Know Cancer

or
forgot password

Subconjunctival Sirolimus for the Treatment of Autoimmune Active Anterior Uveitis


Phase 1
18 Years
N/A
Not Enrolling
Both
Anterior Uveitis

Thank you

Trial Information

Subconjunctival Sirolimus for the Treatment of Autoimmune Active Anterior Uveitis


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.

Inclusion Criteria


- INCLUSION CRITERIA:

- 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.

EXCLUSION CRITERIA:

- 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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Authority:

United States: Federal Government

Study ID:

090116

NCT ID:

NCT00876434

Start Date:

April 2009

Completion Date:

February 2011

Related Keywords:

  • Anterior Uveitis
  • Sirolimus
  • Anterior Uveitis
  • Autoimmune Disease
  • Uveitis
  • Uveitis
  • Chorioretinitis
  • Uveitis, Anterior
  • Iridocyclitis

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892