Graft Vs Host DiseasePhase 4NCT04728646
Evaluation of Dextenza in Patients With Ocular GVHD and Effects on Ocular Surface Disease Outcomes
A Phase 4 study testing DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use and Regular dissolvable intracanalicular plug in people with Graft Vs Host Disease, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
Trial summary
To evaluate the safety and efficacy of Dextenza intracanalicular insert in patients with ocular graft-versus-host disease (GVHD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Vs Host Disease
- What is being tested?
- DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use and Regular dissolvable intracanalicular plug
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2021to 13 Dec 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients diagnosed as chronic ocular GVHD
- Age >= 18 years
- Corneal Fluorescein Staining ≥ 4
- Ocular Surface Disease Index ≥22.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Dextenza in Patients With Ocular Graft Vs Host Disease (GVHD) and Effect on Ocular Surface Disease Outcomes.
To evaluate the safety and efficacy of Dextenza intracanalicular insert in patients with ocular graft-versus-host disease (GVHD).
Read the 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.
- Conditions
- Graft Vs Host Disease
- Being tested
- DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use, Regular dissolvable intracanalicular plug
- Keywords
- graft vs Host disease, GVHD, Dextenza, eye, ocular surface disease
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular useDrug
Inserted During Screening/Baseline: Day Zero in either the right or left eye (depending on randomization)
Regular dissolvable intracanalicular plugDevice
Inserted During Screening/Baseline: Day Zero in either the right or left eye (depending on randomization)
| Study group | Role | What they receive |
|---|---|---|
| DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use | Experimental | All patients will receive Dextenza insert in one eye and a regular dissolvable intracanalicular plug in the fellow-eye (randomized). Receives: Drug: DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use |
| Dissolvable intracanalicular plug | Other | All patients will receive Dextenza insert in one eye and a regular dissolvable intracanalicular plug in the fellow-eye (randomized). Receives: Device: Regular dissolvable intracanalicular plug |
What is being measured
The primary outcome is the main question the study is designed to answer.
Corneal Fluorescein Staining Score
Difference in the reduction of corneal fluorescein staining (CFS) compared to the contralateral eye. The cornea is divided into five zones (central, superior, temporal, nasal, and inferior) and for each zone, the severity of corneal fluorescein staining is graded on a scale from 0 to 3. Therefore, the maximum score is 15 for each eye. A higher score correlates to higher severity.
Measured: 4 weeks
Lissamine green staining score
The difference in the reduction of lissamine green staining compared to the contralateral eye. Six regions are graded for each eye (3 nasal conjunctival regions and 3 temporal conjunctival regions) from 0-3. Thus, a maximum score of 18 is possible for each eye. A higher score correlates to higher severity.
Measured: 4 Weeks
Symptomatic Relief
The difference in symptomatic relief from baseline to 4 weeks, as compared to the contralateral eye using The Symptom Assessment Questionnaire iN Dry Eye Questionnaire (SANDE). SANDE is a visual analog scale questionnaire that quantifies the severity and frequency of dry eye symptoms. Subjects mark on a 100 mm horizontal linear visual analog scale, with a pen or pencil, their frequency, and severity. By measuring, in mm, where each scale was marked, a score can be obtained, from 0 to 100, where a higher score correlates to more frequent and more severe symptoms.
Measured: 4 Weeks
Secondary outcomes (3)
The Symptom Assessment Questionnaire iN Dry Eye Questionnaire
The difference in the improvement of the symptom assessment in dry eye (SANDE) questionnaire score compared to the contralateral eye at 4 and 8 week. SANDE is a visual analog scale questionnaire that quantifies the severity and frequency of dry eye symptoms. Subjects mark on a 100 mm horizontal linear visual analog scale, with a pen or pencil, their frequency, and severity. By measuring, in mm, where each scale was marked, a score can be obtained, from 0 to 100, where a higher score correlates to more frequent and more severe symptoms.
Measured: 8 Weeks
Schirmer's Test
The differences in the improvement of Schirmer's test compared to the contralateral eye. Topical anesthetic is placed in the eye, and Schirmers test strips are placed in the temporal fornix of each eye. Patients are then instructed to close their eyes and after 5 minutes, the Schirmer strips are removed. The amount of wetting of each strip is read off of the strip and recorded. Values range from 0 to 35. Lower scores indicate lower tear production and greater ocular surface disease.
Measured: 8 Weeks
Tear Break Up Time
The differences in the improvement of Tear Break Up Time (TBUT) compared to the contralateral eye. After instillation of fluorescein, the patient is asked to close their eyes, then open the eye and keep it open. The amount of time between opening the eye and visible disruption of the tear film is recorded in seconds. The same procedure is repeated for the fellow eye. Time can range from 0 seconds (instantaneous break up) to >10 seconds. Lower times indicate greater ocular surface disease.
Measured: 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2021
- Study startSep 2021 (estimated)
- Primary completion13 Dec 2021
- Study completion13 Dec 2021
Why it stopped: Due to difficulty enrolling subjects whom had not meet the inclusion criteria
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Vs Host DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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).
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Collaborators
- Ocular Therapeutix, Inc.
- Responsible party
- Principal investigator, Reza Dana, MD, Massachusetts Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04728646
- Sponsor's protocol ID
- 2020P003125
- Status last verified
- Dec 2021
- First submitted
- 21 Jan 2021
- Last updated
- 5 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Dextenza in Patients With Ocular Graft Vs Host Disease (GVHD) and Effect on Ocular Surface Disease Outcomes.
- ClinicalTrials.gov ID
- NCT04728646
- Acronym / sponsor ID
- 2020P003125
- Conditions
- Graft Vs Host Disease
- Keywords
- graft vs Host disease, GVHD, Dextenza, eye, ocular surface disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to difficulty enrolling subjects whom had not meet the inclusion criteria
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Collaborators
- Ocular Therapeutix, Inc.
- Study start
- Sep 2021 (estimated)
- Primary completion
- 13 Dec 2021 (actual)
- Study completion
- 13 Dec 2021 (actual)
- First posted
- 28 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use | Experimental | Drug: DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular useAll patients will receive Dextenza insert in one eye and a regular dissolvable intracanalicular plug in the fellow-eye (randomized). |
| Dissolvable intracanalicular plug | Other | Device: Regular dissolvable intracanalicular plugAll patients will receive Dextenza insert in one eye and a regular dissolvable intracanalicular plug in the fellow-eye (randomized). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- All patients diagnosed as chronic ocular GVHD
- Age >= 18 years
- Corneal Fluorescein Staining ≥ 4
- Ocular Surface Disease Index ≥22.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular useInserted During Screening/Baseline: Day Zero in either the right or left eye (depending on randomization) | Drug | DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use |
| Regular dissolvable intracanalicular plugInserted During Screening/Baseline: Day Zero in either the right or left eye (depending on randomization) | Device | Dissolvable intracanalicular plug |
Primary outcome
Corneal Fluorescein Staining Score
Time frame: 4 weeks
Difference in the reduction of corneal fluorescein staining (CFS) compared to the contralateral eye. The cornea is divided into five zones (central, superior, temporal, nasal, and inferior) and for each zone, the severity of corneal fluorescein staining is graded on a scale from 0 to 3. Therefore, the maximum score is 15 for each eye. A higher score correlates to higher severity.
Lissamine green staining score
Time frame: 4 Weeks
The difference in the reduction of lissamine green staining compared to the contralateral eye. Six regions are graded for each eye (3 nasal conjunctival regions and 3 temporal conjunctival regions) from 0-3. Thus, a maximum score of 18 is possible for each eye. A higher score correlates to higher severity.
Symptomatic Relief
Time frame: 4 Weeks
The difference in symptomatic relief from baseline to 4 weeks, as compared to the contralateral eye using The Symptom Assessment Questionnaire iN Dry Eye Questionnaire (SANDE). SANDE is a visual analog scale questionnaire that quantifies the severity and frequency of dry eye symptoms. Subjects mark on a 100 mm horizontal linear visual analog scale, with a pen or pencil, their frequency, and severity. By measuring, in mm, where each scale was marked, a score can be obtained, from 0 to 100, where a higher score correlates to more frequent and more severe symptoms.
3 secondary outcomes
The Symptom Assessment Questionnaire iN Dry Eye Questionnaire
Time frame: 8 Weeks
Schirmer's Test
Time frame: 8 Weeks
Tear Break Up Time
Time frame: 8 Weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
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Graft vs Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg, for intracanalicular use and Regular dissolvable intracanalicular plug in people with Graft Vs Host Disease, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Corneal Fluorescein Staining Score (time frame: 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022.