Graft Versus Host Disease in EyePhase 4NCT05294666
Evaluation of 0.05% CsA and 0.1% FK506 Eye Drops in Ocular GVHD Treatment
A Phase 4 study testing Cyclosporine and tacrolimus in people with Graft Versus Host Disease in Eye, run by Peking University Third Hospital at 1 site in China.
Trial summary
It is planned to explore the efficacy and safety of local 0.05% cyclosporine eye drops in the treatment of chronic graft-versus-host eye disease. Through the comparative study with 0.1% tacrolimus eye drops, to clarify the short-term and long-term efficacy of 0.05% CSA in these patients, and to explore the benefits of… Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Graft Versus Host Disease in Eye
- What is being tested?
- Cyclosporine and tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2020to 1 Jul 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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosed as chronic ocular GVHD
- Did not receive eye local immunosuppressive therapy
- Non pregnant patients
Who cannot join
- Have a history of eye surgery in the past six months
- Suffering from other eye diseases (autoimmune diseases, glaucoma, serious infection, retinopathy, allergy, cataract, eye trauma, etc.)
- Hormones or immunosuppressants were used before enrollment
Trial locations and contacts
1 site in 1 country.
China1 site
Peking University Third Hospital
Beijing, Beijing Municipality, 100000
About this study
Official title: Evaluation of Efficacy, Safety and Tolerability of 0.05% Cyclosporine and 0.1% Tacrolimus Eye Drops in the Treatment of Chronic Ocular Graft-versus-host Disease
It is planned to explore the efficacy and safety of local 0.05% cyclosporine eye drops in the treatment of chronic graft-versus-host eye disease. Through the comparative study with 0.1% tacrolimus eye drops, to clarify the short-term and long-term efficacy of 0.05% CSA in these patients, and to explore the benefits of long-term maintenance of local cyclosporine to patients.
Read the detailed description
Chronic graft-versus-host disease (GVHD) is a common and serious complication after allogeneic hematopoietic stem cell transplantation. Its clinical presentation is similar to that of an autoimmune disease and can affect many organs, including the skin, liver, gastrointestinal tract, lungs and eyes. Ocular GVHD occurs in 30-60% of patients undergoing hematopoietic stem cell transplantation and 60-90% of patients with other systemic GVHD. Chronic ocular GVHD usually occurs 9-24 months after hematopoietic stem cell transplantation and mainly affects the cornea, conjunctiva, lacrimal gland, eyelid and meibomian gland, and leads to inflammation and fibrosis of these tissues. The characteristic manifestations of chronic GVHD include dry keratoconjunctivitis, cicatric conjunctivitis, punctate keratopathy, corneal ulcer and perforation. Severe dry eye is the most common manifestation of ocular GVHD. Patients have burning sensation, foreign body sensation, photophobia, dry eye, itching and other symptoms. This is associated with reduced tear secretion due to damage to the lacrimal gland as well as with goblet cell loss and tear film instability due to meibomian gland dysfunction. Chronic eye GVHD has the potential to cause severe visual impairment and significantly reduce the patient's quality of life. The principle of topical treatment of ocular GVHD is to lubricate the ocular surface, reduce ocular surface inflammation, prevent tear evaporation, and promote epithelial repair. Specific local treatment options include glucocorticoids, immunosuppressants, growth factors and artificial tears. Local glucocorticoids are the first-line treatment at the present stage, but the side effects of hormone therapy are relatively large. Long-term use can lead to damaged epithelial formation, thinning of the cornea, increased intraocular pressure, cataract, infectious keratitis, etc. Therefore, it is necessary to closely monitor the treatment period and minimize the use time. At present, the most commonly used topical immunosuppressants are tacrolimus (FK506) and cyclosporine (CsA). Both belong to calcineurin inhibitors, which can inhibit the activation of calcium-dependent T cells, thus exerting immunosuppressive effect. 0.05% CsA is an eye drop mainly used for the treatment of moderate and severe dry eye, with good therapeutic effect and tolerability [18-23], but slow onset of effect. In the treatment of patients with chronic ocular GVHD, previous studies have shown that cyclosporine eye drops can improve patients' dry eye symptoms, reduce corneal fluorescence staining, and increase tear film rupture time. However, the number of clinical studies on the treatment of chronic ocular GVHD with 0.05% CsA eye drops is limited, with a small number of patients enrolled and relatively short follow-up time. The immunosuppressive effect of tacrolimus is significantly higher than cyclosporine, which is 100 times higher than reported in literature. Therefore, tacrolimus is mainly used for the treatment of rejection after corneal transplantation and immune-related ocular surface diseases. What is the efficacy and tolerability of such a powerful immunosuppressant in treating GVHD? There are few literature reports, but long-term ocular application can reduce local immunity and increase the risk of local infection. At the same time, tacrolimus is very irritating, and some patients cannot tolerate it and choose to stop using the drug. At present, there is still a lack of clinical evidence to compare the efficacy of cyclosporine and tacrolimus eye drops in patients with chronic ocular GVHD. Therefore, by comparing the effectiveness, safety and tolerance of 0.05% CsA eye drops and 0.1% tacrolimus eye drops in the treatment of chronic eye graft-versus host eye disease, this study aims to explore a reasonable treatment plan for chronic eye GVHD and provide theoretical basis for clinical application.
- Conditions
- Graft Versus Host Disease in Eye
- Being tested
- Cyclosporine, tacrolimus
- Keywords
- ocular graft-versus-host disease, dry eye, cyclosporine, tacrolimus, prospective study
- Medical subject headings
- Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclosporineDrug
Also called CsA
The chronic ocular GVHD patients in cyclosporine group received local 0.05% cyclosporine 4 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months
tacrolimusDrug
Also called FK506
The chronic ocular GVHD patients in tacrolimus group received local 0.05% tacrolimus 2 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months
| Study group | Role | What they receive |
|---|---|---|
| cyclosporine group | Experimental | The chronic ocular GVHD patients in cyclosporine group received local 0.05% cyclosporine 4 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months Receives: Drug: Cyclosporine |
| tacrolimus group | Experimental | The chronic ocular GVHD patients in tacrolimus group received local 0.05% tacrolimus 2 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months Receives: Drug: tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
visual acuity
visual acuity
Measured: Within 4 hours of initial enrollment
visual acuity
visual acuity
Measured: At the first month of enrollment
visual acuity
visual acuity
Measured: At the third month of enrollment
visual acuity
visual acuity
Measured: At the sixth month of enrollment
Intraocular pressure
Intraocular pressure
Measured: Within 4 hours of initial enrollment
Intraocular pressure
Intraocular pressure
Measured: At the first month of enrollment
Intraocular pressure
Intraocular pressure
Measured: At the third month of enrollment
Intraocular pressure
Intraocular pressure
Measured: At the sixth month of enrollment
Ocular Surface Disease Index
Ocular Surface Disease Index
Measured: Within 4 hours of initial enrollment
Ocular Surface Disease Index
Ocular Surface Disease Index
Measured: At the first month of enrollment
Ocular Surface Disease Index
Ocular Surface Disease Index
Measured: At the third month of enrollment
Ocular Surface Disease Index
Ocular Surface Disease Index
Measured: At the sixth month of enrollment
Corneal fluorescein staining
Corneal fluorescein staining
Measured: Within 4 hours of initial enrollment
Corneal fluorescein staining
Corneal fluorescein staining
Measured: At the first month of enrollment
Corneal fluorescein staining
Corneal fluorescein staining
Measured: At the third month of enrollment
Corneal fluorescein staining
Corneal fluorescein staining
Measured: At the sixth month of enrollment
Tear break-up time
Tear break-up time
Measured: Within 4 hours of initial enrollment
Tear break-up time
Tear break-up time
Measured: At the first month of enrollment
Tear break-up time
Tear break-up time
Measured: At the third month of enrollment
Tear break-up time
Tear break-up time
Measured: At the sixth month of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2022
- Study start1 Apr 2020
- Primary completion1 Jun 2021
- Study completion1 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host Disease in EyeStudies of the same condition, open and under way.
- More trials run by Peking University Third HospitalThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking University Third Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05294666
- Sponsor's protocol ID
- 99304
- Status last verified
- Jan 2022
- First submitted
- 7 Feb 2022
- Last updated
- 24 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Efficacy, Safety and Tolerability of 0.05% Cyclosporine and 0.1% Tacrolimus Eye Drops in the Treatment of Chronic Ocular Graft-versus-host Disease
- ClinicalTrials.gov ID
- NCT05294666
- Acronym / sponsor ID
- 99304
- Conditions
- Graft Versus Host Disease in Eye
- Keywords
- ocular graft-versus-host disease, dry eye, cyclosporine, tacrolimus, prospective study
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Peking University Third HospitalUniversity, hospital or other
- Study start
- 1 Apr 2020 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 24 Mar 2022 (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.
It is planned to explore the efficacy and safety of local 0.05% cyclosporine eye drops in the treatment of chronic graft-versus-host eye disease. Through the comparative study with 0.1% tacrolimus eye drops, to clarify the short-term and long-term efficacy of 0.05% CSA in these patients, and to explore the benefits of long-term maintenance of local cyclosporine to patients.
Detailed description
Chronic graft-versus-host disease (GVHD) is a common and serious complication after allogeneic hematopoietic stem cell transplantation. Its clinical presentation is similar to that of an autoimmune disease and can affect many organs, including the skin, liver, gastrointestinal tract, lungs and eyes. Ocular GVHD occurs in 30-60% of patients undergoing hematopoietic stem cell transplantation and 60-90% of patients with other systemic GVHD. Chronic ocular GVHD usually occurs 9-24 months after hematopoietic stem cell transplantation and mainly affects the cornea, conjunctiva, lacrimal gland, eyelid and meibomian gland, and leads to inflammation and fibrosis of these tissues. The characteristic manifestations of chronic GVHD include dry keratoconjunctivitis, cicatric conjunctivitis, punctate keratopathy, corneal ulcer and perforation. Severe dry eye is the most common manifestation of ocular GVHD. Patients have burning sensation, foreign body sensation, photophobia, dry eye, itching and other symptoms. This is associated with reduced tear secretion due to damage to the lacrimal gland as well as with goblet cell loss and tear film instability due to meibomian gland dysfunction. Chronic eye GVHD has the potential to cause severe visual impairment and significantly reduce the patient's quality of life. The principle of topical treatment of ocular GVHD is to lubricate the ocular surface, reduce ocular surface inflammation, prevent tear evaporation, and promote epithelial repair. Specific local treatment options include glucocorticoids, immunosuppressants, growth factors and artificial tears. Local glucocorticoids are the first-line treatment at the present stage, but the side effects of hormone therapy are relatively large. Long-term use can lead to damaged epithelial formation, thinning of the cornea, increased intraocular pressure, cataract, infectious keratitis, etc. Therefore, it is necessary to closely monitor the treatment period and minimize the use time. At present, the most commonly used topical immunosuppressants are tacrolimus (FK506) and cyclosporine (CsA). Both belong to calcineurin inhibitors, which can inhibit the activation of calcium-dependent T cells, thus exerting immunosuppressive effect. 0.05% CsA is an eye drop mainly used for the treatment of moderate and severe dry eye, with good therapeutic effect and tolerability [18-23], but slow onset of effect. In the treatment of patients with chronic ocular GVHD, previous studies have shown that cyclosporine eye drops can improve patients' dry eye symptoms, reduce corneal fluorescence staining, and increase tear film rupture time. However, the number of clinical studies on the treatment of chronic ocular GVHD with 0.05% CsA eye drops is limited, with a small number of patients enrolled and relatively short follow-up time. The immunosuppressive effect of tacrolimus is significantly higher than cyclosporine, which is 100 times higher than reported in literature. Therefore, tacrolimus is mainly used for the treatment of rejection after corneal transplantation and immune-related ocular surface diseases. What is the efficacy and tolerability of such a powerful immunosuppressant in treating GVHD? There are few literature reports, but long-term ocular application can reduce local immunity and increase the risk of local infection. At the same time, tacrolimus is very irritating, and some patients cannot tolerate it and choose to stop using the drug. At present, there is still a lack of clinical evidence to compare the efficacy of cyclosporine and tacrolimus eye drops in patients with chronic ocular GVHD. Therefore, by comparing the effectiveness, safety and tolerance of 0.05% CsA eye drops and 0.1% tacrolimus eye drops in the treatment of chronic eye graft-versus host eye disease, this study aims to explore a reasonable treatment plan for chronic eye GVHD and provide theoretical basis for clinical application.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cyclosporine group | Experimental | Drug: CyclosporineThe chronic ocular GVHD patients in cyclosporine group received local 0.05% cyclosporine 4 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months |
| tacrolimus group | Experimental | Drug: tacrolimusThe chronic ocular GVHD patients in tacrolimus group received local 0.05% tacrolimus 2 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosed as chronic ocular GVHD
- Did not receive eye local immunosuppressive therapy
- Non pregnant patients
Key exclusion criteria (3 listed)
- Have a history of eye surgery in the past six months
- Suffering from other eye diseases (autoimmune diseases, glaucoma, serious infection, retinopathy, allergy, cataract, eye trauma, etc.)
- Hormones or immunosuppressants were used before enrollment
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 |
|---|---|---|
| CyclosporineAlso: CsAThe chronic ocular GVHD patients in cyclosporine group received local 0.05% cyclosporine 4 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months | Drug | cyclosporine group |
| tacrolimusAlso: FK506The chronic ocular GVHD patients in tacrolimus group received local 0.05% tacrolimus 2 times/day for 3 months, and then changed to 0.05% cyclosporine for 2 times/day for 3 months | Drug | tacrolimus group |
Primary outcome
visual acuity
Time frame: Within 4 hours of initial enrollment
visual acuity
visual acuity
Time frame: At the first month of enrollment
visual acuity
visual acuity
Time frame: At the third month of enrollment
visual acuity
visual acuity
Time frame: At the sixth month of enrollment
visual acuity
Intraocular pressure
Time frame: Within 4 hours of initial enrollment
Intraocular pressure
Intraocular pressure
Time frame: At the first month of enrollment
Intraocular pressure
Intraocular pressure
Time frame: At the third month of enrollment
Intraocular pressure
Intraocular pressure
Time frame: At the sixth month of enrollment
Intraocular pressure
Ocular Surface Disease Index
Time frame: Within 4 hours of initial enrollment
Ocular Surface Disease Index
Ocular Surface Disease Index
Time frame: At the first month of enrollment
Ocular Surface Disease Index
Ocular Surface Disease Index
Time frame: At the third month of enrollment
Ocular Surface Disease Index
Ocular Surface Disease Index
Time frame: At the sixth month of enrollment
Ocular Surface Disease Index
Corneal fluorescein staining
Time frame: Within 4 hours of initial enrollment
Corneal fluorescein staining
Corneal fluorescein staining
Time frame: At the first month of enrollment
Corneal fluorescein staining
Corneal fluorescein staining
Time frame: At the third month of enrollment
Corneal fluorescein staining
Corneal fluorescein staining
Time frame: At the sixth month of enrollment
Corneal fluorescein staining
Tear break-up time
Time frame: Within 4 hours of initial enrollment
Tear break-up time
Tear break-up time
Time frame: At the first month of enrollment
Tear break-up time
Tear break-up time
Time frame: At the third month of enrollment
Tear break-up time
Tear break-up time
Time frame: At the sixth month of enrollment
Tear break-up time
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2022.
- Individual participant dataSharing planned: No
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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 Cyclosporine and tacrolimus in people with Graft Versus Host Disease in Eye, run by Peking University Third Hospital at 1 site in China.
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 3 inclusion and 3 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: finished, as of the sponsor's last update on 24 Mar 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 China. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
visual acuity (time frame: Within 4 hours of initial enrollment). The study lists 20 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 24 Mar 2022.