Clinical trial NCT00280826: Efalizumab to Treat Uveitis
Official title: Treatment of Non-Infectious Intermediate and Posterior Uveitis Associated Macular Edema With Humanized Anti-CD11a Antibody Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Uveitis
Macular Edema
Keywords: OCT
Retinal Disease
Adhesion Molecule
Ocular Inflammation
Raptiva
Macular Edema
Uveitis
Immunosuppression
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2006-01-23
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study examined the safety and potential efficacy 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.

Participants 18 and older with sight-threatening intermediate or posterior uveitis of at least 3 months duration, causing persistent macular edema in one or both eyes, were eligible for this study. The uveitis required 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.

Participants underwent the following tests and procedures:

* Medical history and physical examination.
* Weekly efalizumab treatment.
* Weekly eye examination, including measurement of vision and pressure in the eyes, dilation of the eyes and examination of the front and back parts of the eye.
* 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 were collected to measure how much efalizumab remains in the blood and whether 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 participants' immune response was operating.
* Fluorescein angiography at enrollment and 1 and 3 months after enrollment, unless additional tests are needed, for medical management. This test checked for abnormalities of eye blood vessels. A yellow dye was injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina (the back portion of the eye) were 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 could become pregnant.

Participants returned for treatment and clinic visits weekly for 16 weeks. After 16 weeks, participants whose macular edema had decreased and whose vision may have improved were offered to continue the injections.

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 evaluated 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 was sustained using the SC formulation, then maintenance therapy was continued as clinically indicated.

Methods: This was an open-label, non-randomized, clinical pilot study.

Eligibility criteria: Inclusion Criteria:

* Participant is 18 years of age or older;
* 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 requires 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.
* 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.
* Participant has visual acuity in at least one eye of 20/200 or better.
* Participant has normal renal or liver function or no worse than mild abnormalities as defined by the Common Toxicity Criteria.
* Participant is not currently pregnant or lactating.
* 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.
* Participant must have the ability to understand and sign an informed consent form.

Exclusion Criteria:

* Participants who had received previous treatment with an intercellular adhesion molecule (ICAM) or lymphocyte function-associated antigen-1 (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.
* Participant has a significant active infection.
* Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past 5 years.

Primary outcomes:
measure: Number of Participants With Systemic Toxicities, Adverse Events, or Infections
timeFrame: 16 weeks
Secondary outcomes:
measure: Cystoid Macular Edema in the Worse Eye as Assessed by Optical Coherence Tomography (OCT).
timeFrame: Baseline and 16 weeks
measure: Cystoid Macular Edema in the Better Eye as Assessed by Optical Coherence Tomography (OCT).
timeFrame: Baseline and 16 weeks
measure: Change in Visual Acuity in the Worse Eye From Baseline to 16 Weeks
timeFrame: Baseline and 16 weeks
measure: Change in Visual Acuity in the Better Eye From Baseline to 16 Weeks
timeFrame: Baseline and 16 weeks
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
Study officials:
affiliation: National Eye Institute (NEI)
name: Robert Nussenblatt, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Djalilian AR, Nussenblatt RB. Immunosuppression in uveitis. Ophthalmol Clin North Am. 2002 Sep;15(3):395-404, viii. doi: 10.1016/s0896-1549(02)00036-6.
citation: Leonardi CL. Efalizumab: an overview. J Am Acad Dermatol. 2003 Aug;49(2 Suppl):S98-104. doi: 10.1016/s0190-9622(03)01141-1.
citation: 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. doi: 10.1016/s0014-4835(05)80001-6.
citation: Faia LJ, Sen HN, Li Z, Yeh S, Wroblewski KJ, Nussenblatt RB. Treatment of inflammatory macular edema with humanized anti-CD11a antibody therapy. Invest Ophthalmol Vis Sci. 2011 Sep 1;52(9):6919-24. doi: 10.1167/iovs.10-5896.