Subconjunctival Sirolimus for the Treatment of Autoimmune Active Anterior Uveiti

NCT00876434 | Completed Phase 1

• 2 other identifiers: 09011609-EI-0116
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.
• 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 ...

Conditions

Anterior Uveitis

Keywords

Sirolimus; Anterior Uveitis; Autoimmune Disease; Uveitis

Outcome Measures

Primary Outcomes (1)

• 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.

Interventions

Sirolimus DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 16196117 BACKGROUND

• Gritz 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.

  PMID: 15019324 BACKGROUND

• Wakefield 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.

  PMID: 3768171 BACKGROUND

• Sen 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.

  PMID: 22465364 DERIVED

MeSH Terms

Conditions

Uveitis, Anterior; Autoimmune Diseases; Uveitis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Panuveitis; Uveal Diseases; Eye Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 3, 2009
• First Posted: April 6, 2009
• Study Start: April 1, 2009
• Primary Completion: February 10, 2011
• Study Completion: February 10, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-02-10

Locations

US (1)