Efalizumab to Treat Uveitis

Condition(s) targeted: Uveitis; Intraocular Inflammatory Diseases

Intervention: Raptiva (efalizumab) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Eye Institute (NEI)

Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

This study will examine the safety and effectiveness of the monoclonal antibody efalizumab (Raptiva) for treating sight-threatening uveitis (eye inflammation). Efalizumab controls the activity of white blood cells called lymphocytes that cause inflammation. The drug is currently approved in the United States to treat patients with moderate to severe psoriasis.

Patients 18 and older with sight-threatening intermediate or posterior uveitis of at least 3 months duration, causing persistent macular edema (swelling in the back part of the eye responsible for fine vision) in one or both eyes, may be eligible for this study. The uveitis must require treatment with at least 20 milligrams per day of prednisone, or the equivalent, or a combination of two or more anti-inflammatory treatments such as prednisone, methotrexate, cyclophosphamide, cyclosporine, etc. Patients must have visual acuity of 20/100 or better in at least one eye.

Participants undergo the following tests and procedures:

- Medical history and physical examination.

- Weekly efalizumab treatment. Patients receive an injection of efalizumab under the skin

once a week.

- Weekly eye examination, including measurement of vision and pressure in the eyes,

dilation of the eyes and examination of the front part of the eye (lens, cornea and pupils) and the back part of the eye (retina and macula).

- Weekly blood tests to measure the number and types of cells in the blood and to check

for signs of inflammation and treatment side effects. At some visits, blood samples are collected to measure how much efalizumab remains in the blood and if the body has developed an immune response to the medicine.

- Blood draw at enrollment and at 2 and 4 months for research tests to examine how

patients' immune response is operating.

- Fluorescein angiography at enrollment and 1 and 3 months after enrollment, unless

additional tests are needed, for medical management. This test checks for abnormalities of eye blood vessels. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina (the back portion of the eye) are taken with a special camera that flashes a blue light into the eye. The pictures show whether any dye has leaked from the vessels into the retina, indicating possible abnormalities.

- Monthly pregnancy test for women who can become pregnant.

Patients return for treatment and clinic visits weekly for 16 weeks. After 16 weeks, patients whose macular edema has decreased and whose vision may have improved may be offered to continue the injections.

Official title: Treatment of Non-Infectious Intermediate and Posterior Uveitis Associated Macular Edema With Humanized Anti-CD11a Antibody Therapy

Study design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Reduction of macular edema

Detailed description: Background: 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. Consequently, an effective treatment with a safer side effect profile is highly desirable.

Aims: This protocol will evaluate the safety and potential efficacy of subcutaneous (SC) efalizumab (anti-CD11a) treatments for uveitis while reducing or eliminating standard medications commensurate with the standard of care. If the therapeutic benefit is sustained using the SC formulation, then maintenance therapy will continue as clinically indicated.

Methods: This is a Phase II non-randomized pilot study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

- INCLUSION CRITERIA:

1. Participant is 18 years of age or older;

2. Participant has a diagnosis of sight-threatening, intermediate or posterior uveitis of at least three months duration prior to original enrollment that is causing persistent cystoid macular edema in one or both eyes. Their disease require treatment to control their intraocular inflammatory disease with at least 20 mg/day of prednisone (or equivalent) or any combination of two or more anti-inflammatory treatments for uveitis, including for example prednisone, cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, methotrexate, etc.

3. Participant exhibits intolerance to the indicated systemic medications required for their uveitis or, though their uveitis may be under control, wish to be taken off their present medications due to potential or actual unacceptable side effects.

4. Participant has visual acuity in at least one eye of 20/100 or better.

5. Participant has normal renal or liver function or no worse than mild abnormalities as defined by the Common Toxicity Criteria.

6. Participant is not currently pregnant or lactating.

7. Both men and women with reproductive potential and who are sexually active agree to use acceptable birth control methods throughout the course of the study and for six weeks following the last administration of the study medication.

8. Participant must have the ability to understand and sign an informed consent form.

EXCLUSION CRITERIA:

1. Participants who had received previous treatment with an ICAM or LFA-1 directed monoclonal antibody or any other investigational agent that would interfere with the ability to evaluate the safety, efficacy or pharmacokinetics of efalizumab.

2. Participant has a significant active infection.

3. Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past 5 years.

Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting

NIH Clinical Center Detailed Web Page

Related publications:

Djalilian AR, Nussenblatt RB. Immunosuppression in uveitis. Ophthalmol Clin North Am. 2002 Sep;15(3):395-404, viii. Review.

Leonardi CL. Efalizumab: an overview. J Am Acad Dermatol. 2003 Aug;49(2 Suppl):S98-104. Review.

Whitcup SM, Hikita N, Shirao M, Miyasaka M, Tamatani T, Mochizuki M, Nussenblatt RB, Chan CC. Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit endotoxin-induced uveitis. Exp Eye Res. 1995 Jun;60(6):597-601.

Starting date: January 2006
Last updated: July 18, 2008