Clinical trial NCT04728646: Evaluation of Dextenza in Patients With Ocular GVHD and Effects on Ocular Surface Disease Outcomes
Official title: Evaluation of Dextenza in Patients With Ocular Graft Vs Host Disease (GVHD) and Effect on Ocular Surface Disease Outcomes.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Graft Vs Host Disease
Keywords: graft vs Host disease
GVHD
Dextenza
eye
ocular surface disease
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: Ocular Therapeutix, Inc.
First posted: 2021-01-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Eyes of enrolled patients will be randomized to treatment arms in a 1:1 ratio (Dextenza insert:control insert). All study participants will receive the Dextenza insert in the lower puncta of one eye (treatment eye) and a standard dissolvable intracanalicular plug in the lower puncta of the fellow eye (control eye).
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of Dextenza intracanalicular insert in patients with ocular graft-versus-host disease (GVHD).

Detailed description: Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative, established treatment modality for a variety of malignant and nonmalignant hematologic disorders. Despite an increase in patient survival with HSCT, Graft-Versus-Host Disease (GVHD), in which donor immune cells detect recipient cells as foreign and attack the host tissue, is associated with significant morbidity and mortality after allo-HSCT. Ocular surface involvement is one of the most common manifestations of chronic GVHD with up to 60-90% of patients affected. Dry eye (DE) is the typical finding in ocular GVHD, and severe, chronic inflammation plays a crucial role in the pathogenesis. Therefore, topical steroids have been commonly used in patients with ocular GVHD (oGVHD). Although a healing effect of topical steroids has been shown in oGVHD, the efficacy of treatment might be reduced if it is not applied appropriately; poor patient compliance and improper drop administration (such as missing the eye and instilling an insufficient amount of medication) might diminish medication efficacy. Additionally, even if drops are applied appropriately, only approximately 5% of the administered dose can reach the target tissue because of blinking, nasolacrimal drainage, and low corneal permeability. Furthermore, the intermittent administration of topical drops results in a variable drug concentration in the target tissue and produces a suboptimal pharmacologic effect. Additionally, the prolonged use of topical steroids can also be toxic to the ocular surface due to preservatives such as benzalkonium chloride, which is used for its anti-microbial properties to prevent the contamination of drops. This toxicity might further disrupt the corneal epithelial barrier, which is already disrupted because of existing ocular surface inflammation.

To address all of these obstacles associated with topical steroids in patients with oGVHD, a sustained-released preservative-free intracanalicular insert (Dextenza, Ocular Therapeutix) may be beneficial. The purpose of this clinical trial is evaluate the safety and efficacy of Dextenza intracanalicular inserts in patients with ocular GVHD.

Eligibility criteria: Inclusion Criteria:

* All patients diagnosed as chronic ocular GVHD
* Age \>= 18 years
* Corneal Fluorescein Staining ≥ 4
* Ocular Surface Disease Index ≥22.

Exclusion Criteria:

* History of immune diseases other than GVHD, herpetic keratitis or ocular malignancy
* Treatment regimen changes with topical cyclosporine, autologous serum, anakinra, or oral tetracycline compounds within 30 days prior to enrollment;
* Treatment regimen changes with systemic immunosuppressants or topical anti-glaucoma medications within 15 days prior to enrollment
* Current use of topical steroids more than twice a day
* Current or history of steroid induced ocular hypertension or glaucoma
* Family history of steroid induced ocular hypertension or glaucoma
* History of any intra-ocular surgery in the past 3 months or contact lens use within 2 weeks prior to enrollment
* History of collagen (prolong) intra-canalicular plug within 6 months
* Inability to cooperate for a comprehensive ocular examination
* History of lid deformity or neuroparalytic lid disease
* Active ocular infection including herpetic disease

Primary outcomes:
measure: Corneal Fluorescein Staining Score
timeFrame: 4 weeks
measure: Lissamine green staining score
timeFrame: 4 Weeks
measure: Symptomatic Relief
timeFrame: 4 Weeks
Secondary outcomes:
measure: The Symptom Assessment Questionnaire iN Dry Eye Questionnaire
timeFrame: 8 Weeks
measure: Schirmer's Test
timeFrame: 8 Weeks
measure: Tear Break Up Time
timeFrame: 8 Weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Mass Eye and Ear
state: Massachusetts
Study officials:
References: