Graft Vs Host DiseasePhase 1NCT00102583
Cyclosporine Implant for Ocular Graft-Versus-Host Disease
A Phase 1 study testing Subconjunctival Cyclosporine Implant in people with Graft Vs Host Disease, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
Graft-vs.-Host Disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT) commonly affecting the skin, liver, gastrointestinal tract, and eye. The most common clinical manifestations of ocular GVHD generally result from involvement of the lacrimal gland and the conjunctiva. Read more about this study
- Who is it for?
- Ages 9 years and older
- Conditions the study is for
- Graft Vs Host Disease
- What is being tested?
- Subconjunctival Cyclosporine Implant
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Oct 2004to 15 Mar 2011
- Phase
- Phase 1
- 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 9 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- To be eligible for the study each participant must satisfy all of the following inclusion criteria:
- Male or female greater than or equal to 9 years of age.
- Must be greater than or equal to 30 days post-hematopoietic stem cell transplantation (SCT) and have systemic GVHD diagnosed by the transplant physician.
- Must have lacrimal gland dysfunction from GVHD following SCT as defined by Schirmer tear test score (with anesthesia) of greater than or equal to 1 mm but less than or equal to 9 mm in both eyes.
- Must have open puncta and no puncta plug placement at the time of enrollment.
- If using topical corticosteroids, must be equal dose in both eyes of less than or equal to 4 drops per day.
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- Topical lubrication using tear substitutes (includes eye drops, gels, and ointments) are permitted with equal dosing in both eyes.
- Must understand and sign informed consent or assent.
- Must be willing and able to comply with study evaluation and testing schedule.
- Females of childbearing potential and all males must agree to use an effective form of birth control for duration of the study.
- Females of childbearing potential must have a negative serum pregnancy test at baseline evaluation.
Who cannot join
- To be eligible for the study, participants must not satisfy any of the following exclusion criteria.
- Use of a topical ophthalmic cyclosporine formulation less than or equal to 30 days prior to enrollment.
- Diagnosed with active ocular infection.
- History of recurrent herpes keratitis or active disease less than or equal to 6 months prior to enrollment.
- Aqueous tear deficiency or KCS related to previous irradiation, Stevens-Johnson syndrome, cicatricial pemphigoid, alkali burns, trachoma or Sjogren's syndrome.
- Seropositive for Hepatitis C (i.e. positive anti-HCV antibody) or seropositive for HIV with testing performed no earlier than 4 months before the date of stem cell transplantation.
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- Diagnosis of active sarcoidosis.
- Use of a drug with anticholinergic activity within less than 4 times the half-life of the drug prior to enrollment (e.g., carbamazepine [Tegretol (R)] has a half-life of 16-24 hours so must not be used within 4 days of enrollment).
- Use of an investigational drug for eye disease within 30 days of enrollment.
- Known allergy or hypersensitivity to cyclosporine, fluorescein, or lissamine green.
- Uncontrolled systemic disease or serious illness that could, in the investigator's opinion, interfere with the participant's ability to comply with study therapy, required follow-up testing, or interfere with interpretation of the study results.
- Pregnant or lactating female.
- Serum creatinine greater than 2.5 mg/dL, absolute neutrophil count (ANC) less than 750/MicroL Platelet count less than 25,000/MicroL, Partial Thromboplastin Time (PTT), or International Normal Ratio (INR) or Prothrombin Time (PT) exceeding the institutional upper limit of normal would require review by the Hematologist for surgical clearance. Hematologist review of the abnormal coagulation value and approval for surgery must be documented in the medical record prior to the surgical procedure.
- Participants that have received total body irradiation or direct eye/orbital radiation greater than 5000 cGy. (Potential participants will be assessed by a study clinician to determine that the cause of the dry eye symptoms is due to GVHD and not radiation. The clinician, in conjunction with the oncology staff as needed, will also assess the participant's clinical exam and medical history).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Clinical Trial to Study the Safety of a Sustained-Release Subconjunctival Cyclosporine Implant for Ocular Graft-vs-Host Disease (GVHD1)
Graft-vs.-Host Disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT) commonly affecting the skin, liver, gastrointestinal tract, and eye. The most common clinical manifestations of ocular GVHD generally result from
involvement of the lacrimal gland and the conjunctiva. Lacrimal gland involvement can lead to aqueous tear deficiency resulting in severe keratoconjunctivitis sicca (KCS) which can significantly increase the morbidity of patients with chronic GVHD.
Read more
Systemic immunosuppressants such as cyclosporine (CsA) can be effective for treating ocular GVHD including lacrimal gland dysfunction. However, systemic immunosuppression is not generally prescribed for patients whose sole manifestation of GVHD is ocular complications as it may negate the overall graft-vs.-tumor effect and decrease patient survival. Topical CsA and corticosteroids are generally not effective for treating aqueous tear deficiency possible due to epithelial barriers preventing penetration of the drugs to the lacrimal gland. A sustained-release subconjunctival CsA implant was developed to bypass these epithelial barriers and significantly increase the CsA concentrations in the lacrimal gland to treat aqueous tear deficiency related to GVHD.
The objective of this randomized pilot study is to investigate the safety and potential efficacy of a CsA implant in patients with lacrimal gland involvement and aqueous tear deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia). Secondary efficacy evaluation will include changes in corneal and conjunctival staining grades, best-corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI), changes in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction.
Patients with active systemic GVHD with aqueous tear deficiency associated with lacrimal gland dysfunction following allogeneic hematopoietic SCT who are nine years of age or older are eligible for inclusion in this pilot study. The study will involve surgical placement of the CsA implant into the subconjunctival space adjacent to the lacrimal gland of one eye in each participant. Participants older than 12 years of age will be randomized to receive one of two implant release rates. All participants under the age of 12 will receive the smaller, lower dose implant. However, all participants under age 12 will not be randomized and will only be eligible to receive the smaller, lower dose implant.
The implant will remain in place for up to two years and then be removed. IF the participant has clinical success, they will be given the option of allowing the implant to remain in place for an additional year. Clinical success is achieved if the participant meets any of the following measures in either eye assessed at the 1-year visit:
Interval change from baseline characteristics
Decrease in corneal staining by greater than or equal to 2
Decrease in temporal or nasal conjunctival staining grades by greater than or equal to 2
Decrease in total staining grade by greater than or equal to 2
Decrease in OSDI calculated score by greater than or equal to 20%
Increase in Schirmer tear test measurement by greater than or equal to 3 mm
Meets mild-moderate KCS characteristics at 1 year
Corneal staining grade less than or equal to 3
Nasal or temporal conjunctival staining grades less than or equal to 3
OSDI calculated score less than or equal to 15
Schirmer tear test measurement greater than or equal to 5 mm
For participants with implant duration of one year, safety evaluations will be conducted at baseline (pre-implantation) and monthly post-implantation for 13 months. Additional safety assessments will be done at 1 day, and at 1 and 2 weeks post-operatively for implant placement and removal procedures. Safety and efficacy evaluations will be conducted at baseline, at 1, 3, 6, 9, and 12 months post-implantation, and at 3 months following implant removal (15 months post-implantation). For participants with clinical success and who choose the implant to remain for another year, visits will be held as described above then conducted at 2-month intervals starting at month 14. Safety evaluations will be conducted every 2 months until the end of the second year. Additional safety assessments will be done at 1 day, and at 1 and 2 weeks post-operatively for implant removal procedures. Safety and efficacy evaluations will be conducted at 16, 20, and 24 months post-implantation, and at 3 months following implant removal (27 months post-implantation).
Read the detailed description
The objective of this randomized pilot study is to investigate the safety and potential efficacy of a CsA implant in participants with lacrimal gland involvement and aqueous tear deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia). Secondary efficacy evaluation will include changes in corneal and conjunctival staining grades, best-corrected visual acuity (BCVA), the Ocular Surface Diseases Index (OSDI), changes in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction.
Participants with active systemic GVHD with aqueous tear deficiency associated with lacrimal gland dysfunction following allogeneic hematopoietic SCT who are nine years of age or older are eligible for inclusion in this pilot study. The study will involve surgical placement of the CsA implant into the subconjunctival space adjacent to the lacrimal gland of one eye in each participant. Participants older than 12 years of age will be randomized to receive one of two implant release rates. However, all participants under age 12 will not be randomized and will only be eligible to receive the smaller, lower dose implant. On each anniversary study visit a participant will be given the opportunity to retain the implant on an annual basis. This will be based upon the determination of clinical success (defined in the Study Design section below) combined with a participant's report of symptom improvement. The Implant will be removed if the Investigator believes the implant is harmful or if the participant requests the implant to be removed.
- Conditions
- Graft Vs Host Disease
- Being tested
- Subconjunctival Cyclosporine Implant
- Keywords
- Dry Eye, Lacrimal Gland, Tear Deficiency, Keratitis Sicca, GVHD, Ocular GVHD, Ocular Graft Vs Host Disease
- Medical subject headings
- Graft vs Host Disease, Dry Eye Syndromes, Keratitis sicca
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Subconjunctival Cyclosporine ImplantDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2005 (estimated)
- Study start14 Oct 2004
- Primary completion15 Mar 2011
- Study completion15 Mar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00102583
- Sponsor's protocol ID
- 050002
- Other IDs
- 05-EI-0002
- Status last verified
- 15 Mar 2011
- First submitted
- 29 Jan 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Bhushan V, Collins RH Jr. Chronic graft-vs-host disease. JAMA. 2003 Nov 19;290(19):2599-603. doi: 10.1001/jama.290.19.2599. No abstract available.
PubMed 14625337Ogawa Y, Okamoto S, Wakui M, Watanabe R, Yamada M, Yoshino M, Ono M, Yang HY, Mashima Y, Oguchi Y, Ikeda Y, Tsubota K. Dry eye after haematopoietic stem cell transplantation. Br J Ophthalmol. 1999 Oct;83(10):1125-30. doi: 10.1136/bjo.83.10.1125.
PubMed 10502571Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.
PubMed 7780125
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial to Study the Safety of a Sustained-Release Subconjunctival Cyclosporine Implant for Ocular Graft-vs-Host Disease (GVHD1)
- ClinicalTrials.gov ID
- NCT00102583
- Acronym / sponsor ID
- 050002
- Conditions
- Graft Vs Host Disease
- Keywords
- Dry Eye, Lacrimal Gland, Tear Deficiency, Keratitis Sicca, GVHD, Ocular GVHD, Ocular Graft Vs Host Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 14 Oct 2004
- Primary completion
- 15 Mar 2011 (actual)
- Study completion
- 15 Mar 2011 (actual)
- First posted
- 31 Jan 2005 (estimated)
- 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.
Graft-vs.-Host Disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT) commonly affecting the skin, liver, gastrointestinal tract, and eye. The most common clinical manifestations of ocular GVHD generally result from
involvement of the lacrimal gland and the conjunctiva. Lacrimal gland involvement can lead to aqueous tear deficiency resulting in severe keratoconjunctivitis sicca (KCS) which can significantly increase the morbidity of patients with chronic GVHD.
Systemic immunosuppressants such as cyclosporine (CsA) can be effective for treating ocular GVHD including lacrimal gland dysfunction. However, systemic immunosuppression is not generally prescribed for patients whose sole manifestation of GVHD is ocular complications as it may negate the overall graft-vs.-tumor effect and decrease patient survival. Topical CsA and corticosteroids are generally not effective for treating aqueous tear deficiency possible due to epithelial barriers preventing penetration of the drugs to the lacrimal gland. A sustained-release subconjunctival CsA implant was developed to bypass these epithelial barriers and significantly increase the CsA concentrations in the lacrimal gland to treat aqueous tear deficiency related to GVHD.
The objective of this randomized pilot study is to investigate the safety and potential efficacy of a CsA implant in patients with lacrimal gland involvement and aqueous tear deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia). Secondary efficacy evaluation will include changes in corneal and conjunctival staining grades, best-corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI), changes in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction.
Patients with active systemic GVHD with aqueous tear deficiency associated with lacrimal gland dysfunction following allogeneic hematopoietic SCT who are nine years of age or older are eligible for inclusion in this pilot study. The study will involve surgical placement of the CsA implant into the subconjunctival space adjacent to the lacrimal gland of one eye in each participant. Participants older than 12 years of age will be randomized to receive one of two implant release rates. All participants under the age of 12 will receive the smaller, lower dose implant. However, all participants under age 12 will not be randomized and will only be eligible to receive the smaller, lower dose implant.
The implant will remain in place for up to two years and then be removed. IF the participant has clinical success, they will be given the option of allowing the implant to remain in place for an additional year. Clinical success is achieved if the participant meets any of the following measures in either eye assessed at the 1-year visit:
Interval change from baseline characteristics
Decrease in corneal staining by greater than or equal to 2
Decrease in temporal or nasal conjunctival staining grades by greater than or equal to 2
Decrease in total staining grade by greater than or equal to 2
Decrease in OSDI calculated score by greater than or equal to 20%
Increase in Schirmer tear test measurement by greater than or equal to 3 mm
Meets mild-moderate KCS characteristics at 1 year
Corneal staining grade less than or equal to 3
Nasal or temporal conjunctival staining grades less than or equal to 3
OSDI calculated score less than or equal to 15
Schirmer tear test measurement greater than or equal to 5 mm
For participants with implant duration of one year, safety evaluations will be conducted at baseline (pre-implantation) and monthly post-implantation for 13 months. Additional safety assessments will be done at 1 day, and at 1 and 2 weeks post-operatively for implant placement and removal procedures. Safety and efficacy evaluations will be conducted at baseline, at 1, 3, 6, 9, and 12 months post-implantation, and at 3 months following implant removal (15 months post-implantation). For participants with clinical success and who choose the implant to remain for another year, visits will be held as described above then conducted at 2-month intervals starting at month 14. Safety evaluations will be conducted every 2 months until the end of the second year. Additional safety assessments will be done at 1 day, and at 1 and 2 weeks post-operatively for implant removal procedures. Safety and efficacy evaluations will be conducted at 16, 20, and 24 months post-implantation, and at 3 months following implant removal (27 months post-implantation).
Detailed description
The objective of this randomized pilot study is to investigate the safety and potential efficacy of a CsA implant in participants with lacrimal gland involvement and aqueous tear deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia). Secondary efficacy evaluation will include changes in corneal and conjunctival staining grades, best-corrected visual acuity (BCVA), the Ocular Surface Diseases Index (OSDI), changes in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction.
Participants with active systemic GVHD with aqueous tear deficiency associated with lacrimal gland dysfunction following allogeneic hematopoietic SCT who are nine years of age or older are eligible for inclusion in this pilot study. The study will involve surgical placement of the CsA implant into the subconjunctival space adjacent to the lacrimal gland of one eye in each participant. Participants older than 12 years of age will be randomized to receive one of two implant release rates. However, all participants under age 12 will not be randomized and will only be eligible to receive the smaller, lower dose implant. On each anniversary study visit a participant will be given the opportunity to retain the implant on an annual basis. This will be based upon the determination of clinical success (defined in the Study Design section below) combined with a participant's report of symptom improvement. The Implant will be removed if the Investigator believes the implant is harmful or if the participant requests the implant to be removed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Ages
- 9 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- To be eligible for the study each participant must satisfy all of the following inclusion criteria:
- Male or female greater than or equal to 9 years of age.
- Must be greater than or equal to 30 days post-hematopoietic stem cell transplantation (SCT) and have systemic GVHD diagnosed by the transplant physician.
- Must have lacrimal gland dysfunction from GVHD following SCT as defined by Schirmer tear test score (with anesthesia) of greater than or equal to 1 mm but less than or equal to 9 mm in both eyes.
- Must have open puncta and no puncta plug placement at the time of enrollment.
Key exclusion criteria (14 listed)
- To be eligible for the study, participants must not satisfy any of the following exclusion criteria.
- Use of a topical ophthalmic cyclosporine formulation less than or equal to 30 days prior to enrollment.
- Diagnosed with active ocular infection.
- History of recurrent herpes keratitis or active disease less than or equal to 6 months prior to enrollment.
- Aqueous tear deficiency or KCS related to previous irradiation, Stevens-Johnson syndrome, cicatricial pemphigoid, alkali burns, trachoma or Sjogren's syndrome.
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 |
|---|---|---|
| Subconjunctival Cyclosporine Implant | Drug | – |
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 14625337Bhushan V, Collins RH Jr. Chronic graft-vs-host disease. JAMA. 2003 Nov 19;290(19):2599-603. doi: 10.1001/jama.290.19.2599. No abstract available.
- Background: PubMed 10502571Ogawa Y, Okamoto S, Wakui M, Watanabe R, Yamada M, Yoshino M, Ono M, Yang HY, Mashima Y, Oguchi Y, Ikeda Y, Tsubota K. Dry eye after haematopoietic stem cell transplantation. Br J Ophthalmol. 1999 Oct;83(10):1125-30. doi: 10.1136/bjo.83.10.1125.
- Background: PubMed 7780125Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.
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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 1 study testing Subconjunctival Cyclosporine Implant in people with Graft Vs Host Disease, run by National Eye Institute (NEI) 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 11 inclusion and 14 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 2 Jul 2017. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00102583, which also lists 3 linked publications.
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 2 Jul 2017.