Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis: Treatment Outcomes

NCT03586284 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-24396
• Study Type: interventional
• Target: 51
• Locations: 2 countries
• Sites: 4

Brief Summary

Cytomegalovirus (CMV) is generally a latent and asymptomatic infection in healthy, immunocompetent individuals. In immunocompromised patients CMV is well known to cause a retinitis that can lead to blindness. In immunocompetent patients, however, CMV can cause recurrent inflammation in the front of the eye (anterior uveitis). CMV anterior uveitis produces complications including pain, glaucoma, corneal failure, and vision loss. CMV anterior uveitis is commonly misdiagnosed as a non-infectious anterior uveitis and treated as such, which can beget further complications. Diagnosis requires directed polymerase chain reaction (PCR) testing. While antiviral therapy exists for CMV, identifying the appropriate therapy has been challenging because no randomized trials comparing routes of therapy (particularly oral or topical) have been performed. Oral antiviral therapy of CMV carries blood and kidney side effects that requires laboratory monitoring. Topical therapy has been reported to be effective, but no consensus as to the appropriate drug concentration exists. Here we propose a double-masked randomized controlled clinical trial comparing the efficacy of oral valganciclovir, topical ganciclovir 2%, and placebo for the treatment of PCR-proven CMV anterior uveitis. This pilot study will provide valuable information concerning the treatment of CMV anterior uveitis with oral and topical medications, including effective concentrations and side-effect profile. The information obtained from this study will help inform future larger clinical trials in CMV anterior uveitis.

Conditions

Cytomegalovirus Anterior Uveitis

Keywords

Cytomegalovirus uveitis; Cytomegalovirus endotheliitis; Cytomegalovirus keratouveitis; Cytomegalovirus iridocyclitis

Outcome Measures

Primary Outcomes (1)

• Change in CMV Viral Load

  Pre-treatment minus day-7 CMV DNA load in aqueous humor, reported as log10 IU/mL (WHO-standardized qPCR). Positive values indicate reduction.

  7 days

Secondary Outcomes (2)

• Number of Participants That Achieved Clinical Quiescence

  Day 0 to Day 21 (final visit)

• Effect of Topical Corticosteroid

  Day 0 (pre-treatment) viral load (IU/mL)

Study Arms (3)

Oral Valganciclovir

ACTIVE COMPARATOR

Oral Valganciclovir 900mg PO BID Topical placebo solution, 1 drop applied 6 times daily

Drug: Valganciclovir Hydrochloride; Drug: Topical placebo

Topical Ganciclovir 2%

ACTIVE COMPARATOR

Topical Ganciclovir 2% solution, 1 drop applied 6 times daily Placebo pills PO BID

Drug: Ganciclovir Sodium; Drug: Placebo Oral Tablet

Placebo

PLACEBO COMPARATOR

Topical placebo solution, 1 drop applied 6 times daily Placebo pills PO BID

Drug: Placebo Oral Tablet; Drug: Topical placebo

Interventions

Ganciclovir Sodium DRUG

21 to 28 days of topical ganciclovir solution treatment

Topical Ganciclovir 2%

Placebo Oral Tablet DRUG

21 to 28 days of placebo pill treatment

Placebo; Topical Ganciclovir 2%

Topical placebo DRUG

21 to 28 days of topical placebo treatment

Oral Valganciclovir; Placebo

Valganciclovir Hydrochloride DRUG

21 to 28 days of oral valganciclovir treatment

Oral Valganciclovir

Eligibility Criteria

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

You may qualify if:

• Clinical impression consistent with CMV anterior uveitis
• Directed PCR positive for CMV OR previous PCR-proven CMV anterior uveitis
• Willingness to use an acceptable method of contraception during the study period (i.e.
• pharmacologic, devices, barrier methods) or abstinence.

You may not qualify if:

• Patients \<18 years of age
• Intermediate or posterior inflammation (involvement of vitreous, choroid, or retina)
• Received antiviral therapy \<14 days prior to enrollment
• Received periocular or intraocular corticosteroid injection \< 8 weeks prior to enrollment
• Currently taking oral corticosteroids
• Immunocompromised (primary or secondary immunosuppressive disorders)
• Prior immunosuppressive therapy in the past 6 months
• Directed PCR negative for CMV
• Directed PCR positive for herpes simplex virus (HSV) or varicella zoster virus (VZV)
• Planning to conceive during the study period, pregnant or breast-feeding (blood or urine pregnancy test for all females of child-bearing age is mandatory within 4 weeks prior to enrollment)
• Complete blood count with white blood cell, absolute neutrophil, or platelet count lower than the lower limit of reference laboratory normal
• BUN or Cr above the upper limit of reference laboratory normal
• Recent ocular surgery within the past 30 days, or planned surgery within the next 45 days
• Systemic autoimmune disease or ocular condition (besides anterior uveitis) anticipated to dictate or alter treatment course

Sponsors & Collaborators

• University of California, San Francisco: lead
• Huang Pacific Foundation: collaborator
• Khon Kaen University: collaborator
• King Chulalongkorn Memorial Hospital: collaborator

Study Sites (4)

Proctor Foundation, UCSF

San Francisco, California, 94158, United States

Location

Chulalongkorn University

Bangkok, Thailand

Location

Chiang Mai University

Chiang Mai, Thailand

Location

Khon Kaen University

Khon Kaen, Thailand

Location

Related Publications (1)

• Takhar JS, Joye AS, Somkijrungroj T, Laovirojjanakul W, Lin CP, Lietman TM, Porco TC, Keenan JD, Gebreegziabher EA, Seitzman GD, Rose-Nussbaumer J, Doan TA, Acharya NR, Gonzales JA. A double masked randomised 4-week, placebo-controlled study in the USA, Thailand and Taiwan to compare the efficacy of oral valganciclovir and topical 2% ganciclovir in the treatment of cytomegalovirus anterior uveitis: study protocol. BMJ Open. 2019 Dec 19;9(12):e033175. doi: 10.1136/bmjopen-2019-033175.

  PMID: 31862739 DERIVED

MeSH Terms

Interventions

Valganciclovir; Ganciclovir

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Small sample and early stopping limited power. Baseline imbalances (e.g., prostaglandin use, viral load) required multivariable adjustment. The 7-day endpoint assesses early antiviral activity and does not address durability, recurrence, or long-term IOP control. Variable aqueous volume made low-end quantitation imprecise; values below the assay's LLOQ were treated as non-quantifiable and set to the LLOQ for analysis. Inference emphasizes adjusted between-arm contrasts.

Results Point of Contact

• Title: John Gonzales, MD
• Organization: F.I. Proctor Foundation, University of California, San Francisco

john.gonzales@ucsf.edu

415-476-1442

Study Officials

• John A Gonzales, MD

  UCSF Proctor Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, double-masked, randomized, placebo-controlled clinical trial

Study Record Dates

• First Submitted: July 2, 2018
• First Posted: July 13, 2018
• Study Start: March 15, 2020
• Primary Completion: November 13, 2024
• Study Completion: November 13, 2024
• Last Updated: March 5, 2026
• Results First Posted: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

TH (3); US (1)