Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00908466
Other study ID # NA_00028588
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date July 2009
Est. completion date February 2013

Study information

Verified date December 2017
Source Johns Hopkins University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to find out about the safety and effectiveness of the study drug, sirolimus, in patients with uveitis and to utilize the potential effectiveness of sirolimus, and yet to avoid the potential complications of systemic use of the drug. In this study, the investigators will administer sirolimus either around (subconjunctival injection) or inside the eye (intravitreal injection). 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.


Description:

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 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.


Recruitment information / eligibility

Status Completed
Enrollment 30
Est. completion date February 2013
Est. primary completion date July 2012
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Males and females greater than or equal to 18 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;

- 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 other treatment; or,

- are receiving prednisone =10 mg/day (or equivalent dose of another corticosteroid) and/or at least 1 other systemic immunosuppressant; or, b. Have inactive disease, defined as having 0.5+ Vitreous Haze or less and a grade of 0.5+ Vitreous Cell Count or less (SUN scale), and:

- are receiving prednisone <10 mg/day (or equivalent dose of another corticosteroid) and/or at least 1 other systemic immunosuppressant.

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

5. Sufficient inflammation to require systemic treatment and, based on the Investigator's decision, warrants intravitreal or subconjunctival treatment;

6. Best-corrected (ETDRS) visual acuity of 20/40 to 20/400 (approximately 70 to 20 letters) in the study eye;

7. 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 the uveitis, and the uveitis in the fellow eyes, in the opinion of the investigator, cannot be controlled with standard local therapies alone;

2. Any significant ocular disease that could compromise vision in the study eye. These include, but are not limited to:

- Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or non-proliferative diabetic retinopathy (NPDR) that compromise the vision.

- Age-related macular degeneration;

- Myopic degeneration with active subfoveal choroidal neovascularization.

3. Any of the following treatments within 90 days prior to Day 0 or anticipated use of any of the following treatments to the study eye:

- Intravitreal injections (including but not limited to steroids or anti-vascular endothelial growth factors);

- Posterior subtenon's steroids.

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

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

6. If the patient has had glaucoma surgery (trabeculectomy or aqueous shunt device), there must be adequate conjunctiva

7. History of vitreoretinal surgery or scleral buckling

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 intraocular pressure (IOP) <25 mmHg are allowed to participate);

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

11. Media opacity that would limit clinical visualization;

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.

Study Design


Intervention

Drug:
Sirolimus (rapamycin)
Will receive intravitreal injections of sirolimus (rapamycin) 352 µg in study eye on Days 0, 60, and 120.
Sirolimus (rapamycin)
Will receive subconjunctival injections of sirolimus 1320 µg in the study eye on Days 0, 60, and 120.

Locations

Country Name City State
United States Wilmer Eye Institute at Johns Hopkins University Baltimore Maryland

Sponsors (2)

Lead Sponsor Collaborator
Johns Hopkins University MacuSight, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants With at Least 2-step Decrease in Vitreous Haze (VH) Vitreous Haze is calculated using a 9 step photographic haze in uveitis patients using fundus photograph 6 months
Secondary Change From Baseline VA by ETDRS 6 and 12 months
See also
  Status Clinical Trial Phase
Recruiting NCT04101604 - Biomarkers of Common Eye Diseases
Active, not recruiting NCT04704609 - Imaging Quantification of Inflammation (IQI)
Completed NCT03173144 - Chronic Inflammatory Disease, Lifestyle and Treatment Response
Withdrawn NCT01280669 - Intravitreal Sirolimus as Therapeutic Approach to Uveitis Phase 2
Terminated NCT02907814 - Measurement of Anterior Chamber Cell Grading Using Ocular Coherence Tomography N/A
Active, not recruiting NCT02252328 - Use of Simvastatin as a Steroid Sparing Agent for Uveitis Patients Phase 2/Phase 3
Completed NCT04183387 - Simvastatin in Uveitis Phase 2
Completed NCT01983488 - Clinical Outcome in Uveitis
Withdrawn NCT00499551 - A Phase I/IIa Study for the Treatment of Uveitis With Iontophoresis Phase 1/Phase 2
Completed NCT00476593 - Retinal OCT and (mfERG) Related to Age, Sex, and the Use of Anti-inflammatory Medications N/A
Terminated NCT00114062 - Study to Treat Uveitis Associated Macular Edema Phase 2
Completed NCT00132691 - Multicenter Uveitis Steroid Treatment (MUST) Trial Phase 4
Completed NCT00001867 - Effect of Pregnancy on Uveitis N/A
Completed NCT00379275 - Eye and Immunogenetic Features of Sarcoidosis N/A
Active, not recruiting NCT03828019 - Adalimumab vs. Conventional Immunosuppression for Uveitis Trial Phase 3
Terminated NCT01939691 - Macular Edema Nepafenac vs. Difluprednate Uveitis Trial Phase 4
Active, not recruiting NCT03889860 - Objective Choroidal Thickness Measurements in Uveitis
Completed NCT00070759 - Daclizumab to Treat Non-Infectious Sight-Threatening Uveitis Phase 2
Recruiting NCT05486468 - The Use of Two YUTIQ Versus Sham for Treatment of Chronic Non Infectious Intraocular Inflammation Affecting the Posterior Segment Phase 3
Active, not recruiting NCT05385757 - UNICORNS: Uveitis in Childhood Prospective National Cohort Study