Intravitreal Sirolimus as Therapeutic Approach to Uveitis



Status:Recruiting
Conditions:Cervical Cancer, Ocular
Therapuetic Areas:Oncology, Ophthalmology
Healthy:No
Age Range:18 - Any
Updated:9/7/2018
Start Date:March 2011
End Date:December 2019
Contact:Quan D Nguyen, MD, MSc
Email:ndquan@stanford.edu
Phone:6507244280

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Sirolimus as a Therapeutic Approach for Uveitis: A Phase 2, Open-label, Randomized Study to Assess the Safety, Tolerability, and Bioactivity of Two Doses of Intravitreal Injection of Sirolimus in Patients With Non-infectious Uveitis

The purpose of this study is to find out about the safety and effectiveness of two different
doses the study drug, sirolimus, administered intravitreally in patients with uveitis. The
potential effectiveness of sirolimus can be utilized to control inflammation in uveitis and
yet avoid the potential complications that are usually associated with the systemic use of
the drug and other immunomodulatory therapies. In this study, the investigators will
administer sirolimus inside the eye (intravitreally) in one of two doses (440mcg/mcL or
880mcg/mcL). Local administration of sirolimus to the eye is not expected to have effects on
the rest of the body. Therefore, it may offer a safer way than the current methods used to
control the inflammation caused by non-infectious uveitis.

Uveitis is a condition in which certain parts of your eye become inflamed. The inflammation
is usually recurrent. If the inflammation is not treated adequately, permanent damage to the
eye and to the vision may occur. The inflammation can be caused by infectious or non
infectious causes. The current research is being done to determine the safety and the
usefulness of treatment of non-infectious uveitis using different doses of intravitreal
injections of a drug called sirolimus.

Current treatment options for uveitis include oral corticosteroids and drugs that weaken the
immune system of the body (i.e., immunosuppressant drugs). Treatment using oral
corticosteroids, especially for long periods, may cause many undesirable side effects and
complications such as high blood sugar, high blood pressure, bone weakness, obesity, stomach
ulcers, abnormal hair growth, and increased risks of infection. In addition to that, in some
cases, the disease cannot be controlled even with the highest dose of steroids.

Injection of steroids around and inside the eye can be used to control uveitis. However, the
inflammation does not always respond to such kind of treatment. The eyes may develop high
pressure and cataract with injections of steroids into the eyes or around the eyes.

On the other hand, despite their potential effectiveness, treatment with drugs that weaken
the immune system may cause severe side effects. Increased risk of infection is a common side
effect of all the immunosuppressant drugs. The immune system protects the body from
infections. When the immune system is suppressed, infections are more likely to happen. Some
of these infections are potentially dangerous. Because the immune system protects the body
against some forms of cancer, immunosuppressant drugs are also associated with a slightly
increased risk of cancer. For example, long-term use of immunosuppressant drugs may carry an
increased risk of developing skin cancer as a result of the combination of the drugs and
exposure to sunlight. The immunosuppressive drugs are very powerful and can cause serious
side effects such as high blood pressure, kidney problems, and liver problems. Some side
effects may not show up until years after the medicine is used.

Inclusion Criteria:

1. Males and females greater than or equal to 12 years of age.

2. Able to give informed consent and attend all study visits.

3. Have diagnosis of uveitis determined by the Investigator to be non-infectious based on
the patient's medical history, history of present illness, ocular examination, review
of systems, physical examination, and any pertinent laboratory evaluations.

4. Meet the following criteria:

- Have active uveitis, defined as having at least 1+ Vitreous Haze and/or at least
1+ Vitreous Cell Count (SUN scale), and:

- are receiving no treatment; or

- are receiving:

- prednisone ≥ 10 mg/day (or equivalent dose of another corticosteroid), or

- at least 1 systemic immunosuppressant other than corticosteroids, or

- combination of prednisone ≥ 10 mg/day (or equivalent dose of another
corticosteroid) and other systemic immunosuppressant.

- Have inactive disease, defined as having 0.5+ Vitreous Haze or less and 0.5+ or
less Vitreous Cell Count (SUN scale), and:

- are receiving:

- prednisone <10 mg/day (or equivalent dose of another corticosteroid), or

- at least 1 systemic immunosuppressant other than corticosteroids, or

- combination of prednisone <10 mg/day (or equivalent dose of another
corticosteroid) and other systemic immunosuppressant.

- Have posterior, intermediate, or panuveitis; for panuveitis, if an anterior
component is present, it must be less than the posterior component.

- Sufficient inflammation to require systemic treatment and, based on the
Investigator's decision, warrants intravitreal treatment.

- Best-corrected ETDRS visual acuity of 20/400 or better (approximately 20 letters)
in the study eye.

- Best-corrected ETDRS visual acuity of 20/400 or better in the fellow eye
(approximately 20 letters).

Exclusion Criteria:

1. Patients with bilateral uveitis who are receiving systemic immunosuppressive therapy
(e.g., methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate
mofetil, tacrolimus, or azathioprine) other than prednisone or other corticosteroids
for the treatment of uveitis and the uveitis in the fellow eye, in the opinion of the
Investigator, cannot be controlled with standard local therapies alone;

2. Any significant ocular disease that could compromise the visual outcome in the study
eye.

3. Intravitreal injections (including but not limited to anti-vascular endothelial growth
factors 60 days prior to the baseline;

4. Posterior subtenon's or intravitreal injection of steroids 90 days prior to Baseline;

5. Intraocular surgery within 90 days prior to Day 0 in the study eye;

6. Capsulotomy within 30 days prior to Day 0 in the study eye;

7. History of vitreoretinal surgery or scleral buckling within 90 days prior to Day 0 in
the study eye;

8. Any ocular surgery (including cataract extraction or capsulotomy) of the study eye
anticipated within the first 180 days following Day 0;

9. Intraocular pressure ≥25 mmHg in the study eye (glaucoma patients maintained on no
more than 2 topical medications with IOP <25 mmHg are allowed to participate);

10. Pupillary dilation inadequate for quality fundus photography in the study eye;

11. Media opacity that would limit clinical visualization, intravenous fluorescein
angiography (IVFA), or OCT evaluation in the study eye;

12. Presence of any form of ocular malignancy in the study eye, including choroidal
melanoma;

13. History of herpetic infection in the study eye or adnexa;

14. Presence of known active or inactive toxoplasmosis in either eye;

15. Ocular or periocular infection in either eye;

16. Participation in other investigational drug or device clinical trials within 30 days
prior to Day 0, or planning to participate in other investigational drug or device
clinical trials within 180 days following Day 0. This includes both ocular and
non-ocular clinical trials.
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Palo Alto, California 94304
Phone: 650-724-4280
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