Rituximab for Autoimmune Retinopathy

• Status: Completed
• Trial end date: 2014-07-08
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Autoimmune retinopathy (AIR) is an inflammatory condition in which the patient s own immune system is attacking his or her eyes and causing vision loss. Patients with AIR are generally treated with immunosuppressive agents to treat the eye inflammation; however, the standard treatment for this disease is still being developed.

• Rituximab, an immunosuppressive agent, is a monoclonal antibody that is directed against a part of the immune system that may be an important cause of AIR. Rituximab is approved for the treatment of non-Hodgkin s lymphoma and rheumatoid arthritis, but is not approved for the treatment of AIR. Researchers are interested in determining whether rituximab may be used to treat AIR.

Objectives:

• To to investigate the safety, tolerability and possible efficacy of rituximab as a treatment for AIR.

Eligibility:

• Individuals at least 18 years of age who have been diagnosed with AIR and have visual acuity of 20/200 or better in at least one eye.

Design:

• Before the start of the study, participants will be screened with a medical history, immunization records, a series of eye examinations, a chest X-ray, an electrocardiogram, and blood tests.

• Participants will receive a maximum of two cycles of rituximab during the 18-month study. Each cycle will involve two separate intravenous infusions of rituximab given 2 weeks apart.

• Participants will return to the clinic 6 weeks after the first cycle of rituximab for a safety visit, which will include a routine eye and physical examinations. They will also provide blood and other samples for study.

• After the safety visit, participants will return every 3 months for follow-up visits.

• At the 6-month visit, participants who have successfully or partially responded to rituximab will receive another cycle of treatment. Those who do not respond will not receive another cycle, but will continue to be monitored until the end of the study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Eye Institute (NEI)
• Treatments: Rituximab

Criteria

• INCLUSION CRITERIA:

Participant must be 18 years of age or older.

Participant must understand and sign the protocol s informed consent document.

Participant must be willing to comply with the study procedures and expected to be able to return for all study visits.

Participant must have a diagnosis of AIR according to the features listed below.

Participants must have demonstrated evidence of anti-retinal antibodies as noted in criterion a and one or more of the clinical manifestations listed in either criterion b or c in order to be considered eligible.

1. Serologic or immunohistochemical demonstration of serum anti-retinal antibodies (on normal, unfixed, frozen rhesus monkey or human retinas.

2. Visual field changes

i. Defects in visual fields [on HFA (30-2) or GVF]

ii. Enlarged blind spot

c. ERG changes

i. Abnormal amplitudes

ii. Prolonged implicit times.

Participant must have visual acuity of 20/200 or better in at least one eye.

Participant must have normal renal function, liver function and blood cell counts, OR has mild abnormalities and is cleared for enrollment by internal medicine.

Participant must agree not to receive any live or live-attenuated vaccinations (e.g., nasal flu vaccine [FluMist ] or Zostavax ) for the duration of the study.

Participant must have clear ocular media and adequate pupillary dilation to permit quality imaging.

Participant must have a negative PPD screening test as defined by the Centers for Disease Control (CDC) unless otherwise cleared by internal medicine (i.e., previously treated for a positive PPD or a history of Bacillus of Calmette and Guerin (BCG) vaccination).

Female participants of childbearing potential must not be pregnant or breast-feeding, must have a negative serum pregnancy test at screening and must be willing to undergo 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 contraception throughout the course of the study and for 12 months following the last administration of the investigational product. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation or vasectomy).

*Childbearing potential must be determined

**Participants with a hysterectomy or vasectomy (or who have a partner with a hysterectomy or vasectomy) are exempt from using two methods of contraception. However, 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 contraception.

EXCLUSION CRITERIA:

Participant received other biologic agents (e.g., infliximab, daclizumab or adalimumab) within three months prior to study enrollment.

Participant is receiving more than two immunosuppressive agents or experienced a change in his/her AIR immunosuppressive medication regimen within the two months prior to enrollment.

Participant received intraocular or periocular steroid injections within two months prior to study enrollment.

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 is HIV positive or has syphilis.

Participant has a history of cancer (other than a non-melanoma skin cancer or non-Hodgkin s lymphoma [NHL]) diagnosed within the past five years.

Participant has or is a carrier of hepatitis B or C.

Participant has a known hypersensitivity to sodium fluorescein dye.

Participant has congestive heart failure, abnormal cardiac function or significant pulmonary disease.

Participant is participating in another simultaneous investigational product treatment trial.

Participant received a live or live-attenuated vaccine within the previous four weeks prior to study enrollment

Participant had ocular surgery within 60 days prior to study enrollment or is anticipated to require elective intraocular surgery.

Participant has inadequately controlled diabetes.

Participant has a condition that, in the opinion of the investigator, would pose a significant hazard to the participant if the investigational product was initiated.

Participant has any other condition that would be contraindicated to treatment with rituximab or their current immunosuppressive agent.