	Shreveport	Louisiana
United States	Medstar Georgetown University Hospital	Washington	District of Columbia
United States	Eye Health Services	Weymouth	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
NYU Langone Health	National Eye Institute (NEI), National Institutes of Health (NIH)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first occurrence of Dendriform epithelial keratitis, Stromal keratitis, Endothelial keratitis or Iritis	The primary outcome measure is time to first occurrence of Dendriform epithelial keratitis, Stromal keratitis, Endothelial keratitis,OR Iritis, associated with pre-specified definitions of these disease manifestations and associated treatment requirements, in study participants assigned to valacyclovir compared to placebo, during one year of study treatment.	12 months

External Links

•   Study website