Rituximab for Autoimmune Retinopathy

NCT01086631 | Completed Phase 1

• 2 other identifiers: 10004010-EI-0040
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Autoimmune Disease

Keywords

Autoimmune Retinopathy; RITUXAN; Rituximab; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• The primary outcome is the number of participants who meet the definition of treatment success within six months from baseline.

Secondary Outcomes (1)

• Changes in visual acuity, number of treatment successes or partial responders, changes in ERG, HFA, OCT or FA, changes in serum antibody staining, changes in color vision, and changes in quality-of-life.

Interventions

Rituximab DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Weinstein JM, Kelman SE, Bresnick GH, Kornguth SE. Paraneoplastic retinopathy associated with antiretinal bipolar cell antibodies in cutaneous malignant melanoma. Ophthalmology. 1994 Jul;101(7):1236-43. doi: 10.1016/s0161-6420(94)31183-3.

  PMID: 8035987 BACKGROUND

• Jacobson DM, Thirkill CE, Tipping SJ. A clinical triad to diagnose paraneoplastic retinopathy. Ann Neurol. 1990 Aug;28(2):162-7. doi: 10.1002/ana.410280208.

  PMID: 2171418 BACKGROUND

• Weleber RG, Watzke RC, Shults WT, Trzupek KM, Heckenlively JR, Egan RA, Adamus G. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol. 2005 May;139(5):780-94. doi: 10.1016/j.ajo.2004.12.104.

  PMID: 15860281 BACKGROUND

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hatice N Sen, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2010
• First Posted: March 15, 2010
• Study Start: January 22, 2010
• Study Completion: July 8, 2014
• Last Updated: July 5, 2018

Record last verified: 2014-07-08

Locations

US (1)