Anterior UveitisPhase 1NCT00876434
Subconjunctival Sirolimus for the Treatment of Autoimmune Active Anterior Uveiti
A Phase 1 study testing Sirolimus in people with Anterior Uveitis, run by National Eye Institute (NEI) at 1 site in United States.
Trial summary
Background: Uveitis is an inflammatory condition in which the patient's own immune system attacks the eye, causing eye inflammation and vision loss. Patients with uveitis may be treated with immunosuppressive medications to reduce the inflammation and prevent vision loss. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anterior Uveitis
- What is being tested?
- Sirolimus
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2009to 10 Feb 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant has the ability to understand and sign the informed consent document.
- Participant is 18 years of age or older.
- Participant's uveitis is considered active on current regimen.
- Participant has a diagnosis of non-infectious anterior uveitis requiring treatment to control their intraocular inflammatory disease with systemic and/or topical anti-inflammatory medications at high frequency intervals (greater than or equal to T.I.D.) or local steroid treatment (periocular steroid injections) is contraindicated because of significant IOP elevation with local steroid treatments in the past (steroid responder).
- Participant has anterior uveitis with at least a grade of 1+ for anterior chamber cells 1 in the study eye.
- Participant has visual acuity in the study eye of 20/400 or better (or ETDRS equivalent).
Show all 15Show fewer
- Participant has normal renal or liver function, or no worse than mild abnormalities as defined by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE).
- Participant has no history of intraocular surgery within three months prior to study enrollment and agrees not to undergo elective ocular surgery (e.g., cataract extraction) for the duration of the study.
- Participant has an absolute neutrophil count (ANC) above 750/mm(3)
- Participant is able to undergo full ophthalmic examination for assessment of anterior chamber cells.
- Participant understands there is an increased risk for skin cancer with sirolimus usage and agrees to practice skin protective measures for two weeks following their injection. Skin protective measures include: 1) staying out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible; 2) wearing protective clothing, including a hat and sunglasses; 3) applying a sun block product that has a skin protection factor (SPF) of at least 15 (some participants may require a product with a higher SPF number, especially if they have a fair complexion); 4) applying a sun block lipstick that has a SPF of at least 15 to protect the lips; and 5) not using a sun lamp or tanning booth or bed.
- Participant is willing and able to comply with the study procedures.
- Female participants of childbearing potential must not be pregnant or breast-feeding, must have a negative urine pregnancy test at screening and must be willing to undergo urine pregnancy tests throughout the study.
- Both female participants of childbearing potential and male participants able to father a child must agree to practice two forms of adequate birth control throughout the course of the study and for three months post-injection. Acceptable methods of birth control include hormonal contraception (birth control pills, injected hormones or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom and spermicide) or surgical sterilization (hysterectomy, tubal ligation or vasectomy).
- Participants with a hysterectomy or vasectomy (or have a partner with a hysterectomy or vasectomy) are exempt from using two methods of contraception. However, female participants with a tubal ligation (or male participants who have a female partner with a tubal ligation) are not exempt, and are required to practice another acceptable method of birth control.
Who cannot join
- Participant has a significant active infection (an infection requiring treatment as determined by the medical team) or a history of chronic or recurrent infections.
- Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years.
- Participant has used latanoprost (Xalatan (Registered Trademark)) within two weeks prior to study enrollment or is likely to need it at any point during the study as determined by the investigator.
- For participants with active anterior uveitis in both eyes, the participant's non-study eye is anticipated to require periocular steroids or it is anticipated that an increase in systemic immunosuppressive treatments including steroids may be required during the course of the study.
- Participant has a media opacity that precludes assessment of anterior chamber inflammation.
- Participant has active joint or systemic inflammation requiring immediate addition or increase in systemic anti-inflammatory medications.
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: Subconjunctival Sirolimus for the Treatment of Autoimmune Active Anterior Uveitis
Background:
- Uveitis is an inflammatory condition in which the patient's own immune system attacks the eye, causing eye inflammation and vision loss. Patients with uveitis may be treated with immunosuppressive medications to reduce the inflammation and prevent vision loss.
- Sirolimus is an immunosuppressive medication that is approved by the U.S. Food and Drug Administration (FDA) to prevent organ rejection following a kidney transplant. Researchers think that sirolimus may affect the part of the immune system that may be an important cause of uveitis, and may decrease the inflammation that causes uveitis.
- In this study, sirolimus will be given as an injection under the outer layer of your eye. The FDA has permitted the investigational use of sirolimus for this study.
Read more
Objectives:
- To determine if subconjunctival injection of sirolimus is safe for treatment of uveitis.
- To see if sirolimus is an effective treatment for uveitis.
Eligibility:
- Patients 18 years of age and older with active uveitis in one or both eyes. If a patient has uveitis in both eyes, the one in which the inflammation is worse will be treated during the study. The vision in the study eye must be at least 20/400.
- Patients must have good liver function, and must be willing to practice sun protection measures for 2 weeks following the treatment.
Design:
- Treatment with sirolimus in the study eye:
- Antibiotic and numbing eye drops will be given before the sirolimus injection.
- 1 dose of sirolimus will be injected directly into the subconjunctiva (white part of the eye).
- Antibiotic drops will be given for topical application 3 times per day for 2 days after the injection.
- Patients will be followed for 16 weeks after sirolimus injection (initial visit and follow-up visits in Weeks 2, 4, 8, 12, and 16).
- Evaluations during the treatment period and follow-up visits:
- Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
- Full medical and ophthalmic history, involving questionnaires and discussion with researchers.
- Eye examination, dilation, and photography, including measurements of retinal thickness and fluorescent dye tests of blood flow in the eye.
- Blood and urine tests.
- Because of the increased risk of skin cancer associated with sirolimus, patients ...
Read the detailed description
Objective: Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects and many patients continue to experience disease flare-ups. Sirolimus suppresses cytokine-driven T-cell proliferation and thus, inhibits the production, signaling and activity of many growth factors relevant to uveitis. Subconjunctival sirolimus administration could reduce or eliminate the need for topical and/or systemic immunosuppressive drugs that could result in reduced morbidity. This protocol will investigate subconjunctival sirolimus as a possible treatment for active anterior uveitis.
Study Population: Five participants with active anterior uveitis will be initially accrued in this study. Participants must require treatment for their uveitis with systemic and/or topical anti-inflammatory medications at high frequency intervals [greater than or equal to three times daily (T.I.D.)] or local steroid treatment (periocular steroid injections) is contraindicated because of significant intraocular pressure (IOP) elevation with local steroid treatments in the past (i.e., steroid responder), have at least a grade of 1+ for anterior chamber cells and have visual acuity of at least 20/400 in the study eye. Up to seven participants may be enrolled, as up to two participants may be accrued to replace enrolled participants who withdraw from the study prior to receiving any study medication.
Design: This is a Phase I, non-randomized, prospective, uncontrolled single-center study to evaluate subconjunctival sirolimus as a treatment for active anterior uveitis. All participants will receive a single 30-microL (1,320 microg) subconjunctival sirolimus injection in the study eye at baseline and will be followed for 16 weeks post-injection.
Outcome Measures: The primary outcome is the number of participants who experience at least a 2-step reduction in anterior chamber inflammation within four weeks post-injection. Secondary outcomes include changes in visual acuity and anterior chamber inflammation grading, the number of participants who experience a disease flare within the 16-week study duration and, of the participants who experience a disease flare, the number of days to disease flare from baseline. Secondary outcomes also include the presence or extent of cystoid macular edema.
- Conditions
- Anterior Uveitis
- Being tested
- Sirolimus
- Keywords
- Sirolimus, Anterior Uveitis, Autoimmune Disease, Uveitis
- Medical subject headings
- Uveitis, Anterior, Autoimmune Diseases, Uveitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is the number of participants who experience at least a 2-step reduction in inflammation within four weeks post-injection.
Secondary outcomes (1)
Changes in VA; changes in AC cells & flare-ups; number of disease flares, number of days until the first disease flare; the presence or extent of CME; the amount of retino-vascular leakage; and changes in retinal thickening.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2009 (estimated)
- Study start1 Apr 2009
- Primary completion10 Feb 2011
- Study completion10 Feb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Anterior UveitisStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 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
- NCT00876434
- Sponsor's protocol ID
- 090116
- Other IDs
- 09-EI-0116
- Status last verified
- 10 Feb 2011
- First submitted
- 3 Apr 2009
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. doi: 10.1016/j.ajo.2005.03.057.
PubMed 16196117Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004 Mar;111(3):491-500; discussion 500. doi: 10.1016/j.ophtha.2003.06.014.
PubMed 15019324Wakefield D, Dunlop I, McCluskey PJ, Penny R. Uveitis: aetiology and disease associations in an Australian population. Aust N Z J Ophthalmol. 1986 Aug;14(3):181-7. doi: 10.1111/j.1442-9071.1986.tb00034.x.
PubMed 3768171Sen HN, Larson TA, Meleth AD, Smith WM, Nussenblatt RB. Subconjunctival sirolimus for the treatment of chronic active anterior uveitis: results of a pilot trial. Am J Ophthalmol. 2012 Jun;153(6):1038-42. doi: 10.1016/j.ajo.2011.12.018. Epub 2012 Apr 1.
PubMed 22465364
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
- Subconjunctival Sirolimus for the Treatment of Autoimmune Active Anterior Uveitis
- ClinicalTrials.gov ID
- NCT00876434
- Acronym / sponsor ID
- 090116
- Conditions
- Anterior Uveitis
- Keywords
- Sirolimus, Anterior Uveitis, Autoimmune Disease, Uveitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 1 Apr 2009
- Primary completion
- 10 Feb 2011 (actual)
- Study completion
- 10 Feb 2011 (actual)
- First posted
- 6 Apr 2009 (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.
Background:
- Uveitis is an inflammatory condition in which the patient's own immune system attacks the eye, causing eye inflammation and vision loss. Patients with uveitis may be treated with immunosuppressive medications to reduce the inflammation and prevent vision loss.
- Sirolimus is an immunosuppressive medication that is approved by the U.S. Food and Drug Administration (FDA) to prevent organ rejection following a kidney transplant. Researchers think that sirolimus may affect the part of the immune system that may be an important cause of uveitis, and may decrease the inflammation that causes uveitis.
- In this study, sirolimus will be given as an injection under the outer layer of your eye. The FDA has permitted the investigational use of sirolimus for this study.
Objectives:
- To determine if subconjunctival injection of sirolimus is safe for treatment of uveitis.
- To see if sirolimus is an effective treatment for uveitis.
Eligibility:
- Patients 18 years of age and older with active uveitis in one or both eyes. If a patient has uveitis in both eyes, the one in which the inflammation is worse will be treated during the study. The vision in the study eye must be at least 20/400.
- Patients must have good liver function, and must be willing to practice sun protection measures for 2 weeks following the treatment.
Design:
- Treatment with sirolimus in the study eye:
- Antibiotic and numbing eye drops will be given before the sirolimus injection.
- 1 dose of sirolimus will be injected directly into the subconjunctiva (white part of the eye).
- Antibiotic drops will be given for topical application 3 times per day for 2 days after the injection.
- Patients will be followed for 16 weeks after sirolimus injection (initial visit and follow-up visits in Weeks 2, 4, 8, 12, and 16).
- Evaluations during the treatment period and follow-up visits:
- Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
- Full medical and ophthalmic history, involving questionnaires and discussion with researchers.
- Eye examination, dilation, and photography, including measurements of retinal thickness and fluorescent dye tests of blood flow in the eye.
- Blood and urine tests.
- Because of the increased risk of skin cancer associated with sirolimus, patients ...
Detailed description
Objective: Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects and many patients continue to experience disease flare-ups. Sirolimus suppresses cytokine-driven T-cell proliferation and thus, inhibits the production, signaling and activity of many growth factors relevant to uveitis. Subconjunctival sirolimus administration could reduce or eliminate the need for topical and/or systemic immunosuppressive drugs that could result in reduced morbidity. This protocol will investigate subconjunctival sirolimus as a possible treatment for active anterior uveitis.
Study Population: Five participants with active anterior uveitis will be initially accrued in this study. Participants must require treatment for their uveitis with systemic and/or topical anti-inflammatory medications at high frequency intervals [greater than or equal to three times daily (T.I.D.)] or local steroid treatment (periocular steroid injections) is contraindicated because of significant intraocular pressure (IOP) elevation with local steroid treatments in the past (i.e., steroid responder), have at least a grade of 1+ for anterior chamber cells and have visual acuity of at least 20/400 in the study eye. Up to seven participants may be enrolled, as up to two participants may be accrued to replace enrolled participants who withdraw from the study prior to receiving any study medication.
Design: This is a Phase I, non-randomized, prospective, uncontrolled single-center study to evaluate subconjunctival sirolimus as a treatment for active anterior uveitis. All participants will receive a single 30-microL (1,320 microg) subconjunctival sirolimus injection in the study eye at baseline and will be followed for 16 weeks post-injection.
Outcome Measures: The primary outcome is the number of participants who experience at least a 2-step reduction in anterior chamber inflammation within four weeks post-injection. Secondary outcomes include changes in visual acuity and anterior chamber inflammation grading, the number of participants who experience a disease flare within the 16-week study duration and, of the participants who experience a disease flare, the number of days to disease flare from baseline. Secondary outcomes also include the presence or extent of cystoid macular edema.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Participant has the ability to understand and sign the informed consent document.
- Participant is 18 years of age or older.
- Participant's uveitis is considered active on current regimen.
- Participant has a diagnosis of non-infectious anterior uveitis requiring treatment to control their intraocular inflammatory disease with systemic and/or topical anti-inflammatory medications at high frequency intervals (greater than or equal to T.I.D.) or local steroid treatment (periocular steroid injections) is contraindicated because of significant IOP elevation with local steroid treatments in the past (steroid responder).
- Participant has anterior uveitis with at least a grade of 1+ for anterior chamber cells 1 in the study eye.
Key exclusion criteria (6 listed)
- Participant has a significant active infection (an infection requiring treatment as determined by the medical team) or a history of chronic or recurrent infections.
- Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years.
- Participant has used latanoprost (Xalatan (Registered Trademark)) within two weeks prior to study enrollment or is likely to need it at any point during the study as determined by the investigator.
- For participants with active anterior uveitis in both eyes, the participant's non-study eye is anticipated to require periocular steroids or it is anticipated that an increase in systemic immunosuppressive treatments including steroids may be required during the course of the study.
- Participant has a media opacity that precludes assessment of anterior chamber inflammation.
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 |
|---|---|---|
| Sirolimus | Drug | – |
Primary outcome
The primary outcome is the number of participants who experience at least a 2-step reduction in inflammation within four weeks post-injection.
1 secondary outcome
Changes in VA; changes in AC cells & flare-ups; number of disease flares, number of days until the first disease flare; the presence or extent of CME; the amount of retino-vascular leakage; and changes in retinal thickening.
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 16196117Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. doi: 10.1016/j.ajo.2005.03.057.
- Background: PubMed 15019324Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004 Mar;111(3):491-500; discussion 500. doi: 10.1016/j.ophtha.2003.06.014.
- Background: PubMed 3768171Wakefield D, Dunlop I, McCluskey PJ, Penny R. Uveitis: aetiology and disease associations in an Australian population. Aust N Z J Ophthalmol. 1986 Aug;14(3):181-7. doi: 10.1111/j.1442-9071.1986.tb00034.x.
- Derived from this study: PubMed 22465364Sen HN, Larson TA, Meleth AD, Smith WM, Nussenblatt RB. Subconjunctival sirolimus for the treatment of chronic active anterior uveitis: results of a pilot trial. Am J Ophthalmol. 2012 Jun;153(6):1038-42. doi: 10.1016/j.ajo.2011.12.018. Epub 2012 Apr 1.
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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 Sirolimus in people with Anterior Uveitis, 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 15 inclusion and 6 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.
What does the primary outcome measure?
The primary outcome is the number of participants who experience at least a 2-step reduction in inflammation within four weeks post-injection.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00876434, which also lists 4 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.